Comprehensive Management of Skull Base Tumors

about the book… The management of tumors in and adjacent to the skullbase is challenging given the complex and critically important anatomy of the region and the wide diversity of tumor pathologies that may be encountered. To help navigate the complexities of contemporary multidisciplinary management of these patients, Drs. Hanna and DeMonte bring you Comprehensive Management of Skull Base Tumors, a comprehensive guide filled with updated information from authorities around the world. Comprehensive Management of Skull Base Tumors is divided into three sections consisting of: • general principles • site specific surgery • tumor specific management Filled with scientific tables and lavishly illustrated, this text is written with an emphasis on surgery, radiation and chemotherapy, and will appeal to all neurosurgeons, otolaryngologists, plastic surgeons, maxillofacial surgeons, ophthalmologists, medical and radiation oncologists, and radiologists. about the editors... EHAB Y. HANNA is Professor of Head and Neck Surgery and Neurosurgery, The University of Texas M.D. Anderson Cancer Center, and Adjunct Professor of Otolaryngology, Baylor College of Medicine, Houston, Texas, USA. Dr. Hanna is also Vice Chair for Clinical Affairs and Medical Director of the Head and Neck Center at M.D. Anderson Cancer Center. He obtained his M.D. from Ain Shams University School of Medicine, Cairo, Egypt. Dr. Hanna currently serves on the editorial boards of several publications; he is Editor-in-Chief of Head and Neck and Editor of the Head and Neck Cancers Section of Current Oncology Reports. He is an involved member of the American Head and Neck Society, the North American Skull Base Society, the American Academy of Otolaryngology-Head and Neck Surgery, the American College of Surgeons, and the National Cancer Institute. Dr. Hanna has been nationally recognized as one of “America’s Top Doctors” and “America’s Top Doctors for Cancer”. He has been a frequent invited guest speaker at national and international conferences and lectures and has contributed to numerous peer-reviewed publications in the fields of head and neck cancer and skull base tumors. FRANCO DEMONTE is Professor of Neurosurgery and Head and Neck Surgery, Deputy Chairman of the Department of Neurosurgery, and Medical Director of the Brain and Spine Center, The University of Texas M.D. Anderson Cancer Center, Houston, Texas, USA. Dr. DeMonte is also an adjunct professor of neurosurgery at Baylor College of Medicine, Houston, Texas, USA. He received his M.D. from the University of Western Ontario, London, Canada. He is an active member of several organizations, including the Society of Neurological Surgeons, the American Association of Neurological Surgeons, and the Canadian Neurosurgical Society. He has served as president of the North American Skull Base Society and of the Houston Neurological Society. His clinical and educational activities have been recognized through his national and international presentations as well as by several teaching awards and inclusion in “Best Doctors in America” and “America’s Top Doctors”. Printed in the United States of America

Comprehensive Management of Skull Base Tumors

Otolaryngology/Neurosurgery

Comprehensive Management of Skull Base Tumors Edited by

Ehab Y. Hanna & Franco DeMonte

Hanna DK054X

•

DeMonte



Comprehensive Management of Skull Base Tumors

Comprehensive Management of Skull Base Tumors Edited by

Ehab Y. Hanna

The University of Texas M.D. Anderson Cancer Center Houston, Texas, USA

Franco DeMonte

The University of Texas M.D. Anderson Cancer Center Houston, Texas, USA

Informa Healthcare USA, Inc. 52 Vanderbilt Avenue New York, NY 10017
C

2009 by Informa Healthcare USA, Inc. Informa Healthcare is an Informa business No claim to original U.S. Government works Printed in the United States of America on acid-free paper 10 9 8 7 6 5 4 3 2 1 International Standard Book Number-10: 0-8493-4054-3 (Hardcover) International Standard Book Number-13: 978-0-8493-4054-3 (Hardcover) This book contains information obtained from authentic and highly regarded sources. Reprinted material is quoted with permission, and sources are indicated. A wide variety of references are listed. Reasonable efforts have been made to publish reliable data and information, but the author and the publisher cannot assume responsibility for the validity of all materials or for the consequence of their use. No part of this book may be reprinted, reproduced, transmitted, or utilized in any form by any electronic, mechanical, or other means, now known or hereafter invented, including photocopying, microfilming, and recording, or in any information storage or retrieval system, without written permission from the publishers. For permission to photocopy or use material electronically from this work, please access www.copyright.com (http://www.copyright.com/) or contact the Copyright Clearance Center, Inc. (CCC) 222 Rosewood Drive, Danvers, MA 01923, 978-750-8400. CCC is a not-for-profit organization that provides licenses and registration for a variety of users. For organizations that have been granted a photocopy license by the CCC, a separate system of payment has been arranged. Trademark Notice: Product or corporate names may be trademarks or registered trademarks, and are used only for identification and explanation without intent to infringe.

Library of Congress Cataloging-in-Publication Data Comprehensive management of skull base tumors / edited by Ehab Y. Hanna, Franco DeMonte. p. ; cm. Includes bibliographical references and index. ISBN-13: 978-0-8493-4054-3 (hardcover : alk. paper) ISBN-10: 0-8493-4054-3 (hardcover : alk. paper) 1. Skull base–Cancer. 2. Skull base–Tumors–Surgery. I. Hanna, Ehab Y. II. DeMonte, Franco. [DNLM: 1. Skull Base Neoplasms. WE 707 C7374 2008] RD662.5.C66 2008 616.99 481–dc22 2008036404

For Corporate Sales and Reprint Permissions call 212-520-2700 or write to: Sales Department, 52 Vanderbilt Avenue, 16th floor, New York, NY 10017. Visit the Informa Web site at www.informa.com and the Informa Healthcare Web site at www.informahealthcare.com

This book is dedicated to My wife, Sylvie, for her grace, gentle spirit, and beauty; Our daughters, Gabrielle Grace “Gigi” Hanna and Camille Lauren Hanna, for the joy and blessing they bring to our lives; My parents, who encouraged me to follow my dreams; My Fellows, residents, and students, who continue to teach me; And my patients, Whose endurance, resilience, and faith continue to amaze me. Ehab Y. Hanna, MD

My parents, Dolinda and Giacomo, for their love, their sacrifices, and their dedication to my education. To my children, Evan and Madeline who fill me with pride. And, with limitless love, to Paula, my wife and best friend. Franco DeMonte, MD

Preface

Section two covers site-specific information regarding the various anatomic regions of the cranial base, including surgical anatomy, regional pathology, differential diagnosis, clinical assessment, diagnostic imaging, and surgical approaches. This regional classification includes the anterior cranial fossa, sinonasal region, nasopharynx, clivus, infratemporal fossa, parapharyngeal space, temporal bone, sella turcica, middle cranial fossa, petrous apex, cerebellopontine angle, jugular foramen, and craniovertebral junction. Section three covers comprehensive multidisciplinary discussion of tumor-specific topics such as tumor incidence and epidemiology, pathology, staging, treatment, outcome, and prognosis. This section covers the following tumors of the cranial base: squamous and nonsquamous cell carcinoma, olfactory neuroblastoma, melanoma, sarcomas, angiofibromas and other vascular tumors, chordomas and chondrosarcomas, meningiomas, schwannomas, paragangliomas, pituitary adenomas, craniopharyngiomas, epidermoid and dermoid cysts, fibro-osseous lesions, and metastatic tumors. This organizational schema is intended to provide a simple yet comprehensive way for readers to find the information they need. For example, the reader who wants to know about the latest advances in radiation therapy of skull base tumors is referred to the first section, a reader who has a patient with a tumor of the petrous apex is referred to the second section, and another who wants to know all the available treatment options and prognostic factors for esthesioneuroblastoma is referred to the third section. With such an organizational structure, some redundancy is unavoidable, but not, as you will see, detrimental. As with any textbook, some omissions are inevitable and we hope our readership will forgive any shortcomings of this work. We believe that the greatest value of this book is the incredible expertise of the contributing authors. They truly represent the world’s experts on their specific topics. We are honored by their contribution and humbled by their graciousness to join us in this work.

The management of patients with tumors of the skull base has evolved significantly in the last two decades. Major advances have been achieved in the surgical management of these patients, particularly in the areas of tumor resection and surgical reconstruction. These advances can be mainly attributed to the collaborative efforts of dedicated teams representing various surgical disciplines including neurosurgery, head and neck surgery, neuro-otology, oromaxillofacial surgery, ophthalmology, and plastic and reconstructive surgery. Meanwhile significant advances in radiation delivery using various methods of conformal therapy, including three-dimensional computerized tomography (3D-CT), intensity-modulated radiation therapy (IMRT), proton beam therapy, and stereotactic radiation, as well as advances in chemotherapy and targeted biologic therapy have added significantly to the menu of treatment options for patients with tumors of the skull base. Although there are many excellent references describing the surgical management of patients with tumors of the cranial base, this textbook is intended to be a comprehensive guide to help navigate the complexity of contemporary multidisciplinary management of these patients. In addition, we hope that this reference will also provide the reader with deeper understanding of the unique biologic behavior and the underlying molecular and genetic aberrations of the various tumor types originating from or involving the cranial base, and the potential for these molecular derangements to be putative targets for future development of more effective biologic therapy. To address these goals, we have organized the book in three sections: general principles, site-specific chapters, and tumor-specific chapters. Section one covers general topics pertinent to all patients with neoplasms of the skull base, regardless of specific location or tumor type. These topics include anatomy, pathology, genetics, clinical evaluation, diagnostic imaging, anesthesia, minimally invasive surgery, surgical reconstruction, prosthetic rehabilitation, radiation and radiobiology, chemotherapy, evaluation and rehabilitation of speech and swallowing, functional outcomes and quality of life issues, neurocognitive assessment, and cerebrovascular management.

Ehab Y. Hanna Franco DeMonte

v

Contents

Preface . . . . v Contributors . . . . ix

12. Rehabilitation of Speech and Swallowing of Patients with Tumors of the Skull Base 181 Gail L. Davie, Denise A. Barringer, and Jan S. Lewin

Section 1: General Principles

13. Quality of Life of Patients with Skull Base Tumors 189 Ziv Gil and Dan M. Fliss

1. Anatomy of the Cranial Base 3 Carolina Martins and Albert L. Rhoton, Jr.

14. Neurocognitive Assessment of Patients with Tumors of the Skull Base 201 Mariana Witgert and Tracy Veramonti

2. Pathology of Tumor and Tumor-like Lesions of the Skull Base 43 Michelle D. Williams and Adel K. El-Naggar

15. Cerebrovascular Management in Skull Base Tumors 207 Sabareesh Kumar Natarajan, Basavaraj Ghodke, and Laligam N. Sekhar

3. Genetic Abnormalities of Skull Base Tumors 63 Ziv Gil and Dan M. Fliss 4. Imaging of Skull Base Neoplasms 81 Lawrence E. Ginsberg

Section 2: Site-Specific Considerations

5. Head, Neck, and Neuro-otologic Assessment of Patients with Tumors of the Skull Base: Clinical Examination, Auditory Testing, Vestibular Testing, and Equilibrium 95 Paul W. Gidley

16. Surgical Management of Tumors of the Nasal Cavity, Paranasal Sinuses, Orbit, and Anterior Skull Base 227 Ehab Y. Hanna, Michael Kupferman, and Franco DeMonte

6. Anesthesia and Intraoperative Monitoring of Patients with Tumors of the Skull Base 119 Walter S. Jellish and Steven B. Edelstein

17. Tumors of the Nasopharynx 267 William Ignace Wei and Paul K. Y. Lam 18. Clival Tumors 277 Franco DeMonte, Mark J. Dannenbaum, and Ehab Y. Hanna

7. Minimally Invasive Techniques: Endonasal Endoscopic Skull Base Surgery 131 Allan D. Vescan, Ricardo L. Carrau, Carl H. Snyderman, Amin B. Kassam, Arlan Mintz, and Paul Gardner

19. Tumors of the Anterior Skull Base 293 Vijayakumar Javalkar, Bharat Guthikonda, Prasad Vannemreddy, and Anil Nanda

8. Reconstruction of Skull Base Defects 139 Peter C. Neligan, Christine B. Novak, and Patrick J. Gullane

20. Infratemporal/Middle Fossa Tumors 305 Paul J. Donald

9. Prosthetic Rehabilitation of Patients Undergoing Skull Base Surgery 149 Theresa M. Hofstede, Rhonda F. Jacob, Pattii C. Montgomery, Peggy J. Wesley, Jack W. Martin, and Mark S. Chambers

21. Tumors of the Parapharyngeal Space 331 Eric J. Moore and Kerry D. Olsen 22. Tumors of the Temporal Bone 345 Sam J. Marzo and John P. Leonetti

10. Radiobiology and Radiation Therapy of Skull Base Tumors 159 Simon S. Lo, John H. Suh, and Eric L. Chang

23. Evaluation and Management of Sellar Tumors 355 Jay Jagannathan, Edward R. Laws, and John A. Jane, Jr.

11. Chemotherapy for Skull Base Tumors 175 Bilal Ahmed, Ehab Y. Hanna, and Merrill S. Kies

24. Tumors of the Middle Cranial Fossa 367 Ali A. Baaj, Siviero Agazzi, and Harry R. van Loveren

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viii

Contents

25. Tumors of the Petrous Apex 375 Ricardo Ramina, Maur´ıcio Coelho Neto, Yvens Barbosa Fernandes, Erasmo Barros da Silva, Jr., and Kristofer Luiz Fingerle Ramina 26. Tumors of the Cerebellopontine Angle 389 Bryan C. Oh, Daniel J. Hoh, and Steven L. Giannotta 27. Tumors of the Jugular Foramen 403 Samer Ayoubi, Badih Adada, and Ossama Al-Mefty 28. Tumors of the Craniovertebral Junction 417 Douglas Fox, Scott Wait, Steve Chang, G. Vini Khurana, Curtis A. Dickman, Volker K. H. Sonntag, and Robert F. Spetzler

Section 3: Tumor-Specific Considerations 29. Squamous Cell Carcinoma of the Nasal Cavity and Paranasal Sinuses 429 Patrick Sheahan, Snehal G. Patel, and Jatin P. Shah 30. Nonsquamous Cell Carcinoma of the Nasal Cavity and Paranasal Sinuses 445 ` Carlo L. Solero, Stefano Riccio, and Giulio Cantu, Sarah Colombo 31. Esthesioneuroblastoma 453 Valerie J. Lund and David J. Howard 32. Melanoma of the Nasal Cavity and Paranasal Sinuses 459 Ziv Gil, Mark H. Bilsky, and Dennis H. Kraus 33. Sarcomas of the Skull Base 473 Katherine A. Thornton and Robert S. Benjamin

34. Angiofibromas and Vascular Tumors of the Skull Base 481 Andrew G. Sikora and Randal S. Weber 35. Chordoma and Chondrosarcoma of the Skull Base 495 Gordon T. Sakamoto and Griffith R. Harsh 36. Meningioma 503 Ashwin Viswanathan and Franco DeMonte 37. Schwannomas of the Skull Base 513 Daniel W. Nuss and Emily Lifsey Burke 38. Paragangliomas of the Head and Neck 539 David P. Goldstein, Mark G. Shrime, Bernard Cummings, and Patrick J. Gullane 39. Pituitary Adenomas 557 Mark Hornyak and William T. Couldwell 40. Craniopharyngioma: Neurosurgical Management 573 Douglas James Cook and James T. Rutka 41. Epidermoids, Dermoids, and Other Cysts of the Skull Base 583 Samuel P. Gubbels and Bruce J. Gantz 42. Fibro-Osseous Lesions of the Skull Base 597 Ian T. Jackson 43. Metastatic Skull Base Tumors 615 Krishna Satyan and Sujit S. Prabhu Index . . . . 619

Contributors

Maur´ıcio Coelho Neto Department of Neurosurgery, Neurological Institute of Curitiba, Curitiba, Brazil

Badih Adada Department of Neurosurgery, The University of Arkansas for Medical Sciences, Little Rock, Arkansas, U.S.A.

Sarah Colombo Cranio-Maxillo-Facial Department, National Cancer Institute, Milano, Italy

Siviero Agazzi Department of Neurosurgery, University of South Florida, Tampa, Florida, U.S.A.

Douglas James Cook Division of Neurosurgery, University of Toronto, Toronto, Ontario, Canada

Bilal Ahmed Departments of Thoracic/Head and Neck Medical Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, Texas, U.S.A.

William T. Couldwell Department of Neurosurgery, University of Utah, Salt Lake City, Utah, U.S.A.

Ossama Al-Mefty Department of Neurosurgery, University of Arkansas for Medical Sciences, Little Rock, Arkansas, U.S.A.

Bernard Cummings Department of Radiation Oncology, Princess Margaret Hospital, University of Toronto, Toronto, Ontario, Canada

Samer Ayoubi Department of Neurosurgery, Abbassi Medical Center, Damascus, Syria

Mark J. Dannenbaum Department of Neurosurgey, The University of Texas M.D. Anderson Cancer Center, Houston, Texas, U.S.A.

Ali A. Baaj Department of Neurosurgery, University of South Florida, Tampa, Florida, U.S.A.

Gail L. Davie Department of Head and Neck Surgery, The University of Texas M.D. Anderson Cancer Center, Houston, Texas, U.S.A.

Denise A. Barringer Department of Head and Neck Surgery, The University of Texas M.D. Anderson Cancer Center, Houston, Texas, U.S.A.

Franco DeMonte Department of Neurosurgey, The University of Texas M.D. Anderson Cancer Center, Houston, Texas, U.S.A.

Erasmo Barros da Silva, Jr. Department of Neurosurgery, Neurological Institute of Curitiba, Curitiba, Brazil, Postgraduate Course in Surgery, Pontifical Catholic University of Parana, Curitiba, Brazil

Curtis A. Dickman Division of Neurological Surgery, Barrow Neurological Institute, St. Joseph’s Hospital and Medical Center, Phoenix, Arizona, U.S.A.

Robert S. Benjamin Department of Sarcoma Medical Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, Texas, U.S.A.

Paul J. Donald Department of Otolaryngology-Head and Neck Surgery, University of California-Davis, Sacramento, California, U.S.A.

Mark H. Bilsky Department of Neurosurgery, Memorial Sloan-Kettering Cancer Center, Cornell University Medical College, New York, New York, U.S.A.

Steven B. Edelstein Loyola University Medical Center and Loyola University Stritch School of Medicine, Department of Anesthesiology, Maywood, Illinois, U.S.A.

Emily Lifsey Burke Department of Otolaryngology-Head & Neck Surgery, Louisiana State University Health Sciences Center, New Orleans and Baton Rouge, Louisiana, U.S.A.

Adel K. El-Naggar Department of Pathology, The University of Texas M.D. Anderson Cancer Center, Houston, Texas, U.S.A.

Giulio Cantu´ Cranio-Maxillo-Facial Department, National Cancer Institute, Milano, Italy

Yvens Barbosa Fernandes Department of Neurosurgery, Neurological Institute of Curitiba, Department of Neurosurgery, State University of Campinas (UNICAMP), Campinas, Brazil

Ricardo L. Carrau Department of Otolaryngology and Head & Neck Surgery, Department of Neurological Surgery, and Minimally Invasive Endoneurosurgery Center, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, U.S.A.

Dan M. Fliss Department of Otolaryngology Head and Neck Surgery, Tel-Aviv Sourasky Medical Center, Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel

Mark S. Chambers Section of Oncologic Dentistry and Prosthodontics, Department of Head and Neck Surgery, The University of Texas M.D. Anderson Cancer Center, Houston, Texas, U.S.A.

Douglas Fox

Private practice, Austin, Texas, U.S.A.

Bruce J. Gantz Department of Otolaryngology/Head and Neck Surgery, University of Iowa Hospitals and Clinics, Iowa City, Iowa, U.S.A.

Eric L. Chang Department of Radiation Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, Texas, U.S.A.

Paul Gardner Department of Neurological Surgery and Minimally Invasive Endoneurosurgery Center, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, U.S.A.

Steve Chang Division of Neurological Surgery, Barrow Neurological Institute, St. Joseph’s Hospital and Medical Center, Phoenix, Arizona, U.S.A. ix

x

Contributors

Paul W. Gidley Department of Head and Neck Surgery, The University of Texas M.D. Anderson Cancer Center, Houston, Texas, U.S.A.

Vijayakumar Javalkar Department of Neurosurgery, Louisiana State University Health Sciences Center — Shreveport, Louisiana, U.S.A.

Basavaraj Ghodke Departments of Neurological Surgery, and Neuroradiology, University of Washington, Seattle, Washington, U.S.A.

Walter S. Jellish Department of Anesthesiology, Loyola University Hospital Medical Center, Maywood, Illinois, U.S.A.

Steven L. Giannotta Department of Neurological Surgery, Keck School of Medicine, University of Southern California, Los Angeles, California, U.S.A.

Amin B. Kassam Department of Neurological Surgery, Department of Otolaryngology and Head & Neck Surgery, and Minimally Invasive Endoneurosurgery Center, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, U.S.A.

Ziv Gil Department of Otolaryngology Head and Neck Surgery, Tel-Aviv Sourasky Medical Center, Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel Lawrence E. Ginsberg Department of Radiology, The University of Texas M.D. Anderson Cancer Center, Houston, Texas, U.S.A. David P. Goldstein Department of Surgical Oncology, Princess Margaret Hospital, Toronto, Ontario, Department of Otolaryngology– Head and Neck Surgery, University of Toronto, Toronto, Ontario, Canada Samuel P. Gubbels Department of Surgery, Division of Otolaryngology/Head and Neck Surgery, University of Wisconsin, Madison, Wisconsin, U.S.A. Patrick J. Gullane Department of Otolaryngology– Head and Neck Surgery, University of Toronto, Department of Surgical Oncology, Princess Margaret Hospital, Toronto, Ontario, Canada Bharat Guthikonda Department of Neurosurgery, Louisiana State University, Health Sciences Center—Shreveport, Louisiana, U.S.A.

G. Vini Khurana The Canberra Hospital, Department of Neurosurgery, Canberra Medical School, Australian National University, Canberra, Australian Capital Territory, Australia Merrill S. Kies Departments of Thoracic/Head and Neck Medical Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, Texas, U.S.A. Dennis H. Kraus Head and Neck Service, Department of Surgery, Memorial Sloan-Kettering Cancer Center, Cornell University Medical College, New York, New York, U.S.A. Michael Kupferman Department of Head and Neck Surgery, The University of Texas M.D. Anderson Cancer Center, Houston, Texas, U.S.A. Paul K. Y. Lam Division of Otorhinolaryngology, Head and Neck Surgery, University of Hong Kong Medical Centre, Queen Mary Hospital, Hong Kong SAR, P.R. China Edward R. Laws Department of Neurosurgery, Harvard University, Boston, Massachusetts, U.S.A.

Ehab Y. Hanna Department of Head and Neck Surgery, The University of Texas M.D. Anderson Cancer Center, Houston, Texas, U.S.A.

John P. Leonetti Department of Otolaryngology, Head and Neck Surgery, Loyola University Health System, Maywood, Illinois, U.S.A.

Griffith R. Harsh Department of Neurosurgery, Stanford University, Palo Alto, California, U.S.A.

Jan S. Lewin Department of Head and Neck Surgery, The University of Texas M.D. Anderson Cancer Center, Houston, Texas, U.S.A.

Theresa M. Hofstede Section of Oncologic Dentistry and Prosthodontics, Department of Head and Neck Surgery, The University of Texas M.D. Anderson Cancer Center, Houston, Texas, U.S.A. Daniel J. Hoh Department of Neurological Surgery, Keck School of Medicine, University of Southern California, Los Angeles, California, U.S.A. Mark Hornyak Department of Neurosurgery, University of Utah, Salt Lake City, Utah, U.S.A.

Simon S. Lo Department of Radiation Medicine, Arthur G. James Cancer Hospital and Richard J. Solove Research Institute, Ohio State University Medical Center, Columbus, Ohio, U.S.A. Valerie J. Lund Royal National Throat Nose and Ear Hospital, Ear Institute, University College London, London, U.K.

David J. Howard Royal National Throat Nose and Ear Hospital, Ear Institute, University College London, London, U.K.

Jack W. Martin Section of Oncologic Dentistry and Prosthodontics, Department of Head and Neck Surgery, The University of Texas M.D. Anderson Cancer Center, Houston, Texas, U.S.A.

Ian T. Jackson Craniofacial Institute, Southfield, Michigan, U.S.A.

Carolina Martins Medical School of Pernambuco IMIP & ´ Hospital Getulio Vargas, Recife, Brazil

Rhonda F. Jacob Section of Oncologic Dentistry and Prosthodontics, Department of Head and Neck Surgery, The University of Texas M.D. Anderson Cancer Center, Houston, Texas, U.S.A.

Sam J. Marzo Department of Otolaryngology, Head and Neck Surgery, Loyola University Health System, Maywood, Illinois, U.S.A.

Jay Jagannathan Department of Neurosurgery, University of Virginia Health Sciences Center, University of Virginia, Charlottesville, Virginia, U.S.A. John A. Jane, Jr. Department of Neurosurgery, University of Virginia Health Sciences Center, University of Virginia, Charlottesville, Virginia, U.S.A.

Arlan Mintz Department of Neurological Surgery and Minimally Invasive Endoneurosurgery Center, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, U.S.A. Pattii C. Montgomery Section of Oncologic Dentistry and Prosthodontics, Department of Head and Neck Surgery, The University of Texas M.D. Anderson Cancer Center, Houston, Texas, U.S.A.

Contributors

Eric J. Moore Department of Otolaryngology, The Mayo Graduate College of Medicine, The Mayo Clinic, Rochester, Minnesota, U.S.A. Anil Nanda Department of Neurosurgery, Louisiana State University Health Sciences Center—Shreveport, Louisiana, U.S.A. Sabareesh Kumar Natarajan Department of Neurological Surgery, University of Washington, Seattle, Washington, U.S.A. Peter C. Neligan Division of Plastic Surgery, University of Washington, Seattle, Washington, U.S.A. Christine B. Novak Wharton Head and Neck Center, University Health Network, University of Toronto, Toronto, Ontario, Canada Daniel W. Nuss Department of Otolaryngology-Head & Neck Surgery, and Department of Neurological Surgery, Louisiana State University Health Sciences Center, New Orleans and Baton Rouge, Louisiana, U.S.A. Bryan C. Oh Department of Neurological Surgery, Keck School of Medicine, University of Southern California, Los Angeles, California, U.S.A. Kerry D. Olsen Department of Otolaryngology, The Mayo Graduate College of Medicine, The Mayo Clinic, Rochester, Minnesota, U.S.A. Snehal G. Patel Head and Neck Service, Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, New York, U.S.A. Sujit S. Prabhu Department of Neurosurgery, The University of Texas M.D. Anderson Cancer Center, Houston, Texas, U.S.A. Kristofer Luiz Fingerle Ramina Department of ¨ ¨ Neurosurgery, University of Tubingen, Tubingen, Germany Ricardo Ramina Department of Neurosurgery, Neurological Institute of Curitiba, Curitiba, Brazil, Postgraduate Course in Surgery, Pontifical Catholic University of Parana, Curitiba, Brazil Albert L. Rhoton, Jr. Department of Neurosurgery, University of Florida, Gainesville, Florida, U.S.A. Stefano Riccio Cranio-Maxillo-Facial Department, National Cancer Institute, Milano, Italy James T. Rutka Division of Neurosurgery, The Hospital for Sick Children, The University of Toronto, Toronto, Ontario, Canada Gordon T. Sakamoto Stanford University, Palo Alto, California, U.S.A. Krishna Satyan Department of Neurosurgery, The University of Texas M.D. Anderson Cancer Center, Houston Texas, U.S.A.

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Mark G. Shrime Department of Surgical Oncology, Princess Margaret Hospital, Toronto, Ontario, Department of Otolaryngology– Head and Neck Surgery, University of Toronto, Toronto, Ontario, Canada Andrew G. Sikora Department of Otolaryngology, Mount Sinai School of Medicine, New York, New York, U.S.A. Carl H. Snyderman Department of Otolaryngology and Head & Neck Surgery, Department of Neurological Surgery, and Minimally Invasive Endoneurosurgery Center, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, U.S.A. Carlo L. Solero Second Neurosurgical Unit, Istituto Nazionale Neurologico “C. Besta”, Milano, Italy Volker K. H. Sonntag Division of Neurological Surgery, Barrow Neurological Institute, St. Joseph’s Hospital and Medical Center, Phoenix, Arizona, U.S.A. Robert F. Spetzler Division of Neurological Surgery, Barrow Neurological Institute, St. Joseph’s Hospital and Medical Center, Phoenix, Arizona, U.S.A. John H. Suh Department of Radiation Oncology, The Cleveland Clinic Foundation, Cleveland, Ohio, U.S.A. Katherine A. Thornton Johns Hopkins University School of Medicine, Sidney Kimmel Comprehensive Cancer Center, Baltimore, Maryland, U.S.A. Harry R. van Loveren Department of Neurosurgery, University of South Florida, Tampa, Florida, U.S.A. Prasad Vannemreddy Department of Neurosurgery, Louisiana State University Health Sciences Center — Shreveport, Louisiana, U.S.A. Tracy Veramonti Department of Neuro-Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, Texas, U.S.A. Ashwin Viswanathan Department of Neurosurgery, The University of Texas M.D. Anderson Cancer Center, Houston, Texas, U.S.A. Allan D. Vescan Department of Otolaryngology and Head & Neck Surgery, and Minimally Invasive Endoneurosurgery Center, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, U.S.A. Scott Wait Division of Neurological Surgery, Barrow Neurological Institute, St. Joseph’s Hospital and Medical Center, Phoenix, Arizona, U.S.A. Randal S. Weber Department of Head and Neck Surgery, The University of Texas M.D. Anderson Cancer Center, Houston, Texas, U.S.A. William Ignace Wei Division of Otorhinolaryngology, Head and Neck Surgery, University of Hong Kong Medical Centre, Queen Mary Hospital, Hong Kong SAR, P.R. China

Laligam N. Sekhar Department of Neurological Surgery, University of Washington, Seattle, Washington, U.S.A.

Peggy J. Wesley Section of Oncologic Dentistry and Prosthodontics, Department of Head and Neck Surgery, The University of Texas M.D. Anderson Cancer Center, Houston, Texas, U.S.A.

Jatin P. Shah Head and Neck Service, Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, New York, U.S.A.

Michelle D. Williams Department of Pathology, The University of Texas M.D. Anderson Cancer Center, Houston, Texas, U.S.A.

Patrick Sheahan Head and Neck Service, Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, New York, U.S.A.

Mariana Witgert Department of Neuro-Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, Texas, U.S.A.

Section 1 General Principles

1 Anatomy of the Cranial Base Carolina Martins and Albert L. Rhoton, Jr.

OVERVIEW

galli and the cribriform plate of the ethmoid bone anteriorly and the planum of the sphenoid body posteriorly. The lateral part, which covers the orbit and the optic canal, is formed by the frontal bone and the lesser wing of the sphenoid bone, which blends medially into the anterior clinoid process (Figs. 3 and 4). The foramen caecum in the midline serves as the site of passage of an emissary vein and the cribriform plate is pierced by the filaments of the olfactory nerve. The optic canal transmits the optic nerve and the ophthalmic artery. The anterior cranial base faces the frontal lobes with the gyri recti medially and the orbital gyri laterally, along with the branches of the anterior cerebral arteries medially and middle cerebral arteries laterally.

No part of the cranial base is immune to surgical pathology or to its use as a pathway to access lesions in the intra- or extracranial spaces. Tumors and multiple other lesions can involve any of the intracranial fossae, and can appear in the paranasal sinuses, nasal cavity, infratemporal and pterygopalatine fossae, orbit, and in the retropharyngeal and craniocervical regions (Fig. 1). Managing these lesions requires an extensive knowledge of the anatomy of the cranial base and its intra- and extracranial relationships. This chapter provides a concise review of the cranial base. The skull is divided into the cranium and the facial skeleton. The cranium is divided into the calvarium and the cranial base. The cranial base has an endocranial surface, which faces the brain, and an exocranial surface, which faces the nasal cavity and sinuses, orbits, pharynx, infratemporal and pterygopalatine fossae, and the parapharyngeal and infrapetrosal spaces (Fig. 2). Both surfaces are connected by canals, foramina, and fissures through which numerous neural and vascular structures pass. Both the endocranial and exocranial cranial base surfaces are divided into anterior, middle, and posterior parts, each of which has a central and paired lateral portions. On the intracranial side, the three parts correspond to the anterior, middle, and posterior cranial fossae (Figs. 2 and 4) (1,2). On the endocranial side, the border between the anterior and middle cranial bases is the sphenoid ridge joined medially by the chiasmatic sulcus, and the border between the middle and posterior cranial bases is formed by the petrous ridges joined by the dorsum sellae and posterior clinoid processes. On the exocranium side, the anterior and middle cranial bases are divided at the level of a transverse line extending through the pterygomaxillary fissures and the pterygopalatine fossae at the upper level and the posterior edge of the alveolar process of the maxilla at a lower level. Medially, this corresponds to the anterior part of the attachment of the vomer to the sphenoid bone. The middle and posterior cranial bases are separated by a transverse line crossing at or near the posterior border of the vomer– sphenoid junction, the foramen lacerum, carotid canal, jugular foramen, styloid process, and the mastoid tip. The osseous structures, their foramina and fissures, canals and their muscular, and neural and vascular relationships are described in this chapter.

Exocranial Surface On the exocranial side, the anterior cranial base is divided in a medial part related to the ethmoid and the sphenoid sinuses with the nasal cavity below and a lateral part that corresponds to the orbit and maxilla (Figs. 2, 6, 7, and 8) (1). The ethmoid bone forms the anterior and middle third and the sphenoid body forms the posterior third of the medial part. The ethmoid is formed by the cribriform plate with the olfactory fila traveling through it, the perpendicular plate, which joins the vomer in forming the nasal septum, and two lateral plates located in the medial walls of the orbits. The lateral plates separate the lateral wall of the nasal cavity and the orbit. The superior turbinate, an appendage of the ethmoid bone, projects into the superior part of the nasal cavity. The body of the sphenoid bone harbors the sphenoid sinus just below the planum sphenoidale, with the anterior orifices located above the superior turbinate. The orbital roof is formed by the lesser sphenoid wing and by the orbital plate of the frontal bone; the lateral wall is formed by the greater sphenoid wing and the zygomatic bone; the inferior wall is formed by the zygomatic, maxillary, and palatine bones; and the medial wall is formed by maxillary, lacrimal, and ethmoid bones (3,4). The main foramina of the region are the anterior and posterior ethmoidal foramen located in the superomedial orbital wall, transmitting the anterior and posterior ethmoidal nerves and arteries; the supraorbital and supratrochlear notches or foramina, transmitting the arteries and nerves of the same name; and the optic canal, through which the optic nerve and ophthalmic artery pass (Figs. 4, 5, and 7). The superior orbital fissure is located between the lesser and greater wing of the sphenoid bone on the lateral side of the optic canal. The inferior orbital fissure, located between the greater sphenoid wing behind and the maxillary and palatine bones anteriorly, is closed by fibrous tissue and orbital muscle. Covered with periorbita and filled with a great amount of fat, the orbit is divided into an anterior space where the globe lies and a posterior space that shelters the nerves, vessels, and muscles behind the globe (5). The

ANTERIOR CRANIAL BASE Endocranial Surface The anterior endocranial surface, formed by the ethmoid, sphenoid, and frontal bones, is divided into medial and lateral portions (Figs. 3–5). The medial part, covering the upper nasal cavity and the sphenoid sinus, is formed by the crista 3

4

Martins and Rhoton

A

Car. A.

B

Orbit roof Sphen. sinus Eth. sinus

V3 V2

Pterygopal. fossa Infratemp. fossa

Car. A.

V2 V3

Sphen. sinus Nasal septum

Nasal cavity

Maxilla

Pterygopal. fossa Nasal cavity

Eth. sinus Maxilla

Orbit roof

C

D

Pit. stalk

Car. A.

Car. A.

Sella Orb. apex

Max. sinus Eust. tube Vomer

Sphen. sinus

V3 Front. N. V2 Max. A. CN II Eth. air cell Pterygopal. fossa Nasopharynx Max. sinus

Septal cart.

Infraorb. N. Max. sinus Nasolac. duct

Sphen. sinus

V3 Pterygopal. gang.

Pteryg. M. Max. A. Br. Vomer Nasal cavity

Maxilla Alv. part

Figure 1

Chapter 1: Anatomy of the Cranial Base

annular tendon of Zinn, a fibrous ring that surrounds the central part of the superior orbital fissure and the optic canal, gives attachment to the superior, medial, inferior, and lateral rectus muscles (Fig. 4). The superior oblique attaches above the annular tendon and the inferior oblique arises from the inferomedial orbital wall just behind the rim. The oculomotor foramen, located inside the annular tendon and through which the oculomotor nerve passes, is located between the upper and lower attachment of the lateral rectus muscle. Just before passing through the superior orbital fissure and the oculomotor foramen in the annular tendon, the oculomotor nerve divides into an upper division supplying the superior rectus and levator muscles and a lower division to the medial and inferior rectus and inferior oblique muscles. The oculomotor nerve gives rise to the parasympathetic motor root to the ciliary ganglion which lies lateral to the optic nerve. The abducens nerve passes through the oculomotor foramen and enters the medial surface of the lateral rectus muscle. The ophthalmic nerve divides just behind the annular tendon into lacrimal and frontal nerves which pass outside the annular tendon, and into the nasociliary nerve which passes through the annular tendon. The ophthalmic nerve gives rise to the long ciliary nerves and the sensory root to the ciliary ganglion; the former conveys the sympathetic pupillomotor fibers and the latter conveys corneal sensation. The trochlear nerve passes above and outside the superomedial edge of the annular tendon. The optic nerve passes superior and medial from the globe to reach the optic canal and divides the retro-orbital space in medial and lateral parts. The main arterial supply to the orbit is by the ophthalmic artery and its branches. This artery courses below the optic nerve in the optic canal, crosses to the lateral side of the nerve at the orbital apex, and then courses from lateral to medial above the optic nerve. The main branches are the central retinal artery and the lacrimal, ciliary, ethmoidal, supraorbital, and dorsal nasal arteries, plus numerous muscular branches. The main venous drainage of the orbit is through the superior and inferior ophthalmic veins that exit the orbit by passing outside the annular tendon and through the superior orbital fissure. The lacrimal gland, located in the superolateral part of the orbit, receives its sensory innervation from the lacrimal nerve, and its parasympathetic and sympathetic innervation from the greater and deep petrosal nerves. The petrosal nerves

5

join to form the vidian nerve that enters the pterygopalatine ganglion, which sends branches to the zygomatic nerve that anastomose with the lacrimal nerve to reach the gland.

MIDDLE CRANIAL BASE Endocranial Surface The endocranial surface of the middle portion of the middle cranial base, formed by the sphenoid and temporal bones, has medial and lateral parts (Figs. 2, 3, 5, and 9). The medial part is formed by the body of the sphenoid bone, the site of the tuberculum sellae, pituitary fossa, middle and posterior clinoid processes, the carotid sulcus, and the dorsum sellae (Fig. 8). The lateral part is formed by the lesser and greater sphenoid wings, with the superior orbital fissure between them (Figs. 3 and 5). The lesser wing is connected to the body of the sphenoid bone by an anterior root, which forms the roof of the optic canal, and by a posterior root, also called the optic strut, which forms the floor of the optic canal and separates the optic canal from the superior orbital fissure (Fig. 3). The greater wing forms the largest part of the endocranial surface of the middle fossa, with the squamosal and the petrosal parts of the temporal bone completing this surface. The superior orbital fissure transmits the oculomotor, trochlear, ophthalmic, and abducens nerves, a recurrent meningeal artery, and the superior and inferior ophthalmic veins (6). The maxillary and mandibular nerves pass through the foramen rotundum and ovale, both located in the greater wing of the sphenoid. The not infrequently occurring sphenoidal emissary foramen, located anteromedial to the foramen spinosum, gives passage to a vein connecting the cavernous sinus and the pterygoid venous plexus. The upper surface of the petrous bone is grooved along the course of the greater and lesser petrosal nerves (Fig. 5) (7). The carotid canal extends upward and medially and provides passage to the internal carotid artery and carotid sympathetic nerves in their course to the cavernous sinus. The posterior trigeminal root reaches the middle fossa and the impression on the upper surface of the petrous bone where Meckel’s cave and the semilunar ganglion sit. The roof of the carotid canal opens below the trigeminal ganglion near the distal end of the carotid canal (Figs. 5, 6, and 9). The arcuate eminence approximates

←−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−− Figure 1 Anterior and middle cranial base. (A) On the left side, the floor of the anterior fossa and the upper portion of the maxilla have been removed to expose the structures deep to the anterior and middle cranial fossa. The frontal, ethmoidal, and sphenoid sinuses and the nasal cavity lie below the medial part of the anterior cranial base. The orbit and maxilla are located below the lateral part of the anterior cranial base. The sphenoid sinus and sella are located in the medial part of the middle cranial base, and the infratemporal and pterygopalatine fossa are located below the lateral part of the middle cranial base. The carotid arteries pass upward on the medial part of the middle cranial base and are intimately related to the sphenoid and cavernous sinuses. The infratemporal fossa, which contains branches of the mandibular nerve, pterygoid muscles, pterygoid venous plexus, and maxillary artery, is located below the middle cranial base and greater sphenoid wing. The alveolar process of the maxilla, which encloses the roots of the upper teeth, has been preserved on the left side. The maxillary nerve enters the pterygopalatine fossa, which is located medial to the infratemporal fossa between the posterior wall of the maxilla and the pterygoid process of the sphenoid bone. (B) Superior view of the anterior and middle cranial base. The infratemporal fossa is located posterolateral to the maxilla. The right ethmoid air cells are exposed on the medial side of the right orbit. The nasal cavity extends upward between the ethmoid sinuses. (C) Oblique anterior view. The facial structures on the right side have been removed to expose the orbital apex located above the maxillary sinus. The wall of the right maxillary sinus forms the floor of the orbit, much of the lateral wall of the nasal cavity, and the anterior wall of the pterygopalatine and infratemporal fossa. On the left side, the mandibular nerve enters the infratemporal fossa. The maxillary nerve enters the pterygopalatine fossa, which is located in the lateral wall of the nasal cavity and contains the maxillary nerve, pterygopalatine ganglion, and terminal branches of the maxillary artery. (D) Anterior view. The orbital apex is located above the pterygopalatine fossa. The frontal branch of the ophthalmic nerve passes along the roof of the orbit, and the infraorbital branch of the maxillary nerve courses in the floor of the orbit. The posterior ethmoid air cells are located medial to the orbital apex. The vomer forms the posterior part of the nasal septum and attaches to the maxilla and palatine bones below and to the body of the sphenoid bone above. The sphenoid sinus is located in the middle cranial base below the sella turcica. The upper brain stem is seen in the posterior part of the exposure (1).) Abbreviations: A., artery; Alv., alveolar; Br., branch; Car., carotid; Cart., cartilage; CN, cranial nerve; Eth., ethmoid; Eust., eustachian; Front., frontal; Gang., ganglion; Infraorb., infraorbital; Infratemp., infratemporal; M., muscle; Max., maxillary; N., nerve; Nasolac., nasolacrimal; Orb., orbital; Pit., pituitary; Pteryg., pterygoid; Pterygopal., pterygopalatine; Sphen., Sphenoid.

6

Martins and Rhoton

A Semicirc. canals Trautman’s triangle

Temp. dura Lat. Rec. M. CN III CN II CN IV

Vestibule Cochlea Jug. bulb V1

Gr. Pet. N.

Inf. Rec. M.

Car. N.

V3

V2

Infraorb. N.

Vidian N. Car. A.

Pterygopal. fossa Max. sinus Eust. tube Max. A.

Vert. A. Int. Jug. V. Infratemp. fossa

B Front. lobe Temp. lobe Ped.

Lat. Rec. M.

CN V

V1 Sphen. sinus

Gr. Pet. N. Cochlea

V2 Vidian N.

CN IX-XI

V3

Pterygopal. fossa Zygoma Eust. tube Max. A.

Car. A. Infratemp. fossa Figure 2 Lateral view of the anterior, middle, and posterior cranial base. (A) The bone and structures lateral to the orbit, infratemporal, and pterygopalatine fossa, and the parapharyngeal space and petrous part of the temporal bone have been removed to expose the structures below the anterior, middle, and posterior cranial base. The orbit and maxillary sinus are located below the anterior cranial base. The infratemporal and pterygopalatine fossae and the parapharyngeal space are located below the middle cranial base, and the suboccipital area is located below the temporal and occipital bones. The first trigeminal division is related to the upper part of the orbit. The second trigeminal branch is related to the lower part of the orbit and maxilla. The mandibular nerve exits the cranium through the foramen ovale and enters the infratemporal fossa. The pterygoid and levator and tensor veli palatini muscles have been removed to expose the eustachian tube and its opening into the nasopharynx. The lateral part of the temporal bone has been removed to expose the cochlea, vestibule, and semicircular canals. The petrous carotid passes upward and turns medially below the cochlea. The sigmoid sinus turns downward under the semicircular canals and vestibule where the jugular bulb is located. The segment of the vertebral artery passing behind the atlanto-occipital joint is located below the posterior cranial base. (B) The dura has been opened to show the relationships of the frontal and temporal lobes and the cerebellum to the cranial base. The orbit is exposed below the frontal lobe. The pterygopalatine and infratemporal fossae and the temporal bone are located below the temporal lobe. The jugular bulb and internal jugular vein have been removed to show cranial nerves IX through XII exiting the jugular foramen (1). Abbreviations: A., artery; Car., carotid; CN, cranial nerve; Eust., eustachian; Front., frontal; Gr., greater; Inf., inferior; Infraorb., infraorbital; Infratemp., infratemporal; Int., internal; Jug., jugular; Lat., lateral; M., muscle; Max., maxillary; N., nerve; Ped., peduncle; Pet., petrosal; Pterygopal., pterygopalatine; Rec., rectus; Semicirc., semicircular; Sphen., sphenoid; Temp., temporal; V., vein; Vert., vertebral.

Chapter 1: Anatomy of the Cranial Base

7

B

A

Crib. plate Front. bone

Eth. bone Sphen. ridge

Maxilla

Less. wing Vomer Optic canal Sphen. body For. lacerum For. ovale For. ovale Temp. bone Car. canal Temp. bone Jug. for. Pet. part

Gr. wing Ant. clin. For. spinosum Pet. Ridge

C

Palat. bone Horiz. plate Gr. wing Pteryg. proc. Mandib. fossa Clivus Occip. bone

D

Front. bone

Infraorb. for.

Supraorb. notch

Zygoma

Sup. Orb. Fiss. Maxilla Nasal bone Inf. Orb. Fiss.

Less. wing Gr. wing

Palat. bone Horiz. plate Vomer

Pteryg. proc. Mandib. fossa

Eth. Perp. plate Inf. concha

Vomer

Temp. bone Pet. part

Occip. bone

Jug. for.

Maxilla

Mandible

Figure 3 Osseous relationships of the anterior and middle cranial base. (A) On the endocranial surface, the anterior and middle cranial bases correspond to the anterior and middle fossae. The anterior part of the cranial base is separated from the middle fossa by the sphenoid ridge and the chiasmatic sulcus. The middle cranial base is separated from the posterior cranial base by the dorsum sellae and the petrous ridges. The upper surface of the anterior cranial base is formed by the frontal bone, which roofs the orbit; the ethmoid bone, which is interposed between the frontal bones and the site of the cribriform plate; and the lesser wing and anterior part of the body of the sphenoid, which forms the posterior part of the floor of the anterior fossa. The upper surface of the middle cranial base floor is formed by the greater sphenoid wing and posterior two-thirds of the sphenoid body anteriorly and the upper surface of the temporal bone posteriorly. The posterior part of the cranial base is formed by the temporal and occipital bones. The cribriform plate, sella, and clivus are located in the medial part of the cranial base. The lateral part of the cranial base is located above the orbits, pterygopalatine and infratemporal fossae, and the subtemporal and lateral part of the suboccipital areas. (B) Exocranial surface of the cranial base. This surface is more complicated than the endocranial surface. It is not demarcated into three well-defined fossae as is the endocranial surface. The exocranial surface is formed by the maxilla, zygomatic, palatine, sphenoid, temporal, and occipital bones, and the vomer. The maxilla, orbits, and nasal cavity are located below the anterior fossa. The anterior part of the hard palate is formed by the maxilla and the posterior part is formed by the palatine bone. The anterior part of the zygomatic arch is formed by the zygoma and the posterior part by the squamosal part of the temporal bone. The mandibular fossa on the lower surface of the temporal squama is located below the posterior part of the middle fossa. The vomer attaches to the lower part of the body of the sphenoid and forms the posterior part of the nasal septum. (C) Anterior view. The orbital rim is formed by the frontal bone, zygoma, and maxilla. The roof of the orbit is formed by the frontal and sphenoid bones; the lateral wall by the greater sphenoid wing and the zygomatic bone; the floor by the maxilla, except for a small part of the posterior floor formed by the palatine bone; and the medial wall of the orbit by the maxilla, lacrimal, and ethmoid bones. The nasal bone is interposed above the anterior nasal aperture between the maxillae. The nasal cavity is located between the ethmoid bones above and the maxillae and palatine bones, and sphenoid pterygoid process below. It is roofed by the frontal and ethmoid bones and the floor is formed by the maxillae and palatal bones. The osseous nasal septum is formed by the perpendicular ethmoid plate and the vomer. The inferior concha is a separate bone, and the middle and superior conchae are appendages of the ethmoid bone. The orbit opens through the superior orbital fissure into the middle fossa and through the inferior orbital fissure into the pterygopalatine and infratemporal fossae. (D) Anteroinferior view of the cranial base. The anterior part of the hard palate is formed by the maxillae and the posterior part is formed by the horizontal plate of the palatine bone. The vomer forms the posterior part of the nasal septum and divides the posterior nasal aperture in the midline. The infratemporal fossa is located below the greater sphenoid wing. The clivus is formed above by the body of the sphenoid bone and below by the basal part of the occipital bone. The petrous apex is interposed between the greater sphenoid wing and the clival part of the occipital bone. The mandibular condyles sit in the mandibular fossa located below the posterior part of the middle fossa on the inferior surface of the squamosal part of the temporal bone. (E) The cranial base is formed, in the lateral view, from anterior to posterior, by the maxilla and the frontal, zygomatic, sphenoid, temporal, and occipital bones. The zygomatic and frontal bones form the lateral part of the orbital rim. The pterion on the greater sphenoid wing marks the lateral end of the sphenoid ridge. The keyhole, a burr hole that exposes the dura of the anterior fossa and the periorbita in its depth, is located just above the frontozygomatic suture, behind the superior temporal line. The zygomatic arch is formed by the zygomatic bone and the squamosal part of the temporal bone. The condylar fossa, in which the mandibular condyle sits, is positioned above on the lower surface of the squamosal part of the temporal bone and posteriorly on the tympanic part of the temporal bone. The lower end of the pterygoid process unites with the posterior maxilla, but above, the process separates from the maxilla to create the pterygomaxillary fissure, which opens medially into the pterygopalatine fossa. (Continued).

8

Martins and Rhoton

E

F Keyhole Pterion

Temp. bone Squam. part Mandib. fossa Occip. bone

Zygoma Infraorb. for. Maxilla Pteryg. Proc. Mandib. cond. Max. sinus

Eth. perp. plate

Eth. Air Cells

Coronoid proc. Vomer Pterygopal. fossa

Pteryg. proc.

For. ovale

H

G Maxilla Front. bone

Supraorb. for.

Front. bone

Zygoma Eth. sinus Sup. orb. fiss. Less. sing

Eth. air cells Gr. wing Inf. orb. fiss. Vomer Vidian canal Pteryg. Proc. removed

Palat bone Gr. wing Horiz. plate Infratemp. fossa For. ovale Temp. bone For. spinosum

Clivus Occip. bone

For. rotundum Sphen. sinus Mandib. fossa

H

Figure 3 (Continued) (F) Inferior view of a cross section extending through the maxillae. The maxilla, which contains a large air-filled sinus, forms the anteromedial wall of the infratemporal fossa, the anterior wall of the pterygopalatine fossa, the lateral wall of the nasal cavity, the anterior portion of the hard palate, and much of the floor of the orbit. The pterygopalatine fossa is located between the pterygoid process and the posterior maxillary wall. The nasal septum is formed anteriorly and above by the perpendicular ethmoid plate and posteriorly and below by the vomer. (G) The right half of the maxilla and zygomatic arch has been removed. The inferior orbital fissure is located between the greater sphenoid wing and the maxilla. The right orbital roof and ethmoid air cells have been preserved. The right pterygoid process has been removed at its junction with the sphenoid body. The roof of the vidian canal, which extends through the base of the pterygoid process, has been preserved. (H) Anteroinferior view of the cranial base. The midline of the cranial base is formed, from anterior to posterior, by the frontal, ethmoid, sphenoid, and occipital bones. The roof of the orbit is formed by the frontal bone and lesser sphenoid wing. The ethmoidal sinuses are located anterior to the sphenoid sinus between the orbits. (I) Lateral view of the pterygomaxillary fissure. The pterygomaxillary fissure is located between the posterior maxillary wall and the pterygoid process. The pterygomaxillary fissure opens from the infratemporal fossa into the pterygopalatine fossa. The mandibular fossa is formed above by the squamosal part of the temporal bone and posteriorly by the tympanic part of the temporal bone, which also forms the anterior and lower wall of the external auditory meatus. (J) Anterior view through the maxillary sinus. The anterior and posterior walls of the maxillary sinus have been removed to expose the pterygoid process, which forms the posterior wall of the pterygopalatine fossa. The lower part of the superior orbital fissure is seen through the upper part of the maxillary sinus. The foramen rotundum opens into the pterygopalatine fossa and is separated from the superior orbital fissure by the maxillary strut. The vidian canal opens through the pterygoid process below and medial to the foramen rotundum. (K) Anterior view of a cranium sectioned through the posterior part of the ethmoid and maxillary sinuses. The ethmoidal sinuses are located anterior to the sphenoid body and sphenoid sinus. The part of the posterior wall of the maxilla forming the anterior wall of the pterygopalatine fossa has been preserved. The perpendicular plate of the palatine bone forms the medial wall of the pterygopalatine fossa. The ethmoidal sinus overlaps the lateral margin of the sphenoid ostia. The superior orbital fissure is located between the lesser and greater sphenoid wings and the sphenoid body. The infratemporal fossa is located below the greater wing of the sphenoid. The temporal fossa, which contains the temporalis muscle, is located between the greater wing and the zygomatic arch. (L) The posterior wall of the maxilla and ethmoidal sinuses have been removed to expose the sphenoid sinus and pterygopalatine fossa. The lateral wing of the sphenoid sinus extends laterally into the pterygoid process below the foramen rotundum. Septae divide the sphenoid sinus. The vidian canal opens through the base of the pterygoid process into the pterygopalatine fossa. (M) The osseous cross section has been extended posteriorly to just in front of the superior orbital fissure. The optic strut extends from the base of the anterior clinoid to the sphenoid body and separates the optic canal from the superior orbital fissure. The foramen rotundum is located below the medial part of the superior orbital fissure. The vidian canal opens into the pterygopalatine fossa below and medial to the foramen rotundum. (Continued).

Chapter 1: Anatomy of the Cranial Base

Gr. wing

I

9

J

Temp. bone Squam. part Mandib. fossa

Inf. orb. fiss. Zygoma

Pterygomax. fiss. Infratemp. fossa

Sup. orb. fiss.

For. rotundum

Maxilla Vidian canal Pteryg. proc. Pteryg. proc.

K Sup. orb. fiss. Gr. wing

Less. wing Sphen. ostia

Max. sinus Post. wall Ant. wall

L Gr. wing

Sphen. septa Sphen. sinus For. rotundum

Eth. sinus Temp. bone Squam. part

Max. strut

Infratemp. fossa Palat. bone Perp. plate

Vidian canal

Pteryg. proc.

Max. sinus Post. wall

M

Gr. waing

Optic canal

N

Ant. clin. Less. wing Optic strut Sup. orb. fiss. Sup. orb. fiss. For. rotundum Gr. wing Vidian canal Pteryg. proc.

Zygoma

Ant. clin. Optic canal Optic strut Sphen. body Vidian canal Pteryg. proc. Maxilla Med. pteryg. plate

Lat. pteryg. plate Palat. bone Horiz. plate

Figure 3 (Continued) (N) Posterior view of the specimen in K showing the anterior part of the middle fossa from behind. The superior orbital fissure is positioned below the lesser sphenoid wing. The optic strut extends from the base of the anterior clinoid to the sphenoid body and separates the optic canal from the superior orbital fissure. The greater wing extends laterally to form part of the floor and anterior and lateral walls of the middle fossa. The medial and lateral pterygoid plates project backward from the pterygoid process. The horizontal plate of the palatine bone forms the posterior part of the hard palate. The posterior opening into the vidian canal is located above the medial pterygoid plate and extends forward through the pterygoid process at its junction with the sphenoid body (1). Abbreviations: Ant., anterior; Car., carotid; Clin., clinoid; Cond., condyle; Crib., cribriform; Eth., ethmoid; Fiss., fissure; For., foramen; Front., frontal; Gr., greater; Horiz., horizontal; Inf., inferior; Infraorb., infraorbital; Infratemp., infratemporal; Jug., jugular; Lat., lateral; Less., lesser; Mandib., mandibular; Max., maxillary; Med., medial; Orb., orbital; Occip., occipital; Palat., palatine; Perp., perpendicular; Pet., petrosal, petrous; Post., posterior; Proc., process; Pteryg., pterygoid; Pterygomax., pterygomaxillary; Pterygopal., pterygopalatine; Sphen., sphenoid; Squam., squamosal; Sup., superior; Supraorb., supraorbital; Temp., temporal.

10

Martins and Rhoton

A

B

Front. sius Front. bone Eth. sinus Front. N. CN IV Sphen. ridge

Crib. plate

Olf. bulb

Eth. bone Olf. Tr.

Planum Optic sheath

Sphen. bone

Less. wing MCA

ACA

D

C Front. N.

Trochlea Lac. N. CN IV

Sup. ophth. V. Crib. plate

Sup. Obl. M. Lev. M.

Olf. Tr.

Front. N. Nasocil. N. Sup. rec. M. Sup. ophth. V.

Eth. sinus

Sphen. sinus

Optic sheath MCA CN II Ant. Clin. removed Car. A.

Figure 4 Anterior fossa, orbit, and perinasal sinuses. (A) Superior view. The anterior cranial fossa is formed by the frontal, ethmoid, and sphenoid bones. The frontal bone splits anteriorly into two laminae, which enclose the frontal sinus. The ethmoid bones, which contain the ethmoid air cells and are the site of the crista galli and cribriform plate, are interposed between the frontal bones. Posteriorly, the frontal and ethmoid bones join the sphenoid bone, which encloses the sphenoid sinus and has the pituitary fossa on its upper surface. The olfactory bulbs and tracts have been preserved. (B) The roof of the right orbit has been removed to expose the periorbita. The right anterior clinoid process and roof of the optic canal have been removed to expose the optic nerve enclosed within the optic sheath as it passes through the optic canal to reach the orbital apex. (C) The frontal, trochlear, and lacrimal nerves can be seen through the periorbita. The trochlear nerve crosses above the orbital apex to reach the superior oblique muscle. (D) The orbital fat has been removed and the sphenoid sinus opened. The frontal branch of the ophthalmic nerve courses above the levator muscle. The ophthalmic artery, nasociliary nerve, and superior ophthalmic vein are located medially in the anterior part of the orbit and cross between the optic nerve and the superior rectus muscle and are thus situated on the lateral side of the optic nerve at the orbital apex. (E) Enlarged view. The superior oblique muscle has been retracted medially to expose the anterior and posterior ethmoidal branches of the ophthalmic artery and nasociliary nerve entering the anterior and posterior ethmoidal canal. The trochlea of the superior oblique muscle is attached to the superomedial margin of the orbit just behind the orbital rim. The frontal nerve divides into supraorbital and supratrochlear branches. (F) The levator and superior rectus muscle have been retracted posteriorly to expose the nasociliary nerve, ophthalmic artery, and superior ophthalmic vein passing above the optic nerve. (G) Superior view of the anterior fossa in another specimen. The nasal cavity, sphenoid sinus, and orbit have been unroofed. The dura has been removed from the roof and lateral wall of the cavernous sinus. The medial strip below the anterior cranial base is formed, from anterior to posterior, by the frontal, ethmoidal, and sphenoid sinuses. The orbital fat has been removed to expose the intraorbital structures. The frontal nerve courses above the levator muscle. The trochlear nerve passes above the annular tendon to reach the superior oblique muscle. The trochlea of the superior oblique muscle is attached in the superomedial part of the anterior orbit. The lacrimal nerve courses above the lateral rectus muscle. The ophthalmic artery and superior ophthalmic vein are seen in the interval between the levator and superior oblique muscle. The anterior and posterior ethmoidal branches of the ophthalmic artery course through the anterior and posterior ethmoidal canals. (Continued).

Chapter 1: Anatomy of the Cranial Base

E

11

F

Supratroch. N.

Supraorb. N.

Trochlea Sup. Ophth. V. Ant. Eth. A. & N.

Ophth. A.

Nasocil. N.

Front. N. Sup. Obl. M.

Post. Eth. A. & N.

Med. Rec. M. Sup. Obl. M.

Sup. Rec. M. Ophth. A.

Lev. M.

Sup. Ophth. V. Nasocil. N.

Sup. Ophth. V. Lev. M.

Sup. Rec. M.

G

H

Nasocil. N.

Trochlea Lev. M. Sup. Obl. M. Lev. M. CN IV Sup. Rec. M. Sup. Rec. M.

Sup. Obl. M. Ophth. A. Ant. Eth. A.

Clin. Seg. Sup. Ophth. V.

CN II

CN III

Anular tendon

CN II Front. N. Lac. N. Ophth. A.

Post. Eth. A. CN IV Ophth. A.

Car. A.

Ophth. A.

V2 V1

V2 CN III Cav. Seg. CN IV

V1 V3

Figure 4 (Continued) (H) Enlarged view of cavernous sinus, superior orbital fissure, and orbital apex. The superior oblique, levator, and superior rectus muscles have been removed. The ophthalmic artery and nasociliary nerve enter the orbital apex on the lateral side of the optic nerve and cross between the optic nerve and superior rectus muscle to reach the medial part of the orbit. The optic nerve has been elevated to expose the ophthalmic artery, which courses through the optic canal on the lower side of the optic nerve and enters the orbital apex on the lateral side of the optic nerve. The ophthalmic artery then crosses medially between the optic nerve and the superior rectus muscle, as does the nasociliary nerve. The maxillary nerve exits the foramen rotundum to enter the pterygopalatine fossa, and the mandibular nerve exits the foramen ovale to enter the infratemporal fossa (1). Abbreviations: A., artery; ACA, anterior cerebral artery; Ant., anterior; Car., carotid; Cav., cavernous; Clin., clinoid; CN, cranial nerve; Crib., cribriform; Eth., ethmoid, ethmoidal; Front., frontal; Lac., lacrimal; Less., lesser; Lev., levator; M., muscle; Med., medial; MCA, middle cerebral artery; N., nerve; Nasocil., nasociliary; Obl., oblique; Olf., olfactory; Ophth., ophthalmic; Post., posterior; Rec., rectus; Seg., segment; Sphen., sphenoid; Sup., superior; Supraorb., supraorbital; Supratroch., supratrochlear; Tr., tract; V., Vein.

12

Martins and Rhoton

A

B Temp. M. Temp. M. Max. A.

CN II Ophth. A.

V2 Lat. Pteryg. M.

Gr. wing

V2 V1 CN III Cav. Seg. CN IV

CN III CN IV V3

Mandib. Cond.

V3

Pteryg. Plex.

CN VI

CN VI

Eust. Tube

Pet. Seg. Gr. Pet. N. CN VII Mast. antrum CN VIII CN IX-XI

CN VII CN VIII

C Lat. Pteryg. M. Mandib. Cond.

Max. A.

Ext. Ac. meatus V2

Chorda Tymp. N. Gr. Pet. N. Eust. tube Cochlea Semicirc. canal

V3 V1 Pet. Seg. CN III CN IV

Mast. antrum

D V1 V2 V3 Vidian N.

Petroling. Lig. Cav. Seg. CN VI CN IV CN III Petrosphen. Lig.

Chorda Tymp. N. Less. Pet. N. Deep Pet. N. Gr. Pet. N.

Pet. Seg. CN VII

CN VIII

Figure 5 Superior view of middle cranial base. (A) The floor of the middle fossa has been preserved. The anterior part of the floor of the middle fossa is formed by the greater sphenoid wing, which roofs the infratemporal fossa, and the posterior part of the floor is formed by the upper surface of the temporal bone. The internal acoustic meatus, mastoid antrum, and tympanic cavities have been unroofed. The dural roof and lateral wall of the cavernous sinus have been removed. The petrous segment of the internal carotid artery is exposed lateral to the trigeminal nerve. The temporalis muscle is exposed in the temporal fossa lateral to the greater sphenoid wing. (B) The floor of the middle fossa has been removed to show the relationship below the floor. The temporalis muscle descends medial to the zygomatic arch in the temporal fossa to insert on the coronoid process of the mandible. The infratemporal fossa is located medial to the temporal fossa, below the greater sphenoid wing, and contains the pterygoid muscles and venous plexus and branches of the mandibular nerve and maxillary artery. The mandibular condyle is located below the posterior part of the middle fossa floor, which is formed by the temporal bone. (C) Enlarged view of the posterior part of the area below the middle fossa floor. The roof of the temporal bone, which forms the posterior part of the floor of the middle fossa, has been opened to expose the mastoid antrum, eustachian tube, semicircular canals, cochlea, the nerves in the internal acoustic meatus, and the mandibular condyle. (D) The trigeminal nerve has been reflected forward. The abducens nerve passes below the petrosphenoid ligament and through Dorello’s canal. The petrous segment of the carotid passes below the petrolingual ligament to enter the cavernous sinus. The greater petrosal nerve is joined by the deep petrosal branch of the carotid sympathetic plexus to form the vidian nerve, which passes forward in the vidian canal, which has been unroofed. The lesser petrosal nerve arises from the tympanic branch of the glossopharyngeal nerve, which passes across the promontory in the tympanic nerve plexus and regroups to cross the floor of the middle fossa, exiting the cranium to provide parasympathetic innervation through the otic ganglion to the parotid gland. The tensor tympani muscle and eustachian are layered, with the former above the latter, along and separated from the anterior surface of the petrous carotid by a thin layer of bone (1). Abbreviations: A., artery; Ac., acoustic; Cav., cavernous; CN, cranial nerve; Cond., condyle; Eust., eustachian; Ext., external; Gr., greater; Lat., lateral; Less., lesser; Lig., ligament; M., muscle; Mandib., mandibular; Mast., mastoid; Max., maxillary; N., nerve; Ophth., ophthalmic; Petroling., petrolingual; Pet., petrosal, petrous; Petrosphen., petrosphenoid; Plex., plexus; Pteryg., pterygoid; Seg., segment; Semicirc., semicircular; Temp., temporalis; Tymp., tympani.

Chapter 1: Anatomy of the Cranial Base

B

13

Crib. Plate

Nasolac. duct

A

Maxilla Max. sinus Palat. Bone

Inf. meatus

Eth. sinus

Vome r

Inf. Orb. Fiss. Vidian canal

Pteryg. Proc . Gr. Wing Gr. wing For. Oval e For. Lacerum Pterygopal. fossa Sulc. Tuba e

Pteryg. Proc. removed Car. canal

Vomer Palat. bone Perp. palate Pteryg. Proc.

Infratemp. fossa For. ovale

C

D

Max. A.

Max. sinus

Mid. concha Pteryg. Plex.

Infraorb. N. Temp. M.

Lat. Pteryg. M.

Max. sinus

Mandible Cond. Proc.

Pterygopal. fossa

Max. A.

Eust. Tube Tens. Vel. Pal. M. Lev. Vel. Pal. M.

Pteryg. Proc. Infratemp. fossa Mandible Max. A. Car. A. Parotid Gl. Int. Jug. V.

Car. Sheath Eust. tube Styloid Proc. Rosenmueller’s faossa Clivus Parotid Gl. Int. Jug. V.

Long. Cap. M.

Car. A.

CN IX-XII

Rec. Cap. Lat. M.

Figure 6 (A) Inferior view of cranial base. The right pterygoid process has been sectioned and removed at its junction with the greater wing and body of the sphenoid bone to expose the pterygopalatine fossa and the vidian canal. The vidian nerve, formed by the union of the superficial and deep petrosal nerves, courses in the vidian canal, which passes through the root of the pterygoid process. It opens posteriorly at the anterolateral margin of the foramen lacerum and anteriorly into the medial portion of the pterygopalatine fossa. The sulcus tubae, which is the attachment site of the cartilaginous part of the eustachian tube to the cranial base, is located on the extracranial surface of the sphenopetrosal fissure, anterolateral to the foramen lacerum and the carotid canal, and posteromedial to the foramina ovale and spinosum. The lateral part of the inferior orbital fissure opens into the infratemporal fossa, located below the greater sphenoid wing, and the medial part opens into the pterygopalatine fossa, located below the orbital apex between the maxilla and pterygoid process. The right zygomatic arch has been removed. (B) Inferior view of axial section of a cranium at the level of the maxillary sinus. The pterygopalatine fossa is located between the posterior wall of the maxillary sinus and the pterygoid process. The roof of the maxillary sinus forms the floor of the orbit. The infratemporal fossa is located below the greater wing of the sphenoid and opens medially into the pterygopalatine fossa. The medial wall of the pterygopalatine fossa is formed by the perpendicular plate of the palatine bone, which has an opening, the sphenopalatine foramen, through which branches of the maxillary artery and nerve reach the nasal cavity. The ethmoid air cells are located medial to the orbit. (Continued).

14

Martins and Rhoton

Max. sinus

E Max. A.

F

Max. sinus

Pterygopal. fossa Max. A.

Lat. Pteryg. M. Pteryg. Proc. Max. A. V3

Gr. wing

Eust. tube

Pterygopal. fossa Palat. bone Perp. plate Pteryg. Proc.

Infratemp. fossa Rosenmueller’s fossa Vomer

Mandible

V3

H

G Infraorb. N. Zygo. N.

Infraorb. N. V2

Pterygopal. Gang.

V2 V3

Lat. Pteryg. M.

Eust. tube

For. rotundum Vidian N. V3 For. ovale Eust. tube

Sphen. sinus Sella Pet. Seg. Clivus

Styloid Proc. Pet. Seg. CN VII For. lacerum Int. Jug. V.

CN IX-XII Sig. sinus

Figure 6 (Continued) (C) Inferior views of an axial section of the cranial base. The infratemporal fossa is surrounded by the maxillary sinus anteriorly, the mandible laterally, the pterygoid process anteromedially, and the parapharyngeal space posteromedially. It contains the mandibular nerve and maxillary artery and their branches, the medial and lateral pterygoid muscles, and the pterygoid venous plexus. The posterior nasopharyngeal wall is separated from the lower clivus by the longus capitis, and the nasopharyngeal roof rests against the upper clivus and floor of the sphenoid sinus. (D) Enlarged view with highlighting of the pre- (red) and poststyloid (yellow) compartments of the parapharyngeal space. The styloid diaphragm, formed by the anterior part of the carotid sheath, separates the parapharyngeal space into pre- and poststyloid parts. The prestyloid compartment, a narrow fat-containing space between the medial pterygoid and tensor veli palatini muscle, separates the infratemporal fossa from the medially located lateral nasopharyngeal region containing the tensor and levator veli palatini and the eustachian tube. The poststyloid compartment, located behind the prestyloid part, contains the internal carotid artery, internal jugular vein, and the cranial nerves IX through XII. (E) Some of the lateral pterygoid muscle has been removed to expose the branches of the mandibular nerve in the infratemporal fossa. The lower part of the pterygoid process has been removed to expose the maxillary artery in the pterygopalatine fossa. The pharyngeal recess (fossa of Rosenm¨uller) projects laterally from the posterolateral corner of the nasopharynx below the foramen lacerum. (F) Enlarged view. The pterygopalatine fossa is located between the posterior maxillary wall anteriorly, the sphenoid pterygoid process posteriorly, the perpendicular plate of the palatine bone medially, and the infratemporal fossa laterally. The medial part of the eustachian tube has been removed. (G) The pterygoid process has been removed to expose the maxillary nerve passing through the foramen rotundum to enter the pterygopalatine fossa where it gives rise to the infraorbital and zygomatic nerves and communicating rami to the pterygopalatine ganglion. The vidian nerve exits the vidian canal and joins the pterygopalatine ganglion. The terminal part of the petrous carotid is exposed above the foramen lacerum. (H) Enlarged view of the region of the carotid canal and jugular foramen. The bone below the carotid canal has been removed to expose the petrous carotid. The deep portion of the parotid gland has been removed to expose the facial nerve at the styloid foramen. The sigmoid sinus hooks downward from the posterior fossa and opens into the internal jugular vein. A portion of the occipital condyle has been removed to expose the hypoglossal nerve joining the nerves exiting the jugular foramen to pass downward in the carotid sheath. The styloid process and facial nerve at the stylomastoid foramen are located on the lateral side of the internal jugular vein. The right half of the floor of the sphenoid sinus has been removed to expose the sella (1). Abbreviations: A., artery; Cap., capitis; Car., carotid; CN, cranial nerve; Cond., condyle; Crib., cribriform; Eth., ethmoid; Eust., eustachian; Fiss., fissure; For., foramen; Gang., ganglion; Gl., gland; Gr., greater; Inf., inferior; Infraorb., infraorbital; Infratemp., infratemporal; Int., internal; Jug., jugular; Lat., lateral, lateralis; Lev., levator; Long., longus; M., muscle; .Max., maxillary; Mid., middle; N., nerve; Nasolac., nasolacrimal; Orb., orbital; Pal., palatini; Palat., palatine; Perp., perpendicular; Pet., petrosal, petrous; Plex., plexus; Proc., process; Pteryg., pterygoid; Pterygopal., pterygopalatine; Rec., rectus; Seg., segment; Sig., sigmoid; Sphen., sphenoid; Sulc., sulcus; Temp., temporalis; Tens., tensor; V., vein; Vel., veli; Zygo., Zygomatic.

the position of the superior semicircular canal. A thin lamina of bone, the tegmen tympani, roofs the area above the middle ear and auditory ossicles on the anterolateral side of the arcuate eminence. The internal auditory canal can be identified below the floor of the middle fossa by drilling along a line

approximately 60 degrees medial to the arcuate eminence, near the middle portion of the angle between the greater petrosal nerve and arcuate eminence (Fig. 5). The petrous apex, medial to the internal acoustic meatus, is free of important structures.

Chapter 1: Anatomy of the Cranial Base

15

B

A

Front. N.

Olf. bulb Crib. plate

Sup. Ophth. V. Nasocil. N.

Lev. M. Front. N. Sup. Obl. M. Lac. N. CN IV

Ophth. A. Optic sheath CN IV Ant. Clin. removed

Optic canal

Ant. Clin. removed

Car. A.

CN II MCA ACA

C

D

Anular tendon Orb. apex

Max. Sinus Nasolac. duct Infraorb. N.

Optic Strut Falc. Lig.

Zygo. N.

Planum Optic sheath Clin. Seg.

Pit. Stalk

Orb. apex Optic sheath

Lam. Term.

Figure 7 Superior view of the anterior cranial base. (A) Both orbits have been unroofed to expose the periorbita. The optic canals have been unroofed and the anterior clinoids removed to expose the optic nerves, which are enclosed in the optic sheath within the optic canal. The frontal, trochlear, and lacrimal nerves can be seen through the periorbita. The roof of the ethmoidal sinuses and the olfactory bulbs sitting on the cribriform plate has been preserved. The anterior cerebral arteries course above the optic chiasm. (B) The intraorbital fat has been removed and the levator and superior rectus muscles have been retracted laterally to expose both globes, ophthalmic arteries, superior ophthalmic veins, and nasociliary nerves. (C) The orbital contents have been removed to expose the lateral wall and floor of the orbit. The maxillary sinuses are exposed below the orbital floors. The maxillary nerves give rise to the infraorbital nerve, which courses along the floor of the orbit to reach the cheek, and the zygomatic nerve, which courses along the lateral wall of the orbit to reach the malar eminence and temple. (D) Enlarged view. The optic nerves are enclosed within the optic sheath as they course through the optic canal. The annular tendon, from which the rectus muscles arise, surrounds the optic nerve and medial portion of the superior orbital fissure. Removal of the anterior clinoid exposes the clinoid segment of the carotid artery. The optic strut, which separates the optic canal and superior orbital fissure, has also been removed. The segment of anterior cerebral arteries passing above the chiasm has been removed to expose the lamina terminalis. The falciform dural fold extends across the optic nerve at the entrance into the optic canal (1). Abbreviations: A., artery; ACA, anterior cerebral artery; Ant., anterior; Car., carotid; Clin., clinoid; CN, cranial nerve; Crib., cribriform; Falc., falciform; Front., frontal; Infraorb., infraorbital; Lac., lacrimal; Lam., lamina; Lev., levator; Lig., ligament; M., muscle; Max., maxillary; MCA, middle cerebral artery; N., nerve; Nasocil., nasociliary; Nasolac., nasolacrimal; Obl., oblique; Olf., olfactory; Ophth., ophthalmic; Orb., orbital; Pit., pituitary; Seg., segment; Sup., superior; Term., terminalis; Zygo., zygomatic.

The middle cranial base can be divided into a lateral portion, containing the middle cranial fossa and the upper surface of the temporal bone, and a medial portion, the sellar and the parasellar region, where the pituitary gland and cavernous sinus are located (Figs. 3 and 8) (8). The basal temporal lobe, formed by the parahippocampal, occipitotemporal, infratemporal gyri, and uncus and supplied by branches of the anterior choroidal, posterior cerebral, and middle cerebral arteries, rests on the middle fossa floor. The cavernous sinus, situated between two layers of dura, is formed by an outer layer facing the brain, and inner or periosteum layer, covering the bone of the middle fossa (9). The inner layer splits into two parts when it reaches the cavernous sinus; one invests the

nerves and forms the inner layer of the lateral wall, and the medial layer faces the sphenoid body and forms the medial wall of the sinus. The same inner layer invests the oculomotor, trochlear, and ophthalmic nerves and the distal part of the abducens nerve in their course through the lateral wall of the cavernous sinus. The internal carotid artery with its vertical posterior bend, horizontal anterior bend, and clinoidal segments runs inside the cavernous sinus. The clinoidal segment of the internal carotid artery is between the distal and proximal dural rings and is covered by a layer of dura, which forms a collar, the carotid collar, around the artery (10). In a previous study, we found that the venous plexus, forming the cavernous sinus, extends through the lower

16

Martins and Rhoton

B

A

CN VI Crib. plate Sphenoeth. Rec. Sup. concha Mid. concha Inf. concha

Sup. Orb. Fiss. Sphen. sinus Sup. concha Int. Car. A. Mid. concha Eust. tube

V2 Cav. sinus

Inf. concha

D

C Front. sinus Crib. plate

Periorbita

Front. sinus ostium Max. sinus ostium

CN II Chiasm

Olf. bulb

Rosenmueller’s fossa

Infraorb. N. Max. Sinus Max. A.

Sup. Orb. Fiss. CN VI V2 Vidian N. Pterygopal. Fossa

F

E

CN VI Zygo. N. Infraorb. N.

Sup. Obl. M. Med. Rec. M.

Sphenopal. A. Sphenopal. Gang. Vidian N.

Anular tendon Max. A.

Inf. Rec. M. Gr. Palat. N.

Figure 8 Structures below the medial part of the anterior and middle cranial fossae. (A) Midsagittal section of the anterior and middle cranial base to the right of the nasal septum. The area below the medial part of the anterior cranial fossa is formed by the frontal and ethmoidal sinuses and the nasal cavity. The nasal cavity is divided into the inferior, middle, and superior meati and the sphenoethmoidal recess by the inferior, middle, and superior conchae. The inferior meatus is located below the inferior turbinate, and the sphenoethmoidal recess, into which the sphenoid sinus opens, is located above the superior turbinate. The central part of the middle cranial base is formed by the body of the sphenoid bone, which contains the sphenoid sinus and sella with the pituitary gland. The cribriform plate is located in the roof of the nasal cavity. The nasopharynx and the opening of the eustachian tube are located below the sphenoid sinus. (B) Some of the mucosa has been removed from the concha. The inferior concha is a separate bone attached to the maxilla. The middle and superior concha are appendages of the ethmoid bone. The carotid artery courses along the lateral margin of the sphenoid sinus. The prominence within the sphenoid sinus, formed by the superior orbital fissure, is located anterior to the intracavernous carotid, and the prominence overlying the maxillary nerve is located below the intracavernous carotid. (C) The middle and superior turbinates have been removed to expose the ostia of the maxillary and frontal sinuses. Both open into the middle meatus below the middle turbinate. The nasolacrimal duct opens below the inferior concha. Rosenm¨uller’s fossa is located behind the eustachian tube. (D) The medial wall of the maxillary sinus and the ethmoid air cells have been removed to expose the orbit. The optic nerve enters the orbit above the superior orbital fissure. The maxillary nerve exits the foramen rotundum to enter the pterygopalatine fossa. The vidian nerve passes through the vidian canal and enters the posterior margin of the sphenopalatine ganglion in the pterygopalatine fossa. The floor of the anterior cranial fossa forms much of the roof of the orbit and maxillary sinus forms most of the floor of the orbit. The abducens nerve is seen below the intracavernous segment of the internal carotid artery. The pterygopalatine fossa is located anterior to the sphenoid sinus and below the orbital apex. (E) The intraorbital fat has been removed to expose the superior oblique and medial and inferior rectus muscles. (F) Enlarged view of the pterygopalatine fossa. The maxillary nerve exits the foramen rotundum to enter the pterygopalatine fossa, where it gives rise to the infraorbital, zygomatic, and palatine nerves and communicating rami to the pterygopalatine ganglion. The vidian nerve exits the vidian canal to enter the pterygopalatine ganglion. The pterygopalatine fossa contains branches of the maxillary nerve, the junction of the vidian nerve with the pterygopalatine ganglion, and terminal branches of the maxillary artery (1). Abbreviations: A., artery; Car., carotid; Cav., cavernous; Crib., cribriform; CN, cranial nerve; Eust., eustachian; Fiss., fissure; Front., frontal; Gang., ganglion; Inf., inferior; Infraorb., infraorbital; Int., internal; M., muscle; Max., maxillary; Med., medial; Mid., middle; N., nerve; Obl., oblique; Olf., olfactory; Orb., orbital; Palat., palatine; Pterygopal., pterygopalatine; Rec., recess, rectus; Sphen., sphenoid; Sphenoeth., sphenoethmoidal; Sphenopal., sphenopalatine; Sup., superior; Zygo., zygomatic.

Chapter 1: Anatomy of the Cranial Base

A

17

B Sup. Temp. A.

Orb. Oculi M. Orb. Oculi M. CN VII Frontotemp. Plex. Parotid duct Parotid gland Mass. M. Parotid duct

C

Front. M.

CN VII Frontotemp. Plex.

D

E Temp. M. Temp. M.

Orb. Oculi M.

CN VII to Front. M.

Sup. Temp. A.

Sup. Temp. A. Zygomatic M.

Orb. Oris M.

Zygo. arch Sup. Temp. A.

CN VII Brs.

TM joint

Parotid duct Mass. M. CN VII Brs. Parotid gland Bucc. M.

Zygoma Mandib. Cond.

CN VII

Coronoid Proc.

Mass. M. Bucc. M. Bucc. M.

Platysma M.

Figure 9 (A) The branches of the facial nerve, which form a fine plexus in the fat pad overlying the temporalis fascia and are directed to the orbicularis oculi and frontalis muscle, have been dissected free and a small piece of black material placed deep to their fine branches to highlight this neural network in the fat pad. (B) Enlarged view of the facial nerve plexus innervating the orbicularis oculi and frontalis muscle. (C) Lateral view of the structures superficial to the anterior and middle cranial base. The frontotemporal and zygomatic branches of the facial nerve are exposed anterior to the parotid gland. The orbicularis oculi surrounds the orbit, and the frontalis muscle extends upward from the superior orbital rim. The levators of the lip and zygomaticus muscles are located in front of the maxilla. The orbicularis oris surrounds the mouth and the buccinator muscle surrounds the oral cavity deep to the masseter muscle. The parotid duct crosses the masseter muscle. The superficial temporal artery divides into anterior and posterior branches. The parotid gland has been removed to show the branches of the facial nerve. (D) The parotid gland has been removed to expose the facial nerve exiting the stylomastoid foramen. The facial nerve branch to the frontalis muscle has been preserved in the dissection and has been laid back against the temporalis muscle to show it crossing the zygomatic arch in its course to the forehead. The superficial temporal artery passes deep to the facial nerve in front of the ear. (E) The masseter muscle has been removed to expose the temporalis muscle inserting on the coronoid process. The buccinator muscle, which surrounds the oral cavity, is situated on the deep side of the masseter muscle. (F) The coronoid process and lower part of the temporalis muscle have been removed to expose the deep temporal branches of both the maxillary artery and the mandibular nerve passing upward along the greater sphenoid wing and temporal squama to enter the deep side of the temporalis muscle. The lateral pterygoid muscles extend backward from the pterygoid process and greater wing of the sphenoid to insert along the mandibular condyle and temporomandibular joint. (G) A craniotomy has been done to expose the floor of the middle fossa, and the lateral wall of the orbit has been removed to expose the extraocular muscles. The mandibular condyle has been removed and the pterygoid muscles reflected to expose the mandibular nerve at the foramen ovale. The pterygopalatine fossa is located behind the maxilla. The floor of the orbit and the upper part of the maxilla has been removed to expose the nasal cavity. (Continued).

18

Martins and Rhoton

F

G

Temp. M.

Front. lobe

Sup. Temp. A. Deep Temp. A. & N. Temp. lobe Lat. Rec. M.

Lat. Pteryg. M. Inf. Obl. M. Mandib. Cond.

Infraorbital N. Pterygopal. fossa

Mid. fossa floor Mandib. fossa Max. A. V3

Maxilla Inf. concha

Med. Pteryg. M.

H

I V2 Orbit V1

Pet. Seg.

Tymp. Memb. Rec. Cap. Ant. M. Long. Cap. M.

V2 Chorda Tymp. N. Gr. Pet. N. V3

V3

CN VII

Car. A.

Vert. A.

Eust. tube

Int. Jug. V. CN XI

CN VII

J

K Sig. sinus

Sup. Pet. sinus Sup. Pet. Sinus V1 Car. canal

Sig. sinus Jug. Bulb

V2

CN V Post. root

V3 Pons CN IX-XII

Car. A.

Car. A. Vert. A.

Figure 9 (Continued) (H) Enlarged view following resection of the floor of the middle fossa and the external auditory canal to expose the tympanic membrane and the mandibular nerve below the foramen ovale. The mastoid segment of the facial nerve has been preserved. The greater petrosal nerve crosses above the petrous carotid. The tensor tympani muscle and eustachian tube are layered along the anterior margin of the petrous carotid. (I) The eustachian tube and tensor tympani have been resected to expose the upper cervical and petrous carotid. The nasopharyngeal mucosa has been opened to expose the longus capitus and rectus capitus anterior muscles. (J) The carotid artery has been reflected forward out of the carotid canal. This exposes the petrous apex in front of the jugular foramen on the medial side of the internal carotid artery. (K) The petrous apex has been drilled and the dura opened below the trigeminal nerve to expose the upper anterior part of the posterior cranial fossa. A segment of the internal jugular vein and jugular bulb has been resected to expose the IX through XII cranial nerves below the jugular foramen and hypoglossal canal (1). Abbreviations: A., artery; Ant., anterior; Brs., branches; Bucc., buccinator; Cap., capitis; Car., carotid; CN, cranial nerve; Cond., condyle; Eust., eustachian; Front., frontal, frontalis; Frontotemp., frontotemporal; Gr., greater; Inf., inferior; Int., internal; Jug., jugular; Lat., lateral; Long., longus; M., muscle; Mandib., mandibular; Mass., masseter; Max., maxillary; Med., medial; Memb., membrane; N., nerve; Obl., oblique; Orb., orbital; Pet., petrosal, petrous; Plex., plexus; Post., posterior; Proc., process; Pteryg., pterygoid; Pterygopal., pterygopalatine; Rec., rectus; Seg., segment; Sig., sigmoid; Sup., superior; Temp., temporal, temporalis; Tymp., tympani, tympanic; V., vein; TM, temporomandibular; Vert., vertebral; Zygo., zygomatic.

Chapter 1: Anatomy of the Cranial Base

19

B

A

Ophth. A. Eth. sinus CN II

Orbit Med. Rec. M. Eth. sinus Sphen. ostia

Lat. Rec. M .

Septum Max. A.

Mid. concha Mid. meatus Mid. concha

Max. sinus

Inf. concha

Inf. meatus

Max. sinus

Inf. meatus

CN II Ophth. A.

D

C

Cav. Seg.

CN III CN II V1

Ophth. A. Cav. Seg.

CN II

Med. Rec. M.

CN VI

CN VI V2

Lat. Rec. M. Cav. sinus

Sphen. sinus

For. Rotundum

Inf. Rec. M. Pet. Seg. Infraorb. N.

Pet. Seg.

Pterygopal. fossa

Vidian N. Pterygopal. Gang. Max. A. Infratemp. fossa

Pterygopal. fossa Max. A.

Gr. Palat. N.

Max. sinus Pteryg. Proc. Eust. tube

Infratemp. fossa Lat. Pteryg. M.

Figure 10 (A) Anterior view of a coronal section, anterior to the sphenoid sinus, through the nasal cavity, orbits, and maxillary sinuses. The upper part of the nasal cavity is separated from the orbits by the ethmoidal sinuses. The lower part of the nasal cavity is bounded laterally by the maxillary sinuses. The middle concha projects medially from the lateral nasal wall at the junction of the roof of the maxillary and ethmoidal sinuses. The posterior ethmoid air cells are located in front of the lateral part of the sphenoid sinus. (B) The middle and inferior nasal conchae on the left side and the nasal septum and the posterior ethmoidal sinuses on both sides have been removed to expose the posterior nasopharyngeal wall, the anterior aspect of the sphenoid body, and the sphenoid ostia. The posterior ethmoid air cells overlap the lateral margin of the sphenoid ostia. (C) Enlarged view showing the relationships of the nasal cavity, pterygopalatine and infratemporal fossae, orbit, and sphenoid sinus. The nasopharynx is located below the sphenoid sinus. The pterygopalatine fossa is located in the lateral wall of the nasal cavity behind the upper part of the maxillary sinus and below the orbital apex. The posterior maxillary wall is so thin that the maxillary artery coursing in the pterygopalatine fossa can be seen through the bone. The sphenopalatine branch of the maxillary artery passes through the sphenopalatine foramen to reach the walls of the nasal cavity and the sphenoid face. (D) The posterior wall of the maxillary sinus has been removed to expose the pterygopalatine and infratemporal fossae and the internal carotid artery and nerves coursing through the cavernous sinus. The maxillary artery passes through the infratemporal fossa and enters the pterygopalatine fossa, where it gives rise to branches that follow the branches of the maxillary nerve. Some of these arteries course along the sphenoid face where careful hemostasis during transsphenoidal surgery reduces the need for nasal packing after transsphenoidal operations. The maxillary nerve exits the foramen rotundum to enter the pterygopalatine fossa where it gives rise to the infraorbital and greater palatine nerves and communicating rami to the pterygopalatine ganglion. The eustachian tube opens into the nasopharynx along the posterior edge of the medial pterygoid plate (1). Abbreviations: A., artery; Cav., cavernous; CN, cranial nerve; Eth., ethmoid; Eust., eustachian; For., foramen; Gang., ganglion; Gr., greater; Inf., inferior; Infraorb., infraorbital; Infratemp., infratemporal; Lat., lateral; M., muscle; Max., maxillary; Med., medial; Mid., middle; N., nerve; Ophth., ophthalmic; Palat., palatine; Pet., petrosal; Proc., process; Pteryg., pterygoid; Pterygopal., pterygopalatine; Rec., rectus; Seg., segment; Sphen., sphenoid.

20

Martins and Rhoton

A

B

Sphen. sinus

Sphen. sinus

Car. A. Cav. sinus

Infratemp. fossa Lat. Pteryg. M.

Clivus

Med. Pteryg. M.

V3 Max. A.

Nasopharynx Car. A. Palate

For. magnum

Mass. M. Oropharynx

D

C

Bas. A. Eust. tube V3

Lat. Pteryg. M.

V3 Car. A.

Vert. A. Alar Lig.

Max. A. Long. Cap. M. Car. A.

Atlas

Int. Jug. V. Car. A.

Mandib. Cond. Trans. Lig.

Odontoid

Styloid M. Vert. A. Long. Colli M.

E

F Eth. sinus

Infraorb. N. V2

Pterygopal. fossa

Infraorb. N.

V2 Pterygopal. Gang.

Sup. concha Comm. rami Max. A. Pterygopal. Gang.

Mid. concha

Gr. Palat. N. & A.

Inf. concha

Vidian N. Sphenopal. A.

Max. A.

Gr. Palat. N. & A.

Figure 11 Anterior view. Stepwise dissection of a cross section showing the relationships below the middle cranial base. (A) The soft palate, which has been preserved, is located at the level of the foramen magnum. The infratemporal fossa, located below the greater sphenoid wing and middle cranial fossa, contains the pterygoid muscles, maxillary artery, mandibular nerve branches, and the pterygoid venous plexus and opens posteriorly into the area around the carotid sheath as shown on the left side. (B) Enlarged view. The soft palate has been divided in the midline, and the leaves reflected laterally. The atlanto-occipital joints and the foramen magnum are located at approximately the level of the hard palate. The anterior arch of C1 and the dens are located behind the oropharynx and the clivus is located behind the nasopharynx and sphenoid sinus. The prominence over the longus capitus and the anterior arch of C1 are seen through the pharyngeal mucosa. (C) The mucosa lining the posterior pharyngeal wall has been reflected to the right, exposing the longus capitus, which attaches to the clivus, and the part of the longus colli that attaches to the anterior arch of C1. The left eustachian tube has been divided. (D) The clivus and anterior arch of C1 have been removed. The dura has been opened to expose the vertebral and basilar arteries. The dens has been preserved. The structures in the right infratemporal fossa and a segment of the right carotid artery and mandible have been removed to expose the right vertebral artery ascending between the C2 and C1 transverse processes. (E) Cross section through the ethmoidal and maxillary sinuses and the nasal cavity in front of the posterior maxillary wall. The posterior wall of the maxillary sinus has been removed to expose the pterygopalatine fossa and ganglia on both sides. The maxillary nerves enter the pterygopalatine fossa by passing through the foramen rotundum. The maxillary arteries enter the pterygopalatine fossa laterally by passing through the pterygomaxillary fissure and give rise to its terminal branches in the pterygopalatine fossa. Another branch enters the greater palatine canal with the greater palatine nerves. (F) Enlarged view of the pterygopalatine fossa. The vidian nerve exits the vidian canal to enter the pterygopalatine ganglion, which receives communicating rami from the maxillary nerve. The sphenopalatine branch passes through the sphenopalatine foramen to enter the lateral nasal cavity (1). Abbreviations: A., artery; Bas., basilar; Cap., capitis; Car., carotid; Cav., cavernous; Comm., communicating; Cond., condyle; Eth., ethmoid; Eust., eustachian; For., foramen; Gang., ganglion; Gr., greater; Inf., inferior; Infraorb., infraorbital; Infratemp., infratemporal; Int., internal; Jug., jugular; Lat., lateral; Lig., ligament; Long., longus; M., muscle; Mandib., mandibular; Mass., masseter; Max., maxillary; Med., medial; Mid., middle; N., nerve; Palat., palatine; Pteryg., pterygoid; Pterygopal., pterygopalatine; Sphen., sphenoid; Sphenopal., sphenopalatine; Sup., superior; Trans., transverse; V., vein; Vert., Vertebral.

Chapter 1: Anatomy of the Cranial Base

A

21

Sphenoid bone

Temp. bone

Occip. bone

Int. Ac. meatus

Jug. For.

Occip. condyle Occip. bone

B

PCA CN III

SCA Bas. A.

CN IV CN V Tent. edge CN VI CN VII, VIII

AICA

CN IX, X

CN XII Vert. A.

P.I.C.A.

CN XI

Figure 12 (A) Superior view of the posterior cranial fossa. The osseous walls of the posterior fossa are formed by the occipital, temporal, and sphenoid bones. The fossa is bounded in front by the dorsum sellae and posterior part of the sphenoid bone and the clival part of the occipital bone; behind by the lower portion of the squamosal part of the occipital bone; and on each side by the petrous and mastoid parts of the temporal bone, and the lateral part of the occipital bone. One small part above the temporal bone is formed by the inferior angle of the parietal bone. (B) Nerves and arteries of the posterior fossa. Only two of the twelve pairs of cranial nerves course entirely outside the posterior fossa. The tentorium, which is attached along the petrous ridges, roofs the posterior fossa. The superior cerebellar artery courses below the oculomotor and trochlear nerves and above the trigeminal nerve; the anteroinferior cerebellar artery courses near the abducens, facial, and vestibulocochlear nerves; and the posteroinferior cerebellar artery courses near the glossopharyngeal, vagus, accessory, and hypoglossal nerves (12). Abbreviations: A., artery; Ac., acoustic; AICA, anteroinferior cerebellar artery; Bas., basilar; CN, cranial nerve; For., foramen; Int., internal; Jug., jugular; Occip., occipital; PCA, posterior cerebral artery; PICA, posteroinferior cerebellar artery; SCA, superior cerebellar artery; Temp., temporal; Tent., tentorial; Vert., vertebral.

22

Martins and Rhoton

A

B Zygomatic proc. Ant. Root Trig. Impress. Squamosal part Groove for Gr. Pet. N. Zygomatic Proc. Post. Root

Petrous part Squamosal part

Petrous part

Mandib. fossa

Arc. Emin. Car. canal

Tymp. Part Styloid proc.

Jug. fossa

Squamosal part Tegmen

Stylomast. For.

Mastoid part

Mastoid part

D

C

Vert. crest

Squamosal part

Facial canal Arc. Emin.

Trans. crest

Sup. Vest. area

Trig. Impress. Sig. sulcus Petrous part Int. Ac. Meatus

Cochlear area Mastoid part

Inf. Vest. area

Vest. Aqueduct

Figure 13 Temporal bone. (A) and (B) Inferior views of temporal bone. (A) The temporal bone has a squamosal part, which forms some of the floor and lateral wall of the middle cranial fossa. It is also the site of the mandibular fossa in which the mandibular condyle sits. The tympanic part forms the anterior, lower, and part of the posterior wall of the external canal, part of the wall of the tympanic cavity, the osseous portion of the eustachian tube, and the posterior wall of the mandibular fossa. The mastoid portion contains the mastoid air cells and mastoid antrum. The petrous part is the site of the auditory and vestibular labyrinth, the carotid canal, the internal acoustic meatus, and the facial canal. The petrous part also forms the anterior wall and the dome of the jugular fossa. The styloid part projects downward and serves as the site of attachment of three muscles. (B) Superior view. The medial part of the upper surface is the site of the trigeminal impression in which Meckel’s cave sits. Further laterally is the prominence of the arcuate eminence overlying the superior semicircular canal. Anterior and lateral to the arcuate eminences is the tegmen, a thin plate of bone overlying the mastoid antrum and epitympanic area. The temporal bone articulates anteriorly with the sphenoid bone, above with the parietal bone, and posteriorly with the occipital bone. The zygomatic process of the squamosal part has an anterior and a posterior root between which, on the lower surface, is located the mandibular condyle. (C) Posterior view of a right temporal bone. The sigmoid sulcus descends along the posterior surface of the mastoid portion. The internal acoustic meatus enters the central portion of the petrous part of the bone. The trigeminal impression and arcuate eminence are located on the upper surface of the petrous part. The vestibular aqueduct connects the vestibule in the petrous part with the endolymphatic sac, which sits on the posterior petrous surface inferolateral to the internal acoustic meatus. (D) Enlarged view of the right internal acoustic meatus. The transverse crest divides the meatal fundus into superior and inferior parts. The anterior part above the transverse crest is the site of the facial canal and the posterior part is the site of the superior vestibular area. Below the transverse crest the cochlear area is anterior and the inferior vestibular area is posterior. The vertical crest, also called “Bill’s Bar,” separates the facial and superior vestibular areas (7). Abbreviations: Ac., acoustic; Ant., anterior; Arc., arcuate; Car., carotid; Emin., eminence; For., foramen; Gr., greater; Impress., impression; Inf., inferior; Int., internal; Jug., jugular; Mandib., mandibular; N., nerve; Pet, petrosal; Post, posterior; Proc., process; Sig., sigmoid; Stylomast., stylomastoid; Sup., superior; Trans., transverse; Trig., trigeminal; Tymp., tympanic.; Vert., vertebral; Vest., vestibular.

Chapter 1: Anatomy of the Cranial Base

23

A Basal Part (Clivus)

Car. canal

Styloid Proc.

B Clivus

Jug. For. Stylomast. For. Occip. Cond.

Condylar part

Petrocliv. Fiss. Jug. tubercle

Jug. For. Occip. Cond.

Digast. groove Sig. sulcus

Occip. A. groove

Vermian fossa Ext. Occip. crest Int. Occip. crest Sup. nuchal line Squamosal part Inion

Sup. sag. Sinus sulcus

Trans. sinus sulcus

D

C

For. ovale For. lacerum Clivus

Petrocliv. Fiss. Styloid Proc.

Pharyng. tubercle Jug. For.

Styloid Proc.

Stylomast. For.

Occip. Cond.

Car. canal

Clivus

Jug. For.

Condylar part

21 mm

Occip. Cond. 8 mm

Occip. bone Jug. Proc.

Squamosal Part

E

F For. Ovale Int. Ac. meatus

Petrocliv. Fiss.

Clivus

Coch. aqueduct Pet. part

Clivus

Vest. aqueduct

Petrocliv. Fiss. Car. canal

Coch. aqueduct Intrajug. Proc. Sig. Part

Hypogl. canal Occip. Cond.

Pet. part Sig. part Occip. bone Jug. Proc.

Figure 14 Occipital bone, foramen magnum, and jugular foramen. (A–D) Occipital bone and foramen magnum. (A) Inferior view. (B) Superior view. (C, D) Anteroinferior views. (A–C) The occipital bone surrounds the oval shaped foramen magnum, which is wider posteriorly than anteriorly. The narrower anterior part sits about the odontoid process and is encroached on from laterally by the occipital condyles. The wider posterior part transmits the medulla. The occipital bone is divided into a squamosal part located above and behind the foramen magnum; a basal (clival) part situated in front of the foramen magnum; and paired condylar parts located lateral to the foramen magnum. The basilar part of the occipital bone, which is also referred to as the clivus, is a thick quadrangular plate of bone, concave from side to side, that extends forward and upward to join the sphenoid bone just below the dorsum sellae. The clivus is separated on each side from the petrous part of the temporal bone by the petroclival fissure, which ends posteriorly at the jugular foramen. The condylar parts of the occipital bone, on which the occipital condyles are located, are situated lateral to the foramen magnum on the external surface. The hypoglossal canal is situated above the condyle. The jugular process of the occipital bone extends laterally from the posterior half of the condyle and articulates with the jugular surface of the temporal bone. The sulcus of the sigmoid sinus crosses the superior surface of the jugular process. The jugular foramen is bordered posteriorly by the jugular process of the occipital bone and anteriorly by the jugular fossa of the petrous temporal bone. (Continued).

24

Martins and Rhoton

ring, inside the collar of dura, and around the clinoid segment to the level of the upper ring. The meningohypophyseal trunk, with its tentorial, inferior hypophyseal, and dorsal meningeal branches, and the inferolateral trunk, also called the artery of the inferior cavernous sinus, arise from the intracavernous carotid artery. The proximal abducens nerve passes through Dorello’s canal, located below the petrosphenoid ligament, and receives sympathetic branches from the internal carotid nerve, which pass to the ophthalmic nerve to enter the orbit. The main venous afferents to the cavernous sinus are the superior and inferior ophthalmic veins and the sphenoparietal sinus (Figs. 4 and 7). Several venous compartments, named according to their relationship to the cavernous carotid artery, empty mainly in the basilar and superior and inferior petrosal sinuses, or, by way of the foramina in the middle fossa floor, into the pterygoid venous plexus (4). The sella houses the pituitary gland and is partially closed above by the diaphragma sellae. Anterolateral to the diaphragm, the carotid cave, a dural depression at the level of the distal dural ring, extends downward medial to the initial intradural segment of the internal carotid artery. The tensor tympani muscle and eustachian tube cross medial to the foramen spinosum, below the floor of the middle fossa, and anterior to the horizontal segment of the petrous carotid (Fig. 5). The greater petrosal nerve crosses the area above and parallel to the petrous carotid artery, laterally joins the geniculate ganglion, and medially joins the deep petrosal branch of the carotid sympathetic nerves to form the vidian nerve, which enters the pterygopalatine ganglion (Figs. 2, 5, and 6). The lesser petrosal nerve runs anterior to the greater petrosal nerve and exits the cranium, passing through the foramen spinosum to join the otic ganglion. The cochlea is situated below the floor of the middle cranial fossa, at the apex of the angle between the greater petrosal and labyrinthine segment of the facial nerve.

Exocranial Surface The exocranial surface of the middle cranial base is also divided into central and lateral parts (Figs. 2, 3, 6, and 9) (1). The central part encompasses the sphenoid body and the upper part of the basal (clival) part of the occipital bone and corresponds to the sphenoid sinus and the nasopharynx. The lateral part is formed by the greater sphenoid wing; the petrous, tympanic, and squamous parts of the temporal bone; the styloid process; and the zygomatic, palatine, and maxillary bones. The medial and lateral parts are separated by a parasagittal plane passing through the medial pterygoid plate. The foramen lacerum is located at the union of the sphenoid, occipital, and petrous bones and is enclosed on its lower side by fibrocartilaginous tissue to form the inferior wall of the carotid canal. Structures transversing the lateral part include the carotid artery in the carotid canal, the glossopharyngeal, vagus, and accessory nerves in the jugular foramen, the third trigeminal division in the foramen ovale, the middle meningeal artery in the foramen spinosum, and the facial nerve in the facial canal. The pterygomaxillary fissure is the lateral opening of the pterygopalatine fossa into the infratemporal fossa. The glenoid fossa harbors the mandibular condyle. The roof of the fossa is divided into anterior and posterior parts by the squamotympanic fissure, along which the chorda tympani passes. The area below the middle cranial base includes the infratemporal fossa, parapharyngeal space, infrapetrosal space, and pterygopalatine fossa (Figs. 6, 9, 10, and 11). The boundaries of the infratemporal fossa are the middle pterygoid muscle and the pterygoid process medially, the mandible laterally, the posterior wall of the maxillary sinus anteriorly, the greater wing of the sphenoid superiorly, and the medial pterygoid muscle joining the mandible and the pterygoid fascia posteriorly. The fossa opens into the neck below. The infratemporal fossa contains the branches of mandibular nerve, the maxillary artery, and the pterygoid muscles and venous plexus. The mandibular nerve, after exiting the

←−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−− Figure 14 (Continued) The jugular tubercle lies on the internal surface above the hypoglossal canal. The squamous part is internally concave. The convex external surface of the squamosal part has several prominences. The largest prominence, the external occipital protuberance (inion), is situated at the central part of the external surface. The superior nuchal line radiates laterally from the protuberance. A vertical ridge, the external occipital crest, descends from the external occipital protuberance to the midpoint of the posterior margin of the foramen magnum. The internal surface of the squamous part has a prominence, the internal occipital protuberance near its center. The internal occipital crest bifurcates above the foramen magnum to form a V-shaped ridge between the limbs of which is the vermian fossa. (D) Inferior view of the occipital condyles and foramen magnum. The occipital condyles are located along the lateral margin of the anterior half of the foramen magnum. Their articular surfaces are convex, face downward and laterally, and articulate with the superior facet of C1. A probe inserted through the hypoglossal canal passes forward approximately 45 degrees from the midsagittal plane in an anterolateral direction. The hypoglossal canal is located above the middle third of the occipital condyle and is directed from posterior to anterior and from medial to lateral. The intracranial end of the hypoglossal canal is located approximately 5 mm above the junction of the posterior and middle third of the occipital condyle and approximately 8 mm from the posterior edge of the condyle. The extracranial end of the canal is located approximately 5 mm above the junction of the anterior and middle third of the condyle. The average length of the longest axis of the condyle is 21 mm. The large arrow shows the direction of the transcondylar approach and the cross-hatched area shows the portion of the occipital condyle that can be removed without exposing the hypoglossal nerve in the hypoglossal canal. The stylomastoid foramen is situated lateral to the jugular foramen. The styloid process is located anterior and slightly medial to the stylomastoid foramen. (E, F) Jugular foramen. (E) Posterosuperior view. The jugular foramen is located between the temporal and occipital bones. The sigmoid groove descends along the mastoid and crosses the occipitomastoid suture where it turns forward on the upper surface of the jugular process of the occipital bone and enters the foramen by passing under the posterior part of the petrous temporal bone. The foramen has a larger lateral sigmoid part through which the sigmoid sinus empties and a smaller anteromedial petrosal part through which the inferior petrosal sinus empties. The two parts are separated by the intrajugular processes of the occipital and temporal bones. The glossopharyngeal, vagus, and accessory nerves pass through the intrajugular portion of the foramen located between the sigmoid and petrosal parts. The foramen is asymmetric from side to side, with the right side often being larger as shown. The cochlear aqueduct opens just above the anterior edge of the petrosal part. The vestibular aqueduct opens into the endolymphatic sac, which sits on the back of the temporal bone superolateral to the sigmoid part of the jugular foramen. (F) Anteroinferior view. The roof over the jugular foramen, formed by the jugular fossa of the temporal bone, is shaped to accommodate the jugular bulb. The posterior margin of the foramen is formed by the jugular process of the occipital bone, which connects the basal (clival) part of the occipital bone to the squamosal part. The petroclival fissure intersects the anteromedial margin of the petrosal part of the foramen. The entrance into the carotid canal is located directly in front of the medial half of the jugular foramen. (A–C) (13), (D) (14), (E–G) (18). Abbreviations: A., artery; Ac., acoustic; Car., carotid; Coch., Cochlear; Cond., condyle; Digast., digastric; Ext., external; Fiss., fissure; For., foramen; Hypogl., hypoglossal; Int., internal; Intrajug., intrajugular; Jug., jugular; Occip., occipital; Petrocliv., petroclival; Pet., petrous; Pharyng., pharyngeal; Proc., process; Sag., sagittal; Sig., sigmoid; Stylomast., stylomastoid; Sup., superior; Trans., transverse; Vest., vestibular.

Chapter 1: Anatomy of the Cranial Base

A

25

B Sup. Pet. V. Subarc. A. CN VII

CN V

CN VIII

Sup. Vest. N. Nerv. Intermed. Inf. Vest. Coch. N.

Labyr. A. A.I.C.A.

Flocc.

Flocc. CN VI CN IX CN IX PICA

PICA CN X

CN X-XI

Chor. Plex.

CN XI

D

C

CN V CN V

CN VII Sup. Vest. N. Nerv. Intermed.

Coch. N.

Sup. Vest. N.

Inf. Vest. N. AICA

Subarc. A. CN VII Inf. Vest. N. Coch. N. Labyr. A.

Flocc.

Inf. Vest. N. Flocc.

CN VI

CN IX

CN VI

CN IX

Chor. Plex. PICA

AICA

Chor. Plex. PICA

Figure 15 Retrosigmoid exposure of the nerves in the right cerebellopontine angle. (A) The vestibulocochlear nerve enters the internal acoustic meatus with a labyrinthine branch of the AICA. The PICA courses around the glossopharyngeal, vagus, and accessory nerves. The abducens nerve ascends in front of the pons. The subarcuate branch of the AICA enters the subarcuate fossa superolateral to the porus of the meatus. Choroid plexus protrudes into the cerebellopontine angle behind the glossopharyngeal and vagus nerves. (B) The posterior wall of the internal acoustic meatus has been removed. The cleavage plane between the upper bundle, formed by the superior vestibular nerve, and the lower bundle, formed by the inferior vestibular and cochlear nerves, was begun laterally where the nerves normally separate near the meatal fundus and extended medially. The nervus intermedius arises on the anterior surface of the vestibulocochlear nerve, has a free segment in the cistern and/or meatus, and joins the facial nerve distally. The facial nerve is located anterior to the superior vestibular nerve and the cochlear nerve is anterior to the inferior vestibular nerve. (C) The cleavage plane between the cochlear and inferior vestibular nerves, which is well developed in the lateral end of the internal acoustic meatus, has been extended medially. Within the cerebellopontine angle, the superior vestibular nerve is posterior and superior, the facial nerve anterior and superior, the inferior vestibular nerve posterior and inferior, and the cochlear nerve anterior and inferior. (D) The superior and inferior vestibular nerves have been divided to expose the facial and cochlear nerves. A labyrinthine branch of the AICA enters the internal meatus (15). Abbreviations: A., artery; AICA, anteroinferior cerebellar artery; Chor. Plex., choroid plexus; CN, cranial nerve; Coch., cochlear; Flocc., flocculus; Inf., inferior; Intermed., intermedius; Labyr., labyrinth; N., nerve; Nerv., nervus; Pet., petrosal; PICA, posteroinferior cerebellar artery; Subarc., subarcuate; Sup., superior; V., vein; Vest., vestibular.

26

Martins and Rhoton

B

A Pon. Mes. Sulcus

CN VI Pon. Med. Sulcus CN IX, X, XI Olive Medulla

CN VII CN VII, VIII CN VIII Chor. Plex. Pyramids AICA Pet. Surface CN IX, X CN XII CN XII CN XI PICA Vert. A. PCA CN IV SCA

PCA CN III SCA

D

AICA

PICA

CN XII

Ant. Hem. V.

Ant. Sp. A.

PICA Vert. A.

Vert. A.

CN V CN VI AICA

PICA

Ped. V.

CN VI Trans. Pon. V. AICA Sup. Pet. V. CN IX -XI

CN VII, VIII

CN III SCA

CN V

Pons

C

CN V

CN IV

Midbrain

Med. Ant. Pon. Mes. V. V. Cer. Pon. Fiss.

Ant. Hem. V. V. Pon. Med. sulcus Trans. Med. V.

Med. Ant. Med. V.

Figure 16 Brain stem, anterior cerebellar surface, and posterior skull base. (A) The petrosal (anterior) surface of the cerebellum, called the petrosal surface, and front of the brain stem face the endocranial surface of the posterior fossa. The fourth ventricle is positioned behind the pons and medulla. The midbrain and pons are separated by the pontomesencephalic sulcus and the pons and medulla by the pontomedullary sulcus. The trigeminal nerves arise from the midpons. The abducens nerve arises in the medial part of the pontomedullary sulcus, rostral to the medullary pyramids. The facial and vestibulocochlear nerves arise at the lateral end of the pontomedullary sulcus immediately rostral to the foramen of Luschka. The hypoglossal nerves arise anterior to the olives and the glossopharyngeal, vagus, and accessory nerves arise posterior to the olives. Choroid plexus protrudes from the foramen of Luschka behind the glossopharyngeal and vagus nerves. (B) Anterior view of the brain stem with the arteries preserved. (C) Posterior view of the skull base with the cranial nerves and arteries preserved. (B, C) The SCA arises at the midbrain level and encircles the brain stem near the pontomesencephalic junction. The SCA courses below the oculomotor and trochlear nerves and above the trigeminal nerve. The SCA loops down closer to the trigeminal nerve in C than in B. The AICA arises at the pontine level and courses by the abducens, facial, and vestibulocochlear nerves. In B, both AICAs pass below the abducens nerves. In C, the left abducens nerve passes in front of the AICA and the right abducens nerve passes behind the AICA. The PICAs arise from the vertebral artery at the medullary level and course in relation to the glossopharyngeal, vagus, accessory, and hypoglossal nerves. The origin of the SCAs is quite symmetrical from side to side. There is slight asymmetry in the level of origin of the AICAs and marked asymmetry in the level of the origin of the PICAs, especially in B. (D) The veins on the anterior surface of the pons and medulla and the petrosal cerebellar surface drain predominantly into the superior petrosal veins which empty into the superior petrosal sinuses. The median anterior pontomesencephalic and median anterior medullary veins ascend on the front of the brain stem. The transverse pontine and transverse medullary veins run transversely across the pons and medulla surfaces. The anterior hemispheric veins drain the petrosal cerebellar surface and commonly empty into the vein of the cerebellopontine fissure, which ascends to join the superior petrosal veins. The vein of the pontomedullary sulcus passes across the pontomedullary junction. The peduncular vein crosses the cerebral peduncle. Abbreviations: A., artery; AICA, anteroinferior cerebellar artery; Ant., anterior; Cer. Pon., cerebellopontine; Chor., choroid; CN, cranial nerve; Fiss., fissure; Hem., hemispheric; Med., medial, medullary; Pet., petrosal; PCA, posterior cerebral artery; Ped., peduncular; PICA, posteroinferior cerebellar artery; Plex., plexus; Pon., pontine; Pon. Med., pontomedullary; Pon. Mes., pontomesencephalic; SCA, superior cerebellar artery; Sulc., sulcus; Sp., spinal; Sup., superior; Trans., transverse; V., vein; Vert., vertebral.

foramen ovale, lies anterolateral to the otic ganglion and divides immediately into its terminal branches: the pterygoid, buccal, masseteric, and temporal branches along the superior wall of the fossa; the inferior alveolar and the lingual branches, after being joined by the chorda tympani, descend between both pterygoid muscles; and the auriculotemporal branch with the maxillary artery course between the mandible and the sphenomandibular ligament. The auriculotemporal nerve carries the parasympathetic innervation of

the parotid gland, which travels through the tympanic branch of the glossopharyngeal nerve, which in turn forms the lesser petrosal nerve, to reach the otic ganglion before joining the auriculotemporal nerve. The maxillary artery, which arises as a terminal branch of the external carotid artery with the superficial temporal artery, is divided into three segments. The first, or mandibular segment, passes between the sphenomandibular ligament and the mandibular neck and gives rise to the deep auricular, anterior tympanic, middle meningeal,

Chapter 1: Anatomy of the Cranial Base

A

27

B Post. Digast. M. Rec. Cap. Post. Maj. M.

Sup. Obl. M. Suboccip. triangle

Trans. Proc. C1

Inf. Obl. M.

X

Lev. Scap. M.

C

C

CN IX, X

D

th P.I.C.A. 4 Vent.

PICA

CN XI CN XI

Occip. Cond. Atl. Occip. Joint

CN XII C1 Cond. CN XII Vert. A. Dural cuff

Dent. Lig.

C1 Cond. Vert. A. C1 Trans. Proc. C1

Hypogl. canal

Vert. A. Vert. A.

Figure 17 (A–D) Far-lateral and transcondylar approach. (A) A suboccipital scalp flap is commonly selected for the far-lateral exposure. The medial limb extends downward in the midline so that a wide upper cervical laminectomy can be completed if needed. The lateral limb extends below the level of the C1 transverse process (×), which can be palpated between the mastoid tip and the angle of the jaw, to access the vertebral artery as it ascends through the C1 transverse process. The muscles superficial to the suboccipital triangle can be reflected from the suboccipital area in a single layer with the scalp flap, leaving a cuff of suboccipital muscle and fascia attached along the superior nuchal line to aid in closure. (B) The scalp and muscles are reflected in a single layer to expose the suboccipital triangle in the depths of which the vertebral artery courses behind the atlanto-occipital joint and across the posterior arch of C1. The triangle is located between the superior and inferior oblique and the rectus capitis posterior major. (C) A suboccipital craniectomy has been completed, the posterior arch of C1 has been removed, the posterior root of the transverse foramen of the C1 has been removed, the area above the occipital condyle has been drilled to expose the hypoglossal canal, and the dura has been opened. The dural incision completely encircles the vertebral artery, leaving a narrow dural cuff on the artery, so that the artery can be mobilized. The drilling in the supracondylar area can be extended extradurally to the level of the jugular tubercle to increase access to the front of the brain stem. (D) Comparison of the exposure with the far-lateral and transcondylar approaches. On the right side, the far-lateral exposure has been extended to the posterior margins of the atlantal and occipital condyles and the atlanto-occipital joint. The prominence of the condyles limits the exposure along the anterolateral margin of the foramen magnum. On the left side, a transcondylar exposure has been completed by removing the posterior part of the condyles. The dura can be reflected further laterally with the transcondylar approach than with the far-lateral approach. The condylar drilling provides an increased angle of view of the clivus and front of the brain stem. The dentate ligament and accessory nerve ascend from the region of the foramen magnum (18). Abbreviations: A., artery; Atl., atlanto; Cap., capitis; CN, cranial nerve; Cond., condyle; Dent., dentate; Digast., digastric; Hypogl., hypoglossal; Inf., inferior; Lev., levator; Lig., ligament; M., muscle; Maj., major; Obl., oblique; Occip., occipital; PICA, posteroinferior cerebellar artery; Post., posterior; Proc., process; Rec., rectus; Scap., scapula; Suboccip., suboccipital; Sup., superior; Trans., transverse; Vent., ventricle; Vert., vertebral.

accessory middle meningeal (enters through the foramen ovale), and the inferior alveolar artery. The second, or pterygoid segment, courses through the middle of the infratemporal fossa and gives rise to the posterosuperior alveolar, infraorbital, masseteric, pterygoid, temporal, and buccal branches. The third, or pterygopalatine segment, courses in

the fossa of the same name. The pterygoid venous plexus connects through the middle fossa foramina and inferior orbital fissure with the cavernous sinus and empties into the retromandibular and facial veins. The pterygopalatine fossa is located between the maxillary sinus in the front, the pterygoid process behind, the

28

Martins and Rhoton

Ant. tubercle Ant. arch

A

B

Ant.tubercle

Ant. arch

Trans. proc.

Sup. Art. Facet Trans. Proc.

Inf. Art. Facet

Lat. mass. Trans. For. Trans. For. Post. arch

Groove for Vert. A.

Post. arch

Post. tubercle

C

Post. tubercle

D

Sup. Art. Facet

Sup. Art. Facet

Trans. Proc. Groove for Vert. A. Trans. Proc.

Post. arch

Ant. arch

Ant. tubercle

Inf. Art. Facet

E

Odontoid proc.

Post. tubercle

Inf. Art. Facet

F Odontoid proc.

Art. facet Sup. Art. Facet

Spinous proc.

Sup. Art. Facet

Sup. Art. Facet Trans. For.

Trans. proc.

Lamina

Trans. for.

Trans. proc. Body

Body Trans. proc.

Inf. Art. Facet Inf. Art. Facet

Inf. Art. Facet

G

Odontoid proc. Sup. Art. Facet Trans. proc.

Sup. Art. Facet Trans. proc.

Body

H Trans. for Trans. ror.

Body

Trans. proc.

Trans. for. Inf. Art. Facet

Pedicle

Inf. Art. Facet

Inf. Art. Facet Inf. Art. Facet Lamina

Lamina

Spinous proc. Spinous proc.

Figure 18 Atlas and Axis. (A–D) The atlas. (A) Superior view. (B) Inferior view. (C) Anterior view. (D) Posterior view. The atlas consists of two thick lateral masses situated at the anteromedial part of the ring, and which are connected in front by a short anterior arch and posteriorly by a longer curved posterior arch. The anterior and posterior tubercles are at the anterior and posterior midline. The superior articular facet is an oval, concave facet that faces upward and medially to articulate with the occipital condyle. The inferior articular facet is a circular, flat, or slightly concave facet that faces downward, medially, and slightly backward and articulates with the superior articular facet of the axis. The medial aspect of each lateral mass has a small tubercle for the attachment of the transverse ligament of the atlas. The transverse process projects from the lateral masses. The transverse foramina transmit the vertebral arteries. The upper surface of the posterior arch adjacent to the lateral masses has paired grooves in which the vertebral arteries course. (E–H) The axis. (E) Anterior view. (F) Lateral view. (G) Superior view. (H) Inferior view. The axis is distinguished by the odontoid process (dens). On the front of the dens is an articular facet that forms a joint with the facet on the back of the anterior arch of the atlas. The dens is grooved at the base of its posterior surface where the transverse ligament of the atlas passes. The oval superior articular facets articulate with the inferior facets of the atlas. The superior facets are anterior to the inferior facets. The pedicles and laminae are thicker than on the other cervical vertebra and the lamina fuses behind to form a large spinous process. The transverse foramina are directed superolaterally, thus permitting the lateral deviation of the vertebral arteries as they pass up to the more widely separated transverse foramina in the atlas. The inferior articular facets face downward and forward (13). Abbreviations: A., artery; Ant., anterior; Art., articular; For., foramen; Inf., inferior; Lat., lateral; Mass., masses; Post., posterior; Proc., process; Sup., superior; Trans., transverse; Vert., vertebral.

Chapter 1: Anatomy of the Cranial Base

29

Nasal bone B

A Zygoma

Nasal bone

Maxilla Med. Canthal Lig.

Front. bone

Nasolac. duct Lac. bone Periorbita

D

C Maxilla

Nasal cavity Med. Canthal Lig.

Nasolac. duct

Sup. concha

Lac. bone Nasal bone Eth. Perp. plate Ant. Eth. A. Eth. sinus Crib. plate

Frontonasal suture

Periorbita

Dura

E

F Sphenopal. A. Clivus

Vomer Ant. Eth. A.

Septa Car. A.

Sphen. sinus

Sphen. ostia Sphen. sinus Crib. plate Crib. plate

Figure 19 (A–F). Relationships in the transbasal and extended frontal approaches. (A) The inset shows the bicoronal scalp incision. A large bifrontal craniotomy and a fronto-orbitozygomatic osteotomy have been completed. The osteotomized segment may extend through the nasal bone and from one to the other lateral orbital rims, as shown. However, for most lesions, a more limited bone flap and osteotomy will suffice and can be tailored as needed to deal with the involvement of the cranial base, nasal cavity, paranasal sinuses, or orbit. For an orbital lesion, an orbitofrontal craniotomy, elevating only the superior orbital rim (yellow arrows) and orbital roof, is all that is needed. For a cavernous sinus or unilateral lesions of the anterior or middle fossa, an orbitozygomatic osteotomy will usually suffice (blue arrow). For a clival lesion, a more limited bifrontal approach (red arrow) will suffice. (B) The periorbita has been separated from the walls of the orbit in preparation for the osteotomies. Division of the medial canthal ligament is not necessary for most lesions, but may be required for lesions extending into the lower nasal cavity or orbit. The ligaments should be re-approximated at the end of the operation. (C) The right medial canthal ligament has been divided and the orbital contents retracted laterally to expose the nasolacrimal duct and the anterior ethmoidal branch of the ophthalmic artery at the anterior ethmoidal foramen. (D) The osteotomies have been completed and the frontal dura elevated. The dura remains attached at the cribriform plate. The upper part of both orbits are exposed. (E) An osteotomy around the cribriform plate leaves it attached to the dura and olfactory bulbs, a maneuver that has been attempted in order to preserve olfaction but has been uncommonly successful. The anterior face of the sphenoid sinus and both sphenoid ostia are exposed between the orbits. (F) The sphenoid sinus has been opened to expose the septa within the sinus. The sphenopalatine arteries cross the anterior face of the sphenoid. (Continued).

30

Martins and Rhoton

G

H

Vomer

Vomer Clival dura

Car. A. Cav. Seg.

Clivus

Car. A. Optic canal

Bas. sinus Pit. gland

Pit. gland Optic canal

I

J Med. Pteryg. plate Olf. Tr.

Eust. tube Pteryg. Proc. Max. A. Pterygopal. Gang. Infraorb. N. Sphen. Sinus

CN II Chiasm MCA

MCA

V2 ACA

Car. A. Figure 19 (Continued) (G) The septa within the sphenoid sinus, the sellar floor, and the lateral sinus wall have been removed to expose the intracavernous carotid, pituitary gland, and optic canals. (H) The clivus has been opened to expose the dura facing the brain stem. The basilar sinus, which interconnects the posterior parts of the cavernous sinus, is situated between the layers of dura on the upper clivus. (I) The exposure has been extended laterally by opening the medial and posterior wall of the maxillary sinus to expose the branches of the maxillary nerve and artery in the pterygopalatine fossa, located behind the posterior maxillary wall. The posterior wall of the pterygopalatine fossa is formed by the pterygoid process. The maxillary nerve enters the pterygopalatine fossa where it gives rise to the infraorbital nerve, which courses along the floor of the orbit and to the palatine nerves, which descend to the palatal area. The eustachian tube opens into the nasopharynx by passing along the posterior edge of the medial pterygoid plate. The lateral wing of the sphenoid sinus extends laterally below the maxillary nerve. (J) The frontal dura has been opened and the frontal lobes elevated to expose the olfactory and optic nerves and the internal carotid and anterior and middle cerebral arteries (1). Abbreviations: A., artery; ACA, anterior cerebral artery; Ant., anterior; Bas., basilar; Car., carotid; Cav., cavernous; CN cranial nerve; Crib., cribriform; Eth., ethmoid, ethmoidal; Eust., eustachian; Front., frontal; Gang., ganglion; Infraorb., infraorbital; Lac., lacrimal; Lig., ligament; Max., maxillary; Med., medial; MCA, middle cerebral artery; N., nerve; Nasolac., nasolacrimal; Olf., olfactory; Perp., perpendicular; Pit., pituitary; Proc., process; Pteryg., pterygoid; Pterygopal., pterygopalatine; Seg., segment; Sphen., sphenoid; Sphenopal., sphenopalatine; Sup., superior; Tr., Tract.

palatine bone medially and the body of the sphenoid bone above (Figs. 3, 6, 10, and 11). The fossa opens laterally through the pterygomaxillary fissure into the infratemporal fossa and medially through the sphenopalatine foramen to the nasal cavity. Both the foramen rotundum for the maxillary nerve and the pterygoid canal for the vidian nerve open through the posterior wall of the fossa formed by the sphenoid pterygoid process. The palatovaginal canal carrying the pharyngeal nerve and artery and the greater and lesser palatine canals conveying the greater and lesser palatine arteries open into the pterygopalatine fossa. The inferior orbital fissure, across which the orbital muscle stretches, lies in front of the pterygopalatine fossa. This fossa contains branches of the maxillary nerve, vidian nerve, the pterygopalatine ganglion, and the pterygopalatine segment of the maxillary artery. The

maxillary nerve passes through the foramen rotundum to enter the fossa and, after giving communicating rami to the pterygopalatine ganglion, divides into the posterosuperior alveolar, infraorbital, and zygomatic nerves. The zygomatic nerve, in addition to its sensory fibers, carries the parasympathetic fibers from the pterygopalatine ganglion to the lacrimal gland. The vidian (nerve of the pterygoid canal) ends in the pterygopalatine ganglion, which sends rami to the maxillary nerve and gives rise to the greater and lesser palatine, pharyngeal nerves, and nasal branches. The third part of the maxillary artery enters the fossa and divides into its terminal lesser and greater palatine, sphenopalatine, vidian, and pharyngeal branches. The parapharyngeal space lies between the structures in the pharynx wall medially, the medial pterygoid muscle

31

Chapter 1: Anatomy of the Cranial Base

A

C

B

Hard Palate Clivus

Clivus

Soft palate reflected Long. Cap. M.

Soft palate Uvula For. magnum

Ant. Arch C1

Ant. Arch C1

Dens Long. Colli M.

D

E Nasal septum

Osteotomy

Vert. A.

Max. sinus

E

Maxilla Max. sinus Gr. Palat. A. & N.

Nasal septum Max. sinus

Nasal floor

Figure 20 (A) Anterior view through the open mouth. The soft palate, which extends backward from the hard palate, will block the view of the upper clivus. An incision has been outlined in the midline of the soft palate. (B) The soft palate has been divided to expose the mucosa lining the lower clivus. (C) The pharyngeal mucosa has been opened in the midline and the left longus capitus and longus coli have been reflected laterally. (D) The transverse maxillary (Le Fort I) osteotomy extends through the maxillary sinus above the apex of the teeth and below the infraorbital canals. (E) The lower maxilla has been displaced downward. A clival window and vertebral arteries are seen through the exposure (1). Abbreviations: A., artery; Ant., anterior; Cap., capitis; For., foramen; Gr., greater; Long., longus; Max., maxillary; M., muscle; N., nerve; Palat., palatine; Vert., vertebral.

and the parotid fascia laterally, and the styloid fascia investing the styloglossus, stylopharyngeal, and the stylohyoid muscles posteriorly (Fig. 6). In its upper medial wall, the eustachian tube, covered below by the tensor and levator veli palatine muscles, runs from the tympanic cavity to the pharyngeal wall. This is predominantly a fat-filled space, but also contains pharyngeal branches of the ascending pharyngeal and facial arteries and branches from the glossopharyngeal nerve. The last of the four spaces below the middle fossa is the infrapetrosal space, also referred to as the poststyloid part of the parapharyngeal space. It is located behind the styloid fascia, below the petrous bone, and medial to the mastoid process (Figs. 2, 6, and 9). Among the foramina in the area connecting the intra- and extracranial spaces is the jugular foramen containing the jugular bulb and lower end of the inferior petrosal sinus. It also contains branches of the ascending pharyngeal artery, the glossopharyngeal, vagus, and accessory nerves, and the opening of the carotid canal through which the carotid artery and the carotid sympathetic

nerves pass. Two tiny foramina located between the jugular foramen and carotid canal carry the tympanic branch of the glossopharyngeal nerve and the auricular branch of the vagus nerve. The stylomastoid foramen, conveying the facial nerve and the stylomastoid artery, opens between the mastoid tip and the styloid processes. The main fissure in the area is the petroclival fissure on the upper and lower side of which courses the inferior petrosal sinus and the inferior petroclival vein, respectively. The main nerves of the area are the glossopharyngeal nerve coursing below the styloglossus muscle, the vagus nerve descending between the internal carotid artery and the jugular vein, and the accessory nerve passing lateral to the jugular vein on its way to the sternocleidomastoid muscle. The facial nerve runs to the parotid gland where it divides into cervicofacial and temporofacial trunks. The hypoglossal nerve, after exiting the hypoglossal canal, descends between the carotid artery and the jugular vein, turning anteriorly across the lateral wall of the artery below the level of the digastric muscle. The main arteries in the area are the internal carotid artery with its cervical

32

Martins and Rhoton

A Front. bone

Orb. Oculi M.

Nasal bone Eth. bone

C

B

Lac. bone Med. canthal Lig.

Lac. Sac

Lac. Canalic.

Maxilla Max. sinus

Zygoma

Nasolac. duct Nasal cavity

D

Lac. sac Med. canthal Lig.

Lac. Canalic.

Max. sinus

F

E

Pteryg. Gang.

V2 Pterygopal. fossa Nasolac. duct Nasal cavity Max. A.

Pons

Bas. A.

Pteryg. Proc.

Inf. concha Inf. meatus

Pit. gland

Long. Cap. M.

Gr. Palat. N.

Figure 21 Relationships of the medial orbit. (A) The medial part of the orbital rim is formed by the frontal bone and maxilla. The anterior part of the nasolacrimal canal is formed by the maxilla and the posterior part by the lacrimal bone, which joins the ethmoid bone posteriorly and the frontal bone above. (B) The medial part of the orbicularis oculi muscle has been exposed. The anterior band of the medial canthal ligament, which crosses in front of the lacrimal sac, is attached to the frontal process of the maxilla medially and to the superior and inferior tarsi laterally. (C) The medial part of the orbicularis oculi muscle and some of the maxilla have been removed to expose the lacrimal sac, nasolacrimal duct, and a small part of the nasal cavity and maxillary sinus. (D) The anterior band of the medial canthal ligament has been reflected laterally to expose the superior and inferior lacrimal canaliculi joining the lacrimal sac. Additional maxilla has been removed to expose the nasal cavity and inferior turbinate medially and the maxillary sinus laterally. The nasolacrimal duct opens into the inferior nasal meatus. (E) Some of the posterior and medial wall of the maxillary sinus has been removed to expose the pterygopalatine fossa, which contains the maxillary nerve and artery and their branches and the pterygopalatine ganglion. (F) The approach has been directed through the nasal cavity medial to the pterygopalatine ganglion and fossa to the clivus, which has been opened to expose the basilar artery (1). Abbreviations: A., artery; Bas., basilar; Canalic., canaliculi; Cap., capitis; Eth., ethmoid; Front., frontal; Gang., ganglion; Gr., greater; Inf., inferior; Lac., lacrimal; Lig., ligament; Long., longus; M., muscle; Max., maxillary; Med., medial; N., nerve; Nasolac., nasolacrimal; Orb., orbital; Palat., palatine; Pit., pituitary; Proc., process; Pteryg., pterygoid; Pterygopal., pterygopalatine.

and petrous segments. The branches of the petrous segment are the caroticotympanic and vidian arteries. The ascending pharyngeal artery ascends medial to the carotid artery, giving meningeal branches which pass through the hypoglossal canal and jugular foramen as well as pharyngeal branches. The occipital artery passes posteriorly on the medial side of the posterior belly of the digastric muscle. The veins in the area are the internal jugular vein, which receives drainage from the inferior petrosal sinus, and the venous plexus of the hypoglossal canal outside the jugular foramen. The main structures in the area are the styloglossus, stylopharyngeal, and stylohyoid, the digastric nerve, and the stylomandibular ligament. The medial part of the temporal bone is constituted mainly by the internal auditory canal, the carotid canal, and the petrous apex (7,11). Laterally, within the petrous part of the temporal bone on the medial side of the mastoid antrum,

lies the semicircular canals and vestibule enclosed within the otic capsule (Fig. 5). The tympanic segment of the facial nerve passes below the lateral semicircular canal, and the mastoid segment descends to the stylomastoid foramen. The vestibule (vestibular cavity), which communicates with both ends of the semicircular canals, is situated medial to the lateral semicircular canal and below the superior semicircular canal. The aditus of the mastoid antrum opens into the tympanic cavity, which contains the malleus, incus, and stapes; the chorda tympani and tympanic nerve; the tensor tympani; and stapedius muscles. The tympanic cavity is limited laterally by the tympanic membrane, medially by the bone over the cochlea, and opens anteriorly into the eustachian tube. The arteries feeding the area arise from the stylomastoid, anterior tympanic, petrosal, and caroticotympanic arteries. Posterolateral to the otic capsule, anterior to the sigmoid sinus, and inferior to the

Chapter 1: Anatomy of the Cranial Base

A

33

B

Infraorb. N.

Infraorb. N.

Zygoma Infratemp. fossa Max. sinus Infratemp. fossa

Maxilla

C

D Nasolac. duct

Infraorb. canal Pteryg. Ven. Plex. Max. A. Max. sinus Post. wall

V2

Nasal septum

nasal Septum Pterygopal. fossa

Mid. concha Inf. concha Vomer

Lat. Pteryg. M.

Infratemp. fossa

Maxilla

Clivus

V3 Brs.

E

F

Sella Cav. Seg.

V2 Sphen. Septum Pterygopal. Fossa Pteryg. Ven. Plex.

Pterygopal. fossa

Cav. sinus

Max. A. V2 Pet. Seg. CN VI Bas. A.

Vert. A. V3 Brs. For. magnum

Figure 22 (A–C) Transmaxillary exposure of the cranial base. (A) In this dissection, a midfacial soft tissue flap has been reflected laterally to expose the anterior surface of the right maxilla. The operative approach to the maxillary sinus is more commonly performed using a sublabial incision in the gingivobuccal margin rather than through an incision on the face. The approach can be completed without dividing the infraorbital nerve, but in this dissection, it was divided below the infraorbital foramen. The nerve, if divided, can be resutured at the time of closing. The infratemporal fossa, which is situated below the greater sphenoid wing, has been exposed by removing the coronoid process of the mandible and a narrow wedge of zygoma. (B) The anterior wall of the maxillary sinus has been removed. The roof of the maxillary sinus forms the majority of the floor of the orbit. The infratemporal fossa contains the pterygoid muscles, mandibular nerve, maxillary artery, and the pterygoid venous plexus. (C) The medial and lateral walls of the maxillary sinus have been opened, but the posterior part of the sinus wall, which forms the anterior wall of the pterygopalatine fossa, has been preserved. Removing the medial wall of the sinus exposes the nasal cavity, turbinates, and nasal septum. The maxillary artery crosses the lateral pterygoid muscle to reach the pterygopalatine fossa, which is located behind the upper part of the posterior wall of the maxillary sinus and below the orbital apex. (D) The posterior wall of the maxillary sinus has been removed to expose the pterygopalatine fossa and orbital floor. The pterygopalatine fossa is located below the orbital apex and the posteromedial part of the inferior orbital fissure. The maxillary nerve enters the pterygopalatine fossa by passing through the foramen rotundum. The maxillary nerve gives rise to the infraorbital nerve, which passes forward in the infraorbital canal in the sinus roof and orbital floor. (E) Enlarged view of infratemporal and pterygopalatine fossae. Distally, the maxillary artery enters the pterygopalatine fossa, which is located in the lateral wall of the nasal cavity below the orbital apex. (F) The exposure has been directed medially through the nasal cavity to the clivus, which has been opened to expose the vertebral and basilar arteries and the front of the brain stem. The exposure has been extended upward by opening the sphenoid sinus and exposing the left intracavernous carotid. The margin of the foramen magnum has been preserved (1). Abbreviations: A., artery; Bas., basilar; Brs., branches; Cav., cavernous; CN, cranial nerve; For., foramen; Inf., inferior; Infraorb., infraorbital; Infratemp., infratemporal; Lat., lateral; M., muscle; Max., maxillary; Mid., middle; N., nerve; Nasolac., nasolacrimal; Pet., petrosal; Plex., plexus; Post., posterior; Pteryg., pterygoid; Pterygopal., pterygopalatine; Seg., segment; Sphen., sphenoid; Ven., venous; Vert., vertebral.

34

Martins and Rhoton

A

B Temp. M. CN VII Front. Br. Sup. Temp. A.

Lat. canthal Lig. Inf. Obl. M.

Zygoma

Infraorb. N. CN VII

Nasal cavity Max. sinus

Coronoid Proc.

Mass. M.

C

Pterion

D

Cav. sinus V1 Pterygopal. Fossa

Lat. Pteryg. M. Inf. Obl. M. Infraorb. N.

Gr. Palat. N. & A.

V2 Mid. Men. A. Eust. tube V3

Max. A.

Nasal septum

Nasal septum

E

F Front. N.

Lac. gland Lac. gland

Lat. Rec. M. CN IV Inf. Obl. M. Inf. Rec. M.

Sup. Obl. M. Lac. N.

CN III Cav. Sinus V1 V2 Vidian N. Inf. Obl. M.

Infraorb. N.

Lat. Rec. M.

Inf. Rec. M. CN III to Inf. Obl. M.

V3

Figure 23 Upper subtotal maxillotomy. Exposure obtained with mobilization of the upper part of the maxilla. (A) This approach uses paranasal, lower conjunctival, transverse temporal, and preauricular incisions. In the usual approach, the cheek flap is elevated as a single layer using subperiosteal dissection. In this dissection, the layers of the cheek flap were dissected separately to illustrate the structures in the flap. The facial muscles and branches of the facial nerve are exposed. The parotid gland has been removed. The frontal branch of the facial nerve crosses the mid portion of the zygomatic arch. If facial nerve branches are transected in the approach, they are tagged in preparation for re-approximation at closure. (B) A hemicoronal scalp incision and reflection of the temporalis muscle expose the lateral orbital rim. The cheek flap containing the facial muscles, branches of the facial nerve, parotid gland, and masseter muscle has been reflected inferiorly to the level of the maxillary attachment of the buccinator muscle. The orbital, maxillary, and zygomatic osteotomies have been completed and the lower half of the orbital rim; the anterior, medial, and lateral walls of the maxillary sinus; and the zygomatic arch have been reflected. The lower horizontal cut, located at Le Fort I level, extends above the apical dental roots and hard palate and along the inferior nasal meatus medially. The maxillotomy, at this stage, does not include the posterior maxillary wall or cross the greater and lesser palatine canals. The lateral nasal wall was included with the maxillotomy to expose the nasal cavity. The infraorbital nerve, which crosses the orbital floor, may be preserved for reconstruction. (C) The posterior wall of the maxillary sinus has been removed to expose the pterygopalatine fossa and the palatine nerves and arteries. The base of the coronoid process was divided, and the temporalis reflected downward to expose the lateral pterygoid muscle and maxillary artery in the infratemporal fossa. (D) A frontotemporal bone flap has been elevated, and the dura covering the frontal and temporal lobes and lateral wall of the cavernous sinus has been opened, and the temporal lobe has been elevated. The pterygoid muscles, the pterygoid process and plates, and the part of the middle fossa floor formed by the greater sphenoid wing have been removed to expose the nerves passing through the foramina rotundum and ovale. The eustachian tube is exposed behind the mandibular nerve and the middle meningeal artery. (E) Magnified view of the cavernous sinus, superior orbital fissure, and orbit. The oculomotor, trochlear, and ophthalmic nerves course through the lateral wall of the cavernous sinus. The ophthalmic nerve sends its branches along the upper part of the orbit. The maxillary nerve exits the foramen rotundum and passes through the pterygopalatine fossa, where it gives rise to the infraorbital nerve that courses along the floor of the orbit. The mandibular nerve passes through the foramen ovale and sends its branches through the infratemporal fossa. The vidian nerve passes forward in the vidian canal below the maxillary nerve to join the pterygopalatine ganglion in the pterygopalatine fossa. (F) Enlarged view of the orbital exposure. The lacrimal gland sits on the superolateral margin of the globe. The lacrimal nerve courses above the lateral rectus muscle. The inferior oblique muscle passes below the attachment of the inferior rectus muscle and upward between the globe and lateral rectus muscle to insert on the globe near the tendon of insertion of the superior oblique muscle (1). Abbreviations: A., artery; Br., branch; Cav., cavernous; CN, cranial nerve; Eust., eustachian; Front., frontal; Gr., greater; Inf., inferior; Infraorb., infraorbital; Lac., lacrimal; Lat., lateral; Lig., ligament; M., muscle; Mass., masseter; Max., maxillary; Men., meningeal; Mid., middle; N., nerve; Obl., oblique; Palat., palatine; Proc., process; Pteryg., pterygoid; Pterygopal., pterygopalatine; Rec., rectus; Sup., superior; Temp., temporal, temporalis.

Chapter 1: Anatomy of the Cranial Base

35

B

A

Mid. Men. A. V3 V2

Arc. Emin.

Gr. Pet. N. CN V Post. root

C

D Sup. canal

CN VII Laby. Seg. Vert. crest

.

Tens. Tymp. M.

Genic. Gang.

Pet. Car. A. Sup. Vest. N.

Modiolus

Inf. Vest. N.

Coch. N.

Clivus CN V

Inf. Pet. sinus Int. Ac. meatus

CN VII Meat. Seg.

E CN V CN III Bas. A. Post. Comm. A. CN IV Car. A. SCA Ant. Chor. A.

PCA

Figure 24 Middle fossa approach to the internal acoustic meatus. (A) The vertical line shows the site of the scalp incision and the stippled area outlines the bone flap bordering the middle fossa floor. (B) The dura has been elevated to expose the middle meningeal artery, the greater petrosal nerve, and the arcuate eminence. (C) The roof of the meatus has been opened to expose the superior and inferior vestibular, facial, and cochlear nerves. The vestibule and semicircular canals are located posterolateral and the cochlea is located anteromedial to the meatal fundus. In the middle fossa approach, for an acoustic neuroma, the cochlea and semicircular canal are not opened, as seen in this dissection illustrating the important structures which are to be avoided in opening the meatus. The vertical crest (Bill’s Bar) separates the facial and superior vestibular nerves at the meatal fundus. The superior and inferior vestibular nerves are located posteriorly and the facial and cochlear nerves anteriorly in the meatus with the cochlear nerve passing below the facial nerve to enter the modiolus. The labyrinthine segment of the facial nerve courses superolateral to the cochlea. (D) The bone of the petrous apex between the trigeminal nerve and the internal acoustic meatus has been removed to complete an anterior petrosectomy and to expose the inferior petrosal sinus and the lateral edge of the clivus. (E) The dura, exposed in the anterior petrosectomy and facing the posterior fossa and the tentorium, has been opened to expose the upper brain stem, oculomotor, trochlear, and trigeminal nerves and the basilar artery (7). Abbreviations: A., artery; Ac., acoustic; Ant., anterior; Arc., arcuate; Bas., basilar; Car., carotid; Chor., choroidal; CN, cranial nerve; Coch., cochlear; Comm., communicating; Emin., eminence; Gang., ganglion; Genic., geniculate; Gr., greater; Inf., inferior; Int., internal; Laby., labyrinthine; M., muscle; Meat., meatal; Mid., middle; Men., meningeal; N., nerve; PCA, posterior cerebral artery; Pet., petrous, petrosal; Post., posterior; SCA, superior cerebellar artery; Seg., segment; Sup., superior; Tens., tensor; Tymp., tympani; Vert., vertebral; Vest., vestibular.

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A

B Sternocleidomast. M.

Sp. Henle Incus Mast. antrum deep Mastoid Tip Sup. Semicirc. canal Digastric M. Lat. Semicirc. canal Post. Semicirc. canal

Suprameat. Triang.

Suprameat. crest

CN VII Tymp. Seg. CN VII Mast. Seg. Digast. Groove Jug. Bulb Trautman’s Triang.

Mid. fossa dura Asc. Pharyg. A. Br. Longiss. Cap. M. Sinodural angle

D

C CN V motor root CN V AICA Nerv. Intermed. CN VII

Incus Chor. Tymp. N. CN IX CN VII Tymp. Seg. CN VII CN VII Mast. Seg. Stapes Laby. Seg. CN X CN VII Meat. Seg. Jug. bulb Sup. Vest. N. Inf. Vest. N. CN IX CN X CN V CN VIII Flocc. AICA Sig. sinus

CN VIII

Flocc.

F

E Malleus Cochlea Modiolus Scala Tympani Scala Vestibuli Chor. Tymp. N. CN V AICA CN VIII Coch. N. CN VII

Sig. sinus

Clivus Spiral Crest

Inf. Pet. Sinus AICA

CN VII Bas. A.

CN IX

CN VI

Jug. Bulb CN V

Flocc. Pons

CN V Motor Root Figure 25 Mastoidectomy, retrolabyrinthine, partial labyrinthine, translabyrinthine, and transcochlear approaches. (A) Right mastoid. The retroauricular flap and the sternocleidomastoid muscle have been reflected forward and the trapezius and underlying splenius capitus have been reflected backward to expose the mastoid and attachment of the longissimus capitus muscle. The posterior belly of the digastric muscle originates medial to the mastoid tip along the digastric groove. The spine of Henle is positioned at the posterosuperior margin of the external meatus, superficial to the deep site of the lateral semicircular canal and junction of the tympanic and mastoid segments of the facial nerve. The supramastoid crest, a continuation of the superior temporal line, is positioned at approximately the level of the upper margin of the transverse and sigmoid sinuses. The area below the anterior part of the supramastoid crest and behind the spine of Henle, called the suprameatal triangle, is positioned superficial to the mastoid antrum. The semicircular canals are positioned deep to the mastoid antrum. (B) The drilling has been extended to expose the middle fossa dura above, the sigmoid sinus posteriorly and the jugular bulb below. The superior, lateral, and posterior semicircular canals are located deep to the mastoid antrum and suprameatal triangle. The superior canal projects upward below the arcuate eminence. The posterior canal faces the posterior fossa dura. The lateral canal is positioned above the tympanic segment of the facial nerve. The facial nerve passes below the lateral canal and turns downward to form the mastoid segment. The dura between the sigmoid sinus and the semicircular canals, named Trautman’s triangle, faces the anterior surface of the cerebellum and cerebellopontine angle. A meningeal branch of the ascending pharyngeal artery passes through the jugular foramen and ascends in the dura of Trautman’s triangle. The jugular bulb is positioned medial to the cortical bone overlying the digastric groove. The sinodural angle is positioned at the junction of the sigmoid, transverse, and superior petrosal sinuses, and where the sigmoid sinus intersects the middle fossa dura. The short process of the incus points toward the tympanic segment of the facial nerve passing between the lateral semicircular canal and the stapes sitting in the oval window. The endolymphatic sac sits beneath the dura on the posterior surface of the temporal bone above and medial to the lower part of the sigmoid sinus. (Continued).

Chapter 1: Anatomy of the Cranial Base

superior petrosal sinus lies the presigmoid dura, referred to as Trautman’s triangle, under which the endolymphatic sac sits.

POSTERIOR CRANIAL BASE Endocranial Surface The posterior cranial base corresponds to the floor of the posterior fossa, an area around the foramen magnum. It is formed by the sphenoid, temporal, and occipital bones (Figs. 12, 13, and 14) (7,12–14). Medially, it is formed by the dorsum sellae, basilar (clival) portion of the occipital bone, and the foramen magnum. Laterally, the endocranial surface is formed by the posterior surface of the temporal and the occipital bones, with the petro-occipital fissure and the jugular foramen lying between the occipital and temporal bones. The endolymphatic sac, which sits beneath the dura, inferolateral to the internal acoustic meatus, is connected through the endolymphatic duct with the vestibule. The facial–vestibulocochlear nerve complex courses through the internal auditory canal (Fig. 15) (15). The arrangement of the nerves inside the meatus is as follows: the facial nerve, anterior and superior; the superior vestibular nerve, superior and posterior; the inferior vestibular nerve, inferior and posterior; and the cochlear nerve, anterior and inferior (Figs. 5 and 15) (7,11). The intermediate nerve courses with the eighth nerve adjacent to the brain stem and jumps to the seventh nerve at some point along the cisternal or the meatal segments of the facial nerve. The trigeminal nerve exits the posterior fossa by passing through the porus trigeminus, a dural ostium that is located between the superior petrosal sinus and the petrous apex along the posterior margin of the trigeminal impression. The subarcuate fossa, a depression lateral to the internal auditory canal, is pierced by the subarcuate artery, which ends in bone in the region of the superior semicircular canal (Fig. 15). The jugular foramen lies below the internal auditory canal between the petrous part of the temporal bone and the condylar part of the occipital bone (Figs. 12 and 14) (16). It is divided into a medially situated petrosal part, through which the inferior petrosal sinus passes, a laterally situated sigmoid part through which the sigmoid sinus passes, and an intermediately positioned intrajugular part through which the nerves pass. The hypoglossal canal is located below and medial to the jugular tubercle and above the middle third of the occipital condyles, which project downward along the anterior

37

half of the foramen magnum. The posterior condylar canal, located behind the condyle, conveys the posterior condylar vein, which connects the vertebral venous plexus with the sigmoid sinus. The inferior petrosal sinus courses along the petroclival fissure, connecting the posterior cavernous sinus and jugular bulb. The abducens nerve ascends and pierces the dura to course extradural through Dorello’s canal located between the petrosphenoid ligament and the upper edge of the fissure between the dorsum sella and the petrous apex, to enter the cavernous sinus. Below the foramen magnum, at the level of the atlanto-occipital joint, and anterior to the tectorial membrane, the cruciform, apical, and alar ligaments maintain the stability of the odontoid and craniocervical junction. The petrosal cerebellar surface, which faces the posterior surface of the temporal bone, the anterior surface of the brain stem, and the cerebellar peduncles, faces the endocranial surface of the posterior skull base (Fig. 16). The medulla, pons, and mesencephalon face the clivus. The surface of the medulla is divided longitudinally by the preolivary and postolivary sulci, with the pyramid in front and the inferior cerebellar peduncle behind the olive. The hypoglossal nerve arises along the preolivary sulcus and the glossopharyngeal, vagus, and accessory nerves arise near the retroolivary sulcus. The vestibulocochlear and facial nerves arise a few millimeters above the retro-olivary sulcus in the lateral part of the pontomedullary sulcus. The abducens nerve arises in the medial part of the pontomedullary sulcus and ascends behind the clivus. The trigeminal nerve arises from the anterolateral surface of the midpons with the rootlets which join to form the motor root arising around the superior third of the sensory root. The trochlear nerve arises below the inferior colliculus and passes forward along the pontomesencephalic sulcus in the quadrigeminal and ambient cisterns to enter the tentorial edge just behind the cavernous sinus. The oculomotor nerve crosses the interpeduncular cistern and pierces the roof of the cavernous sinus. Both vertebral arteries enter the cranium at the posterior edge of the occipital condyles and ascend to join in the midline, thus forming the basilar artery (Figs. 12 and 16). The main branches of the intradural vertebral artery are the posterolateral spinal artery, which supplies the posterior third of the medulla and upper spinal cord; the anterior spinal artery, which joins its mate from the opposite side on the anterior surface of the cord to supply the anterior two-thirds of the medulla and upper spinal cord; and the

←−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−− Figure 25 (Continued) (C) The retrolabyrinthine exposure has been completed and the dura has been opened to expose cranial nerves V to X in the cerebellopontine angle. The vestibulocochlear nerve has been depressed to expose the facial nerve and the nervus intermedius. The motor root of the trigeminal nerve is exposed superomedial to the main sensory root. The glossopharyngeal and vagus nerves are at the lower margin of the exposure. The flocculus protrudes from the foramen of Luschka behind the vestibulocochlear nerve. The anteroinferior cerebellar artery loops laterally between the facial and vestibulocochlear nerves. (D) The translabyrinthine approach has been completed to expose the vestibulocochlear and facial nerves in the internal acoustic meatus. The meatal and labyrinthine segments of the facial nerve are exposed proximal and the tympanic and mastoid segments are exposed distal to the geniculate ganglion. The dura of Trautman’s triangle has been opened to expose the trigeminal, glossopharyngeal, and vagus nerves in the cerebellopontine angle. The anteroinferior cerebellar artery loops laterally into the meatus before turning back toward the brain stem. The facial and superior and inferior vestibular nerves are exposed at the fundus of the meatus. The cochlear nerve is hidden anterior to the inferior vestibular nerve. (E) The greater petrosal nerve has been sectioned just distal to the apex of the geniculate ganglion and the facial nerve has been displaced posteriorly for removal of the cochlea in the transcochlear approach. The semicircular canals and vestibule, the end organs of the superior and vestibular nerves, have been removed. The incus has been removed but the malleus remains attached to the tympanic membrane. Drilling has been extended forward into the cochlea. The cochlear nerve enters the modiolus in the center of the spiral turns of the cochlea. (F) Removal of the cochlea opens the channel for removing the remainder of the petrous apex. The exposure extends to the lateral edge of the clivus and the inferior petrosal sinus. The basilar artery and anterior surface of the pons are at the deep end of the exposure. The abducens nerve passes behind the anteroinferior cerebellar artery and lateral to the basilar artery. Abbreviations: A., artery; AICA, anteroinferior cerebellar artery; Asc., ascending; Bas., basilar; Br., branch; Cap., capitis; Chor., chorda; CN, cranial nerve; Coch., cochlear; Digast., digastric; Flocc., flocculus; Inf., inferior; Intermed., intermedius; Jug., jugular; Laby., labyrinthine; Lat., lateral; Longiss., longissimus; M., muscle; Mast., mastoid; Meat., meatal; Mid., middle; N., nerve; Nerv., nervus; Pet., petrosal; Pharyng., pharyngeal; Post., posterior; Seg., segment; Semicirc., semicircular; Sig., sigmoid; Sp., spine; Sternocleidomast., sternocleidomastoid; Sup., superior; Suprameat., suprameatal; Triang., triangle; Tymp., tympani, tympanic; Vest., vestibular.

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Martins and Rhoton

A

B

CN III

Sup. Pet. sinus V. of Labbe’

CN IV

Trautman’s triangle Otic capsule

S.C.A. Sup. Pet. V.

Sp. Henle CN V

Jug. bulb

Bas. A. CN VI CN VII CN VIII

AICA

PICA Vert. A. CN X

C

CN IX

D SCA

CN IV

SCA Marg. Br. CN V V. of Labbe’

Int. Ac. meatus Sup. canal

CN VII CN VIII

CN V Lat. canal CN VII CN VIII

Post. canal

Chor. Tymp. N. CN IX CN X

CN VII

CN VII CN IX CN X

Figure 26 Presigmoid approach. (A) The insert shows the temporo-occipital craniotomy and the mastoid exposure. The mastoidectomy has been completed and the dense cortical bone around the labyrinth has been exposed. The tympanic segment of the facial nerve and the lateral canal are situated deep to the spine of Henle. Trautman’s triangle, the patch of dura in front of the sigmoid sinus, faces the cerebellopontine angle. (B) Retrolabyrinthine exposure. The presigmoid dura has been opened and the superior petrosal sinus and tentorium divided, taking care to preserve the vein of Labb´e, which joins the transverse sinus, and the trochlear nerve, which enters the anterior edge of the tentorium. The abducens and facial nerves are exposed medial to the vestibulocochlear nerve. The PICA courses in the lower margin of the exposure with the glossopharyngeal and vagus nerves. The SCA passes below the oculomotor and trochlear nerves and above the trigeminal nerve. (C) The semicircular canals have been opened. The superior canal is located under the middle fossa’s arcuate eminence and the posterior canal is located immediately lateral to the posterior wall of the internal acoustic meatus. (D) The labyrinthectomy has been completed to expose the internal acoustic meatus (7). Abbreviations: A., artery; Ac., acoustic; AICA, anteroinferior cerebellar artery; Bas., basilar; Br., branch; Chor., chorda; CN, cranial nerve; Int., internal; Lat., lateral; Marg., margin; N., nerve; Pet., petrosal; PICA, posteroinferior cerebellar artery; Post., posterior; SCA, superior cerebellar artery; Sp., spine; Sup., superior; Tymp., tympani; V., vein; Vert., vertebral.

Chapter 1: Anatomy of the Cranial Base

A

39

B Occip. A.

Int. Car. A.

Post. Aur. N. Sup. nuchal line

Parotid Gl. Gr. Aur. N. Sternocleidomast. M.

Stylomast. A. CN VII

C1 Trans. Proc. Int. Jug. V.

Digastric M. Jug. bulb

Inf. Obl. M. Sup. Obl. M.

Semicirc. canals Sig. sinus

C

D CN VII

CN VII Incus

Chor. Tymp. N. CN VII Jug. Bulb

Lat. canal Sup. canal

Sig. Sinus

Pet. Car. A.

Mid. fossa Int. Jug. V.

Stapes Round window Lat. canal

Tympanic N.

Post. canal Jug. Bulb

F

E Symp. Tr. Sup. Laryn. N. CN XII CN X

Post. canal

Int. Car. A. CN VII

CN XII CN IX Int. Car. A. CN X, XI CN IX Intrajug. ridge C1 Trans. Proc. Intrajug. Proc. Inf. Pet. sinus

CN XI

Jug. bulb Med. wall

CN IX CN X, XI

Occip. A. Figure 27 (A–D) Postauricular exposure of the jugular foramen. (A) The C-shaped retroauricular incision (insert) provides access for the mastoidectomy, neck dissection, and parotid gland displacement. The scalp flap has been reflected forward to expose the sternocleidomastoid muscle and the posterior part of the parotid gland. (B) The more superficial muscles and the posterior belly of the digastric have been reflected to expose the internal jugular vein and the attachment of the superior and inferior oblique muscles to the transverse process of C1. A mastoidectomy has been completed to expose the facial nerve, sigmoid sinus, and the semicircular canals. (C) Enlarged view of the mastoidectomy. The jugular bulb is exposed below the semicircular canals. The chorda tympani arises from the mastoid segment of the facial nerve and passes upward and forward. The tympanic segment of the facial nerve courses below the lateral canal. (D) The external auditory canal has been transected and the middle ear structures have been removed, except the stapes, which remains in the oval window. The lateral edge of the jugular foramen has been exposed by completing the mastoidectomy, transposing the facial nerve anteriorly, and fracturing the styloid process across its base and reflecting it caudally. The petrous carotid is surrounded in the carotid canal by a venous plexus. (E) A segment of the sigmoid sinus, jugular bulb, and internal jugular vein has been removed. The lateral wall of the jugular bulb has been removed while preserving the medial wall and exposing the opening of the inferior petrosal sinus into the jugular bulb. Removing the medial venous wall exposes the portion of the glossopharyngeal, vagus, accessory, and hypoglossal nerves that are hidden deep to the vein. The main inflow from the petrosal confluens is directed between the glossopharyngeal and vagus nerves. (F) The medial venous wall of the jugular bulb has been removed. The intrajugular ridge extends forward from the intrajugular process and divides the jugular foramen between the sigmoid and petrosal parts. The glossopharyngeal, vagus, and accessory nerves enter the dura on the medial side of the intrajugular process, but only the glossopharyngeal nerve courses through the foramen entirely on the medial side of the intrajugular ridge (14). Abbreviations: A., artery; Aur., auricular; Car., carotid; Chor. Tymp., chorda tympani; CN, cranial nerve; Gl., gland; Gr., greater; Inf., inferior; Int., internal; Intrajug., intrajugular; Jug., jugular; Laryn., laryngeal; Lat., lateral; M., muscle; Med., medial; Mid., middle; N., nerve; Obl., oblique; Occip., occipital; Pet., petrosal, petrous; Post., posterior; Proc., process; Semicirc., semicircular; Sig., sigmoid; Sternocleidomast., sternocleidomastoid; Stylomast., stylomastoid; Sup., superior; Symp., sympathetic; Tr., trunk; Trans., transverse; V., vein.

40

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posteroinferior cerebellar artery (PICA), which courses around the medulla and supplies the suboccipital cerebellar surface. The main branches of the basilar artery are the anteroinferior cerebellar artery (AICA), which passes around the pons and supplies the petrosal cerebellar surface and the nerves entering the internal auditory canal; the superior cerebellar artery (SCA), which encircles the midbrain and upper pons and supplies the tentorial cerebellar surface and dentate nucleus; and the posterior cerebral artery (PCA), which passes to the supratentorial area. The main venous drainage is by way of the petrosal veins, which join the superior and inferior petrosal veins emptying into the superior and inferior petrosal sinuses. The vascular and neural structures of the posterior fossa can be divided into upper, middle, and lower groups related to the three cerebellar arteries: the upper group is related to the SCA, which encircles the midbrain, courses on the superior cerebellar peduncle and within the cerebellomesencephalic fissure, passes below the oculomotor and trochlear nerves and above the trigeminal nerve, and supplies the tentorial cerebellar surface; the middle group is related to the AICA, which encircles the pons, courses on the middle cerebellar peduncle, dips in the cerebellopontine fissure passing by and sending branches to the facial and vestibulocochlear nerves, and supplies the petrosal cerebellar surface; and the lower group is related to the PICA, which encircles the medulla, passes near or between the rootlets of the lower four cranial nerves to course on the inferior cerebellar peduncle, dips into the cerebellomedullary fissure, and supplies the suboccipital cerebellar surface (Figs. 12 and 16) (17).

Exocranial Surface This portion is divided in central and lateral portions (Fig. 14) (14,18,19). The center portion is formed by the basal (clival) part of the occipital bone, which slopes upward from the foramen magnum and has the pharyngeal tubercle for the attachment of the superior pharyngeal constrictor on its lower surface, and the occipital condyles lateral to its lower portion at the anterolateral margin of the foramen magnum. The hypoglossal foramen, conveying the hypoglossal nerve, crosses above the middle one-third of the long axis of the condyle. The posterior condylar canal carries the posterior condylar vein interconnecting the vertebral venous plexus with the sigmoid sinus. Lateral to the condyle lies the jugular process of the occipital bone, which forms the posterior edge of the jugular foramen, connects the squamosal and basal parts of the occipital bone, and receives the attachment of the rectus capitus lateralis muscle posterior to the jugular foramen and jugular bulb. Two grooves lateral to the jugular process, a medial one for the occipital artery and a lateral one, the digastric groove, for the origin of the posterior belly of the digastric muscle, separate the jugular process from the mastoid process. The remaining muscles are the longus capitis attached to the lower clivus and the rectus capitis anterior attached in front of the occipital condyle. The nerves of the area are the hypoglossal and C1 nerves. The vertebral artery ascends through the C1 transverse process and crosses medially behind the superior articular pillar of the atlas or the atlanto-occipital joint to enter the dura (Figs. 17 and 18). The first segment of the vertebral artery ascends from the subclavian artery running up to the transverse foramen of C6. The second segment runs from C6 to C2, where the artery changes to a more lateral direction. The third segment ascends laterally to reach the C1 transverse foramen and turns medially and horizontally behind the atlanto-occipital joint

to course in the depths of the suboccipital triangle delimited by three muscles: the superior oblique extending from the occipital bone to the C1 transverse process, the inferior oblique extending from the C1 transverse process to the C2 spine, and the rectus capitus posterior major extending from the C2 transverse process to the occipital bone (Figs. 17 and 18). The fourth segment of the vertebral artery extends from the dural entrance to the vertebrobasilar junction. The third segment gives rise to the posterior meningeal and muscular arteries and occasionally the PICA. The other vascular structures in the area are the occipital and ascending pharyngeal arteries, the vertebral venous plexus, and the posterior and anterior condylar veins.

DISCUSSION With the development of microsurgical techniques and skull base surgical principles, it has become possible to access all parts of the cranial base. Lesions involving the central part of the anterior two-thirds of the cranial base and clivus can be accessed through intracranial routes, such as the orbitozygomatic, transcranial–transbasal, or extended frontal approaches, or by subcranial routes utilizing the various modifications of the transnasal, transoral, transsphenoidal, transmandibular, transmaxillary, transcervical, or facial translocation approaches or by a combination of the intracranial and subcranial routes (Figs. 19–23). The approaches can also be extended to the middle skull base by using the orbitozygomatic, preauricular infratemporal fossa, subtemporal anterior petrosectomy, or other extensions of the middle fossa routes (Fig. 24). Further posteriorly, approaches directed through the temporal bone, such as the retrolabyrinthine, translabyrinthine, transcochlear, and combined supra-infratentorial presigmoid approaches, or a combination of preauricular and postauricular transtemporal approaches, may be considered (Figs. 25 and 26). Lesions in the posterior fossa and posterior skull base may be reached through the retrosigmoid or suboccipital routes or the farlateral approach and its transcondylar, supracondylar, and paracondylar modifications (Fig. 24) (19). The jugular foramen is most often accessed by a postauricular transtemporal approach (Fig. 27). Cranial base tumors frequently invade intracranial and subcranial spaces and require innovative combinations of these transcranial, subcranial, and combined approaches. Thoughtful consideration of skull base anatomy is essential to successful surgery for these tumors. REFERENCES 1. Rhoton AL Jr. The anterior and middle cranial base. Neurosurgery. 2002;51(1 Suppl):S273–S302. 2. Rhoton AL Jr., Seoane E. Surgical anatomy of the skull base. In: Harsh, G., ed. Chordomas and Chondrosarcomas of the Skull Base and Spine. New York: Thieme Medical Publishers Inc, 2003:57–79. 3. Rhoton AL Jr. The orbit. Neurosurgery. 2002;51(1 Suppl):S303– S334. 4. Rhoton AL Jr., Natori Y. The Orbit and Sellar Region: Microsurgical Anatomy and Operative Approaches. New York, NY: Thieme Medical Publishers Inc, 1996:3–25. 5. Natori Y, Rhoton AL Jr. Transcranial approach to the orbit: Microsurgical anatomy. J Neurosurg. 1994;81:78–86. 6. Natori Y, Rhoton AL Jr. Microsurgical anatomy of the superior orbital fissure. Neurosurgery. 1995;36:762–775. 7. Rhoton AL Jr. The temporal bone and transtemporal approaches. Neurosurgery. 2000;47(3 Suppl):S211–S265.

Chapter 1: Anatomy of the Cranial Base 8. Rhoton AL Jr. The sellar region. Neurosurgery. 2002;51(1 Suppl): S335–S374. 9. Rhoton AL Jr. The cavernous sinus, the cavernous venous plexus, and the carotid collar. Neurosurgery. 2002;51(1 Suppl): S375– S410. 10. Seoane E, Rhoton AL Jr., de Oliveira E. Microsurgical anatomy of the dural collar (carotid collar) and rings around the clinoid segment of the internal carotid artery. Neurosurgery. 1998;42:869– 886. 11. Pait TG, Zeal AA, Harris FS, et al. Microsurgical anatomy and dissection of the temporal bone. Surg Neurol. 1977;8:363– 391. 12. Rhoton AL Jr. Cerebellum and fourth ventricle. Neurosurgery. 2000;47(3 Suppl): S7–S27. 13. Rhoton AL Jr. The foramen magnum. Neurosurgery. 2000;47(3 Suppl):S155–S193.

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14. Rhoton AL Jr. Jugular foramen. Neurosurgery. 2000;47(3 Suppl): S267–S285. 15. Rhoton AL Jr. The cerebellopontine angle and posterior fossa cranial nerves by the retrosigmoid approach. Neurosurgery. 2000;47(3 Suppl):S93–S129. 16. Katsuta T, Rhoton AL Jr., Matsushima T. The jugular foramen: Microsurgical anatomy and operative approaches. Neurosurgery. 1997;41:149–202. 17. Rhoton AL Jr. The cerebellar arteries. Neurosurgery. 2000;47(3 Suppl):S29–S68. 18. Rhoton AL Jr. The far-lateral approach and its transcondylar, supracondylar, and paracondylar extensions. Neurosurgery. 2000;47(3 Suppl):S195–S209. 19. Wen HT, Rhoton AL Jr., Katsuta T, et al. Microsurgical anatomy of the transcondylar, supracondylar, and paracondylar extensions of the far-lateral approach. J Neurosurg. 1997;87:555–585.

2 Pathology of Tumor and Tumor-like Lesions of the Skull Base Michelle D. Williams and Adel K. El-Naggar

INTRODUCTION

to avoid complications such as CSF leak. Generally, these lesions present as smooth, homogenous, tan soft tissue mimicking brain parenchyma. Histologically, they are typically composed of neural tissue with fibrosis and astrocytic and gametocytic cell proliferation.

The skull base regions are composed of complex tissue structures that give rise to histogenetically and biologically heterogeneous neoplasms of ectodermal, endodermal, and mesodermal origins. The morphologic and histogenetic differences are complicated by overlapping features and frequently pose diagnostic difficulties. The vast majority of tumors at these locations are malignant with a small percentage being benign or tumor-like lesions (Table 1). Accurate diagnosis and understanding of the clinical and pathologic presentations of the varied tumor entities in this region are essential for proper management. Although the majority of tumors at this location are of primary origin, metastasis can be encountered and will be discussed. Nonmetastatic tumors are either primary or an extension from neighboring structures.

Differential Diagnosis This entity can be differentiated from encephalocele, which frequently shows meninges.

Respiratory Epithelial Adenomatoid Hamartoma This is a benign proliferation of minor seromucinous glands of the sinonasal tract, occurring more commonly in men than women in their sixth decade of life. The major symptoms include nasal obstruction, epistaxis, and recurrent sinusitis. These lesions appear normally as polypoid tan to reddishbrown and rubbery tissue nodules (4–6). Histologically, they are formed of numerous glandular structures lined by ciliated respiratory epithelium with thickened basement membrane and intervening fibrotic and/or edematous stroma (Fig. 2).

Biopsies and Frozen Sections The evaluation of sinonasal pathology typically requires a tissue biopsy that may be limited dependent upon the accessibility of the target region. Obtaining adequate and representative materials is essential for accurate diagnosis and better planning of patient management. The initial assessment of these tumors is commonly conducted intraoperatively for either provisional or definitive diagnosis and/or verifying adequacy for representative tissue. Communication with the pathologist at the time of frozen section is key to coordinating patient care. At this stage, non-neoplastic processes, lymphoma, and metastatic neoplasms can be determined. For primary tumors, the frozen tissue biopsy may be adequate for diagnosis and planning ancillary tests but efforts to secure additional tissue for permanent processing is strongly recommended for optimal morphologic assessment and biomarker characterization.

Differential Diagnosis These lesions may be confused with Schneiderian inverted papilloma and sinonasal adenocarcinomas. The benign glandular structures lined by columnar cells that form these lesions are key to differentiating it from both of these entities.

Ectopic Pituitary Adenoma Pituitary adenomas may occur in the sphenoid bone and sinuses either as a separate lesion or as an extension from a primary adenoma arising in the sella (7,8). Embryonic residue along the Rathke pouch formation is the presumed derivation. Females are more affected than males (2:1 ratio). Patients may present with nasal obstruction, headache, or epistaxis. Approximately half of patients manifest hormonal abnormalities. Histologically, an ectopic pituitary adenoma is identical to that of a conventional pituitary adenoma with monotonous round cells (Fig. 3).

NON-NEOPLASTIC AND CONGENITAL LESIONS Encephalocele Based on the age of the patient and the location of the lesion, the diagnosis of an encephalocele may be made by imaging prior to submitting histology. Frequently, encephaloceles extending into the nasal cavity or sinus include meninges and glial tissue associated with fibrosis (Fig. 1) (1,2).

Differential Diagnosis This lesion should be differentiated from carcinoid tumor, neuroblastoma, and other small undifferentiated tumors at these locations. Immunohistochemical staining for hormonal receptors, especially for ACTH and prolactin, is helpful.

Nasal Glial Heterotopia This is a congenital malformation in which ectopic glial tissue is found without connection to intracranial structures (3). Nasal glial heterotopia may present as an extranasal, intranasal, or mixed intranasal and subcutaneous mass. Patients may also present with symptoms and findings of nasal polyp, chronic sinusitis, and otitis media. Radiological confirmation of the lack of intracranial communication is stressed

Inflammatory Pseudotumor This is a benign reactive process where a spindle cell tumor– like proliferation with inflammatory component is the cardinal feature (9–11). They may arise at any site in the skull base regions. 43

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Williams and El-Naggar Table 1

Incidence of Malignant Sinonasal Tumors∗

Feature

%

Sites • Maxillary • Nasal cavity • Ethmoid • Frontal & sphenoid

60% 22% 15% 3%

Derivation • Epithelial • Mesenchymal • Neuroectodermal • Others

55% 30% 15% 5%

∗ ∗

<1% of all neoplasms or tumors 3% of head and neck malignancy

Figure 3

Pituitary adenoma with uniform endocrine cells.

Histopathology These tumors are composed of spindle cell proliferation admixed with chronic inflammatory and plasma cells. Immunohistochemically, the spindle cells express weak smooth muscle actin (Fig. 4) characteristic of myofibroblast.

Differential Diagnosis These lesions may be confused with some benign and malignant mesenchymal tumors and fibromatosis. The inflammatory cells and the myofibroblastic nature are keys to their proper identification.

Sinonasal Polyps

Figure 1 Encephalocele with glial brain tissue (arrow).

These are polypoid growth originating from the Schneiderian epithelial lining of the sinonasal cavities. They evolve as a result of fluid accumulation of the mucosa, most commonly due to nasal allergy and repeated sinusitis. Frequently, maxillary polyps may extend via the sinus openings into nasal or nasopharyngeal locations. The majority of polyps

Figure 2 Adenomatoid hamartoma composed of respiratory epithaliel lined spaces and glandular structures.

Figure 4 Inflammatory pseudotumor with admixed spindled and inflammatory cells.

Chapter 2: Pathology of Tumor and Tumor-like Lesions of the Skull Base

45

Figure 5 Vasular sinonasal polyp with scattered inflammatory cells and infammatory edematous stroma. Figure 6 Cylindrical cell papilloma with characteristic bland columnar epithelial lined papillae and microcystic formation.

occurring in children are associated with asthma or cystic fibrosis (20–30%). In adult patients, they are often secondary to chronic sinusitis and allergy (12–14). Generally, sinonasal polyps grossly appear smooth, glistening, and translucent or opaque. Histologically, the epithelium of nasal polyps is commonly respiratory with and without mild hyperplasia or squamous metaplasia. The core is edematous with numerous vessels and with scattered inflammatory cells. In allergic polyps, the dominant cells are eosinophils, whereas in inflammatory polyps, there are chronic and a few acute inflammatory cells. Scattered minor salivary gland structures are also seen. Commonly, secondary changes due to infarction and organization are observed (Fig. 5).

Exophytic Schneiderian Papilloma Generally, exophytic Schneiderian papilloma is a lobular mass composed histologically of bland squamous epithelium around fibrovascular cores.

Cylindrical Cell Papilloma A generally exophytic papillomatous proliferation, histologically lined by multilayered columnar epithelium with and without oncocytic features. Microcysts with neutrophils within the epithelium are common (Fig. 6).

Inverted Schneiderian Papilloma

Differential Diagnosis These lesions should be differentiated from angiofibroma, and small cell tumors forming a polypoid mass. Angiofibroma is a specific benign entity with proliferation of vascular spaces with satellite bland stromal cells in young male patients. Rhabdomyosarcoma, lymphoma, and melanoma are more cellular and can be readily excluded using respective markers.

Schneiderian Papillomas There are three histologic subtypes of this entity: (i) the exophytic which is typically squamous in histology and almost always affecting the nasal septum, (ii) cylindrical cell is characterized by stratified columnar epithelial lining, and (iii) the inverted papilloma is where a transitional-like squamous proliferation in an inward growth constitutes its cardinal feature (15–20). The latter types originate from the lateral nasal wall, middle meatus, and paranasal sinuses. Both cylindrical and inverted papillomas affect one side of the nasal and paranasal sinuses with less than 5% occurring bilaterally.

Grossly, inverted papilloma are typically tan to gray, polypoid soft tissue with a mulberry appearance. These lesions affect more males than females and occur in older age. Keratinization may be present in some lesions and this feature may indicate potential progression. A characteristic feature of this lesion is inward invagination and cellular structures formed of transitional-like epitholium with a intraepithelial microcysts filled macrophages, cellular debris, and mucin like materials. Malignant transformation may occur in 10% of these lesions. Identifying dysplasia and carcinoma in situ in these lesions is critical to predict the malignant progression of these lesions (Fig. 7).

Differential Diagnosis All three types of Schneiderian papillomas must be differentiated from carcinomas: the exophytic type from papillary squamous carcinomas, cylindrical cell papilloma from sinonasal adenocarcinomas, and the inverted type primarily from squamous carcinoma, which will show dyskeratosis, dysplasia, and stromal desmoplasia in response to invasion.

Human Papillomavirus Low- and high-risk human papillomavirus (HPV) subtypes have been identified in inverted and exophytic papillomas by in-situ hybridizations and polymerase chain reactions. No clear association between HPV status and malignant transformation has been established.

INFLAMMATORY AND GRANULOMATOUS CONDITIONS Allergic Fungal Sinusitis This is a specific entity resulting from an allergic reaction to persistent fungal organisms leading to mass

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Figure 7 Inverted Schneiderian papilloma composed of an epithelial proliferation within submucosa.

Figure 9 Invasive fungal sinusitis with fungal hyphae invading vasculature with tissue necrosis. A silver stain highlights the fungal hyphae (inset).

Differential Diagnosis formation (21–23). This may occur at any age, without gender predominance. The main symptoms are nasal discharge and rhinorrhea over a protracted period. The overall appearance of tissues from these lesions is that of tan, butter-like material with debris. The cardinal microscopic features include characteristic alternating layers of mucin and degenerating cells with eosinophilic materials and cells (Fig. 8). Numerous intact and degenerating eosinophils and granules are present. Occasionally, crystalloid eosinophilic deposition (Charcot–Leyden) crystals are found. Tissue invasion by hyphae is not identified in this disorder.

Ancillary Markers Fungal stains may reveal degenerated non-invasive fungal in allergic mucin secretion. Culture is necessary for speciation of the fungal organism. The most common species is Aspergillus.

The most common differential diagnosis of this entity is invasive fungal infection, mycetoma (fungal ball) or inflammatory polyp. Invasive fungal infections are characterized by vascular invasion by fungal organism and tissue necrosis and the lack of layered secretions. Mycetoma shows sheets of fungal hyphae without tissue invasion. Inflammatory polyp can be excluded based on the lack of alternating layers and eosinophilic materials and cells.

Invasive Fungal Sinusitis Invasive fungal sinusitis is a potentially life-threatening condition characterized by fungal organisms invading tissue and blood vessels leading to massive tissue necrosis (24,25). Most commonly it is seen in immunocompromised patients and patients with poorly controlled diabetes mellitus. Infections spread rapidly to involve the central nervous system, which may lead to patient’s death. Normally, tissue fragments are tan-gray, soft, and necrotic. Histologically, fungal hyphae are identified invading tissues and specifically the blood vessels leading to massive necrosis (Fig. 9). Zygomycoses (Rhizopus/Rhizomucor) and Aspergillus are the most common organisms. Cultures should be taken for definitive species identification.

Differential Diagnosis The most common differential diagnoses of this entity are allergic fungal sinusitis and infectious agents. Invasive fungal infections are characterized by vascular invasion by fungal organism and tissue necrosis and the lack of layered secretions. Inflammatory polyp can be excluded based on the lack of alternating layers and eosinophilic materials and cells.

Rhinoscleroma

Figure 8 Allergic fungal sinusitis is hallmarked by Allegic mucin dominated by eosrnophils.

Rhinoscleroma is a chronic progressive granulomatous inflammation caused by Klebsiella rhinoscleromatis, a gramnegative bacterium (26,27). The disease is rare in the United States but is endemic in developing counties. Females are slightly affected more than males in their second to third decades of life. The natural history of the disease includes exudative, proliferative, and fibrotic phases. The exudative stage is characterized by purulent discharge, acute and

Chapter 2: Pathology of Tumor and Tumor-like Lesions of the Skull Base

Figure 10 Rhinoscleroma; inflammatory infiltrate including the characteristic vacuolated histiocytes (Mikulicz cells).

chronic inflammation, and mucosal edema and congestion. The proliferative phase is characterized by granulomatous formation and multiple nodular inflammatory and ulcerating masses. The terminal phase is fibrotic, leading to stenosis. The overall appearance of this lesion is that of polypoid and friable soft tissue in the proliferative phase. The histologic features are those of chronic inflammatory conditions with extensive histiocytic cells with vacuolation containing Klebsiella microorganisms, (Mikulicz cells) (Fig. 10). The fibrotic stage is nondiagnostic of the condition.

Differential Diagnosis Other infectious agents including mycobacterial infections and syphilis also need to be considered.

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Figure 11 Histiocytosis-X (eosinophilic granuloma), characteristic foamy histiocytes and eosinophils are shown.

Histiocytosis-X (Eosinophilic Granuloma) Histiocytosis-X (eosinophilic granuloma) is the most prevalent of these rare conditions, which also include two related ¨ conditions Hand-Schuller-Christian syndrome and Lettere– Siwe disease. This disease can be localized or systemic and frequently involve head and neck sites including the flat bones of the skull and sinonasal tract. Although age at presentation varies widely, it is most common in younger groups (<20 years). Symptoms are nonspecific and include middle ear infections and destructive bony structures (32–36). The cardinal histologic features are proliferation of large histiocytes with cytoplasmic vacuolation and marked eosinophilic infiltrate (Fig. 11). The characteristic electron dense granules, Birbeck, are often seen on electronoptic examinations.

Differential Diagnosis Wegener Granulomatosis A destructive granulomatous condition of unknown etiology. The disease, although systemic in nature, most commonly affects the upper respiratory tract. The disease affects all ages and both genders. Common complaints are nasal stuffiness, rhinitis, and pain. Nasal septal destruction is common in young patients (28–31). Generally, tissues obtained from these lesions are composed of fragments of necrotic appearing materials. Histologically, the characteristic features include small vessel inflammation with granulomatous features, geographic necrosis, and basophilic debris due to cellular degeneration.

Ancillary Markers Up to 85% of patients with Wegener granulomatosis are positive for serologic testing with antineutrophil cytoplasmic antibodies (c-ANCA).

Differential Diagnosis All infections associated with granulomatous inflammation would be included in the differential diagnosis, and should be excluded by negative cultures. NK/T-cell lymphoma may show necrosis and may be included.

The conditions most frequently confused with this entity are Hodgkin disease and lymphoma NK/T-cell type.

Myospherulosis This is an iatrogenically induced lesion caused by reaction to petroleum, lanolin-based products, and fat necrosis (37). Typically, patients present having undergone surgery with petroleum-based nasal packing. Patients’ symptoms include sinusitis, pain, and swelling. The main histologic findings are pseudocystic formations containing nonrefractile small spherules and fibrosis.

Differential Diagnosis Coccidioidomycosis fungal infection.

MALIGNANT EPITHELIAL NEOPLASMS Sinonasal malignancy most commonly affects the maxillary sinus (60%), the nasal cavity (22%), ethmoid sinus (15%), and less frequently the frontal and sphenoid sinuses (3%) (Table 1). A wide variety of malignant neoplasms of different cellular lineages arises in this location. The most common

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Williams and El-Naggar Table 2 Clinicopathologic Features of Undifferentiated Carcinoma of the Skull Base Feature

SNUC

NEC

NPC-type

Grade Incidence M/F LN Mets Mortality Risk factor Site

High Rare 3:1 30% 80% NI Nasal Cavity & sinus

High Rare NI NI 50–60% NI Maxillary sinus

High <0.5% 3:1 Common 50–60% EBV Nasopharynx

Abbreviations: EBV, Epstein–Barr virus: LN Mets, Lymph node metastases; M/F, Male/Female; NEC, neuroendocrine carcinoma; NPC, nasopharyngeal carcinoma; SNUC, sinonasal undifferentiated cancer; NI, no information.

Figure 12 Squamous carcinoma, keratin, forming tumor nest formation with invasive growth pattern.

Histologically, SNUC is composed of sheets of undifferentiated cells with low nuclear-cytoplasmic ratio, prominent nucleoli and reticular and clear nuclei with high mitotic rate and necrotic features (Fig. 13). No squamous or glandular differentiation should be present.

Differential Diagnosis malignancies are carcinomas (55%) followed by nonepithelial tumors (30%), neuroectodermal (15%), and miscellaneous entities (5%) (38,39).

Squamous Carcinoma Squamous carcinoma typically occurs in elderly individuals in their sixth and seventh decades with a tendency for male gender (M:F, 2:1). The most common sites are maxillary sinus, nasal cavity, ethmoid, frontal, and sphenoid sinus (40–43). Usually, these carcinomas are typical ulcerated and indurate with exophytic features, sinus tumors are bulky and composed of friable light tan tumor tissues. Histologically, squamous features should be identified and the extent of differentiation graded (well, moderate, or poor). Tumors originating from the nasal cavity are generally keratinizing and well differentiated (Fig. 12). Tumors of the paranasal sinuses and skull base are nonkeratinizing carcinomas with intermediate to poor differentiation. The poorly differentiated carcinomas are also called Schneiderian carcinoma and most likely originate from preexisting inverted papillomas.

The diagnosis and etiology of this entity is a subject of controversy and frequently arise as management issues. Because of the poor differentiation, they are most often confused with poorly differentiated sinonasal carcinomas (Schneiderian/squamous) as described above, neuroendocrine carcinoma, and the solid form of adenoid cystic carcinoma. Immunohistochemical markers are crucial to the diagnosis of this entity. Positive epithelial lineage markers and absence or focal neuroendocrine marker exclude neuroblastoma, neuroendocrine carcinoma, lymphoma, melanoma, and primitive neuroectodermal tumor (PNET). The lack of lymphoid infiltrate along with accurate localization is crucial for the exclusion of nasopharyngeal-type carcinoma (Table 2).

Nasopharyngeal Carcinoma They are classified into keratinizing and nonkeratinizing phenotypes and correspond to WHO type I and II/III grades (50–56). Pathogenesis is strongly linked to Epstein–Barr virus

Differential Diagnosis Squamous carcinoma may occasionally pose a diagnostic challenge on small biopsy specimens with sialometaplasia, pseudoepitheliomatous hyperplasia, and Schneiderian papilloma and should be differentiated from sinonasal undifferentiated carcinoma.

Sinonasal Undifferentiated Carcinoma Sinonasal undifferentiated carcinoma (SNUC) is a highgrade, undifferentiated carcinoma characterized by primitive malignant epithelial cells with high mitotic figures and cellular necrosis (44–49). Patients are typically elderly males who present in a late stage of disease (Table 2). Tumors originate most commonly from the nasal cavity, ethmoid sinus, and maxillary sinus but site of origin may be difficult to certain at presentation. Generally, these tumors are typically large, involving multiple adjacent structures with ill-defined borders. They present as light-tan, soft tissue fragments.

Figure 13 SNUC, undifferentiated neoplastic cells with prominent nucleoli and necrosis.

Chapter 2: Pathology of Tumor and Tumor-like Lesions of the Skull Base

Figure 14 Nasopharyngeal carcinoma, undifferentiated type (WHO-III) showing undifferentiated neoplastic cells with cleared nuclei in a prominent lymphoid background.

(EBV) infection and a diet high in nitrosamines including salted fish and fermented food (Table 2). The histopathologic characteristics of these tumors vary according to the WHO classification. Keratinizing type (WHO-I) is composed of tumor nests with squamous features including keratinization and intercellular bridges. Nonkeratinizing type (WHO-II/III) are composed of sheets of undifferentiated malignant epithelial cells intimately intermingled with chronic inflammatory infiltrate, which is often EBV positive (Fig. 14).

Ancillary Markers On histologic examination, EBV can be identified by in-situ hybridization for EBV-encoded RNA. Most commonly, EBV is identified in nonkeratinizing types (WHO-II/III). Serology for EBV-encoded RNAis also available.

Differential Diagnosis The nonkeratinizing phenotype must be differentiated mainly from the SNUC and neuroendocrine carcinoma. The presence of lymphocytic infiltrate and the lack of neuroendocrine markers helps to confirm the diagnosis.

Sinonasal Adenocarcinoma These tumors originate from either the respiratory epithelium or the underlying seromucinous glands. Tumors of respiratory epithelial derivation are frequently located in the nasal cavity and the ethmoid sinus, while those arising from the subepithelial glands frequently affect the nasal cavity and the maxillary sinus. Generally, salivary-type tumors appear as large, nodular, light tan soft masses, whereas the intestinal-type adenocarcinomas tend to be bulky, friable, and soft with ulcerated surface.

Salivary-Type Adenocarcinomas The most frequent phenotype affecting minor salivary gland of the skull-base is adenoid cystic carcinoma. Less frequent subtypes are mucoepidermoid, acinic cell, and low-grade papillary adenocarcinoma (57,58).

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Figure 15 Adenoid cystic carcinoma, cribriform type.

The histopathologic features are those of their primary salivary counterparts (Fig. 15).

Differential Diagnosis The differential diagnosis is mainly of the solid form of adenoid cystic carcinoma, which should not be confused with basaloid squamous or neuroendocrine carcinomas. The lack of squamous differentiation, neuroendocrine markers, and anaplastic features favors adenoid cystic carcinoma.

Nonsalivary Gland Adenocarcinoma Tumors under this category are divided into intestinal and nonintestinal (seromucinous) adenocarcinomas. The intestinal adenocarcinoma is identical to those arising in the intestinal tract. These tumors arise in patients with history of exposure to hardwoods, leather, and certain chemical manufacturing. These tumors tend to occur in the ethmoid sinus and nasal cavity. The nonintestinal adenocarcinomas are typically seromucinous adenocarcinoma and affect the ethmoid and maxillary sinuses (59–64). Histologically, the intestinal type is typically that of colonic adenocarcinoma phenotype but may show mucinous and signet-ring features (Fig. 16). The seromucinous type is usually low grade with back-to-back cuboidal-lined glands and cords (Fig. 17).

Differential Diagnosis The intestinal form should be differentiated from metastasis to the skull base areas from salivary and intestinal primaries, which should be clinically excluded (Table 3).

MESENCHYMAL TUMORS Benign Tumors Various benign tumors similar to those originating in other soft tissues may arise in the skull base region.

Lobular Capillary Hemangioma (Pyogenic Granuloma) This is a relatively common benign vascular lesions representing approximately 25% of the nonepithelial neoplasms of the

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Williams and El-Naggar

Figure 16 Sinonasal adenocarcinoma, nonsalivary, intestinal type, forming neoplastic glands with large pseudostratified nuclei.

Figure 18 Pyogenic granuloma with a lobular proliferation of capillaries in the stroma.

sinonasal tract and skull base region. This entity frequently found is the nasal septum (60%) and is most commonly identified in adolescent boys and young women. Local trauma and hormonal factors may play an etiologic role in the development of this entity. Intermittent painless epistaxis is the most common symptom (65,66). Usually, a polypoid red to purple nodular growth is identified with mucosal ulceration. Histologically, lobular capillary hemangiomas are composed of fairly organized vascular proliferations with lobular formation (Fig. 18). An inflammatory infiltrate may be present.

ture is the key finding of capillary hemangioma, which will lack the stellate stroma of an angiofibroma or the highly cellular spindled cells of a hemangiopericytoma.

Differential Diagnosis The differential diagnoses of these lesions are mainly from vascular polyp, nasopharyngeal angiofibroma, hemangiopericytoma, and low-grade angiosarcoma. The lobular architec-

Figure 17 Sinonasal adenocarcinoma, nonsalivary, nonintestinal (seromucinous) type, formed by bland cuboidal back-to-back glands filling the stroma.

Hemangiopericytoma An uncommon nonepithelial neoplasm is composed of spindle cell proliferation of hybrid pericyte and myxoid differentiation. The tumor can present at any age, and patients most commonly complain of nasal obstruction epistaxis and pain. The nasal cavity and the paranasal sinuses are typically affected (67–70). In general, these tumors appear typically as a polypoid gray to red, soft, fleshy tissue mass. Histologically, these lesions manifest subepithelial spindled to round markedly compacted cell proliferation with complex vascularity (Fig. 19). The cells may form a variety of patterns including fascicular, storiform, and palisading morphology with interspersed vascular spaces in different

Figure 19 Hemangiopericytoma showing proliferation of spindled cells with intervening staghorn vascular spaces.

Chapter 2: Pathology of Tumor and Tumor-like Lesions of the Skull Base Table 3

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Sinonasal Adenocarcinomas Nonsalivary

Parameter

Salivary

Intestinal

Seromucinous type

Origin Age (years) Gender Prognosis Recurrence Risk factor

Minor salivary gland 30–70 Equal Depends on stage 50% survival High (60%) unknown

Minor salivary gland 30–70 Equal • Depends on stage • 50% Yes unknown

Markers

S-100, Keratins, SMA

Respiratory mucosa 60–70 More in males • Depends on differention • and stage High • Wood worker • Leather worker K-ras, Keratins 7 and 20

size and forms; mitosis and mild cellular pleomorphism may also be seen.

Ancillary Markers By immunohistochemistry, the spindled cells are positive for smooth muscle actin and negative for CD34, which will highlight the vessels.

Differential Diagnosis This tumor should be readily differentiated from reactive pyogenic granuloma, cellular hemangioma and nasopharyngeal angiofibroma, benign and low-grade smooth muscle tumors, solitary fibrous tumor, and spindle cell sarcomas (synovial sarcoma and fibrosarcoma). Immunohistochemical markers may be used to exclude some of these entities. In solitary fibrosis tumors, there is lower cellularity and positivity for CD34 and bcl-2 in the spindled cells, which is helpful in the differentiation of these entities (73–75).

Nasopharyngeal Angiofibroma A benign highly vascular mesenchymal neoplasm arising predominantly in young males. The lesions arise in the roof of the nasopharynx. Patients’ symptoms typically include nasal obstruction, epistaxis and drainage, less commonly, facial deformities, proptosis, deafness, sinusitis, and palliative swelling (73,75). Usually, angiofibroma presents as rounded, nonencapsulated, gray-white soft tissue masses covered with smooth mucosa and spongy cut surface appearance. The cardinal histologic features of these lesions are richly thin-walled vascular formations in fibrotic connective background with stromal cell proliferation (Fig. 20).

S-100, Keratins, SMA

Histologically, they are characterized by sparsely scattered, stellate-shaped mesenchymal cells in a myxoid background.

Malignant Neoplasms Rhabdomyosarcoma This is a relatively uncommon mesenchymal malignancy of the skull base region. Rhabdomyosarcoma is the most common sarcoma of the head and neck and is the most frequent childhood sarcoma. The sinonasal tract and the nasopharynx are the most commonly affected sites. The embryonal type is the most common type in children while the alveolar subtype predominates in an older age group. Patients present with swelling, bleeding, visual symptoms, and sinusitis (Table 4) (78–82). Normally, the tumor may either be small gray/red in appearance or large, polypoid, and fleshy. The botryoid variant manifests grape-like features. Histologically, they are classified into the embryonal phenotype for the vast majority of skull base rhabdomyosarcomas and are composed of primitive small round to spindled monotonous cell proliferation in sheets (Fig. 21). A myxoid stroma may be present giving rise to the botryoid variant. The alveolar phenotype is less common and is composed of tumor cells with eosinophilic cytoplasm in clusters separated by fibrous septa. Rhabdomyoblasts and multinucleated giant cells may be seen.

Differential Diagnosis Angiofibromas may be confused with vascular and inflammatory polyp, hemangiopericytomas, and vascular proliferations, hemangiomas, and pyogenic granulomas (75–77).

Myxoma These lesions are intraosseous, ill-defined lesions comprised of mucomyxoid stroma with scattered stellate cells. If a fibrous component is visible it is called myxofibroma. Although they most commonly present in the jaw, the maxilla may be affected. These lesions affect more females than males (76,77). Usually, they appear as unencapsulated, wellcircumscribed, nodular, tan to white gelatinous lesions.

Figure 20 Nasopharyngeal angiofibroma with scattered stellate cells in a fibrous stroma with prominent vessels.

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Williams and El-Naggar Table 4 Clinical Features of Rhabdomyosarcoma Subtypes Feature

Embryonal

Site Age Outcome

Nasopharynx same sinonasal tract Children/young adults Young: 60% Adults: 10% 80%

Incidence

Alveolar Adults Poor 20%

Figure 22 Synovial sarcoma with small round primitive cells (top) and spindled cells (bottom).

Normally, the tumor presents as light tan and fleshy with a smooth surface with soft-to-firm consistency. Histologically, the tumor typically forms sweeping spindle cell interlacing bundles extending to surrounding tissue cells with moderate to low mitotic activity.

Differential Diagnosis Figure 21 Rhabdomyosarcoma, round small primitive cells forming sheets surrounding normal glands (lower left).

Ancillary Markers Immunohistochemical markers including desmin, myo-D, and myogenin are necessary for the diagnosis, especially of the embryonal form.

Differential Diagnosis Tumors that may be confused with embryonal rhabdomyosarcoma include lymphoma, neuroblastoma, Ewing sarcoma/PNET and melanoma. Immunophenotyping is critical for the diagnosis (Table 5).

Fibrosarcoma This is the most frequent mesenchymal malignancy of the sinonasal tract affecting most frequently the maxillary sinus, nasal cavity, and the ethmoid region (83–85).

A host of spindle cell benign and malignant tumors must be differentiated from this lesion including neurofibroma, rhabdomyo and synovial sarcomas, hemangiopericytoma, spindle cell carcinoma, and spindle cell melanoma. Also, reactive myofibroblastic tumors and fibromatosis should be included. Immunohistochemical markers will exclude neural, skeletal muscle, and spindle cell carcinoma if keratin is positive. Spindle cell carcinoma, however, is phenotypically more pleomorphic and may contain an epithelial component. Synovial sarcoma may exhibit mixed pattern but testing for the t(X;18) fusion gene is helpful to differentiate a purely spindle cell form.

Synovial Sarcoma Synovial sarcoma may involve the skull base region as extension from oropharynx or adjacent structures. The tumor affects the young age groups with a median of 25 years and a male predominance (86–91). Histologically, synovial sarcoma may present as a pure spindle cell variant (monophasic) or biphasic where both spindle and epithelial components are present (Fig. 22). The

Table 5 Immunohistochemical Markers useful in the Differential Diagnosis of Undifferentiated Skull Base Neoplasms Marker

Neuroblastoma

Ewing/PNET

RMS

Lymphoma

NEC

Melanoma

Keratin Synap HMB45 CD99 Desmin Myogenin S-100 CD45

–/focal +++ – – – – Focal –

– + – +++ – – – –

–/rare – – +/– +++ +++ – –

– – – – – – – +++

+ +++ ++ – – – Focal –

Rare Rare +++ – – – ++ –

Abbreviations: Ewing, Ewing sarcoma; NEC, neuroendocrine carcinoma; PNET, peripheral neuroectodermal tumor; RMS, rhabdomyosarcoma; Synap, Synaptophysin.

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Figure 23 Diagnostic Algorithm for Undifferentiated Skull Base Tumors

Table 6 Molecular Markers of Diagnostic and Therapeutic Potential in Skull Base Tumors

hybridization or polymerase chain reactions for the t(X;18) (p11.2; q11;2) translocation is complementary (Table 6).

Tumor

Alterations

Neuroblastoma 12q22-23 PNET/Ewing’ t(11;22) t(21;22) t(7;22) t(17;22) t(2;22) RMS t(2;13) (alveolar) t(1:13) Synovial Sarc t(X;18)

Gene/transcript

Incidence

Prognosis

Differential Diagnosis

hASH1 FLI-1/EWS EWS/ERG EWS/ETV1 EWS/E1AF FEV/EWS PAX3/FKHR

<90% 85% 5% Rare Rare Rare 60%

? ? ? ? ? ? Poor

This entity should be differentiated from spindle forming tumors including spindle cell carcinoma, fibrosarcoma, melanoma, and metastatic carcinoma to the base of skull. The combined features of clinicopathologic and immunohistochemical markers should be integrated in the diagnosis of this entity.

PAX7/FKHR SYT/SSX1 or SYT/SSX2

10% 64% 33%

Good Poor Poor

Abbreviations: PNET/Ewing, Peripheral neuroectodermal tumor/Ewing sarcoma; Sarc, Sarcoma

Angiosarcoma Angiosarcoma of the skull base region is rare, and if encountered, the diagnosis is based on the identification of abnormal vascular features and the use of immunohistochemical markers to support lineage (Fig. 24) (92,93).

Chordoma epithelioid component is typically formed of cuboidal or columnar epithelial cells forming cords, nests, and pseudoglandular spaces intermingled with a spindle cell proliferation.

Ancillary Markers Cytokeratins of low and high molecular weight and epithelial membrane antigen (EMA) are positive in epithelial tumor cells. In case of monomorphic spindle cells, in-situ

Chordoma is a low- to intermediate-grade malignant neoplasm originating from the notochord. The base of skull involvement is through the sphenoid occipital region, which is the site for approximately 20% of all chordomas. Lesions affecting the head and neck region frequently occur in middleage patients and those in their sixties. Patients typically present with neurological symptoms, headache, and progressive pain (94–98). Generally, chordoma is characteristically lobulated myxoid, expansive mass with mucus and a

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Figure 24 Angiosarcoma with atypical neoplastic cells forming vascular spaces.

Figure 26 Chondrosarcoma comprised of cartilage with increased cellularity of chondrocytes with a haphazard growth pattern.

slippery-appearance. Histologically, it is divided into classic, chondroid, and dedifferentiated phenotypes. The classic type is manifested by lobulated growth pattern with cords and islands of polygonal and vacuolated cells in myxomucoid background (Fig. 25). The characteristic vacuolated and eosinophilic cell is called a physaliphorous cell. The chondroid type manifests the same features along with areas of hyaline cartilaginous tissue. Dedifferentiated signifying transformation to a high-grade sarcoma shows marked cytologic atypia and high cellularity.

the reactivity to keratin and EMA is helpful in the exclusion of chondrosarcoma.

Ancillary Markers Chordoma is characteristically immunoreactive to cytokeratin, S-100, and EMA markers.

Differential Diagnosis Chordoma should be differentiated from mucinous adenocarcinoma, myxoma, and cartilaginous neoplasms. Immunohistochemical stains typically aid in the diagnosis. In particular,

Chondrosarcoma Chondrosarcoma may present as an extension from a maxillary primary. They present in a wide range of age groups, with the mesenchymal phenotype affecting mainly patients in the second and third decades of life. The most common presenting symptoms are craniofacial bone expansion and pain (99–101). Typically, these tumors manifest as translucent, cartilaginous, and scattered calcifications. Myxomatous areas with lobulation are commonly seen. The histologic spectrum seen in these tumors ranges from benign appearing hyaline cartilaginous lesions to highly cellular malignant spindle cell sarcoma. The characteristic malignant chondrocytic cells must be identified (Fig. 26). The tumor can manifest as myxoid, clear cell, dedifferentiated, and mesenchymal phenotypes. Mesenchymal chondrosarcoma is rare and may cause differential diagnostic difficulties. These tumors are composed of highly cellular spindle cell proliferations in interlacing short fascicles with focal cartilaginous formations.

Differential Diagnosis The main differential diagnosis includes enchondroma, osteochondromas, and chondroblastic osteosarcoma and chordomas. Mesenchymal chondrosarcoma should be differentiated from spindle cell malignant tumors and primitive sinonasal tumors. CD99 and SOX9 markers are typically positive in mesenchymal chondrosarcoma and could be of use in the diagnosis of this entity.

Osteosarcoma

Figure 25 Chordoma comprised of vacuolated physaliphorous cells in a myxoid background.

Osteosarcoma is a rare tumor in the skull base region. The tumor most commonly represents an extension from maxillary origin (102,103). Usually, osteosarcoma manifests as an ill-defined, irregular, and tan-yellow tissue mass with gritty (bone) sensation. Histologically, these tumors exhibit malignant cellular proliferation with osteoid bone formation (Fig. 27). The degree of cellularity and anaplastic cellular features reflect the grade of these tumors. The most common type of osteosarcoma is the osteogenic phenotype.

Chapter 2: Pathology of Tumor and Tumor-like Lesions of the Skull Base

Figure 27 Osteosarcoma is hallmarked by the presence of osteoid admixed with neoplastic cells.

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Figure 28 Neuroblastoma comprised primitive small tumor cells.

Differential Diagnosis Differential Diagnosis This tumor should be differentiated from other bone forming lesions, including osteoblastoma, chondrosarcoma with osteoid formation, dedifferentiated chondrosarcoma, and chondroblastic osteosarcoma. Radiologic and histopathologic correlation are important.

Tumors to be differentiated from neuroblastoma include lymphoma, melanoma, small round cell (Ewing sarcoma/PNET) tumor, rhabdomyosarcoma, and adenoid cystic carcinoma (solid form). Immunohistochemical profiles including a spectrum of different cell lineage are crucial to the diagnosis (Table 5).

Ewing Sarcoma/Primitive Neuroectodermal Tumor NEUROGENIC NEOPLASMS The tumors are derived from neuroglial origin and manifest a primitive small cell growth. These morphologic similarities may lead to misclassification. The most frequently encountered entities at the skull base are neuroblastoma and the primitive neuroectodermal group of tumors.

Neuroblastoma This entity arises from neuroepithelium in the upper aspect of the nasal cavity and roof of nose and the cribriform plate of the ethmoid sinus. They comprise approximately 5% sinonasal tract malignancies. Neuroblastoma affects both genders equally with bimodal age clustering at the first and second and the fourth and fifth decades of life. They typically present as a unilateral nasal mass with obstruction and bleeding symptoms (104–109). Comparison with other primitive sinonasal tumors is shown in Table 7. Grossly, neuroblastomas are light tan and soft tissue masses. Histologically, tumors are composed of small uniform sheets and nests of primitive basal cells with minimal cytoplasm with neurofibrillary background and occasionally with neuroepithelial pseudo-resetting features (Homer– Wright structure) (Fig. 28). True rosettes formation with ductlike spaces (Flexner–Wintersteiner rosette) is rare. High-grade tumors are characterized by large pleomorphic cells and necrosis.

Ancillary Markers Negative staining for keratin, synaptophysin, and other neuroendocrine and muscle markers establish the diagnosis of neuroblastoma (Table 7). Amplification of c-Myc oncogene and loss of chromosome 1p have been considered poor prognostic markers.

Ewing sarcoma and primitive neuroectodermal tumor are inter-related primitive round cell malignancies of neuronectodermal derivation. They represent a spectrum of morphologic entities that share common molecular genetic features. They are uncommon childhood and young adult tumors affecting the skull base and the sinonasal tract regions in approximately 5% of the patients. The maxillary sinus and the nasal fossa are the common affected sites (110–115). Generally, these tumors present as light-tan, soft, and fleshy tissues with hemorrhage and mucosal ulceration. Histologically, the tumor presents in sheet and nests of densely uniform small cell proliferation (Fig. 29).

Ancillary Markers CD99 (MIC2) is generally positive; NSE and synaptophysin are less often expressed. PCR-based methods to detect the EWS/FLI gene fusion transcript and in-situ hybridization of chromosomes t(11;22) or t(21;22) are helpful in confirming the diagnosis (Table 6).

Differential Diagnosis The differential diagnosis includes all small round cells tumors, lymphoma, melanoma, rhabdomyosarcoma, small cell carcinoma, and pituitary adenoma. A combined cytomorphologic and immunohistochemical markers panel is sufficient for establishing the diagnosis (Table 5).

NEUROENDOCRINE NEOPLASMS Tumors of neuroendocrine derivation comprise a spectrum of histomorphologic entities that include typical carcinoid (well differentiated) neuroendocrine carcinoma, atypical carcinoid (moderately differentiated) neuroendocrine carcinoma and

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Figure 29 Ewing sarcoma/PNET growing in sheets of monotonous small cells.

Figure 31 Paraganglioma with nested neuroendocrine cells (Zellballen) surrounded by thin vasculature.

small cell neuroendocrine carcinoma (Table 2). These are uncommon tumors at the sinonasal and skull base sites but frequently lead to differential diagnostic difficulties (116–118).

Differential Diagnosis

Carcinoid Tumors Histologically, carcinoid tumors are composed of organoid structures, including cell nests, glandular structures, and cords of monotonous basaloid cells with clear or granular cytoplasm. Atypical carcinoid lesions also exhibit these organized features but also have evidence of mitotic activity, cellular pleomorphism, and necrosis.

Small Cell Carcinoma Small cell carcinoma is generally composed of undifferentiated small cell proliferations, lacking organization with high mitotic activities and necrosis (Fig. 30). The differential diagnosis of these tumors depends on the state of differentiations for carcinoid and atypical carcinoid (119).

The differential diagnosis may include adenocarcinoma and pituitary adenoma. For small cell neuroendocrine carcinoma, a host of small undifferentiated tumors of different lineages should be included in the diagnosis. Immunohistochemical, molecular, as well as histomorphologic characteristics should be integrated.

Paraganglioma Sinonasal and skull base paraganglioma are extremely rare. They are likely to be derived from dispersed neuroendocrine cells with the sinonasal mucosal covering. Tumors at this location may behave in an aggressive fashion (120–122). The histologic characteristics of these tumors are typical of those at traditional sites with classical Zellballen organization and vascularization (Fig. 31).

Ancillary Markers Immunohistochemically, cells comprising these tumors are positive for neuroendocrine markers and negative for keratin. A helpful feature is the positivity for S-100 protein in sustentacular cells bordering the Zellballen.

MELANOMA

Figure 30 Small cell carcinoma showing primitive cells in sheets.

Primary melanoma in the sinonasal tract accounts for less than 1% of all melanomas. They afflict patients in their fifth and sixth decades of life with equal gender distribution. The most frequently affected site is the anterior nasal septum and the maxillary antrum. Symptoms are nasal obstruction, epistaxis, and nasal mass or polyp (Tables 7 and 8) (123–127). Melanomas usually appear small to large sized polypoid mass with light-tan, brown or black colorations. Histologically, the cytomorphologic features are identical to those of melanoma of the skin where spindle, rounded, and epithelioid cells forming nests, sheets and fascicles may be found (Fig. 32). These phenotypes may or may not manifest melanin pigmentation. Mucosal involvement and epidermoid migration of melanocytic cells is a helpful diagnostic feature when present.

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Table 7 Clinicopathologic Features of Sinonasal Small Round Cell Neoplasms Feature Age (years) Site Cranial neuropathy Anaplasia Necrosis Vascular invasion

Neuroblastoma 10–20 & 50 Cribriform plate Rare Occasional Rare Rare

Ewing/PNET <30 Maxillary Rare Rare Common Rare

RMS <20 Any Not uncommon Common Rare Rare

Lymphoma 50–60 Any Common Common Common Common

Melanoma 45–65 Any Rare Common Rare Common

Abbreviations: Ewing: Ewing sarcoma; PNET, peripheral neuroectodermal tumor; RMS, Rhabdomyosarcoma. Table 8 Characteristics of Mucosal Melanoma •<1% of all melanomas •<5% of Sinonasal tumors •M/F: 1:1 •Age: Fifth to eighth decades •Race: Japanese •Site: •Anterior septum •Maxillary antrum •Poor prognosis •Adverse features: •>3.0 cm size •Advanced age •Vascular invasion

LYMPHOPROLIFERATIVE DISORDERS Sinus Histiocytosis with Massive Lymphadenopathy (Rosai–Dorfman Disease) This is a rare, idiopathic, histiocytic, proliferative disorder affecting typically young black women. This disease affects the paranasal sinuses, the nasal cavity, and the eyes. Patients present with nasal obstruction, proptosis, cranial nerve deficits, mass, and fever (128–130). Usually, lymphoreticular tumors appear as polypoid, gray to yellow soft tissue masses. Histologically, they show marked sinus expansion with lymphoplasmacytic proliferation. The sinuses are also filled with histiocytic cell with lymphocytes and red cells in their cytoplasm (lymphophagocytosis/emperipolesis).

Ancillary Markers Ancillary Markers This tumor is negative for keratin and reactive to melanocytic markers including HMB-45, Melan-A, MART-1, tyrosinase, and S-100.

Differential Diagnosis Melanoma at these locations should be differentiated from metastatic melanoma and primary undifferentiated skull base neoplasms including undifferentiated carcinoma, neuroendocrine tumor, neuroblastoma, lymphoma, and small peripheral neuroectodermal tumors and rhabdomyosarcoma. Immunohistochemical markers are fundamental in differentiating these tumors (Table 5).

The diagnosis may be aided by staining of histiocytic markers including S-100 protein and CD68.

Differential Diagnosis Rosai–Dorfman disease must be differentiated from infectious entities, such as rhinoscleroma, lepromatous leprosy, and malignant, histiocytic lymphoma.

Lymphoma Although rare, most lymphoproliferative lesion arise from the skull base region (131–133) are B-cell lineage lymphomas and sinonasal NK/T-cell lymphoma. These tumors may affect the nasal cavity, paranasal sinuses and may extend to involve any adjacent structures. Patients present with nasal obstruction, epistaxis, proptosis, or mass lesion. NK/T-cell lymphoma is seen in adults with a male predominance. Lymphoproliferative tumors appear grossly as soft, tan-gray and often described as “fish-flesh” soft tissue masses. Histology will vary based on the underlying entity, however, most will show sheets of atypical lymphoid cells with a diffuse growth pattern infiltrating the stroma (Fig. 33). The tumor cells are frequently angiocentric around blood vessels in the NK/T-cell type. Prominent necrosis is also common in this specific entity, leading to a midline facial destructive process.

Ancillary Markers

Figure 32 Melanoma showing prominent nucleoli and scattered pigment (melanin) growing in sheets.

The diagnosis is aided by staining of lymphoid markers including CD45 and lineage markers (i.e., B-cell CD20; T-cell CD3, CD4, and CD8) among a multitude of other markers like CD56. On histologic samples, EBV can be identified by in-situ hybridization for EBV-encoded RNA, which is almost universally positive in the NK/T-cell type lymphoma and may be associated with some diffuse B-cell lymphomas. When lymphoma is suspected, fresh tissue should be sent for flow-cytometric analysis along with tissue for permanent histologic examination.

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Figure 33 Diffused B-cell lymphoma composed of sheets of pleomorphic cells and necrosis.

Differential Diagnosis This lesion may mimic small, round, blue cell tumors (Table 7) and undifferentiated carcinomas (sinonasal and nasopharyngeal). If prominent necrosis is present, Wegener granulomatosis and other chronic lesion may be considered. IHC for carcinoma and small round cell tumor and fungal stains are excluding these entities.

MISCELLANEOUS Teratocarcinosarcoma This is a rare skull base and sinonasal tract malignant tumor composed of carcinomatous, sarcomatous, and immature neural elements. The most frequent sites are the ethmoid and maxillary sinuses and the nasal cavity in elderly male patients. Grossly, these rare tumors appear bulky, polypoid, and friable light-tan to red mass. Histologically, the tumor is characteristically composed of a high-grade carcinomatous component admixed with sarcomatous and immature neural elements (Fig. 34). Benign and malignant germ cell elements may also be present. The carcinoma can be either squamous or adeno or neuroendocrine, and the sarcoma can be cartilaginous, bony or skeletal muscle in nature. The neural elements may contain primitive rosettes with neurofibrillary features (134,135).

Figure 34 Teratocarcinosarcoma showing mixed high-grade neoplasms with nests of carcinoma and spindled sarcoma cells between the nests.

Ameloblastoma Ameloblastoma is a tumor of intermediate malignancy and odontogenic origin. They may arise from enamel organ, residual dental lamina, epithelial lining of dentigerous or follicular cysts, or rarely heterotopic embryonal enamel in the sinonasal tract. Ameloblastoma at the base of skull are typically an extension from tumors originating in the molar region of the maxillary antrum. They may frequently present with nasal symptoms without history of dental complaints (138,139). Histologically, the solid form manifests cellular, follicular structures with palisading basal cells with branding cords and cellular islets (Fig. 36). The cystic form manifests varied spaces lined with palisading basal cells with squamous metaplasia with central satellite appearing cells. Extraosseous ameloblastoma may histologically mimic basal cell carcinoma, and efforts to exclude this possibility must be made.

Differential Diagnosis This tumor causes a differential diagnostic dilemma if a dominant component is present on small biopsy samples. The diagnosis may depend on the available tissue component.

Meningioma Histologically, skull base meningiomas are identical morphologically to their primary meningeal origin but tend to be locally invasive, frequently showing characteristic whirling (Fig. 35). They are typically meningothelial or fibroblastic but other types may also be found (136,137).

Figure 35 Meningioma forming nests of small uniform cells within the stroma and vascular spaces.

Chapter 2: Pathology of Tumor and Tumor-like Lesions of the Skull Base

Figure 36 Ameloblastoma showing the palisading basaloid epithelial proliferation with central stellate reticulum mimicking dental elements.

METASTATIC NEOPLASMS Isolated metastatic tumor to this region is very rare. It may, however, occur among metastasis to multiple other sites. Renal cell carcinoma is by far the most common source. Others including breast, lung, melanoma, and testicular tumors follow renal in their frequency. Isolated incidences of metastasis from various other tumors have also been reported. Metastatic tumors affect both genders equally notwithstanding gender specific influence. In female patients, breast, gynecologic, and thyroid tumors are the most frequent primary origins. In male patients, lung, prostate, kidney and bone in decreasing order are the most common sites (140–142). REFERENCES 1. Lai SY, Kennedy, DW, Bolger, WE. Sphenoid encephaloceles: Disease management and identification of lesions within the lateral recess of the sphenoid sinus. Laryngoscope. 2002;112(10): 1800–1885. 2. Jabre A, Tabaddor R, Samaraweera R. Transsphenoidal meningoencephalocele in adults. Surg Neurol. 2000;54(2):183–187. Discussion 187–188. 3. Penner CR, Thompson LD. Nasal glial heterotopia: A clinicopathologic and immunophenotypic analysis of 10 cases with a review of the literature. Ann Diagn Pathol. 2003;7(6):354–359. 4. Mortuaire G, Pasquesoone X, Leroy X, et al. Respiratory epithelial adenomatoid hamartomas of the sinonasal tract. Eur Arch Otorhinolaryngol. 2007;264(4):451–453. 5. Ozolek JA, Hunt JL. Tumor suppressor gene alterations in respiratory epithelial adenomatoid hamartoma (REAH): Comparison to sinonasal adenocarcinoma and inflamed sinonasal mucosa. Am J Surg Pathol. 2006;30(12):1576–1580. 6. Graeme-Cook F, Pilch BZ. Hamartomas of the nose and nasopharynx. Head Neck. 1992;14(4):321–327. 7. Pasquini E, Faustini-Fustini M, Sciarretta V, et al. TSH-secreting pituitary adenoma of the vomerosphenoidal junction. Eur J Endocrinol. 2003;148(2):253–257. 8. Lloyd RV, Chandler WF, Kovacs K, et al. Ectopic pituitary adenomas with normal anterior pituitary glands. Am J Surg Pathol. 1986;10(8):546–552. 9. McCall T, Fassett DR, Lyons G, et al. Inflammatory pseudotumor of the cavernous sinus and skull base. Neurosurg Rev. 2006; 29(3):194–200.

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34. Davis SE, Rice DH. Langerhans’ cell histiocytosis: Current trends and the role of the head and neck surgeon. Ear Nose Throat J. 2004;83(5):340, 342, 344. 35. Boston M, Derkay CS. Langerhans’ cell histiocytosis of the temporal bone and skull base. Am J Otolaryngol. 2002;23(4):246– 248. 36. Brisman JL, Feldstein NA, Tarbell NJ, et al. Eosinophilic granuloma of the clivus: Case report, follow-up of two previously reported cases, and review of the literature on cranial base eosinophilic granuloma. Neurosurgery. 1997;41(1):273–278. 37. Sindwani R, Cohen JT, Pilch BZ, et al. Myospherulosis following sinus surgery: Pathological curiosity or important clinical entity? Laryngoscope. 2003;113(7):1123–1127. 38. Tsai EC, Santoreneos S, Rutka JT. Tumors of the skull base in children: Review of tumor types and management strategies. Neurosurg Focus. 2002;12(5):e1. 39. Richardson MS. Pathology of skull base tumors. Otolaryngol Clin North Am. 2001;34(6):1025–1042. 40. Porceddu S, Martin J, Shanker G, et al. Paranasal sinus tumors: Peter MacCallum Cancer Institute experience. Head Neck. 2004;26(4):322–330. 41. Dulguerov P, Jacobsen MS, Allal AS, et al. Nasal and paranasal sinus carcinoma: Are we making progress? A series of 220 patients and a systematic review. Cancer. 2001;92(12):3012–3029. 42. Wieneke JA, Thompson LD, Wenig BM. Basaloid squamous cell carcinoma of the sinonasal tract. Cancer. 1999;85(4):841–854. 43. Lund VJ, Howard DJ, Wei WI, et al. Craniofacial resection for tumors of the nasal cavity and paranasal sinuses—A 17-year experience. Head Neck. 1998;20(2):97–105. 44. Frierson HF Jr. Sinonasal undifferentiated carcinoma. In: Barnes EL, Eveson JW, Reichart P, Sidransky D, eds. Pathology and Genetic of Head and Neck Tumors. Lyon, France: IARC Press, 2005:19. Kleihues P, Sobin LH, series eds. World Health Organization Classifications of Tumors. 45. Ejaz A, Wenig BM. Sinonasal undifferentiated carcinoma: Clinical and pathologic features and a discussion on classification, cellular differentiation, and differential diagnosis. Adv Anat Pathol. 2005;12(3):134–143. 46. Jeng YM, Sung MT, Fang CL, et al. Sinonasal undifferentiated carcinoma and nasopharyngeal-type undifferentiated carcinoma: Two clinically, biologically, and histopathologically distinct entities. Am J Surg Pathol. 2002;26(3):371–376. 47. Franchi A, Moroni M, Massi D, et al. Sinonasal undifferentiated carcinoma, nasopharyngeal-type undifferentiated carcinoma, and keratinizing and nonkeratinizing squamous cell carcinoma express different cytokeratin patterns. Am J Surg Pathol. 2002;26(12):1597–1604. 48. Cerilli LA, Holst VA, Brandwein MS, et al. Sinonasal undifferentiated carcinoma: Immunohistochemical profile and lack of EBV association. Am J Surg Pathol. 2001;25(2):156–163. 49. Smith SR, Som P, Fahmy A, et al. A clinicopathological study of sinonasal neuroendocrine carcinoma and sinonasal undifferentiated carcinoma. Laryngoscope. 2000;110(10Pt1):1617–1622. 50. Sckolnick J, Murphy J, Hunt JL. Microsatellite instability in nasopharyngeal and lymphoepithelial carcinomas of the head and neck. Am J Surg Pathol. 2006;30(10):1250–1253. 51. Chan JKC, Bray F, McCarron P, et al. Nasopharyngeal carcinoma. In: Barnes El-Eveson JW, Reichart P, Sidransky D, eds. Pathology and Genetics of Head and Neck Tumours. Lyon, France: IARC Press, 2005 :85–97. Kleihues P, Sobin LH, Series eds. World Health Organization Classification of Tumours. 52. Wei WI, Sham JS. Nasopharyngeal carcinoma. Lancet. 2005;365(9476):2041–2054. 53. Lo KW, To KF, Huang DP. Focus on nasopharyngeal carcinoma. Cancer Cell. 2004;5(5):423–428. 54. Shi W, Pataki I, MacMillan C, et al. Molecular pathology parameters in human nasopharyngeal carcinoma. Cancer. 2002;94(7):1997–2006. 55. Choi PH, Suen MW, Huang DP, et al. Nasopharyngeal carcinoma: Genetic changes, Epstein-Barr virus infection, or both. A clinical and molecular study of 36 patients. Cancer. 1993;72(10):2873–2878.

56. Hsu HC, Chen CL, Hsu MM, et al. Pathology of nasopharyngeal carcinoma. Proposal of a new histologic classification correlated with prognosis. Cancer. 1987;59(5):945–951. 57. Neto AG, Pineda-Daboin K, Spencer ML, et al. Sinonasal acinic cell carcinoma: A clinicopathologic study of four cases. Head Neck. 2005;27(7):603–607. 58. Hampton TA, Scheithauer BW, Rojiani AM, et al. Salivary gland-like tumors of the sellar region. Am J Surg Pathol. 1997;21(4):424–434. 59. Yom SS, Rashid A, Rosenthal DI, et al. Genetic analysis of sinonasal adenocarcinoma phenotypes: Distinct alterations of histogenetic significance. Mod Pathol. 2005;18(3):315–319. 60. Cathro HP, Mills SE. Immunophenotypic differences between intestinal-type and low-grade papillary sinonasal adenocarcinomas: An immunohistochemical study of 22 cases utilizing CDX2 and MUC2. Am J Surg Pathol. 2004;28(8):1026–1032. 61. Choi HR, Sturgis EM, Rashid A, et al. Sinonasal adenocarcinoma: Evidence for histogenetic divergence of the enteric and nonenteric phenotypes. Hum Pathol. 2003;34(11):1101–1107. 62. Neto AG, Pineda-Daboin K, Luna MA. Sinonasal tract seromucous adenocarcinomas: A report of 12 cases. Ann Diagn Pathol. 2003;7(3):154–159. 63. Franchi A, Gallo O, Santucci M. Clinical relevance of the histological classification of sinonasal intestinal-type adenocarcinomas. Hum Pathol. 1999;30(10):1140–1145. 64. Franquemont DW, Fechner RE, Mills SE. Histologic classification of sinonasal intestinal-type adenocarcinoma. Am J Surg Pathol. 1991;15(4):368–375. 65. Miller FR, D’Agostino MA, Schlack K. Lobular capillary hemangioma of the nasal cavity. Otolaryngol Head Neck Surg. 1999; 120(5):783–784. 66. Mills SE, Cooper PH, Fechner RE. Lobular capillary hemangioma: The underlying lesion of pyogenic granuloma. A study of 73 cases from the oral and nasal mucous membranes. Am J Surg Pathol. 1980;4(5):470–479. 67. Thompson LD, Miettinen M, Wenig BM. Sinonasal-type hemangiopericytoma: A clinicopathologic and immunophenotypic analysis of 104 cases showing perivascular myoid differentiation. Am J Surg Pathol. 2003;27(6):737–749. 68. Tse LL, Chan JK. Sinonasal haemangiopericytoma-like tumour: A sinonasal glomus tumour or a haemangiopericytoma? Histopathology. 2002;40(6):510–517. 69. Osammor JY, Howat AJ. Nasal haemangiopericytoma. J Laryngol Otol. 1991;105(7):593–595. 70. Batsakis JG, Jacobs JB, Templeton AC. Hemangiopericytoma of the nasal cavity: Electron-optic study and clinical correlations. J Laryngol Otol. 1983;97(4):361–368. 71. Brunnemann RB, Ro JY, Ordonez NG, et al. Extrapleural solitary fibrous tumor: A clinicopathologic study of 24 cases. Mod Pathol. 1999;12(11):1034–1042. 72. Zukerberg LR, Rosenberg AE, Randolph G, et al. Solitary fibrous tumor of the nasal cavity and paranasal sinuses. Am J Surg Pathol. 1991;15(2):126–130. 73. Abraham SC, Montgomery EA, Giardiello FM, et al. Frequent beta-catenin mutations in juvenile nasopharyngeal angiofibromas. Am J Pathol. 2001;158(3):1073–1078. 74. Beham A, Beham-Schmid C, Regauer S, et al. Nasopharyngeal angiofibroma: True neoplasm or vascular malformation? Adv Anat Pathol. 2000;7(1):36–46. 75. Hwang HC, Mills SE, Patterson K, et al. Expression of androgen receptors in nasopharyngeal angiofibroma: An immunohistochemical study of 24 cases. Mod Pathol. 1998;11(11):1122– 1126. 76. Sato H, Gyo K, Tomidokoro Y, et al. Myxoma of the sphenoidal sinus. Otolaryngol Head Neck Surg. 2004;130(3):378–380. 77. Andrews T, Kountakis SE, Maillard AA. Myxomas of the head and neck. Am J Otolaryngol. 2000;21(3):184–189. 78. Lezzoni JC, Mills SE. “Undifferentiated” small round cell tumors of the sinonasal tract: Differential diagnosis update. Am J Clin Pathol. 2005;124(Suppl):S110–S121. 79. Sorensen PH, Lynch JC, Qualman SJ, et al. PAX3-FKHR and PAX7-FKHR gene fusions are prognostic indicators in

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103. Whitehead RE, Melhem ER, Kasznica J, et al. Telangiectatic osteosarcoma of the skull base. Am J Neuroradiol. 1998;19(4):754– 757. 104. Wenig BM, Dulgueron P, Kapadia SB, et al. Neuroendocrine tumours. In: Barnes El-Eveson JW, Reichart P, Sidransky D, eds. World Health Organization Classification of Tumours. Lyon, France: IARC Press, 2005 :65–75. 105. Diaz EM Jr, Johnigan RH III, Pero C, et al. Olfactory neuroblastoma: The 22-year experience at one comprehensive cancer center. Head Neck. 2005;27(2):138–149. 106. Hirose T, Scheithauer BW, Lopes MB, et al. Olfactory neuroblastoma. An immunohistochemical, ultrastructural, and flow cytometric study. Cancer. 1995;76(1):4–19. 107. Frierson HF Jr, Ross GW, Mills SE, et al. Olfactory neuroblastoma. Additional immunohistochemical characterization. Am J Clin Pathol. 1990;94(5):547–553. 108. O’Connor TA, McLean P, Jullard GJF, et al. Olfactory neuroblastoma. Cancer. 1989;63(12):2426–2428. 109. Mills SE, Frierson HF Jr. Olfactory neuroblastoma. A clinicopathologic study of 21 cases. Am J Surg Pathol. 1985;9(5):317– 327. 110. Mhawech-Fauceglia P, Herrmann F, Penetrante R, et al. Diagnostic utility of FLI-1 monoclonal antibody and dual-colour, breakapart probe fluorescence in situ (FISH) analysis in Ewing’s sarcoma/primitive neuroectodermal tumour (EWS/PNET). A comparative study with CD99 and FLI-1 polyclonal antibodies. Histopathology. 2006;49(6):569–575. 111. Windfuhr JP. Primitive neuroectodermal tumor of the head and neck: Incidence, diagnosis, and management. Ann Otol Rhinol Laryngol. 2004;113(7):533–543. 112. Csokonai LV, Liktor B, Arato G, et al. Ewing’s sarcoma in the nasal cavity. Otolaryngol Head Neck Surg. 2001;125(6):665–667. 113. Dagher R, Pham TA, Sorbara L, et al. Molecular confirmation of Ewing sarcoma. J Pediatr Hematol Oncol. 2001;23(4);221–224. 114. O’Sullivan MJ, Perlman EJ, Furman J, et al. Visceral primitive peripheral neuroectodermal tumors: A clinicopathologic and molecular study. Hum Pathol. 2001;32(10):1109–1115. 115. Toda T, Atari E, Sadi AM, et al. Primitive neuroectodermal tumor in sinonasal region. Auris Nasus Larynx. 1999;26(1):83– 90. 116. Barnes L. Neuroendocrine tumours. In: Barnes El-Eveson JW, Reichart P, Sidransky D, eds. Pathology and Genetics of Head and Neck Tumors. Lyon, France: IARC Press, 2005 :125–139. Kleihues P, Sobin LH, series eds. World Health Organization Classification of Tumours. 117. Mills SE. Neuroectodermal neoplasms of the head and neck with emphasis on neuroendocrine carcinomas. Mod Pathol. 2002; 15(3):264–278. 118. Fitzek MM, Thornton AF, Varvares M, et al. Neuroendocrine tumors of the sinonasal tract. Results of a prospective study incorporating chemotherapy, surgery, and combined proton-photon radiotherapy. Cancer. 2002;94(10):2623–2634. 119. Perez-Ordonez B, Caruana SM, Huvos AG, et al. Small cell neuroendocrine carcinoma of the nasal cavity and paranasal sinuses. Hum Pathol. 1998;29(8):826–832. 120. Balatsouras DG, Eliopoulos PN, Economou CN. Multiple glomus tumours. J Laryngol Otol. 1992;106(6):538–543. 121. Woodruff JM, Huvos AG, Erlandson RA, et al. Neuroendocrine carcinomas of the larynx. A study of two types, one of which mimics thyroid medullary carcinoma. Am J Surg Pathol. 1985; 9(11):771–790. 122. Lack EE, Cubilla AL, Woodruff JM. Paragangliomas of the head and neck region. A pathologic study of tumors from 71 patients. Hum Pathol. 1979;10(2):191–218. 123. Thompson LD, Wieneke JA, Miettinen M. Sinonasal tract and nasopharyngeal melanomas: A clinicopathologic study of 115 cases with a proposed staging system. Am J Surg Pathol. 2003;27(5):594–611. 124. Prasad ML, Jungbluth AA, Iversen K, et al. Expression of melanocytic differentiation markers in malignant melanomas of the oral and sinonasal mucosa. Am J Surg Pathol. 2001;25(6):782–787.

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125. Batsakis JG, Suarez P, El-Naggar AK. Mucosal melanomas of the head and neck. Ann Otol Rhinol Laryngol. 1998;107(7):626–630. 126. Billings KR, Wang MB, Sercarz JA, et al. Clinical and pathologic distinction between primary and metastatic mucosal melanoma of the head and neck. Otolaryngol Head Neck Surg. 1995;112(6):700–706. 127. Franquemont DW, Mills SE. Sinonasal malignant melanoma. A clinicopathologic and immunohistochemical study of 14 cases. Am J Clin Pathol. 1991;96(6):689–697. 128. Yoon AJ, Parisien M, Feldman F, et al. Extranodal RosaiDorfman disease of bone, subcutaneous tissue and paranasal sinus mucosa with a review of its pathogenesis. Skeletal Radiol. 2005;34(10):653–657. 129. Kademani D, Patel SG, Prasad ML, et al. Intraoral presentation of Rosai-Dorfman disease: A case report and review of the literature. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2002;93(6):699–704. 130. Shemen L, D’Anton M, Klijian A, et al. Rosai-Dorfman disease involving the premaxilla. Ann Otol Rhinol Laryngol. 1991;100(10):845–851. 131. Rodriguez J, Romaguera JE, Manning J, et al. Nasal-type T/NK lymphomas: A clinicopathologic study of 13 cases. Leuk Lymphoma. 2000;39(1–2):139–144. 132. Jaffe ES, Chan JK, Su IJ, et al. Report of the Workshop on Nasal and Related Extranodal Angiocentric T/Natural Killer Cell Lymphomas. Definitions, differential diagnosis, and epidemiology. Am J Surg Pathol. 1996;20(1):103–111. 133. Abbondanzo SL, Wenig BM. Non-Hodgkin’s lymphoma of the sinonasal tract. A clinicopathologic and immunophenotypic study of 120 cases. Cancer. 1995;75(6):1281–1291.

134. Shimazaki H, Aida S, Tamai S, et al. Sinonasal teratocarcinosarcoma: Ultrastructural and immunohistochemical evidence of neuroectodermal origin. Ultrastruct Pathol. 2000;24(2):115– 122. 135. Pai SA, Naresh KN, Masih K, et al. Teratocarcinosarcoma of the paranasal sinuses: A clinicopathologic and immunohistochemical study. Hum Pathol. 1998;29(7):718– 722. 136. Kjeldsberg CR, Minckler J. Meningiomas presenting as nasal polyps. Cancer. 1972;29(6):153–156. 137. Ho KL. Primary meningioma of the nasal cavity and paranasal sinuses. Cancer. 1980;46(6):1442–1447. 138. Gardner DG, Heikinheima K, Shear M, et al. Ameloblastomas. In: Barnes El-Eveson JW, Reichart P, Sidransky D, eds. Pathology and Genetics of Head and Neck Tumors. Lyon, France: IARC Press, 2005 :296–300. Kleihues P, Sobin LH, series eds. World Health Organization Classification of Tumours. 139. Schafer DR, Thompson LD, Smith BC, et al. Primary ameloblastoma of the sinonasal tract: A clinicopathologic study of 24 cases. Cancer. 1998;82(4):667–674. 140. Neville BW, Dann DD, Allen CM, et al. eds. Oral and Maxillofacial Pathology. Bethesda: Armed Forces Institute of Pathology, 2001: 263–265. Rosai J, Sobin LH, Series ed. Third series, Fascide 29. 141. Kent SE, Majumdar B. Metastatic tumours in the maxillary sinus. A report of two cases and a review of the literature. J Laryngol Otol. 1985;99(5):459–462. 142. Flocks RH, Boatman DC. Incidence of head and neck metastasis from genito-urinary neoplasms. Laryngoscope. 1973;83(9):1527–1539.

3 Genetic Abnormalities of Skull Base Tumors Ziv Gil and Dan M. Fliss

requires fresh tumor samples that can be preserved in a proper medium [i.e., Roswell Park Memorial Institute (RPMI) 1640 with 10–20% fetal calf serum] for 24–36 hours. The samples may be kept on ice, but not frozen, since freezing of the tissue inhibits its ability to grow in culture. Following tissue removal at surgery, the tumor sample is mechanically disintegrated and digested in collagenase, plated and incubated at 37◦ C in 5% CO2 for 6 to 10 days. A chromosome-banding configuration consists of alternating light and dark lines or bands that appear along its length after being stained with a dye. Each chromosome is identified by a unique banding pattern (Fig. 1). Chromosomal aberrations, including chromosome breakage, loss, duplication, or inversions, can be identified according to the representative chromosomal segments revealed by the staining technique. Giemsa has become the most popular staining technique for staining of chromosomes. Staining a metaphase chromosome with a Giemsa stain is referred to as “G-banding.” G-banding preferentially stains the regions of DNA that are rich in adenine and thymine, have high affinity for the dye, and appear as dark bands under light microscope (Fig. 2). The regions of the chromosome that are rich in guanine and cytosine have little affinity for the dye and appear as pallid bands. A standard G-band staining technique allows between 400 and 600 bands to be seen on metaphase chromosomes. With high-resolution G-banding techniques, as many as 2000 different bands have been demonstrated on human chromosomes. The main advantage of the G-banding technique is its simplicity and robustness, which gives the investigator precise resolution for the chromosomal deviations often found in human neoplasms.

John Cruso defined cancer in his book Easy Medicine (published in 1699 by the Royal College of Physicians in London) as: “A malignant ulcer, which the surgeons pronounced a cancer, but could not cure it.” Nowadays, cancer is considered a genetic disease that is characterized by deviation from normal of one or more gene products responsible for the regulation of cell growth and development. Some types of cancer are considered polygenic and multifactorial, originating from an accumulation of molecular changes in both the tumor and the host cells, leading to genetic instability and carcinogenesis. Tumor development is manifested in many cases as chromosomal changes that can be detected microscopically or with the aid of molecular techniques. Karyotypic changes involved in neoplastic transformation include numerical or structural chromosomal changes that tend to progress during time in certain tumors and contribute to malignant transformation. Chromosomal abnormalities associated with cancer development may either be specific for certain tumors or nonspecific, and involve multiple aberrations. Such chromosomal abnormalities are composed of amplification, deletion, or rearrangement of DNA in the form of a whole chromosome or its fragments. Tumors of the skull base are rare neoplasms that grow along various regions of the bottom part of the cranial vault and may be of intracranial or extracranial origin. A wide variety of benign and malignant tumors of endodermal, mesodermal, and epidermal origin may arise in this anatomical compartment, thus posing a considerable diagnostic challenge to the pathologist. These tumors may primarily arise in the skull base or invade the skull base locally from adjacent sites, such as the nasal cavity or paranasal sinuses. Significant progress has been made during the last decade in the understanding of the cytogenetic and molecular pathophysiology of various neoplasms, but cytogenetic information on most skull base tumors is scarce due to their rarity. Improved understanding of genetic mechanisms involved in tumorigenesis might help develop new diagnostic tools and define markers for estimating prognosis and for identifying patients at risk for recurrence. Genetic data may aid in the development of novel therapeutic modalities, including gene therapy and small molecules that directly affect abnormal genes or their products. The current chapter introduces the methods used for diagnosis and research of skull base neoplasms and reviews the current cytogenetic and molecular information that has emerged during the last decade on skull base tumors.

Fluorescent In Situ Hybridization and Spectral Karyotyping Since the introduction of conventional chromosomal banding during the 1970s, the technique has remained the working horse of cytogeneticists for screening of chromosomal aberrations found in human neoplasms. A new technical development based on fluorescence in situ hybridization (FISH) was added to our armamentarium of cancer research tools during the past decade. FISH evolved to solve the main problems of chromosomal banding: it was time consuming, error prone, and dependent upon highly qualified human resources. The main advantage of FISH is its ability to detect complex chromosomal deviations, which are often found in cancer specimens. Several methods utilizing multicolor– FISH (m-FISH) have been described, including multiplex– FISH (M-FISH), combined binary ratio–FISH (COBRA-FISH), rainbow cross-species color banding (Rx-FISH), and spectral karyotyping (SKY). These methods enabled visualization of all 24 human chromosomes, with unique chromosome-painting probes and a specific spectral color for each chromosome

GENETIC METHODS Conventional Chromosomal Analysis Conventional chromosomal staining is performed by Giemsa staining on primary short-term cultures. This analysis 63

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Figure 1

An ideogram of all 24 chromosomes in a normal human karyotype.

Figure 2 A representative karyotype from a conventional chordoma showing a normal 46,XY karyotype.

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Figure 3 Chromosomal staining, using SKY, showing a normal female karyotype (46,XX).

pair. These probes interact with known distinctive sequences along the length of the chromosome. The approach combines Fourier spectroscopy, charge-coupled device imaging, and optical microscopy. Chromosome-specific composite libraries were generated by polymerase chain reaction (PCR) from flow-sorted human chromosomes conjugated to five different fluorescence dyes. Hybridization is carried out at 37◦ C in a humid chamber for 72 hours. The metaphases are captured and analyzed using a dedicated fluorescent microscopy equipped with a triple filter. In order to generate a classified spectral karyotype, the acquired spectral image is analyzed using SKYVIEWTM software. Figure 3 shows a typical chromosomal staining in SKY. This technique of chromosome labeling has a special value as an adjunct to classical karyotyping for confirmation of established translocations and in spotting additional translocations and insertions that were not identified by the banding technique. SKY can also aid in identifying the origin of a chromosomal fragment, such as double minutes. One powerful application of FISH is the use of locusspecific probes (LSPs) aimed at detecting particular DNA sequences present in a single chromosome level. These LSPs can serve as a tool to detect a known genomic deviation (i.e., deletions, amplifications, inversion, and translocation) that may sometimes be the only diagnostic evidence for a specific cancer. Commercially available molecular kits based on FISH are useful diagnostic tools in cases of neoplasms with low mitotic activity, sparse pathologic material, and nonfresh tissue samples.

Comparative Genomic Hybridization Both the conventional G-banding and SKY techniques pose several difficulties when dealing with tumor preparations. First, very few metaphase spreads can be obtained after cell culturing and their quality may be inadequate to allow recog-

nition of chromosomal banding. Second, these techniques require the utilization of fresh tissue samples whereas most tissue preparations are embedded and preserved as paraffin blocks. Third, the introduction of new chromosomal aberrations as an artifact of the culturing process that otherwise would not be a part of the tumor configuration cannot be ruled out. Therefore, another method free of these three drawbacks of conventional cytogenetics is required for our arsenal of cytogenetic research modalities. Comparative genomic hybridization (CGH) was developed to compensate for these problems encountered when looking for recurrent breakpoints in cancer cells DNA. CGH allows scanning of the entire genome of tumor cells in a single step, searching for gains or deletions of chromosomal material compared to normal tissue. The first step of CGH involves isolation of genomic DNAs from the tumor (test) and normal (reference) samples. Each DNA sample is subject to competitive hybridization to normal metaphase chromosomes. Labeling of the DNA is performed by using red and green fluorescent dyes for the tumor and normal samples, respectively. The final analysis is performed by comparing the differential ratio of red and green fluorescence along the longitudinal axis of each chromosome separately. The gains of chromosomal fragments in the tested sample compared to the reference are indicated by green and the deletions are indicated by red. Chromosomal regions that are equally distributed along the chromosome of the test as well as the reference tissue samples are indicated by yellow. Figure 4 shows a summary of DNA sequence copy number gains and losses in 16 specimens of malignant fibrous histiocytoma (MFH) analyzed by CGH. The main advantage of CGH is its ability to analyze numerous samples of tumors preserved in paraffin, allowing comparison studies with the clinical correlates of the tumor karyotypic features. The technique allows detection of recurrent aberrations of rare tumors such as those found in the skull base. Using the CGH technique, Sakabe et al. found

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Figure 4 Summary of DNA sequence copy number gains and losses in 16 specimens of malignant fibrous histiocytoma analyzed by CGH. Losses are shown on the left and gains are shown on the right. Each line represents a genetic aberration seen in one sample. Open boxes signify high-level amplifications of small chromosomal regions. Source: From Ref. 1.

a distinct amplification at 8p23.1 in MFH, leading to the detection of a new gene MASL1 whose expression is enhanced in MFH tumors bearing the 8p amplicon (1). The main limitation of CGH is its inability to detect balanced chromosomal rearrangements, which have a key role in the development of many types of cancer. Genomic imbalances that can be detected by CGH are found in approximately half of the human neoplasms (2).

Identification of Submicroscopic Genetic Deviations The cytogenetic methods described thus far involved chromosomal abnormalities at the microscopical level. Genetic abnormalities involved in carcinogenesis, however, may be submicroscopic in the presence of a normal karyotype. These changes cannot be demonstrated by cytogenetic methods and require molecular analysis. Submicroscopic genetic deviations can involve changes in the DNA, mRNA or protein level. Changes in DNA sequence are detected by PCR or Southern blotting, mRNA deviations by Northern blotting of PCR, and alterations in protein products by Western blotting. Molecular methods are currently used mainly for research, but they will soon provide novel approaches to assist physicians in detecting cancer, in tailoring the modality of treatment and in estimating a patient’s outcome during and after treatment.

Molecular Arrays The development of new methods for mass screening of gene expression, such as CGH-arrays, DNA-arrays, tissue microarrays, and protein-arrays, paved the way for the discovery of

complex cascades of molecular events leading to the development of cancer (3). These technologies allow scientists to monitor change in gene expression during tumor propagation and under different conditions. DNA-arrays allow largescale quantification of tens of thousands of genes in a single experiment. The platform for this technology is a solid stage (the target chip) on which an array of thousands of oligonucleotides (or cDNAs) is printed in a predetermined pattern. The construction of a DNA-array dedicated for human or cancer research can be commercially acquired or constructed according to the experiment prerequisite. Two main systems of DNA-arrays are commercially available to the scientist: the first is an array of cDNA clones robotically mottled on a solid platform, and the second is a technique that utilizes arrays of oligonucleotides directly synthesized on a solid chip. Each oligonucleotide contains 20 to 80 base pairs, which are a signature sequence of specific genes. Commercially available DNA chips contain 36,000 or 60,000 potential genes participating in murine or human cancer, respectively. The first stage is preparation of the tissue samples and array hybridization in the presence of an access target. In this step, fluorescent probes are derived from the specimens’ mRNAs by reverse transcription and hybridized in a complimentary fashion on the target array. The second step is image acquisition, in which the emitted fluorescence is detected by a camera and given a quantitative value for the expression of each gene (Fig. 5). The last and most complicated step of this method is data analysis during which tumors are segregated according to their gene expression profile. The amount of labeled cDNA that hybridizes with its target is proportional to its abundance in the original sample. Intensities are normalized and analyzed with powerful bioinformatic tools and correlated with the clinical characteristics of the tumor and the patient. A complimentary new technology for investigation of protein expression in cancer is antibody microarrays. The technique allows parallel investigation of thousands of proteins and screening of many markers known to participate in tumorigenesis. This method uses an array of different antibodies immobilized on a solid surface which interacts with fluorescence-labeled proteins. The tested protein can be directly labeled using a fluorophore (label-based) or indirectly labeled using a secondary antibody (sandwich) (4). Proteinarrays were used to detect protein expression in squamous cell carcinoma (SCC) of the head and neck as well as other malignancies utilizing laser capture microdissection (5,6). The versatile capability of protein-arrays allows simultaneous screening of thousands of candidate protein markers differentially expressed in distinct tumors and fishing those which are significantly correlated with the clinical status of the patient. The emergence of these powerful genetic tools will aid scientists to molecularly portrait the pathogenetic mechanism underlining the development of cancer. The clinical objectives of these modalities are to develop more accurate classification systems based on gene or protein expression profiles of tumors, to detect molecularly discrete subgroups of patients allowing prognosis stratification and tailoring specific therapy for a particular patient.

COMMON CHROMOSOMAL ABNORMALITIES IN CANCER As noted previously, common chromosomal aberrations found in benign or malignant neoplasms frequently involve change or rearrangement of genetic material in the form of chromosome number or chromosomal fragments.

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Figure 5 Clustering of gene expression in three soft tissue tumors using GeneChip Arrays. (A) Synovial sarcoma, (B) liposarcoma, and (C) schwannoma. The samples were clustered using a set of 2600 known gene fragments. The tissue samples in the tree tumors are joined by very short branches when their gene-expression patterns are very similar; they are joined by increasingly longer branches as their similarity decreases. The color of each square represents the ratio of the gene expression in the indicated sample relative to the average signal of expression of all genes examined. Red indicates the gene expression above the median, green indicates expression below the median, and black indicates expression equal to the median. The intensity of the color reflects the magnitude of divergence from the median. Columns represent the indicated tissue sample; rows represent individual cDNAs. Source: From Ref. 102.

In the following section, we will describe some of the most important chromosomal abnormalities found in tumor specimens (Table 1). Chromosomal deletion involves the loss of a whole chromosome or its fragment (Fig. 6). A deletion that causes removal of a gene that suppresses cell growth and replication may trigger cancer. Such a gene that normally limits the growth of tumors is named tumor suppressor gene. Inactivation of a tumor suppression gene frequently involves mutation of one allele and deletion of a chromosomal region of the second allele. Chromosomal gain involves addition of a whole chromosome or its fragment to the normal 24 human chromosomes (Fig. 7). Deletions and gains of chromosomal fragments or loss of an entire chromosome are common in skull base carcinomas and are probably pathological consequential alterations. Such genomic loss can be detected using a restriction fragment length polymorphism analysis known as loss of heterozygosity (LOH). Translocations occur when two or more chromosomes exchange material (Fig. 8). Translocations induce rearrangement of genetic material that may lead to juxtaposition of genes, resulting in the formation of chimeric genes and abnormal production of protein affecting cell cycle

Table 1 Glossary of Cytogenetic Terms and Abbreviations p q t inv del i + −

dic r ins der

Arm of chromosome above centromere, generally a short arm of a chromosome. Arm of chromosome below centromere, generally a long arm of a chromosome. Translocation: occur when two or more chromosomes exchange material. Inversion: reversal of chromosomal material. Deletion: loss of chromosomal material. Isochromosome: symmetric chromosome composed of duplicated long or short arm with associated centromere. This symbol before a chromosome number indicates an additional whole chromosome and after a chromosome number and arm designation indicates an additional material on that arm. This symbol before a chromosome number indicates loss of a whole chromosome and after a chromosome number and arm designation indicates loss of material on that arm. Dicentric chromosome with two centromeres. Ring chromosome Insertion of extra material within a chromosome Derivative chromosomes: an abnormal chromosome resulting from structural rearrangement involving two or more chromosomes, generally of unbalanced nature.

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Figure 6 A karyotype from a poorly differentiated nonkeratinizing SCC of the skull base showing chromosomal deletion. The karyotype shows two deletions: del(6)(p21) and del(7)(p13) as a part of a complex karyotype (black arrows). Other aberrations are also seen.

and regulation. Genes whose activations contribute to the formation of cancer are known as oncogenes. A number of translocations discovered in human cancer led to the finding of new oncogenes and revealed the mechanism responsible for tumor development (7,8). Many specific translocations were found since the discovery of the first specific abnormality in human cancer t(9;22)(q34;q31) known as the Philadelphia chromosome (9). Translocations are involved in various lymphomas, leukemias, and sarcomas. Among skull base

A

B

Figure 7 A karyotype from a porocarcinoma of the temporal bone showing chromosomal gains. SKY analysis shows gains of chromosomes 6, 8, and 20.

Figure 8 A karyotype from a malignant peripheral nerve sheath tumor of the anterior skull base showing two balanced translocations. G-banding (A) and SKY analysis (B) show translocations involving (2;4)(q35;q31) and (12;X)(q24;q22).

Chapter 3: Genetic Abnormalities of Skull Base Tumors

tumors, alveolar rhabdomyosarcoma, Ewing sarcoma, and synovial sarcoma are characterized by specific translocations. Insertion of a chromosomal fragment to a foreign location or its inversion on the same chromosome may also change the location, resulting in the formation of chimeric genes and the formation of abnormal protein contributing to tumor growth. Gene amplification is defined as an increase in the number of copies of a gene which occurs by replication of the genomic DNA. The MYC and RAS families are genes that are most frequently found to be amplified in various skull base malignancies. Amplification of single or multiple genes can be identified by FISH. Double minutes are extrachromosomal circles of DNA containing up to 2 million base pairs, which form as a result of genetic instability and replicate autonomously. Gene amplification in the form of double-minute chromosomes may result in increasing oncogene products, contributing to malignant tumor formation. Figure 9 shows double-minute chromosomes present in dedifferentiated chordoma of the clivus. In this case, further chromosomal analysis using the SKY technique revealed the origin of DNA contained in these double-minute chromosomes.

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GENETIC ABNORMALITIES OF SKULL BASE TUMORS Most tumors of epithelial origin [i.e., SCC, adenocarcinomas and sinonasal undifferentiated carcinomas (SNUC)] and several of the soft tissue sarcomas (i.e., osteosarcoma and chondrosarcoma) do not show specific chromosomal aberration. They often show complex karyotypes with numerous chromosomal deletions and gains. These changes may derive from a stepwise genetic transformations commonly seen in these tumors. In this scenario, a single genetic alteration may contribute to an increase in cell growth and replication, causing augmentation of the chromosomal aberrations contributing to tumor invasion and metastases, resulting in malignant transformation. Genetic transformations which can be found in a variety of benign tumors can induce cell proliferation without causing malignancy. The earliest work that systematically described the cytogenetic characteristics of 18 skull base tumors was reported by Gollin and Janecka, and about half of the tumors in their study failed to proliferate in culture (10). In a recent study, Gil and Fliss characterized the karyotype of 104 tumors that originated in the cranial base and successfully karyotyped 96% of them (11). The variation in results may be due to differences in the culture conditions or quality of the specimens. A significant increase in the abundance of chromosomal abnormalities is found in malignant skull base tumors compared to benign ones (50% and 20% of the specimens, respectively). Tables 2 and 3 summarize the specific and nonspecific chromosomal changes found in skull base neoplasms, respectively. In the following paragraphs, we present an overview of the cytogenetic properties found in skull base neoplasms.

Squamous Cell and Undifferentiated Carcinoma

C

Less than 4% of carcinomas arise in the skull base and paranasal sinuses (12). Cytogenetic features of these relatively rare tumors have yet to be fully characterized. Most sinonasal SCCs are well-to-moderately differentiated, with a positive stain to cytokeratin. Less frequently, poorly differentiated non-keratinizing SCC, adenocarcinoma, or SNUC, which lack the typical feature of conventional SCC, can arise from the sinonasal epithelium. Non-keratinizing SCC (i.e., transitional cell carcinoma, intermediate cell carcinoma, and schneiderian carcinoma) is considered a variant of SCC, whereas SNUC is a pathologically distinctive neoplasm which also lacks squamous differentiation. The latter tumor is composed of medium-sized undifferentiated cells, with occasional mixed neuroendocrine features. Three reports on five cytogenetically abnormal karyotypes of paranasal SCC have appeared in the English literature and one on undifferentiated carcinoma (10,13–15). Gil and Fliss have found that half of the non-keratinizing SCC specimens displayed an abnormal karyotype (11). Most of the chromosomal abnormalities involved several clones with complex karyotypes. SCC of the upper aerodigestive tracts frequently harbors a highly complex karyotype, as demonstrated in most paranasal SCC. Table 2 Diagnostic Chromosomal Changes in Skull Base Tumors Tumor

Figure 9 A karyotype from a dedifferentiated chordoma of the clivus showing complex karyotype with double minute chromosomes. (A) G-banding of metaphase spread showing polyploid complex karyotype with double minutes. (B) SKY analysis showing staining of chromosome 17. (C) G-banding of the double minute chromosomes.

Alveolar rhabdomyosarcoma Ewing sarcoma Synovial sarcoma Lipoma Myxoid liposarcoma

Chromosomal abnormality t(2;13)(q37;q14) or t(1;13)(p36;q14) t(11;22)(q24;q12) t(X;18)(p11.2;q11.2) t(12;?)(q14;?) t(12;16)(q13;p11)

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Table 3 Recurrent Non-Diagnostic Chromosomal Changes in Skull Base Tumors Tumor Malignant Adenocarcinoma Adenoid cystic carcinoma

Malignant peripheral nerve sheath tumor Esthesioneuroblastoma

Chromosomal abnormality +19p, +Xp22 t(5;9)(q15;q22), t(12;18)(p12;q12), t(1;2)(p36;q31), −9p22, del2(q32;q37) +17q , del(13)(q14−q21)

t(11;22)(q24;q12), t(21;22)(q22;q12), −1p, −3p/q, −8, −9p, −10p/q, +17p13, +20p, + 22q Malignant fibrous histiocytoma +1p, +4q12−21, +8p21, +8q24.1, +9q12−13, +12p11.2, +15q11.2−15, +19p, +7q32 Synovial sarcoma +5p15, 15p11, 19p13, −8, −9, −10p11, −18, −22q11 Osteosarcoma +1, −9, −10, −13, −17 Ewing sarcoma +8, +1q, der(16)t(1;16) Embryonal rhabdomyosarcoma +2, +7, +8, +12, +13, −11p15.5 Benign Meningioma −1p, −6q, −9p, −10, −14q, −18q, −22q12, +1q, +9q, +12q, +15q, +17q, +20q Pleomorphic adenoma t(3;8)(p21;q12) or t(9;12)(p13;q13) Chordoma −1p36, −3, −4, −10, −13, Lipoma del(13)(q12q22), der(6)(p21−23), der(11)(q13) Pituitary adenoma +12 Schwannoma/Neurofibroma −22q12.2

Chromosomal aberrations involving similar breakpoints to those found in the skull base were previously described in SCC of the oral cavity, larynx, hypopharynx, and nasopharynx (14,16,17). Deletion of chromosome Y is a common feature among skull base SCCs and is also frequently found in SCC of other parts of the upper aerodigestive tracts (16–18). Loss of the Y chromosome can be present in both normal and malignant cells and is known to increase with age in both situations. Therefore, the presence of a 45,X,-Y cell population in patients older than 75 years is most likely associated with advancing age, and should not be interpreted as a marker of the malignant clone. Recurrent chromosomal abnormalities involving 1p, 2q, 6q, 7p, 8q, and 12q are frequently found in paranasal SCC (Fig. 10). Although not specific, similar aberrations are found in SCC of the oral cavity, larynx, nasopharynx, and hypopharynx. Chromosomal abnormalities are also found in 60% of SNUC, half of them showing a complex karyotype (Fig. 11). In a recent work, Ariza et al. used CGH to detect recurrent chromosomal abnormalities in patients with sinonasal adenocarcinoma (19). Sinonasal adenocarcinoma differs from other carcinomas of the paranasal sinuses in its histological appearance. Adenocarcinoma has strong association with wood and leather manufacturing, and therefore serves as an excellent model for identification of carcinogenesis initiated by environmental mutagens. Common aberrations found in this tumor involve gain of chromosomal arms 19p and Xp22. Interestingly, gains of chromosomes 19p and Xp22 are also found in paranasal SNUC, suggesting a common mechanism for the development of sinonasal undifferentiated and adenocarcinoma.

Figure 10 Recurrent chromosomal aberrations in paranasal carcinomas. The y-axis shows the number of chromosomal aberrations found in the short (p) and long (q) chromosomal arms of 15 paranasal carcinomas. The x-axis indicates the chromosome number. The graph shows multiple chromosomal breakpoints that are characteristic of this tumor.

Salivary Gland Tumors of the Skull Base The most common salivary gland tumor originating in the skull base area is adenoid cystic carcinoma (ACC). Other tumors include acinic cell carcinoma, carcinoma expleomorphic adenoma, and polymorphous low-grade adenocarcinoma. Twenty-four cases of ACC cytogenetics were described previously in the English literature, and most of them involved the parotid and submandibular gland. Gil et al. analyzed the largest series of ACCs of skull base origin and found that one-third of them had an abnormal karyotype. Frequent chromosomal aberrations of skull base ACC include translocations of chromosome arms 5q15 and 9q22; 12p12 and 18q12; 1p36 and 2q31; as well as deletions of chromosome arms 9p22 and of 2(q32;q37). Other adnexal carcinoma invading the skull base may show a complex karyotype that

Figure 11 A karyotype of a sinonasal undifferentiated carcinoma of the anterior skull base showing a triploid complex karyotype: 60–69,XX,+der(X) add(X)(p22),+der(1) del(1)(q23),+der(1)del(1)(q32),+der(1) t(1;2)(q21; q13), +der(1) t (1; 12) (q21; q13), +2, +4, +5, +der(5)del(5)(q?15), +6, +der(6)i ? (p10),der(7)t(7; 15)(p12; q12), +der(8)t(8; 13)(q24; q11), +9, +12, −13, −13, +16, +16, +18,+19,+20,+der(20)add(20)(p13),+der (21)add(21)(p11), +22, +22, +1 ∼8mar[cp5]. Source: From Ref. 103.

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Figure 12 A karyotype of a porocarcinoma of the lateral skull base showing a complex karyotype. (A) Sky analysis of the primary tumor. (B) Gbanding analysis of a positive neck lymph node metastasis from the same patient. Both specimens showed the same karyotype: 50,XX,inv(2)(p11;q13), +6,inv(7)(p13;p22),+8,+8,+20.

may also be evident in regional lymph node metastases to the neck (Fig. 12).

Clival Chordomas Chordoma is a rare malignant neoplasm derived from remnants of the embryonal notochord along the axial skeleton. It accounts for 1–4% of malignant osseous lesions, arising most frequently in the sacrococcygeal region and rarely in the spheno-occipital (clival) or vertebral regions. Most cytogenetic studies on chordomas have been on those of sacral or spinal origin. Sandberg and Bridge reported 29 cytogenetically abnormal cases of chordoma in a recent review of the literature (20). Fifteen of these cases involved the clivus. Previously reported frequent chromosomal aberrations found in chordomas involved loss of chromosomes 3, 4, 10, and 13, as well as structural rearrangement of chromosome arms 1p and 21q22 (20–22). Gil and Fliss found that one-half of the clival chordomas have an abnormal karyotype and show aberrations similar to sacral chordoma (23). Sawyer et al. reported a normal karyotype in all primary clival chordomas, whereas all recurrent tumors showed chromosomal aberrations (24). The authors therefore postulated that chromosomal aberrations occur late in the progression of chordoma and predominantly in recurrent cases. Genetic analysis using the LOH technique in patients with familial and sporadic chordomas has identified a potential region for a tumor suppression gene at 1p36 (25,26). A malignant variant of chordoma is dedifferentiated chordoma. This tumor shows elements of a conventional chordoma in association with areas of high-grade osteosarcoma. Cytogenetic analysis revealed a polyploid complex karyotype of 71 to 123 chromosomes with double minutes. Interestingly, polyploid karyotypes of 48 to 97 chromosomes with double minutes were also described in cases of highgrade osteosarcoma (26,27). In contrast, of all the previously described chordoma karyotypes, only one involved a polyploid karyotype with 72 chromosomes (28). Using the SKY technique, it was determined that the origin of the double minutes was in chromosome 17 (Fig. 9). Few genes involved in tumorigenesis are located on chromosome 17, among them are TP53, BRCA1, ERBB2, and NF1. Identification of the ex-

act area on chromosome 17 from which the double minutes originate awaits further studies. The growing complexity of the karyotype found in dedifferentiated chordoma is in keeping with the presently accepted view that a multistep process involving oncogenes, loss of tumor suppression genes, and other genetic alteration is cooperatively involved in anaplastic transformation (Fig. 13) (24,29). The pathogenetic evolution of the dedifferentiated chordoma and its relation with simple chordomas is also unknown. It may evolve from a common progenitor stem cell (i.e., the divergent theory) or from separate clones with distinct differentiation pathways (i.e., the collision tumor or convergent theory). If two clones are involved, one clone differentiates into a chordoma and the other (which is void of any differentiation potential) evolves into a high-grade sarcoma (30). Alternatively, it was suggested that the high-grade components of the tumor might emerge directly from the more indolent chordoma by a mechanism of dedifferentiation (31). The exact mechanism of dedifferentiation is not clear: it has been postulated that progression toward an anaplastic component could be regarded as a failure of differentiation rather than a reversal of differentiated cell to an embryonic, undifferentiated cell (32).

Neurogenic Skull Base Tumors Neurogenic tumors that originate in the skull base can be benign or malignant. Two of the most characterized benign tumors that originate in the skull base are schwannomas and neurofibromas. Neurofibroma type 2 (NF2) is an autosomal dominant disorder that is frequently associated with bilateral vestibular schwannomas along with other tumors in the central nervous system. The 100 kb NF2 tumor suppressor gene is located on chromosome arm 22q12.2, and gives rise to a 595 amino acid merlin protein (33,34). This protein is involved in either inter- or intracellular interactions which control cell motility, shape, and communication. Loss of function of the merlin protein results in tumor development due to loss of contact inhibition (35). Mutation of the NF2 gene can also lead to the development of other skull base tumors, such as meningiomas and ependymomas. Half of the patients suffering from NF2 disease have positive family history for the

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Primary clival chordoma

46,XY

Recurrent clival chordoma

Dedifferentiated clival chordoma

46,XX complex karyotype

Polyploid 71-123

Figure 13 A multistep model involving multiple genetic alterations suggested for the development of dedifferentiated chordoma. Three different cases of clival chordoma showing gradual change in karyotype: Primary chordoma showing normal karyotype (left), recurrent chordoma with a complex karyotype (middle), and dedifferentiated clival chordoma with polyploid karyotype (right). Arrowheads indicate chromosomal aberrations.

disorder. The rest are sporadic cases. More than 200 known mutations were identified in patients suffering from NF2 disease, where the more severe form is associated with a truncated protein. Among the common malignant skull base tumors of neuroectodermal origin are esthesioneuroblastomas, Ewing sarcoma, Askin tumor, and malignant peripheral nerve sheath tumor (MPNST). Conventional histopathological classification of these tumors may be complicated since these neoplasms contain similar morphological and cytological features. The common simple translocation found in Ewing sarcoma is t(11;22)(q24;q12), which is found in 78% of the affected patients. This chromosomal rearrangement can be found as a single translocation or as a part of a complex karyotype in which other chromosomes are involved. More than 90% of the tumors can be identified using 22q12 or 11q24 chromosome markers. Additional chromosomal changes found in Ewing sarcoma are trisomy 8 (44%), trisomy 1q (18%), and der(16)t(1;16). Gains or losses of chromosomes 2, 9, and 7 may be each found in 20% of these patients. Esthesioneuroblastoma is a relatively uncommon tumor that arises from the olfactory epithelium in the upper nasal cavity and often shows an intracranial extension. Esthesioneuroblastomas closely resemble Ewing sarcoma and other peripheral primitive neuroectodermal tumors and therefore present a diagnostic challenge to the pathologist. About 1000 cases have been reported in the world literature, but only 3 cases with a whole karyotype have been published (13,36). Two of these cases showed a complex hyperdiploid karyotypes with different numerical and structural aberrations. Several studies have suggested that the t(11;22)(q24;q12) or the t(21;22)(q22;q12) translocation, which is frequently present in peripheral primitive neuroectodermal tumors, including Ewing sarcoma, is also a characteristic finding of esthesioneuroblastomas. In contrast, others failed to find these translocations in esthesioneuroblastoma specimens (Fig. 14) (11,37–39). Some investigators have used CGH to screen for chromosomal breakpoints of esthesioneuroblastomas, and their findings suggested a characteristic pattern consisting of deletions of chromosomes 3p and overrepresentations of 17q (40,41). Other important alterations were deletions of 1p, 3p/q, 9p, 10p/q along with gains of 17p13, 20p, and 22q (41). Amplification of

chromosome 8 was also shown previously to exist in this tumor (11,38,42).Taken together, the recent cytogenetic works provide further evidence that esthesioneuroblastoma is not a part of the peripheral nerve sheath tumor (PNET) family. MPNST, also known as neurofibrosarcoma, malignant schwannoma, or neurogenic sarcoma, is a rare neoplasm of Schwann cell origin. Eighty-three cases of MPNSTs with chromosomal aberrations have been reported in the literature (43). Most of the MPNSTs had a complex karyotype with triploid or tetraploid clones (44). It was suggested that polyploid complex karyotype is a characteristic of MPNST, that it might be associated with high-grade tumors, and that it might serve as a discriminator between malignant and benign peripheral nerve tumors (which almost always display a near-diploid karyotype) (45). The discovery by Gil et al., of a simultaneous occurrence of a t(2;4)(q35;q31) and a t(X;12)(q22;q24) as the only chromosomal abnormalities in a high-grade MPNST, challenges this hypothesis (Fig. 8) (46). Other breakpoints frequently found in this tumor involve the long arm of chromosomes 2 and 4 (47). As stated before, the t(11;22) translocation is found in various neuroectodermal tumors (i.e., Ewing sarcoma esthesioneuroblastoma, peripheral neuroepithelioma, and Askin tumor), suggesting a common pathway for tumorigenesis in these neoplasms. Indeed, it was shown that various oncogenes are expressed in both esthesioneuroblastoma and Ewing sarcoma. Some of these oncogenes are c-myc, c-src, c-myb, and c-mil/raf (47). Analysis of the src protein levels in esthesioneuroblastoma, neuroepithelioma, and Ewing sarcoma demonstrated high protein levels and tyrosine kinase activity in these tumors relative to other neuroendocrine tumors (48). On the other hand, the c-myc oncogene is highly expressed in Ewing sarcoma but not in esthesioneuroblastoma (49). Further studies are warranted to show whether high expression of these oncoproteins is of etiologic significance. It is possible that multiple activated genes take part in cancerous transformation, either independently or in cooperation with one another.

Meningioma Meningioma was the first solid tumor to show characteristic cytogenetic abnormality, that is, loss of chromosome 22 (50).

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Figure 14 A karyotype of a recurrent esthesioneuroblastoma of the anterior skull base showing a complex karyotype: 46,XX,−2,i(2)(q10),t(5;6)(q31; q26), −7,der(7)t(7; ?)(p22; ?), −8, −9,der(9)t(9; ?)(q34; ?), −11,der(12)(t(9:12)(q13;p13),−15,−17,+7mar. Red boxes showing the chromosomal aberrations.

Loss of heterozygosity on chromosome 22q is frequently observed in meningioma, leading to a bi-allelic inactivation of the NF2 tumor suppressor gene (51). After vestibular schwannomas, the second most common disease associated with mutation of the NF2 gene is meningioma (52). In the pediatric population, approximately 40% of the meningiomas are associated with NF2, which must be ruled out in any child with meningioma especially if it is multifocal. Other less common genetic syndromes associated with meningioma are non-NF2-associated meningiomas, Cowden syndrome, Gorlin nevoid basal cell syndrome, Li-Fraumeni syndrome, Turcot/Gardener syndrome, and von Hippel-Lindau disease. Previous studies have found numerous cytogenetic alterations associated with the progression of meningioma as well as with anaplastic and atypical variant. These include dicentric and ring chromosomes; loss of chromosome arms 1p, 6q, 9p, 10, 14q, and 18q; as well as gains of 1q, 9q, 12q, 15q, 17q, and 20q (53,54). A model of meningioma progression based on cytogenetic analysis is shown in Figure 15. As shown in Table 4, a world health organization (WHO) grade I menin-

gioma shows loss of chromosome arm 22q in 58% of the cases, a grade II tumor shows notable loss of 1p (76%) and 22q (71%), whereas a grade III tumor (anaplastic meningioma) is associated with −6q (53%), −10q (68%) and −14q (63%). Olfactory groove meningioma (OGM) is a slowgrowing meningioma that originates in the cribriform area and frequently achieves a large size before detection. In some cases, the tumor may involve surrounding structures, such as optic nerves and cerebral arteries, complicating its removal. Gil and Fliss analyzed a specific subgroup of meningiomas originating in the olfactory groove and found that 25% of them showed an abnormal karyotype, including breakpoint of chromosome arm 22q11 (Fig. 16). Similar abnormalities of OGMs were described by others (10,55). The presence of

Loss on: 22q, 18p

Table 4

Frequency of Cytogenetic Alterations in Meningiomas

WHO classification I II III

Normal

Breakpoint

(%)

22q 1p 22q − 6q −10q −14q

58 76 71 53 68 63

Gain on:1q, 9q, 12q, 15q, 17q, 20q Loss on: 1p, 6q, 10q, 14q, 18q, 22q

Benign meningioma

WHO I

Gain on 17q Loss on 6q: 9p, 10q: 14q

Atypical meningioma

WHO II

Anaplastic meningioma

WHO III

Figure 15 A model of meningioma progression based on cytogenetic analysis.

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Figure 16 Abnormal karyotypes of OGM. A representative hypodiploid karyotype of OGM showing dic(19:22)(p13:q11). The arrow points to the translocation between chromosomes 19p13 and 22q11 that generated a dicentric chromosome.

dic(19;22)(p13;q11) as well as the loss of chromosome arm 22q is consistent with aberrations noted in meningiomas of other areas (56–58). These findings suggest that similar genetic mechanisms take part in the development of meningiomas located in the olfactory groove as well as in other intracranial regions.

Juvenile Nasopharyngeal Angiofibroma Juvenile nasopharyngeal angiofibroma (JNA) is a benign tumor that occurs exclusively in adolescent and young adult males. This is a locally invasive fibrovascular tumor that originates in the sphenopalatine foramen area. The three works that used CGH analysis of JNA were all from the same laboratory (59–61). DNA gains were observed on chromosomes 3q, 4q, 5q, 6q, 7q, 8q, 12p, 12q, 13q, 14q, 18q, 21q, and X, and DNA losses were on chromosomes 17, 19p, 22q, and Y. The deletions of chromosome 17 included regions for the tumor suppressor gene P53 as well as the Her-2/neu oncogene. In 71% of their cases, gene losses were detected for both genes. However, comparison of p53 and Her-2/neu mRNA levels in laser microdissected endothelial and stromal cells were not conclusive to answer the question of the tumor cell of origin in JNA. A significant loss of the chromosome Y and gain of chromosome X was observed in 86% and 71% of the tumors, respectively. A gain of chromosome X leads to androgen receptor gene gain may suggest that JNA is an androgen-dependent tumor. This is supported by the finding that beta-catenin known to be over-expressed in JNAs acts as a co-activator of the androgen receptor. Gil et al. performed the first full karyotype characterization of JNA using the G-banding cytogenetics method (11). All 12 specimens that had been confirmed histologically as JNA showed a normal male karyotype. This result could represent the true chromosomal pattern of this tumor, similar to other benign tumors, particularly those of soft tissue and bone. There is also the possibility that a genetic change was present in some of the tumors, but that this change was submicroscopic and not detectable by a classical cytogenetic method. Another explanation for a normal karyotype is that the findings of G-banding or SKY analysis may represent a normal stromal cell proliferation in culture rather than tumor cell growth, and therefore represent the constitutional karyotype of the patient.

Pleomorphic Adenoma Pleomorphic adenoma is the most common tumor of the salivary glands. Rarely, the tumor may invade the parapharyngeal space, infratemporal fossa, and intracranial compartment. Such tumors are locally aggressive and their biological

behavior may be different from that of ordinary pleomorphic adenomas of the parotid gland. We applied cytogenetic methods in order to delineate the spectrum of chromosomal rearrangements of giant pleomorphic adenomas, which involved the lateral skull base area and found that 80% of them showed an abnormal diploid karyotype. Two major chromosomal subgroups had been recognized earlier in pleomorphic adenoma: one of them was characterized by structural rearrangements of 8q12 (62). This chromosomal rearrangement may be present in up to 60% of the cases with an abnormal karyotype. Translocations involving 8q12 may result in replacement of the promoter region of the PLAG1 gene by that of another gene (63,64). One such candidate gene located on 6q12 is PRL-1 and its expression is elevated in a number of tumor cell lines (65). PRL-1 encodes a 20-kDa protein with an eight-amino-acid consensus protein tyrosine phosphatase active site. The gene is important in normal cellular growth and can promote invasion activity and metastasis (66). Some of the skull base pleomorphic adenomas show a complex karyotype with ring chromosomes and double minutes (67). Such chromosomal aberrations are infrequent in this tumor, and their presence may have contributed to the aggressive behavior of the ones which invade the skull base.

Paraganglioma Familial paraganglioma is inherited in an autosomal dominant manner, with maternal imprinting. In this disease, an individual harboring an abnormal gene can bear a child affected with the disease only if the transmitting parent is the father (69). Genetic analysis of patients with hereditary paraganglioma revealed three genes whose mutations result in the development of tumors. Analysis of two families with hereditary paraganglioma located the underline gene at 11q23 (69,70). Physical analysis of this hereditary paraganglioma type 1 (PLG1) locus revealed a candidate gene encoding the enzyme succinate dehydrogenase D (SDHD). The SDHD gene encodes the 159 amino acid subunit of cytochrome b, located in the mitochondrial complex II. Various mutations of this polypeptide were found in patients with hereditary paraganglioma, responsible for 50% of the familial cases (71,72). Further studies of the SDHD protein complex revealed other genes encoding for this subunit of the mitochondrial complex, including SDHC (PLAG3) located at 1q21 and SDHB (PLAG4) located at 1p36 (73,74). Mutations of the SDHD and SDHB genes are also found in 8–36% of the patients with sporadic paragangliomas (75). The mechanism by which dysfunction of the mitochondrial complex induces tumors is unknown; however, it is conceivable that hypoxic stimulation due to chronic hypoxemia may give rise to proliferation of paraganglioma cells. Astrom et al. have recently demonstrated that higher altitudes and nonsense/splicing mutations are associated with phenotypic severity in patients with hereditary paraganglioma type 1 (76). Their result supports the hypothesis that SDHD mutations impair oxygen sensing. Knowledge of the genetic mechanisms involved in evolution of paragangliomas enabled the development of screening tests for potential candidates in families with hereditary paraganglioma (76).

Sarcomas Soft tissue sarcomas are infrequently found in the head and neck region in the mature population. These tumors are more common in childhood where up to 40% of them occur in the head and neck. Cytogenetic characteristics of soft tissue sarcomas are well established, but limited data exist on soft tissue sarcoma of the cranial base and head

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and neck because of the rarity of this tumor. Histologically, it is difficult to distinguish between skull base soft tissue tumors based on conventional pathological and cytological measures. For example, distinguishing between Ewing sarcoma, embryonal rhabdomyosarcoma, small cell osteogenic sarcoma, and lymphoma may be challenging (78). Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma of childhood, and also the most common skull base malignant tumor in the pediatric population (79). RMS is divided into two major histologic subtypes, embryonal (ERMS) and alveolar (ARMS). ERMS typically occurs in children <10 years of age and most frequently in the head and neck or skull base regions. In contrast, ARMS most commonly occurs in adolescents and young adults and typically in the trunk and extremities. The prognosis of ERMS is generally favorable compared to ARMS which portends a poor prognosis. Chromosomal analyses of ARMS revealed a specific translocation associated only with this disease. The t(2;13)(q35;q14) translocation is found in approximately 70% of patients with ARMS (Fig. 17). Other studies have also shown a t(1;13)(p36;q14) variant translocation which may be identified in the minority of patients. Physical mapping and cloning studies demonstrated that the loci on chromosomes 2 and 1 rearranged by the t(2;13) and t(1;13) are PAX3 and PAX7, respectively (80,81). The chromosome 13 locus juxtaposed with both PAX3 and PAX7 is FKHR (FOX01A), which encodes a novel member of the fork head transcription factor family (82). The translocations break within intron 7 of PAX3 or PAX7 and intron 1 of FKHR and thus create two chimeric genes on the derivative chromosomes. A series of molecular studies demonstrated that these gene fusion events result in alterations at the level of protein function, gene expression, and subcellular localization (82). In contrast to the specific translocations found in ARMS, approximately 75% of ERMS cases have a complex karyotype. The most frequent chromosomal abnormalities of ERMS are translocation breakpoints in the 1p11-q11 region; gains of chromosomes 2, 7, 8, 12, and 13; and losses at chromosome 11p15.5 (83, 84). Gil et al. found that ERMS of the skull base are associated with translocations involving 13q14, which is a frequent finding in this tumor. Other aberrations of skull base ERMS include gains of chromosomes 5, 8, 9, and 12 (11). Synovial sarcoma is a highly malignant tumor infrequently involving the base of skull. It is difficult to distinguish from fibrosarcoma, solitary fibrous tumor, leiomyosarcoma, MPNST, and clear cell sarcoma or from soft tissue tu-

mors, such as esthesioneuroblastoma, rhabdomyosarcoma, and Ewing sarcoma (when it exhibits poorly differentiated features). The characteristic cytogenetic features of synovial sarcoma were fist described by Sandberg in 1986, who described the pathognomonic translocation t(X;18)(p11.2;q11.2) (85,86). Since then, serial cytogenetic examinations of synovial sarcomas established the presence of t(X;18) in more than 90% of the cases, and as the sole chromosomal abnormality in one-third of them (87). Until the publication of this book, nearly all studies have indicated that the (X;18) translocation is found almost exclusively in monophasic and biphasic synovial sarcoma. There is still heated debate on whether other soft tissue tumors, including MPNSTs, show similar translocation (88). In essence, the general consensus is that t(X;18) is characteristic of synovial sarcoma and no other tumor. The (X;18) translocation results in the fusion of two genes, the SYT gene at 18q11.1 and the SSX1 or SSX2 gene at Xp11.2 (89,90). The syt protein is a transcriptional activator located in the cell nucleus, whereas the ssx proteins are thought to act as transcriptional suppressors (91). Survival analysis of the two SYT–SSX fusion types showed that the SSX1 type is associated with shorter metastasis-free survival and poor prognosis compared with the SSX2 variant (92). A recent work by Gil et al. performed on over 100 cases of skull base neoplasms, established the diagnosis of synovial sarcoma in two patients, due to the presence of t(18;X)(q11;p11) (Fig. 18) (11). Other abnormalities, which were previously described in this tumor, including gains of 5p15, 15p11, and 19p13 and losses of 8, 9, 10p11, 18, and 22q11, are also present in synovial sarcoma of the skull base. These data confirmed that t(18;X) might be used for the diagnosis of synovial sarcoma originating in the skull base. MFH is the most common malignant soft tissue tumor in adults. This is also one of the most common sarcomas arising in the skull base. No specific chromosomal anomaly has been reported in MFH and most tumors analyzed thus far showed multiple numerical and structural abnormalities. CGH studies of MFH have found frequent gains at 4q1221, 8p21, 8q24.1, 9q12-13, 12p11.2, and 15q11.2-15 (1). Recurrent breakpoints were also found in 1p36, 1q11, 1q21, 3p12, 11p11, 17p11, and 19p13 (93). It was suggested that a +19p marker as well as gains of 1p and 7q32 might serve as an indicator for aggressive clinical course and dismal prognosis (94,95).

Figure 17 SKY analysis of alveolar rhabdomyosarcoma showing the t(2;13)(q35;q14) translocation. This rearrangement is found in approximately 70% of patients with ARMS.

Figure 18 Translocation involving (X;18) is found in more than 90% of the cases of synovial sarcoma, in third of them as the sole chromosomal abnormality.

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Osteosarcoma is an uncommon tumor of skeletal origin that may involve the skull base and craniofacial area. In children, this is the most common nonhematologic malignant tumor of bone, comprising more than half of the cases of bone malignancy among the pediatric population. Most osteosarcomas are high-grade tumors with propensity to metastasize, resulting in a less than 10% long-term disease-free survival. Unlike synovial sarcoma or ARMS, osteosarcoma is not associated with specific chromosomal abnormalities. Intensive genetic research has shown that genetic alterations in osteosarcoma include multiple, sequential changes involving both over-expression of oncogenes and inactivation of tumor suppression genes (96). A common mechanism believed to participate in the oncogenesis of osteosarcoma is the inactivation of the retinoblastoma gene (RB1) and TP53, leading to impaired regulation of cell proliferation (97). Other oncogenes that were shown to be over-expressed in osteosarcomas are FOS, MYC, MET, SAS, GLI, and ERBB2. The most common cytogenetic feature in osteosarcoma is a complex karyotype which resembles that of chondrosarcoma. Chromosomal abnormalities are found in 70% of the cases, ranging from haploid to hexaploid karyotype. The most frequent structural rearrangements found in osteosarcoma involve gain of chromosome 1 and loss of chromosomes 9, 10, 13, and 17. Other structural abnormalities, such as ring chromosomes, homogeneously staining regions, or double minutes, are frequently seen in conventional osteosarcoma. In a recent study, Gil and Fliss found microscopic genetic changes in 66% of skull base osteosarcomas (11). The majority of these cases were characterized by complex chromosomal abnormalities, multiple clones, and cell-to-cell variations. Cytogenetic abnormalities included complex karyotypes with frequent rearrangements of chromosomes 1, 2, 3, and 17. Single karyotypic changes were not found in skull base osteosarcoma cases.

FUTURE DIRECTIONS IN SKULL BASE GENETICS Gene Therapy Our armamentarium for the treatment of most aggressive skull base tumors lacks an effective modality for significantly improving long-term patient survival. The last decade has witnessed the development of gene therapy for a range of diseases, including inherited metabolic disorders and cardiovascular diseases. This approach has been explored extensively in the field of cancer therapy, resulting in the recent licensing of gene therapy for the routine treatment of head and neck cancer in China. Patients with skull base neoplasms may especially benefit from gene therapy because many of these tumors have already infiltrated cranial nerves and brain parenchyma at the time of diagnosis. The first goal of gene therapy is to replace a defective tumor suppression gene with a normal gene, reestablishing normal cell growth at the molecular level. Alternatively, shutting down an oncogene responsible for tumorigenesis will decrease its level of expression and will lead to the reduction of tumor growth. Unfortunately, many of the skull base malignancies lack a single candidate gene involved in tumorigenesis. Nevertheless, recent studies of benign tumors with a single gene mutation, including meningioma and schwannoma, showed promising results of gene therapy by decreasing tumor growth in vitro (98). Viruses are currently considered the most effective mean for gene delivery. A variety of virus vectors (i.e., adenovirus, vaccinia virus, and retroviruses) have been employed to deliver genes to cells, providing a transient or permanent

transgene expression. Modification of the virus envelope will enable the effective and safe use of systemic delivery methods of these viruses. Viral oncolytic therapy has also been studied extensively as a novel anticancer strategy. Whereas normal cells resist replication, tumor cells have an impaired antiviral response that sensitizes them to oncolytic viruses. Alone or in combination with chemotherapy or radiotherapy, viral oncolytic therapy uses the natural cytotoxicity of viruses to kill tumor cells exclusively. Among the most explored oncolytic viruses are the herpes simplex virus, adenovirus, and vaccinia virus. A number of these oncolytic viruses have the potential to become powerful anticancer agents, especially against advanced solid tumors. It has been 10 years since the beginning of the first clinical trial in which an oncolytic virus was administered to cancer patients. Since then, oncolytic viruses from five different species have been taken to phases I and II clinical trials in over 300 cancer patients. Importantly, the successful development of systemic administration of oncolytic viruses will extend the range of tumors that can be treated using this novel treatment modality and hopefully will allow effective and safe treatment of patients with advanced skull base tumors.

Skull Base Cytogenetics from Bench to Bedside and Back The ability to detect chromosomal aberrations and subtle molecular genetic abnormalities is important when considering cancer therapy and prevention. The emergent cytogenetic data established the development of diagnostic tests utilizing molecular approaches and allowed the development of various grading systems for assessing the diagnosis and prognosis of patients with cancer. The identification of specific translocations can be accomplished by using conventional cytogenetic methods on fresh tissues. New commercially available kits based on reverse transcriptase–polymerase chain reaction (RT-PCR) are a relatively new method for identifying specific cytogenetic abnormalities (99,100). Utilizing RTPCR–based diagnostic tests allows rapid, reliable, and inexpensive examinations of biopsies and fine-needle aspirates of skull base neoplasms in fresh or paraffin-embedded tissue. For example, the development of RT-PCR–based assay for synovial sarcoma showed 94–100% accuracy in a study of paraffin-embedded specimens (101).

SUMMARY Previous studies have demonstrated the prognostic value of cytogenetic data in head and neck epithelial and soft tissue tumors. This chapter reviewed the value of cytogenetic information for the diagnosis of soft tissue tumors, such as synovial sarcoma, ARMS and Ewing sarcoma. Some of the data presented here may serve as a starting point for further investigation on the biological behavior and tumorigenesis of several other skull base tumors, including paranasal carcinomas. To date, the extent of the cytogenetic data on most skull base neoplasms is too limited to furnish a precise association between karyotype and prognosis. The significance of many of the breakpoints discussed here awaits further clarification. Identification of other novel molecular alterations is necessary to improve the diagnosis of these complex tumors and to provide reliable molecular systems for predicting the prognosis and response to treatment of affected patients. Whether genetic data will become an essential adjunct to surgery and pathology in the treatment of skull base tumors awaits further studies.

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67. Mark J, Dahlenfors R, Ekedahl C. On double-minutes and their origin in a benign human neoplasm, a mixed salivary gland tumour. Anticancer Res. 1982;2:261–264. 68. Hall JG. Genomic imprinting: Review and relevance to human diseases. Am J Hum Genet. 1990;46:857–873. 69. Heutink P, van Der Mey AG, Sandkuijl LA, et al. A gene subject to genomic imprinting and responsible for hereditary paragangliomas maps to chromosome 11q23-qter. Hum Mol Genet. 1992;1:7–10. 70. Mariman EC, van Beersum SE, Cremers CW, et al. Analysis of a second family with hereditary non-chromaffin paragangliomas locates the underlying gene at the proximal region of chromosome 11q. Hum Genet. 1993;91:357–361. 71. Baysal BE, Ferrell RE, Willett-Brozick JE, et al. Mutations in SDHD, a mitochondrial complex II gene, in hereditary paraganglioma. Science. 2000;287:848–851. 72. Baysal BE, Farr JE, Rubinstein WS, et al. Fine mapping of an imprinted gene for familial nonchromaffin paragangliomas, on chromosome 11q23. Am J Hum Genet. 1997;60:121–32. 73. Niemann S, Steinberger D, Muller U. PGL3, a third, not maternally imprinted locus in autosomal dominant paraganglioma. Neurogenetics. 1999;2:167–170. 74. Baysal BE. On the association of succinate dehydrogenase mutations with hereditary paraganglioma. Trends Endocrinol Metab. 2003;14:453–459. 75. Bikhazi PH, Messina L, Mhatre AN, et al. Molecular pathogenesis in sporadic head and neck paraganglioma. Laryngoscope. 2000;110:1346–1348. 76. Astrom K, Cohen JE, Willett-Brozick JE, et al. Altitude is a phenotypic modifier in hereditary paraganglioma type 1: Evidence for an oxygen-sensing defect. Hum Genet. 2003;113:228–237. 77. Bikhazi PH, Roeder E, Attaie A, et al. Familial paragangliomas: The emerging impact of molecular genetics on evaluation and management. Am J Otol. 1999;20:639–643. 78. Stephenson CF, Bridge JA, Sandberg AA. Cytogenetic and pathologic aspects of Ewing’s sarcoma and neuroectodermal tumors. Hum Pathol. 1992;23:1270–1277. 79. Gil Z, Constantini S, Spektor S, et al. Skull base approaches in the pediatric population. Head Neck. 2005;27:682–689. 80. Barr FG, Galili N, Holick J, et al. Rearrangement of the PAX3 paired box gene in the paediatric solid tumour alveolar rhabdomyosarcoma. Nat Genet. 1993;3:113–117. 81. Davis RJ, D’Cruz CM, Lovell MA, et al. Fusion of PAX7 to FKHR by the variant t(1;13)(p36;q14) translocation in alveolar rhabdomyosarcoma. Cancer Res. 1994;54:2869–2872. 82. Galili N, Davis RJ, Fredericks WJ, et al. Fusion of a fork head domain gene to PAX3 in the solid tumour alveolar rhabdomyosarcoma. Nat Genet. 1993;5:230–235. 83. Gordon T, McManus A, Anderson J, et al.; United Kingdom Children’s Cancer Study Group; United Kingdom Cancer Cytogenetics Group. Cytogenetic abnormalities in 42 rhabdomyosarcoma: A United Kingdom Cancer Cytogenetics Group Study. Med Pediatr Oncol. 2001;36:259–267. 84. Kullendorff CM, Donner M, Mertens F, et al. Chromosomal aberrations in a consecutive series of childhood rhabdomyosarcoma. Med Pediatr Oncol. 1998;30:156–159. 85. Limon J, Dal Cin P, Sandberg AA. Translocations involving the X chromosome in solid tumors: Presentation of two sarcomas with t(X;18)(q13;p11). Cancer Genet Cytogenet. 1986;23 (1): 87–91. 86. Turc-Carel C, Dal Cin P, Limon J, et al. Involvement of chromosome X in primary cytogenetic change in human neoplasia: Nonrandom translocation in synovial sarcoma. Proc Natl Acad Sci USA. 1987;84:1981–1985. 87. Sandberg AA, Bridge JA. Updates on the cytogenetics and molecular genetics of bone and soft tissue tumors. Synovial sarcoma. Cancer Genet Cytogenet. 2002;133:1–23. 88. O’Sullivan MJ, Kyriakos M, Zhu X, et al. Malignant peripheral nerve sheath tumors with t(X;18). A pathologic and molecular genetic study. Mod Pathol. 2000;13:1336–1346. 89. Clark J, Rocques PJ, Crew AJ, et al. Identification of novel genes, SYT and SSX, involved in the t(X;18)(p11.2;q11.2) translocation

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4 Imaging of Skull Base Neoplasms Lawrence E. Ginsberg

lesions, such as glomus tumors or juvenile angiofibroma, to establish that a lesion is indeed hypervascular and then to assist in surgical planning. The advantages of MR include its ability to distinguish tumor within a paranasal sinus from obstructed secretions, something not always possible with CT. MR is better able to detect small soft tissue tumor components, particularly those near bony surfaces for which the enhancement may be inconspicuous on CT. MR is also more accurate to detect tumor extension through neural foramina and canals, whether by direct or perineural mechanisms.

INTRODUCTION Management of skull base neoplasms requires a team approach, whose members are dedicated and specifically experienced at dealing with these unique tumors. The radiologist is no exception. Imaging plays a vital role in the diagnosis and posttreatment evaluation of skull base tumors. Although radiologists traditionally concern themselves with preoperative diagnosis, it will be my argument that because such a goal is not attainable in every case, there are more important things for us to achieve with our time and technology. The goal of imaging of known or suspected skull base tumors is several-fold. Firstly, some patients not known but only suspected of having a possible skull base tumor (based on pain, cranial neuropathy, etc.) require imaging simply to establish or exclude such a diagnosis. For those with known skull base tumors, the role of imaging is to establish the full extent and location of the abnormality, outline areas of possible spread and secondary effects on adjacent structures, exclude nodal disease, and finally, suggest possible histologic diagnosis (1). In some cases, distinguishing tumor from benign disease entities such as skull base osteomyelitis and other inflammations is a critical role of imaging. Obviously when possible, the radiologist can suggest a diagnosis, and in fact for many lesions the imaging is quite characteristic (1,2). The goals of this chapter will be to provide an overview of the imaging appearances of the more common skull base neoplasms, provide imaging strategies, and review ways in which certain imaging features provide clues as to tumor type or benign versus malignant. It will not be the goal to exhaustively depict every conceivable skull base tumor.

ANTERIOR CRANIAL BASE The anterior cranial base comprises the orbital and ethmoid roofs, and the cribriform plates. Tumors seldom primarily arise within these bony structures—most generally originate intracranially and extend inferiorly through the skull base (3) [e.g., meningioma (Fig. 1)], or by extending intracranially from an origin in the upper nasoethmoid or frontal sinus region. The latter are typically sinonasal malignancies (Figs. 2 and 3). Intracranial meningiomas are quite common, and often arise in the subfrontal or olfactory groove region (Fig. 1) (4). These benign dural tumors may extend inferiorly, growing directly through the ethmoid roof (fovea ethmoidalis) and cribriform plate into the nasal cavity and/or ethmoid sinuses (Fig. 1). In such cases, it is generally evident radiographically that the bulk (or so-called “epicenter”) of the tumor is intracranial. In addition, characteristic imaging features of meningioma, such as relatively homogeneous isointensity on T1 , iso or slightly hyperintense signal on T2 -weighted images, and bright homogeneous enhancement following Gadolinium-based IV contrast administration, often with a so-called dural tail of enhancement, make the diagnosis of meningioma straightforward in most cases (Fig. 1) (4). Sinonasal malignancies may arise in the upper nasoethmoid region, and typical histologic tumor types include olfactory neuroblastoma (esthesioneuroblastoma), sinonasal undifferentiated carcinoma, squamous cell carcinoma, and neuroendocrine carcinoma (3). Other tumor types are less common. While the imaging characteristics of these lesions are relatively nonspecific, imaging is important in evaluating for intracranial spread, which will often have implications for surgical therapy. CT can often make this determination, but MR is better in this regard (Figs. 2 and 3). On CT, sinonasal malignancies generally enhance to a mild or moderate degree, and when they involve bone, the pattern is usually one of destruction; sclerosis of bone is uncommon. With MR, sinonasal malignancies are typically isointense (same signal as) on T1 - and T2 -weighted sequences, and enhance to

SELECTION OF IMAGING MODALITY As opposed to some anatomic sites in the head and neck, for lesions of the sinonasal cavity and skull base, MR and CT are complimentary. At the M. D. Anderson Cancer Center, virtually all patients with such lesions will be imaged with both modalities prior to therapy, and many will have both modalities following therapy, at least early on. The advantages of CT include its ability to detect calcification and bone, which is important in lesions that either destroy bone or produce some characteristic bony or calcific change. The latter include the classic sunburst periosteal new bone formation in osteosarcoma, the mineralized chondroid matrix of chondrosarcoma, or the hyperostotic reaction typical of certain types of meningioma, among others. CT may also have value, due to the multiplanar reconstruction capability of multidetector-row technology, to provide images in virtually any plane of section, of very high quality. Furthermore, CT angiography has value in certain hypervascular 81

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Figure 1 Olfactory groove meningioma in a 53-year-old woman complaining of visual disturbance. (A–C) Axial T1 -weighted, T2 -weighted, and postcontrast T1 -weighted axial MR images, respectively, demonstrate a large subfrontal mass (asterisks). This has classic signal characteristics and bright homogenous enhancement typical of meningioma. The T2 -weighted image demonstrates so-called “CSF-clefts,” representing pockets of trapped CSF between the lesion and brain surface that is characteristic of an extra-axial lesion (arrows in B). (D) Coronal postcontrast T1 -weighted image demonstrating downward, nasoethmoid tumor extension (arrows).

varying degrees with contrast administration (Figs. 2 and 3). Obstructed sinonasal secretions are usually low signal on T1 and high signal on T2 , and if chronic or inspissated, may become hyperintense (high signal) on T1 -weighted images (Fig. 3) (3). By reviewing all sequences, one can generally determine whether sinus is involved with tumor or merely obstructed. It is important to always image the neck in cases of sinonasal malignancy, as such lesions may present with, or recur as, nodal disease.

CENTRAL SKULL BASE The central skull base (CSB) includes primarily the sphenoid bone and its various parts as well as adjacent structures such as the cavernous sinus, sella turcica, and parasellar region. A very large variety of tumors may afflict the CSB (1–3). As with the anterior cranial base, lesions may arise intracranially and secondarily involve the sphenoid bone, arise primarily within

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Figure 2 Squamous cell carcinoma of the frontal and ethmoid sinuses in a 66-year-old woman presenting with bloody nasal and oral secretions and subsequent left eye visual changes. (A and B) Coronal and sagittal T1 weighted postcontrast MR images, respectively, demonstrate a large, somewhat heterogeneously but brightly enhancing mass lesion filling the frontal and nasoethmoid regions with obvious posterior extension into the epidural space (arrows).

it, or arise inferiorly or anteriorly, and secondarily affect it by upward or posterior spread. The most common intracranially arising lesion to affect the CSB is meningioma (4). Various aspects of the CSB may be involved, including the planum sphenoidale and tuberculum sella, the anterior clinoid, the greater sphenoid wing, the parasellar region and cavernous sinus, and the petroclival region (Figs. 4 and 5). In most of these locations, the lesion is merely dural in location; while there may be some reactive bony sclerosis or hyperostosis, the bone is uninvolved (4). Imaging features of meningioma in these locations are no different than elsewhere. There is one exception, hyperostosing en plaque meningioma of the greater sphenoid wing, which is associated with a very striking sclerotic response, or hyperostosis (4,5). This bony reaction indicates actual through and through tumor involvement of the bone, and has a very characteristic radiographic appearance, including intraorbital extension (Fig. 6) (1,4,5). While most meningiomas remain within only the dura, in addition to the hyperostosing en plaque meningioma of the greater sphenoid wing, some meningiomas may invade the CSB in an aggressive, almost malignant manner (1,4). The imaging for such invasion can be fairly dramatic, and if the diagnosis of meningioma is unknown, the radiologic diagnosis may be more difficult (Fig. 7). Such meningiomas may achieve massive size, or extend directly through the bone, or through neural foramina, into extracranial spaces such as the pterygopalatine fossa, orbit, or masticator space. Such lesions may be grossly destructive of bone (Fig. 7). It should be kept in mind, for any location, that dural metastases may be radiographically indistinguishable from meningioma. In a known cancer patient, what may resemble on a first imaging study a meningioma may be a dural metastasis, and the finding of growth on serial imaging should raise that possibility (Fig. 8) (6,7). Finally, another lesion that might be radiographically confused with meningioma is the rare, highly vascular malignancy, hemangiopericytoma. These also have the potential to be highly destructive of the cranial base (Fig. 9). Another common benign CSB lesion is the pituitary adenoma (1,8–11). Some macroadenomas (those greater than 1 cm in size), often but not always endocrinologically nonfunctioning, may achieve a very large size, and be invasive of the central skull base. Such cases may present a diagnostic

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Figure 3 Olfactory neuroblastoma (esthesioneuroblastoma) in the upper nasal cavity in a 47-year-old man complaining of anosmia and subsequent development epistaxis and congestion. (A) Axial postcontrast CT demonstrating relatively nondescript and nonenhancing soft tissue filling left nasoethmoid region and to a lesser extent the right nasal cavity (arrows). There is an enlarged, airless left ethmoid air cell mucocele that is slightly less dense than the tumor (arrowhead). Notice that there is no overt bone destruction evident, though there could be in this entity. (B–D) Axial T1 -weighted, T2 -weighted, and postcontrast axial T1 -weighted MR images, respectively, demonstrate the characteristic findings of sinonasal malignancy. The lesion is isointense to muscle and other soft tissue (arrows in B). Notice on the T2 -weighted image (arrows in C), the tumor is relatively isointense to brain and not nearly as high signal or hyperintense as obstructed secretions in the left ethmoid mucocele (arrowheads in C). (D) The lesion enhances brightly, whereas obstructed secretions in the mucocele do not (arrowhead in D). (E) Coronal postcontrast T1 -weighted MR image shows intracranial extension through the cribriform plate and ethmoid roof (arrows).

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Figure 4 53-year-old woman presenting with decreased visual acuity in the right eye. Dx: optic sheath/canal meningioma with involvement of the clinoid region and planum sphenoidale. (A–C) Axial, coronal, and sagittal T1 -weighted postcontrast MR images, respectively, demonstrate enhancing tumor in a characteristic elongated manner along the surface of the right optic nerve (arrows in A). Tumor extends up onto the planum as can be seen by arrows in B and C.

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Figure 5 Noninvasive greater sphenoid wing meningioma in an asymptomatic 75-year-old woman. This lesion was picked up on a routine lymphoma screening CT. (A and B) Axial and coronal postcontrast T1 -weighted MR images, respectively, reveal a homogenously brightly enhancing mass lesion (arrows) along the left parasellar and greater sphenoid wing region. There is an obvious dural tail or enhancement of dura extending away from the tumor, characteristic but not diagnostic of meningioma (arrowhead in A).

challenge to the radiologist, and there is no specific imaging feature, other than a tendency for the lesion to encompass the sella. It is important, therefore, for the radiologist to consider pituitary adenoma when confronted with a large, destructive central skull base mass, and to at least check hormone levels, specifically prolactin, in such cases (Fig. 10). One relatively uncommon benign tumor that arises near and may secondarily affect the CSB is the juvenile angiofibroma. These highly vascular tumors typically present with epistaxis in teenage males and have very characteristic imaging features (1,12). They arise in or near the sphenopalatine foramen, the opening between the pterygopalatine fossa and the nasal cavity. There are often tumor components in the nasal cavity and nasopharynx, and these aggressive lesions often invade into the clivus and sphenoid sinus. Because of the hypervascularity, these lesions enhance brightly on CT, and have small foci of low signal, so-called flow voids on MR, representing rapidly flowing arterial supply to the tumor (Fig. 11). Vascular studies such as catheter angiography, CT angiography, or MR angiography have value in providing

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a surgical road map or to facilitating preoperative embolization [Fig. 11(E)]. One final intracranial (sometimes both intra- and extracranial) lesion to affect the CSB is the neural sheath tumors arising from the trigeminal nerve, schwannoma, and neurofibroma (2,6). These usually benign lesions can arise from the main trigeminal trunk and extend variously along its branches or may arise within one of its three divisions. Such lesions often cause widening of foramina or other benign bony remodeling (rather than destruction) of the central skull base (Fig. 12). Among malignancies that may affect the CSB, which arise primarily extracranially, probably the most common is nasopharyngeal carcinoma (NPC) (1,8,13,14). Given its location immediately inferior to the clivus, upward spread of NPC very commonly involves the CSB. In some cases, the nasopharyngeal component may be relatively small (Fig. 13), and in such cases the radiologist must bear in mind the possibility of NPC. As opposed to some malignancies that tend to destroy bone, and despite the fact that NPC may do this, it often has a tendency to infiltrate in a nondestructive manner (15). For this reason, MR imaging is more sensitive than CT for detecting such involvement (Fig. 14). Of course, NPC can also cause skull base destruction, in which CT has a role as well (15). Because MR is also more sensitive for detecting intracranial spread via perineural and direct mechanisms, it is our preference to use MR as the main imaging modality in cases of NPC (16). Another type of extracranial malignancy that may secondarily affect the CSB is head and neck malignancy with perineural tumor spread (PNS) (17–19). This is a very extensive topic, and a thorough description is beyond the scope of this chapter. The most common manner in which the CSB is affected is in a patient with a known, or sometimes unknown, malignancy of the face (most commonly in a V2 distribution, like the cheek) (Fig. 15) or a lesion of the lower lip or palate (or other less common mucosal surface). Common tumor types include squamous cell carcinoma, adenoid cystic carcinoma, and desmoplastic melanoma (18). Such lesions may spread proximally, toward the CNS, along the branch of the trigeminal nerve that innervates the primary site. For the cheek and palate, this means the infraorbital (Fig. 15) or palatine nerves (Fig. 16), respectively, with tumor spread to the pterygopalatine fossa (Figs. 15 and 16). From here, tumor can spread

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Figure 6 Hyperostosing en plaque greater sphenoid wing meningioma in a 54-year-old woman presenting with left-sided headaches and progressive visual loss in the left eye. (A) Axial bone window CT image demonstrates gross bone thickening or hyperostosis of the left greater sphenoid wing and lateral orbital wall (arrows). (B and C) Axial precontrast and fat-suppressed postcontrast T1 -weighted MR images, respectively, show that the bone marrow is markedly abnormal (arrows in B) as opposed to the normal marrow in the right sphenoid triangle depicted with an arrowhead. Enhancing soft tissue (extraosseous) tumor can be seen in the left orbit and behind the greater sphenoid wing in C (arrows).

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Figure 7 Massive skull base meningioma in a 61-year-old woman presenting with progressive vision loss in the left eye and subsequent development of proptosis. (A) Axial CT bone window demonstrates a permeative type of bone destruction (arrows). (B–D) Axial T1 -weighted, T2 -weighted, and postcontrast axial T1 -weighted MR images, respectively, demonstrate extensive soft tissue tumor infiltrating the nasoethmoid region, left cavernous sinus, and left orbit (arrows). Note the dural tail along the incisura and sphenoid wing (arrowheads in D). (E) Coronal postcontrast MR image demonstrates the extensive nature of this lesion.

posteriorly along the main trunk of the maxillary nerve, through foramen rotundum, and into the cavernous sinus or further posteriorly into Meckel cave or even onto the main trigeminal trunk (18). For lesions of the lower lip or gingiva, tumor can access the inferior alveolar branch of V3 , and then upward onto the main trunk of the mandibular nerve

(Fig. 17), through foramen ovale, and into Meckel’s cave. Though perhaps best considered in the temporal bone section, the facial nerve may also be involved with tumor spread, mainly from tumors originating within, or that spread to, the parotid gland (Fig. 18). Recognition of this type of spread is a critical function of the radiologist because failure to recognize,

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Figure 9 Masticator space and middle cranial fossa/skull base hemangiopericytoma in a 45-year-old man who presented with headache, nausea, and vomiting. Coronal postcontrast T1 -weighted MR image demonstrates a large, moderately enhancing mass encompassing the middle cranial fossa and obvious destruction through the calvarium (arrows). There is a central area of nonenhancement, representing necrosis. This is indistinguishable from an aggressive meningioma but proved to be a hemangiopericytoma at surgery.

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Figure 8 Dural-based planum sphenoidale metastasis initially believed to be meningioma in a 47-year-old woman with metastatic breast carcinoma. (A) Sagittal T1 postcontrast MR image demonstrates a small enhancing lesion along the planum sphenoidale (arrow). Note similarity with the meningioma shown in Figure 4. (B) Sagittal T1 -weighted postcontrast MR image 8 months later shows clear progression of this lesion (arrows), which prompted surgery.

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Figure 10 Massive pituitary adenoma in a 48-year-old man who presented with only severe headache. (A) Axial CT bone window reveals a large destructive process involving the central skull base (arrows). (B and C) Axial T2 and postcontrast T1 -weighted MR images, respectively, reveal a large minimally and somewhat heterogeneously hyperintense and brightly enhancing mass involving virtually the entire central skull base. (D) Sagittal image revealing complete replacement of the sphenoid sinus and clivus. Notice while the lesion encompasses the sella (asterisk), there is no suprasellar extension, and thus the diagnosis of pituitary adenoma less than obvious. In this patient, the prolactin level was 344214, indicating prolactinoma.

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Figure 11 Juvenile angiofibroma in a 20-year-old man presenting with bilateral nasal congestion but no epistaxis. (A) Axial CT bone window revealing a large mass with destruction of the mid and left aspect of the central skull base (arrows). (B) Contrast-enhanced CT soft tissue window reveals a moderately enhancing mass lesion corresponding to the areas of bone destruction (arrows). (C and D) Axial T2 - and T1 -weighted postcontrast MR images, respectively, reveal a hyperintense, enhancing lesion. Central areas of signal void represent blood vessels and are so-called “flow voids” (arrows in C). (E) Lateral view of an external carotid angiogram in a different patient with a juvenile angiofibroma reveals marked tumor hypervascularity.

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Figure 12 Massive trigeminal/skull base schwannoma in a 44-year-old man who presented with right eye swelling and intermittent visual complaints. (A) Axial CT bone window reveals benign bony remodeling (arrows) with the lateral wall the sphenoid sinus pushed medially. (B–D) Axial T2 postcontrast, axial, and coronal postcontrast T1 MR images, respectively, reveal a very large heterogeneously T2 hyperintense and brightly enhancing extra-axial mass lesion centered at and above the floor of the right middle cranial fossa. The coronal image shows obvious tumor extending into the sphenoid sinus (arrow) and elevation the right temporal lobe (arrowhead). This was not a straightforward diagnosis, but the lack of bony destruction or edema in the brain argued for a slow growing process such as, in this case, schwannoma.

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Figure 13 Nasopharyngeal carcinoma with massive central skull base destruction in a 55-year-old man presenting with headache and subsequent development of diplopia. (A) Axial CT bone window reveals gross destruction of the central skull base (arrows). (B) Axial T1 postcontrast MR image demonstrates a small mass in the right fossa of Rosenm¨uller (arrow). There is also abnormal enhancement in the clivus, indicating tumor involvement (arrowhead). (C and D) Axial T1 and T1 postcontrast MR images, respectively, show replacement of the normal T1 hyperintense bone marrow of the clivus (asterisks in C), and heterogeneously bright contrast enhancement. Skull base involvement in NPC indicates T3 staging.

very common unfortunately, can have a very adverse effect on treatment outcome. Commonly, PNS occurs in the form of, or at the time of, tumor recurrence (Fig. 15), not necessarily at the time of diagnosis or initial therapy. In other cases, sadly, PNS represents progression of disease that was unrecognized initially, and thus not addressed clinically. In terms of malignancies arising in the skull base directly, metastases are the most common (3). Such lesions may be lytic or blastic, depending on the primary malignancy, but both are common (Fig. 19). The imaging is generally straightforward, except to say that small lesions may be subtle. Primary CSB malignancies include chordoma and chondrosarcoma. Chordomas are notochord-derived malignancies that occur in the sacrococcygeal region (50%), spine (15%), and clivus (35%) (1,3). They may also occur off midline occasionally. Most chordomas occur in mid-late adulthood.

Radiographically, they appear as expansile lytic lesions, with internal areas of fragmented bone that are most readily seen on CT (Fig. 20), and on MR they have characteristic T2 signal hyperintensity (Fig. 20). A soft tissue mass is usually present, and some degree of extracranial and/or intracranial extension is typical, the latter often resulting in brain stem compression. Chondrosarcomas may also arise in the CSB (1,3). These cartilage-derived malignancies tend to occur in proximity to the various synchondroses. Common locations include the petroclival fissure and the upper nasal septum/vomer region (Figs. 21–23). They may also involve the greater sphenoid wing more laterally, often with masticator space components (Fig. 23). In terms of imaging appearance, many, though not all, will have a mineralized chondroid matrix seen in chondroid tumors anywhere—a grouping of seemingly organized calcific elements (Figs. 21 and 23). On MR, though the signal intensity varies, there is often marked heterogeneity, particularly on postcontrast T1 -weighted images (Fig. 22). A lesion in the appropriate location and with typical imaging features should suggest the possibility of chondrosarcoma.

POSTERIOR CRANIAL BASE

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Figure 14 Nasopharyngeal carcinoma. (A) Axial CT bone window shows no discernible abnormality in the lower clivus. (B) Axial T1 -weighted MR image shows abnormal hypointense signal in the right side of the clivus (arrows), indicating tumor infiltration. The primary cancer is also visible (squiggly arrow in B). On the T1 MR image, the marrow should be hyperintense or white in color, as seen in the left side of the clivus and left mandibular condyles (asterisks in B). Also, note metastatic disease in the right parotid region (arrowhead in B), and retained secretions in the right mastoid air cells, owing to Eustachian tube obstruction (arrows in A). This case demonstrates the utility of MRI to evaluate for skull bass infiltration in cases where CT may be normal.

For the purpose of this chapter, the posterior cranial base will include the temporal bone, and the lower occipital structures such as the foramen magnum, hypoglossal canal, and the jugular foramen/carotid canal. There is a large variety of tumors that may affect the temporal bone. In terms of extracranial lesions affecting it secondarily, lesions of the external ear are probably the most common (20). Periauricular lesions may also grow into the temporal bone. Histologic tumor types include squamous cell, adenoid cystic carcinoma of the external canal, melanoma, and basal cell carcinoma (20). When imaging skin lesions in and around the ear, CT with high-resolution bone windows is critical to assess the bony structures (Fig. 24.) The temporal bone may also be infiltrated by petrous region meningiomas. While the diagnosis of meningioma is often fairly straightforward, occasionally a meningioma may be primarily infiltrative, without much dural disease; in such cases the diagnosis can be difficult as the imaging may be

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Figure 15 Recurrent squamous cell carcinoma in the left premaxillary region in a 62-year-old man who had previously undergone Mohs resection, now presenting with left facial (V2 ) paresthesias. This case demonstrates perineural tumor spread along the infraorbital branch of the maxillary nerve. (A) Axial postcontrast CT image demonstrates a subcutaneous mass anterior to the left maxillary sinus (straight arrow). There is also abnormal density within the infraorbital foramen and anterior aspect of the left infraorbital canal (curved arrow). (B and C) Axial pre- and postcontrast T1 -weighted MR images, respectively, reveal enhancing tumor in a premaxillary region (small arrows) as well as abnormal signal and enhancement along the course of the infraorbital nerve (curved arrow). More posteriorly, tumor can be seen actually coursing into the pterygopalatine fossa (large arrow in B). (D) Coronal T1 postcontrast MR with fat suppression reveals enlargement of the infraorbital nerve along the orbital floor or maxillary sinus roof (arrow).

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Figure 16 Adenoid cystic carcinoma of the left hard palate with perineural spread along the palatine branches of the maxillary nerve in a 55-year-old whose dentist discovered a palatal mass. There was no clinical evidence of neuropathy. (A) Coronal T1 postcontrast MR image reveals a mass in the left side of the hard palate (arrow). (B) Axial CT bone window shows enlargement of the left greater palatine foramen (arrow). Note the normal right greater palatine foramen (arrowhead). (C) Axial postcontrast T1 MR image shows abnormal enhancement in the left pterygopalatine fossa (arrow), indicating perineural tumor spread to at least this level. From here, tumor can spread posteriorly, in a retrograde fashion, either through foramen rotundum or along the Vidian nerve.

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Figure 17 Recurrent right lower lip squamous cell carcinoma in a 42-year-old man who had previously undergone biopsy and Mohs surgery as well as subsequent wedge resection and neck dissection for prior recurrences. (A) Axial T1 -weighted MR image reveals a large recurrence in the right lower lip, very close to the mental foramen (arrows). Note the probable tumor infiltration of the right mandibular marrow cavity (arrowheads). (B and C) Axial pre- and postcontrast T1 -weighted MR images, respectively, reveal abnormal signal intensity and enhancement in the mandibular foramen for the right inferior alveolar nerve (arrows). (D) Coronal T1 -postcontrast MR image reveals tumor extending in an upward and medial direction from the mandibular foramen along the course of the main mandibular nerve trunk (arrows), approaching foramen ovale (arrowhead).

Chapter 4: Imaging of Skull Base Neoplasms

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Figure 18 Parotid salivary duct carcinoma associated with perineural spread along the descending segment of the right facial nerve in a 67-year-old man who presented with right-sided facial neuropathy for which an initial MR was said to be negative. (A) Axial noncontrast T1 -weighted MR image reveals a mass in the right parotid gland (arrows). Note the posterior extension of disease toward the stylomastoid foramen (curved arrow). (B and C) axial T1 postcontrast MR images at progressively cephalad positions revealing enlargement and excessive enhancement of the right descending facial nerve segment (arrows in B and C).

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Figure 19 Two patients with skull base metastasis. (A) Axial CT bone window demonstrating a large lytic and destructive metastasis from lung carcinoma (arrow). (B) Axial CT bone window in a patient with metastatic breast carcinoma showing blastic lesions in the clivus (arrows) and the right side of the central skull base lateral to the Vidian canal (arrowhead).

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quite nonspecific (Fig. 25). In such cases, only biopsy can differentiate from infiltrative malignancies such as sarcoma or leukemic infiltration (Fig. 26). Intrinsic temporal bone tumors are relatively uncommon, though of course, metastases can occur in the temporal bone (Fig. 27). Vestibular schwannoma will be addressed below in the discussion of cerebellopontine lesions. However, schwannomas of the facial nerve typically present in the intratympanic portion of the facial nerve, and thus deserve mention in a discussion of temporal bone tumors. These benign lesions typically present with facial neuropathy (21). Commonly involved segments include the geniculate ganglion, descending facial nerve, and the greater superficial petrosal nerve. The latter is a branch of the facial nerve containing preganglionic parasympathetic fibers destined to innervate the lacrimal gland and vasomotor nerves of the nasal cavity and palate (22). The nerve emerges from the geniculate ganglion and exits the facial hiatus to become intracranial, along the sphenopetrosal synchondrosis in the floor of the middle cranial fossa (22). A tumor along this portion of the facial nerve can present as an extraaxial mass along the roof, or intracranial surface of the petrous bone, and may be confused radiographically with

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Figure 20 Clival chordoma in a 40-year-old woman complaining of occipital region headache radiating to the right neck. (A) CT bone window demonstrates a large destructive lesion involving the clivus (arrows). (B–D) Axial T1 , T2 , and postcontrast T1 -weighted MR images, respectively, reveal a well-circumscribed mass lesion in the central skull base that is isointense on T1 , hyperintense on T2 , and enhances moderately with some heterogeneity (arrows). The very bright signal on T2 is very suggestive of chordoma.

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Figure 21 Nasoethmoid chondrosarcoma in a 38-year-old woman presenting with progressive sinus symptoms including congestion and epistaxis. (A) Axial CT bone window reveals a destructive mass with internal somewhat organized areas of calcification representing the chondroid matrix (arrows). (B) Axial T2 -weighted MR image revealing a relatively homogeneous isointense mass in the nasoethmoid region (arrows). Chondrosarcomas are often, but not always, heterogeneous on T2 and postcontrast MR images, as in the next figure.

Figure 22 Nasoethmoid chondrosarcoma in a different patient. Axial T1 postcontrast MR image reveals the marked heterogeneity that is characteristic of some chondrosarcomas. Obviously the appearance can be variable.

a meningioma. Recognizing that branches of the facial nerve or enlargement of the facial hiatus, along with the history of facial neuropathy, should suggest the correct diagnosis (Fig. 28).

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Figure 24 Adenoid cystic carcinoma of the left external auditory canal in a 60-year-old man with a 2-year history of “ear congestion” and intermittent otorrhea. (A) Axial postcontrast CT (soft-tissue window) demonstrates a large mass about the left external canal and external ear (arrow). (B) Axial CT bone window reveals gross destruction of the temporal bone (arrow).

Intracranial lesions can involve the posterior cranial base by either growing anteroinferiorly or by arising adjacent to, say, the temporal bone. Examples of anteroinferior extension include posterior fossa meningiomas, which have a tendency to grow through neural foramina such as the jugular foramen (Fig. 29) (4). The meningioma may or may not have a bony reaction, often not, and may be difficult to distinguish from nerve sheath tumors. Nerve sheath tumors, of course, grow through neural foramina by their nature and may involve either the nerves within the jugular foramen (Fig. 30) or less commonly the hypoglossal canal (Fig. 31). These lesions cause a characteristic nondestructive widening or expansion of the neural foramina as seen on CT, and have other typical imaging features on CT and MR (Fig. 30). Other benign intracranial neoplasms adjacent to the temporal bone include the cerebellopontine lesions. These comprise vestibular schwannoma, meningioma, and epidermoid cyst. Vestibular schwannomas are quite variable in size and shape, but generally involve the internal auditory canal (IAC) to some extent. Some are entirely intracanalicular (within the internal auditory canal), and others involve primarily in the cistern but extend into the IAC (Figs. 32 and 33). Vestibular schwannomas typically enhance brightly, but may contain areas of cystic change or necrosis, which do not

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Figure 23 Left central skull base/masticator space chondrosarcoma in a 51-year-old woman presenting with severe headaches. (A) Coronal bone window CT revealing a mass destroying the floor of the middle cranial fossa (arrow). Note the marked chondroid calcifications. (B–D) Axial T1 , T2 , and postcontrast T1 -weighted MR images, respectively, reveal a somewhat heterogeneous mass that is isointense on T1 , hyperintense on T2 , and enhances brightly following gadolinium administration. This is a fairly classic appearance for chondrosarcoma given the heterogeneity as well as chondroid calcifications.

Chapter 4: Imaging of Skull Base Neoplasms

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Figure 25 Infiltrating neoplasm of the right temporal bone. The diagnosis ultimately proved to be meningioma. (A) Axial CT bone window revealing a destructive, somewhat permeative pattern of bony infiltration in the right temporal bone (arrows). (B and C) Axial pre- and postcontrast T1 -weighted MR images, respectively, show a T1 isointense, mildly enhancing mass replacing the normal temporal bone structures and lower clivus (arrows). The imaging is nonspecific and the differential diagnosis should include other entities such including metastasis (see Fig. 26).

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Figure 26 Two patients with nonspecific infiltrative masses of the temporal bone. (A) Axial postcontrast, T1 -weighted MR image reveals a patient with leukemic infiltration of the right temporal bone (arrow). (B) Axial postcontrast T1 -weighted MR revealing a large enhancing mass in the left temporal bone (arrow) that proved to be a high-grade sarcoma. Again, the imaging for these lesions as well as that for the meningioma in Figure 25 is nonspecific.

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Figure 27 Metastasis to the left temporal bone resulting in facial neuropathy in a patient with metastatic carcinoma of the cervix. (A) CT bone window obtained for evaluation of cervical lymphadenopathy, but prior to the onset of facial palsy, showing normal descending left facial nerve canal (arrow). (B) Axial CT bone window following onset of left facial neuropathy. Note the new destructive lytic lesion corresponding to the location of the left descending facial nerve canal (arrow).

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Figure 28 Facial schwannoma with greater superficial petrosal nerve and middle cranial fossa involvement in a 53-year-old woman with a manyyear history of facial neuropathy and progressive hearing loss. (A) Axial CT bone window reveals enlargement of the facial hiatus for the left greater superficial petrosal nerve (arrow). There is a soft tissue mass at the location for the geniculate ganglion (arrowhead). (B) Axial postcontrast T1 -weighted MR image reveals a homogeneous, brightly enhancing mass lesion with a component in the middle cranial fossa (large arrow), the labyrinthine portion of the facial nerve (small arrow), and the internal auditory canal (arrowhead).

enhance. Of course, bilateral vestibular schwannomas as associated with type II neurofibromatosis (Fig. 33), along with schwannomas of other cranial nerves, and meningiomas (6). The most common jugular foramen neoplasm, of course, is the glomus tumor (2). These so-called paragangliomas are hypervascular, usually benign but aggressive tumors that arise from paraganglia cells in various location in the body, but in the head and neck, typically along the carotid sheath (glomus caroticum or vagale), or for this discussion, the jugular foramen (glomus jugulare). On CT, these cause a typical “moth-eaten” or permeative pattern of bone destruction (Fig. 34) that is quite characteristic (2). They also enhance quite brightly due to their hypervascular nature. On MR, when 2.5 cm or so is exceeded, they will usually have internal flow voids representing their vascularity (Fig. 33). Coronal CT reconstructions are probably the best way to determine if the lesion is extending into the hypotympanum (glomus jugulotympanicum). There is a role for angiographic studies, whether by catheter or with MR/CT techniques, to provide

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Figure 29 Left-sided CP angle meningioma with involvement of the jugular foramen in a 43-year-old woman presenting with tinnitus and progressive left-sided hearing loss. (A and B) Axial and sagittal postcontrast T1 -weighted MR images, respectively, reveal a dural-based extra axial mass lesion in the left CP angle (large arrows). Note extension into the jugular foramen (small arrow in B). There is also a so-called dural tail of enhancement best seen in the axial image extending laterally from the lesion (smaller arrow in A). (C)

Figure 32 Assortment of vestibular schwannomas. (A) Axial postcontrast T1 -weighted MR image through the posterior fossa reveals a small intracanalicular enhancing mass representing a vestibular schwannoma in the right internal auditory canal (arrow). (B) Axial postcontrast T1 -weighted MR image revealing a dumbbell-like mass extending from the CP angle into a widened left internal auditory canal (arrow). There appears to be a small dural tail that is extending posterolaterally, away from the lesion; as such, a dural tail is not specific for meningioma and can be seen in other lesions. (C) Axial postcontrast T1 -weighted MR image shows a larger vestibular schwannoma that is primarily cisternal in location with only minimal extension into the IAC (arrow). Acoustic vestibular schwannomas come in different sizes and shapes. (A)

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Figure 30 Jugular schwannoma in a 52-year-old man presenting with a hissing sound in the left ear and left-side sensorineural hearing loss. (A) Axial CT bone window reveals benign expansion and remodeling, without destruction, in the left jugular foramen (arrow). (B) Sagittal postcontrast T1 -weighted MR image shows a heterogeneously but brightly enhancing mass lesion extending from the posterior fossa through a widened jugular foramen (arrows) and into the upper carotid space.

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Figure 31 Left-sided hypoglossal schwannoma in a patient presenting with headache and left tongue fasciculations. (A) Axial postcontrast T1 weighted MR image through the posterior fossa reveals a dumbbell-shaped enhancing tumor with a component in the cerebellomedullary angle (white arrows) and extending out through the hypoglossal canal into the upper carotid space (black arrow in B).

Figure 33 Neurofibromatosis type II in a patient with long-standing disease and multiple manifestations. Axial T1 postcontrast MR image through the posterior fossa and skull base reveals bilateral acoustic vestibular schwannomas, with a larger right-sided lesion (arrowhead) and the left-sided lesion intracanalicular (small arrow). Incidental note is also made of an enhancing mass within the right cavernous sinus (curved arrow) representing a trigeminal schwannoma, and only partially seen on this image, a large plexiform neurofibroma involving the upper eyelid (squiggly arrow).

Chapter 4: Imaging of Skull Base Neoplasms

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Figure 34 Massive skull base glomus tumor in a 32-year-old woman with long-standing occipital region headache and progressive lower cranial neuropathies. (A) Axial CT bone window reveals a permeative type of bony destruction in the right temporal bone in the region of the jugular foramen (arrow). (B and C) Axial T2 and sagittal T1 postcontrast MR images, respectively, reveal a large mass lesion. Note internal areas of heterogeneity, some of which are dot like and some of which are curvilinear (arrows) representing flow voids within this hypervascular lesion. The sagittal image nicely demonstrates inferior extension into the upper carotid space. (D) Axial CT bone window through the temporal bone in a different patient with a jugular foramen glomus tumor (black arrows) with extension into the tympanic cavity (white arrows). As such this is properly termed a glomus jugulotympanicum.

vascular road mapping preoperatively or to facilitate embolization.

SUMMARY Tumors of the skull encompass a huge variety of lesions, and even for a given diagnosis, the imaging appearance can vary. Because of this fact and the often nonspecific nature of imaging findings, diagnosis is not always possible prior to biopsy. It is the radiologist’s job to confirm the presence of disease and to define the extent of tumor with precision. For many cases, this will suggest a likely diagnosis. It is hoped through this chapter that the reader has gained an appreciation and healthy respect for the spectrum of imaging findings associated with skull base neoplasms. The skull base radiologist must accept that they will not always be correct, and only through experience can one learn the many nuances of this field. As difficult as initial diagnosis is, posttreatment and especially postoperative imaging in the patient population is even more difficult. There is no substitute for experience and, frankly, the wisdom born of error. REFERENCES 1. Ginsberg LE. Neoplastic diseases affecting the central skull base: CT and MR imaging. Am J Roentgenol. 1992;159:581–589. 2. Harnsberger HR, Wiggins RH, Hudgins PA, et al. Diagnostic Imaging. Head and Neck, 1st ed. Salt Lake City, UT: Amirsys, 2004:1 v. 3. Som PM, Brandwein MS. Tumors and tumor-like conditions. In: Som PM, Curtin HD, eds. Head and Neck Imaging. St. Louis: Mosby, 2003. 4. Ginsberg LE, Moody DM. Meningiomas: Imaging. In: H. WR, S. RS, eds. Neurosurgery. New York: McGraw-Hill, 1996:855–872. 5. Kim KS, Rogers LF, Goldblatt D. CT features of hyperostosing meningioma en plaque. Am J Roentgenol. 1987;149:1017– 1023. 6. Ginsberg LE. Contrast enhancement in meningeal and extra-axial disease. Neuroimaging Clin N Am. 1994;4:133–152.

7. Laidlaw JD, Kumar A, Chan A. Dural metastases mimicking meningioma. Case report and review of the literature. J Clin Neurosci. 2004;11:780–783. 8. Curtin HD, Rabinov J, Som PM. Skull base: Embryology, anatomy, and pathology. In: Som PM, Curtin HD, eds. Head and Neck Imaging. St. Louis: Mosby, 2003. 9. Fischbein NJ, Kaplan MJ. Magnetic resonance imaging of the central skull base. Top Magn Reson Imag. 1999;10:325–346. 10. Levy RA, Quint DJ. Giant pituitary adenoma with unusual orbital and skull base extension. Am J Roentgenol. 1998;170:194–196. 11. Minniti G, Jaffrain-Rea M-L, Santoro A, et al. Giant prolactinomas presenting as skull base tumors. Surg Neurol. 2002;57:99–103. 12. Weinstein MA, Levine H, Duchesneau PM, Tucker HM. Diagnosis of juvenile angiofibroma by computed tomography. Radiology. 1978;126:703–705. 13. Ishida H, Mohri M, Amatsu M. Invasion of the skull base by carcinomas: Histopathologically evidenced findings with CT and MRI. Eur Arch Otorhinolaryngol. 2002;259:535–539. 14. Chong VF, Mukherji SK, Ng SH, et al. Nasopharyngeal carcinoma: Review of how imaging affects staging. J Comput Assist Tomogr. 1999;23:984–993. 15. Chong VF, Fan YF. Skull base erosion in nasopharyngeal carcinoma: Detection by CT and MRI. Clin Radiol. 1996;51:625–631. 16. Chong VF, Fan YF, Khoo JB. Nasopharyngeal carcinoma with intracranial spread: CT and MR characteristics. J Comput Assist Tomogr. 1996;20:563–569. 17. Ginsberg LE, Demonte F. Palatal adenoid cystic carcinoma presenting as perineural spread to the cavernous sinus. Skull Base Surg. 1998;8:39–43. 18. Ginsberg LE. Imaging of perineural tumor spread in head and neck cancer. In: Som PM, Curtin HD, eds. Head and Neck Imaging. St. Louis: Mosby, 2003. 19. Ginsberg LE. Imaging of perineural tumor spread in head and neck cancer. Semin Ultrasound CT MR. 1999;20:175–186. 20. Dinehart SM, Jansen GT. Cancer of the skin. In: Myers EN, Suen JY, eds. Cancer of the Head and Neck. Philadelphia, PA: W.B. Saunders, 1996:143–159. 21. Ginsberg LE, DeMonte F. Diagnosis please. Case 16: Facial nerve schwannoma with middle cranial fossa involvement. Radiology. 1999;213: 364–368. 22. Ginsberg LE, De Monte F, Gillenwater AM. Greater superficial petrosal nerve: Anatomy and MR findings in perineural tumor spread. Am J Neuroradiol. 1996;17:389–393.

5 Head, Neck, and Neuro-otologic Assessment of Patients with Tumors of the Skull Base: Clinical Examination, Auditory Testing, Vestibular Testing, and Equilibrium Paul W. Gidley

complaint of ear pain, and only after a careful history and physical examination does one discover the cause: vocal fold malignancy.

INTRODUCTION The art of history taking, physical examination, and creation of a differential diagnosis develops over one’s practice. Key to this art is the understanding of the subtleties of symptoms and signs, especially with neurologic diseases. This chapter will discuss the basics of the neuro-otologic examination. Sitespecific symptoms and signs will be explored in order to help the physician learn the cause of these maladies. This chapter is meant to be a foundation from which one can work toward a proper differential diagnosis and treatment plan for each patient. The interaction between physician and patient establishes the basic rapport and tenor of the physician-patient relationship. This interaction is supplanted and not replaced by technology. The daily and long-term outcomes from treatment are readily measured and tracked by noting symptoms and signs of disease. This is true whether at the bedside or in the outpatient setting. It is assumed that the reader, being either a resident or well-seasoned practitioner, is already familiar with the basics of history and physical examination. This chapter’s objectives are to discuss the physical signs associated with neuro-otologic disease and to discuss the ancillary audiometric, vestibular, and electrophysiologic tests used to discern disease processes. Special attention is paid to the cranial nerve examination. This chapter will not discuss individual disease states except to discuss the signs and symptoms that are indicative of a particular disease process.

Head, Scalp, and Skin Occasionally, the obvious does escape our attention. The head and neck are covered by skin, but occasionally this skin is overlooked to examine instead the ear canals or nasal passages. The sun-exposed portions need to be examined for premalignant or malignant conditions. Patients who have already had skin excisions need to be queried regarding the pathologic diagnosis from these sites given the propensity of melanoma and squamous cell carcinoma to metastasize or have perineural spread. At times, the skin of the head and neck provides the diagnosis, as in the case of adenoma sebaceum and tuberous sclerosis or port-wine stain and Sturge–Weber syndrome. Table 1 lists neurocutaneous disorders that affect the head and neck, their constituent findings, and genetic causes (1–9).

Eye, Orbit, and Eye Movements Typically, patients with primary eye complaints are seen first by an ophthalmologist. Certainly, patients who present with skull base tumors that affect the orbit, eye movements, or visual pathways should have a rigorous ophthalmologic evaluation. A close working relationship with a neuroophthalmologist is necessary for any skull base team. The following description of the eye examination is provided to highlight the important signs and symptoms to discover and note in patients with skull base tumors.

PHYSICAL EXAMINATION

Eye and Orbit

Due to the compact and complex regional anatomy of the head and neck, the neuro-otologic examination requires practice and experience to refine. As with a general physical examination, a head-to-toe organization is systematic and simple to perform for completeness. In doing so, cranial nerves are checked as one moves from site to site, though a dedicated and rigorous cranial nerve examination requires additional techniques and observation. On initial introduction to the patient, one might identify an obvious facial paralysis or a wet, weak or hoarse voice. Yet, the examining physician should avoid being sidetracked by these overt signs, and instead conduct a systematic review to look for all abnormalities. The reader probably has experienced the patient who has long-standing facial paralysis and whose presenting complaint is totally unrelated to that finding. Additionally, patients frequently present with a

The symmetry of the orbits and eyes should be compared. The globes should be compared to look for proptosis. The status of the lids should be examined not only for lesions but also for their conformity to the globe. Ectropion is very common with facial paralysis, and corrective measures can be performed to minimize its effects. The status of the conjunctiva should be noted for inflammation or irritation, as this too is a frequent sign accompanying facial paralysis. The size and reactivity of the pupils should be documented. This is done both with a flashlight looking for direct and indirect responses and with convergence. Visual fields can be estimated by testing peripheral vision. Lastly, an estimate of vision can be gained by testing each eye separately using a handheld Snellen eye chart that is held about 14 in from the eyes. 95

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Gidley A Listing of Neurocutaneous Disorders That Affect the Head and Neck, Their Congeners, Associated Findings, and Genetic Cause

Diagnosis

Dermatologic manifestation

Ataxia telangiectasia (1,2)

Cutaneous telangiectasia

Neurofibromatosis Type 1 (2,4)

Caf´e au lait spots

Neurofibromatosis Type 2 (5, 6)

PHACE syndrome (7)

Cutaneous and airway hemangiomas

Sturge–Weber syndrome (3,8)

Port wine stain

Tuberous sclerosis (3)

Adenoma sebaceum (facial angiomatosis)

Von-Hippel Lindau (5,9)

Associated findings

Genetic cause

Progressive neurologic deterioration Immunodeficiency High incidence of neoplasms (lymphoid tumors, 10–15%) Multiple neurofibromas Lisch nodules of the iris Optic glioma Bilateral acoustic neuromas Schwannomas of other nerves Meningiomas Ependymomas Gliomas Posterior fossa malformations (Dandy–Walker) Arterial anomalies Coarctation of the aorta and cardiac defects Eye abnormalities Leptomeningeal angioma Choroidal angioma Epilepsy (80%) Learning disabilities Epilepsy (78%) Learning disabilities Giant cell astrocytoma Cardiac rhabdomyosarcoma Lymphangiomatosis Renal angiomyolipoma Cerebellar hemangioblastoma (60%) Retinal angiomas (60%) Renal, pancreatic cysts Renal cell carcinoma (40%) Pheochromocytomas Endolymphatic sac tumors (ELST)

ATM

17q11.2-Neurofibromin

NF2-22q12.2-Merlin

?X-linked dominance ?Developmental disorder

Sporadic ?somatic mutation

TSC1-9q34-hamartin TSC2-16p13.3-tuberin

VHL-3q 11-“VHL protein”

? Indicates possible.

nystagmus (13). In pendular nystagmus, the two phases of nystagmus are of equal length. Jerk nystagmus, which has more relevance in this discussion, has two components: a slow phase followed by a fast phase. Its direction is named for the direction of the fast component. The primary plane or axis of nystagmus is described as horizontal, vertical, rotatory, or direction changing. Classically, horizontal nystagmus is associated with peripheral lesions. The fast component is toward the unaffected ear. Vertical and direction-changing nystagmus are generally signs of central pathology. The time of onset can be described as spontaneous (occurring without provocation), latent (meaning there is some delay in onset, usually after a change in position), gaze-evoked (brought out with certain eye movements), or positional (brought out by certain positions).

Eye Movements Normal eye movements depend on the equal function of the cranial nerves III, IV, and VI and their innervated muscles. A basic test of eye movements includes having the patient follow the examiner’s finger. All of the extraocular muscles are tested in nine different positions (straight ahead, right, left, up, down, as well as diagonally right up right down, left up and left down) (10). The cranial nerves, their muscles, and their actions are noted in Table 2 (11).

Nystagmus Nystagmus is an involuntary, rhythmic movement of the eyes, and the term is derived from the Greek word nystagmos for nodding (12). Generally, nystagmus can be divided into two large categories: jerk nystagmus and pendular Table 2 Eye Movements: The Cranial Nerves, Muscles, Actions, and Deficits Cranial nerve III—oculomotor

Muscle Medial rectus Superior rectus Inferior rectus Inferior oblique

III—oculomotor, parasympathetics VI—superior oblique

Ciliary muscle Superior oblique

VI—abducens

Lateral rectus

Source: Ref. 11.

Action Adduction 1. Elevation 2. Adduction, intorsion 1. Depression 2. Adduction and extorsion 1. Elevation 2. Extorsion and abduction Constriction of the pupil 1. Depression 2. Intortion and abduction Abduction

Deficit Eye is outward, downward, and dilated; upper lid ptosis

Skew deviation, head tilted toward weak side Cannot move eye laterally past midline

Chapter 5: Head, Neck, and Neuro-otologic Assessment of Patients with Tumors of the Skull Base

Spontaneous nystagmus represents an imbalance in the vestibular-ocular reflex (VOR) and can be either central or peripheral in origin (14). Spontaneous nystagmus is best evaluated by examining the eyes through Frenzel lenses. These +10 diopter lenses not only magnify fine movements but also eliminate visual fixation, which could overpower a vestibular nystagmus (14). Spontaneous nystagmus that does not abate with visual fixation probably represents central pathology. Pure vertical, torsional, or linear nystagmus cannot be explained by involvement of a single canal or single labyrinth and implies a central etiology (14). Gaze nystagmus can be elicited by having the patient follow the examiner’s finger performing a “+” type movement, thus evoking either lateral gaze or upward or downward gaze nystagmus. Gaze-evoked nystagmus most often occurs as a side effect of medications or toxins (10). Horizontal gaze-evoked nystagmus usually indicates a lesion in the brainstem or cerebellum; vertical gaze-evoked nystagmus is found in midbrain lesions involving the interstitial nucleus of Cajal (15). Gaze nystagmus has been described as first degree (occurs only with gazing in the direction of the fast component), second degree (occurs in the direction of the fast component and straight ahead), and third degree (occurs in all three directions of gaze). The significance of these distinctions is that first-degree nystagmus is seen with a peripheral lesion and second- and third-degree are seen with central pathology (16). Congenital nystagmus generally beats horizontally at various frequencies and amplitudes and increases with fixation (10). Bruns nystagmus is associated with large posterior fossa tumors. This nystagmus is a coarse, large amplitude horizontal gaze nystagmus toward the tumor side and a fine, high frequency gaze nystagmus away from the tumor side (14). This is thought to be due to compression of the flocculus bilaterally (17). Dynamic vestibular imbalance can be assessed by passive head movement and observation of the patient’s eyes. Dynamic visual acuity is assessed by passively rotating the head at above 2 Hz while the patient reads a Snellen eye chart at the standard distance. A drop in visual acuity of more than one line indicates abnormal gain in the VOR (18). A computerized form of this test has also been developed (19), and might be useful as a clinical tool to separate unilateral from bilateral vestibular hypofunction. Positional nystagmus is provoked by using (Margaret) Dix-(Charles) Hallpike maneuver (20). In this test, the patient is seated on an examining table or bed. The patient is instructed to turn the head to the right side and then to recline backwards as quickly as possible. The examiner watches the patient’s eyes for any nystagmus and asks whether the patient feels dizzy. If nystagmus is present, its length of latency and duration should be noted. Once this nystagmus or dizziness disappears, the patient is asked to return to an upright sitting position. Again the eyes are examined for nystagmus. Patients who have benign paroxysmal positional vertigo will have a latent (usually 2–5 seconds), geotropic (nystagmus beats toward the ground), rotatory nystagmus that reverses (reversibility) when seated upright. The duration and strength of the nystagmus lessens with each subsequent test when performed in repetition (fatigability). Head Thrust Test The head thrust test is a bedside test to assess the VOR (21). The test is performed by asking the patient to focus on a target. The examiner gently grasps the head, and a small am-

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plitude (5–10 degree), high acceleration (3,000–4,000 degrees/ sec2 ) thrust is applied. The examiner watches the eyes at the end of the head thrust for a corrective saccade. Normal individuals do not use a corrective saccade, the eyes stay fixed on the target. Patients with vestibular hypofunction use a corrective saccade after the head thrust, and the saccade is toward the side of the lesion. This corrective saccade returns the eye to the target and indicates a decreased gain (eye velocity/head velocity) of the VOR (22). The specificity of head thrust test to identify lateral semicircular canal pathology is very high (95–100%), and it correlates 100% with surgical vestibular nerve section (23). In patients with lesser degrees of unilateral hypofunction, the sensitivity is as low as 34% to 39% while the specificity remains high as 95% to 100% (24– 26). Sensitivity of this test can be improved by 30 degrees of cervical flexion (making the horizontal canal horizontal) (22). Head-Shaking Nystagmus Head-shaking nystagmus (27) is used to demonstrate asymmetry in the velocity storage that can occur with either central or peripheral lesions. In this test, the patient’s head is shaken either actively or passively in the horizontal plane for 10 to 15 seconds with the eyes closed. After stopping and opening the eyes, nystagmus will be seen beating away from the side of the lesion (14). In this test, Frenzel lenses are indispensable since the nystagmus is often fine and fleeting. Head-shaking nystagmus can also be performed with electronystagmography, and is discussed in the electronystagmography section.

Ear Pinna and External Auditory Canal The external ear includes the pinna, the membranous external auditory meatus, and the bony ear canal. In one’s zest to examine the eardrum, the pinna might be overlooked. Around 15% to 20% of head and neck skin cancer occur on the external ear, and 55% are along the helix (28–30). The examination should not be limited to just the protruding parts of the pinna, but should also include the postauricular skin as well (Fig. 1). A distinction is made here between the external auditory meatus, which is the cartilaginous outer one-third of the ear canal, and the bony ear canal, which is the

Figure 1 Benign lesion behind left ear.

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Figure 4 Otoendoscopy showing glomus tympanicum tumor. Figure 2 Squamous cell cancer confined to the ear canal. This tumor does not extend past the eardrum into the middle ear and does not extend into the conchal bowl.

bony two-thirds of the external ear canal. The membranous meatus has a thick squamous epithelium, is hair covered, and contains the cerumen glands, while the bony canal is lined by a thin squamous epithelium without any modified sweat glands or hair (Figs. 2 and 3).

Tympanic Membrane and Middle Ear These structures are best evaluated with a handheld otoscope and an otomicroscope. Each modality gives a slightly differ-

ent, but complementary view of the ear canal and tympanic membrane. Each also allows testing of tympanic membrane movement with either a bulb attachment to the otoscope or through a Siegle otoscope viewed through the microscope. Occasionally, patients have a narrowed or oddly shaped ear canal that cannot be adequately evaluated with an oval or round speculum. For this circumstance, using either a pediatric or adult nasal speculum is helpful. Ear endoscopes have been available for the last few decades, but have not found wide use throughout the community. These endoscopes measure 6 cm in length and 2.7 or 4 mm in diameter. Zero- and 30-degree varieties are available. These endoscopes can provide a view of middle ear structures that is unparalleled and not available through a microscope or a handheld otoscope. Additionally, high-quality photodocumentation of ear canal, eardrum, and middle ear pathology can be captured easily with an endoscope (Figs. 4 and 5).

Tuning Fork Examination In a bygone era, tuning fork examination represented the state of the art in audiometric assessment. With the advent of calibrated audiometers, the tuning fork examination has

Figure 3 Squamous cell cancer filling external auditory meatus. This cancer fills much of the conchal bowl but does not extend medially past the bony–cartilaginous junction in the ear canal.

Figure 5 Cholesteatoma of left middle ear as seen with an otoendoscope.

Chapter 5: Head, Neck, and Neuro-otologic Assessment of Patients with Tumors of the Skull Base

lost its centrality in measuring a patient’s hearing. However, it has not lost its importance in giving the attentive clinician valuable information regarding hearing. While the history of otology and audiometry describes several different tuning fork tests, only the Weber and Rinne tests are performed routinely. The Weber test is performed by striking the tuning fork and then placing it on the patient’s forehead, philtrum, or upper incisors and asking the patient where the sound is heard best: right side, left side, or midline (or equally in both ears). The sound is heard better in an ear with a conductive loss or in an ear with better sensorineural hearing when no conductive component is present in the other ear. Interestingly, patients with unilateral, congenital conductive hearing loss do not have lateralization to that side. The Rinne test is performed by striking the tuning fork and then asking the patient to compare for loudness the sound produced with the fork on the mastoid versus in front of the ear canal. A normal result (also called a “positive Rinne”) is that the loudness is greater in front of the ear by air conduction than it is by bone conduction (also noted as AC > BC). In a conductive loss more than about 25 dB with a 512 Hz fork, the sound is louder on the bone than it is through air conduction (noted as a “negative Rinne” or as BC > AC). These tests are easy to perform in the outpatient clinic or at the bedside. They provide a quick assessment of hearing and can be used as a check on audiometric findings (31,32).

Nose and Nasopharynx Anterior rhinoscopy demonstrates the health of the nasal mucosa, the status of the turbinates, and the anatomy of the septum. Boggy, purplish, congested turbinates with thin, clear nasal mucus are often an indicator of allergic or irritant rhinitis. Polyps and other masses are noted. Pathology in the nose should be more closely examined with rigid nasal endoscopes. This allows evaluation of the paranasal sinus meati and permits an adequate measurement of extent of disease. The nasopharynx can be examined indirectly with a heated mirror through the oral cavity; however, only a few patients permit an adequate examination with this approach. The nasopharynx is much better assessed with endoscopes. In this circumstance, the Eustachian tube orifice, posterior and lateral pharyngeal wall, and palate movement can be examined. Palatal myoclonus is best examined with nasopharyngeal endoscopy since the mouth opening required for a peroral examination eliminates this tremor. Fine Eustachian tube endoscopes are developed and are being evaluated. They might help to shed light and treat disorders such as patulous or obstructed Eustachian tube (33).

Oral Cavity and Oropharynx Even a cursory evaluation of the oral mucosa allows examination of the state of the oral mucosa, the teeth, and the tongue. Pathologies in the oral cavity are a frequent cause of referred otalgia. Tongue protrusion and movement from side to side denotes normal hypoglossal nerve function. Fasciculations and atrophy are indicators of abnormal hypoglossal function. The protruding tongue will point to the side of the lesion. The parotid and submandibular ducts are easily assessed by examining their drainage while massaging the respective gland. The oropharynx is bounded by a plane through the hard-soft palate junction superiorly and the circumvallate papillae inferiorly. It contains the palatine tonsils, if still present, lingual tonsils, soft palate, and mucosa of the lateral and posterior pharyngeal walls. The examiner should

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note the status of this mucosa. Frequently, chronic postnasal drainage will produce cobblestoning of the posterior pharyngeal wall. The movement of the palate should be noted. Unilateral palate weakness, from a glossopharyngeal injury, will allow the uvula to be pulled toward the intact (normal) side. Gag reflex can be elicited by touching the base of the tongue or the lateral pharyngeal walls. A uvula that is bifid or that contains a thin membrana pellucida might be indicator of a submucous cleft palate. This finding warrants digital palpation of the hard palate to assess for occult cleft.

Larynx Laryngeal assessment begins with the interview, noting the patient’s voice quality. Wet, weak or breathy voices are signs of vocal fold weakness. Speech fluency, on the other hand, is directed by higher, cortical structures. Expressive aphasia from a lesion in Broca area is an example of an abnormal fluency. Dysarthria or difficult, poorly articulated speech might be due to abnormal hypoglossal or facial nerve function. A basic examination of laryngeal function includes mirror examination; however, only an exceptional patient permits an unhurried examination with this technique. Flexible fiberoptic endoscopy under topical nasal anesthetic is the preferred initial method to assess vocal fold function. Patients who have or will have vocal fold paralysis should be evaluated by a speech pathologist. Videostroboscopy provides an excellent assessment of vocal fold anatomy and function, and can discern various degrees of weakness better than flexible endoscopy. Additionally, videographic and photographic documentation of vocal fold function and appearance is much better with videostroboscopy than through a flexible fiberoptic scope. Laryngeal function is controlled by the vagus nerve. The vagus nerve is a mixed nerve carrying motor, sensory, and parasympathetic impulses. Its first branch in the neck is the superior laryngeal nerve, which has two branches: an internal laryngeal branch that carries sensation from the mucosa above the true vocal folds and an external branch that is motor to the cricopharyngeal muscles. This muscle tilts the thyroid cartilage on the cricoid cartilage and produces the tightening of the vocal fold needed to make high-pitch phonation. The remainder of the laryngeal muscles and the sensation of the vocal folds and mucosa of the tracheobronchial tree are innervated by the vagus and its inferior or recurrent laryngeal nerve. This nerve branch loops under the arch of the aorta on the left side of the neck and the subclavian on the right side. Nonrecurrent nerves (nerves that do not descend into the mediastinum before going to the larynx) have been well described. This situation occurs more commonly on the right side, and is constantly on the minds of thyroid surgeons. The recurrent laryngeal nerve innervates both the adductors and abductors of the vocal folds. For this reason, recovery from laryngeal neurotmesis might be limited due to synkinesis of laryngeal innervation. Injury or loss of vagal (and for that matter glossopharyngeal) function at the skull base can produce severe dysphagia and aspiration since both the motor and sensory functions lost, resulting in loss of the protective mechanisms of the upper aerodigestive tract.

Neck, Parotid, and Thyroid The neck and, by extension, the parotid glands should be examined by palpation for any masses or lymphadenopathy. Cervical adenopathy should be reported based on its

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location and size. For malignant disease, location and size of lymphadenopathy is important for tumor staging. The parotid glands should be palpated for any masses, especially in patients with facial paralysis. Loss of a single branch of the facial nerve is due to malignant involvement until proven otherwise. Complete facial paralysis can occur from parotid tumors at the stylomastoid foramen. Deep lobe tumors can also cause facial paralysis and can escape palpation; only imaging studies can show these tumors. The thyroid gland sits on top of the trachea, just below the level of the cricoid cartilage and above the sternal notch. Asking the patient to swallow while one palpates this part of the neck moves the gland under the examiner’s fingers. A normal gland is usually not able to be palpated. A solitary tumor should be further investigated with ultrasound and fine needle aspiration. Diffuse swelling of the gland might indicate goiter. Vocal fold paralysis associated with a thyroid nodule is due to malignant disease until proven otherwise. Lastly, the spinal accessory nerve, CN XI, function is tested. This nerve innervates the sternocleidomastoid (SCM) and trapezius muscles. To test the SCM muscle, the patient is asked to turn the head slightly to the right while the examiner applies an opposite force against the right jaw and face and palpates the strength in the left SCM. The head is turned slightly to the left to test the right SCM muscle strength. The patient should be asked to shrug shoulders while the examiner applies resistance to measure trapezius strength.

Cranial Nerves “Any symptom suggestive of cranial neuropathy must alert the clinician to the possibility of a skull base or intracranial space occupying lesion” (34). For the most part, the cranial nerve examination is performed as one progresses through the head and neck physical examination. Eye, palate, tongue, vocal fold, and shoulder/head movement have already been discussed in those sections related to each organ system. This space does not permit a discussion of the complex anatomy of the cranial nerves, their brainstem, and skull base relations. Some of this detail has been summarized in Table 3 (35–37). Here, the nerves that are not readily examined in a routine examination are described to be performed as part of a neuro-otologic examination.

Olfactory Nerve Although taste and smell provide great sensory stimulation, they are perhaps the least tested sensory functions (38). The sense of smell occurs when odorants come into contact with olfactory receptors in olfactory receptor neurons (39). The olfactory receptor neurons are bipolar cells that penetrate the cribriform plate to synapse with glomeruli cells in the olfactory bulb. These glomeruli cells then synapse with mitral cells that carry the signal into the piriform cortex. From the piriform, connections with the hippocampus, amygdala, and the orbitofrontal cortex combine to give the associated sensory, memory, or hedonic reactions (39). Tests on olfaction are becoming more important as their significance in predicting Parkinson disease and Alzheimer disease is recognized (39,40). Anosmia or the inability to smell can be evaluated based on conductive or sensorineural causes (41). Olfactory epithelium is located high inside the nose on the upper middle turbinate and roof of the nose. Odorants must be able to pass through a patent nasal airway, and the patient must be able to generate enough nasal airflow (sniff) to bring odorants into contact with the olfactory epithelium. The patient

with severe obstructive nasal polyposis represents a form of conductive anosmia since the polyps prevent any airflow through the nose. Furthermore, a laryngectomee is unable to move any air through the nasal passages since all of the airflow is through the tracheostoma. Sensorineural anosmia can be due to either damaged olfactory mucosa as might occur following a viral upper respiratory tract infection or shearing of the olfactory nerve as a result of head trauma. Tumors in the sinonasal tract and esthesioblastomas can produce anosmia through obstruction and/or destruction along the olfactory pathway. Olfactory loss from intracerebral tumors (glioma, olfactory meningioma, esthesioneuroblastoma, and adenocarcinoma) has been described (39). For this reason, patients with anosmia and a normal nasal endoscopic examination should undergo MRI imaging (39). Olfaction can be measured in several different ways. A simple test of smell might include using household products such as coffee, cinnamon, mint, or water and asking the patient to respond to the question of “Do you smell this item?” with a “yes” or “no” answer when the item is waved under the nose and closed eyes (13,42). Eighty percent of the normal population can identify the odor of coffee (34). A patient who professes not to smell anything can be further tested with ammonium in a similar fashion. Ammonium triggers response from V2 since it is a mucosal irritant. All normal patients sense the nasal irritation of ammonia (34). A “no” response in this circumstance might indicate that the patient is being less than honest in his responses. A better form of testing uses the University of Pennsylvania Smell Identification Test (43). This test uses 40 scratch and sniff odors that patients try to identify by matching to a four-option response panel. Patients are required to answer all questions and to guess at an answer even if they do not smell anything. The number of correct answers is matched in a normogram divided by gender and age range to determine the level of olfaction: normal, hyposmia, anosmia, malingering. Since there is always a one in four chance of getting any question correct through guessing, a patient who has missed all 40 questions has probably intentionally avoided correct answers (40). This test is performed with both nostrils open and thus cannot give side specific values. Nonetheless, this method of testing has been widely verified and is used for its accuracy in providing a qualitative measurement of smell (41).

Trigeminal Nerve The trigeminal nerve is perhaps the most complex nerve of the head and neck. It has origins from four different brainstem nuclei; it carries both sensory and motor functions; its three main trunks pass through three different foramina in the skull base; and each trunk has an associated parasympathetic ganglion. The trigeminal nerve has general somatic and general visceral afferent function. The somatic afferents are for cutaneous sensation of the skin of the head and neck. The first division, V1 , supplies sensation to the cornea and conjunctiva, the upper eyelid, the eyebrow, and the scalp as far posterior as the vertex. The second division, V2 , supplies sensation to the skin of the nose, cheek, upper lip, to the maxillary teeth, and to the mucosa of the nose, and the roof of the mouth. The third division, V3 , provides sensation to the skin of the lower lip, chin, and lower one-third of the face; to the mandibular teeth; and to the mucosa of the cheeks, lower lip, and floor of mouth. The general somatic afferents of CN V are also carried on V3 to the anterior two-thirds of the tongue. Light touch,

None (ganglion cell layer in retina, optic tracts project to lateral geniculate body) Oculomotor nucleus (lateral somatic cell column) Oculomotor nucleus (caudal central group)

II—optic

Principal sensory, geniculate ganglion Descending, spinal tract and nucleus of V, geniculate ganglion Mesencephalic nucleus of V (no peripheral ganglion) Abducens nucleus Facial motor nucleus Intermediate nerve, geniculate ganglion, spinal trigeminal tract Intermediate nerve, geniculate ganglion, nucleus solitarius (“gustatory nucleus”) Superior salivatory nucleus, intermediate nerve

Cochlear nuclei (dorsal and ventral)

V—trigeminal, sensory (GSA) V—trigeminal, sensory (GSA)

VII—facial, sensation (GSA)

VII—facial, parasympathetics (GVE)

VIII—cochlear nerve

VII—facial, sensation (SVA)

VI—abducens (GSE) VII—facial, motor (SVE)

V—trigeminal, sensory (GSA)

Motor nucleus of V

Superior cervical ganglion of sympathetic chain Trochlear nucleus

V—trigeminal, motor (SVE)

IV—trochlear, motor (GSE)

III—oculomotor, parasympathetics (GVE) III—oculomotor, sympathetics

III—oculomotor (SVE) Edinger–Westphal nucleus

None (olfactory glomerulus in olfactory bulb)

I—olfactory

III—oculomotor

Brainstem nucleus

Cranial nerve

Table 3 Cranial Nerves, Their Nuclei, Brainstem Location, and Function

Pons

Pons

Pons

Pons

Pons Pons

Midbrain

Pontine tegmentum Pons to C2-C4

Midbrain (level of inferior colliculus) Pontine tegmentum

Midbrain (level of superior colliculus) Midbrain (level of superior colliculus) Midbrain (level of superior colliculus)

None (olfactory tract to anterior perforated substance and pyriform lobe) None (diencephalon)

Brainstem location

Sensation of taste for anterior 2/3 of the tongue Lacrimal gland and nasal mucosa via GSPN and PtPG (V2 ) Submandibular gland via chorda tympani (and lingual nerve, V3 ) Hearing

Motor to lateral rectus mus Muscles of facial function, buccinators, platysma, stapedius mm Sensation of ear canal

Proprioception from the TMJ

Muscles of mastication, accessory muscles of mastication (tensor tympani, tensor veli palatini) Light touch and pressure Pain and temperature

Constrictor of pupil Mueller muscle in upper eyelid Superior oblique

Dilator of the pupil via NCG of V1

Levator palpebrae

Extraocular muscle movement

Vision

Olfaction

Function

Deafness

?dry eyes, nose, mouth

(Continued)

Loss of taste, anterior 2/3 of the tongue

Diplopia, eye does not abduct Facial paralysis, loss of stapedial reflex (hyperacusis) Numbness of ear canal (Hitzelberger sign)

Loss of jaw jerk reflex

Loss of sensation in distribution Loss of sensation in distribution

Vertical diplopia (trouble walking down stairs) Weakness of muscles of mastication

Horner syndrome

“Blown pupil”

Diplopia, outward and downward deviation of eye Ptosis

Blindness

Anosmia

Deficit

Chapter 5: Head, Neck, and Neuro-otologic Assessment of Patients with Tumors of the Skull Base

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Hypoglossal nucleus

Spino-medullary junction

Spino-medullary junction Medulla and C1–C3

Spino-medullary junction

Spino-medullary junction

Spino-medullary junction

Spino-medullary junction

Motor to the tongue

Parasympathetic to the GI tract Motor to SCM and trapezius

Hypopharynx, larynx, and tracheobronchial tree Taste, tip of epiglottis

Parotid gland via otic ganglion (lesser petrosal nerve and auriculotemporal br of V3 ) Vocal fold movement, pharyngeal constrictors, cricopharyngeus Postauricular skin and ear canal

Dysarthria

Weakness of shoulder

Lack of laryngeal taste

Dysphagia, aspiration

Numbness

Hoarseness, dysphagia, aspiration

Lack of pharyngeal taste, loss of carotid sinus reflex ?xerostomia

Dysphagia

Loss of gag reflex

Numbness

Imbalance

Deficit

Abbreviations: GSA, general somatic afferent; GSE general somatic efferent; GVA, general visceral afferent; GSPN, greater superficial petrosal nerve; NCG, nasociliary ganglion; PtPG, pterygopalatine ganglion; SCM, sternocleidomastoid; SVA, special visceral afferent; SVE, somatic visceral efferent. Source: Refs. 35–37.

X—vagus, parasympathetics (GVE) XI—spinal accessory, cranial root (SVE) XI—spinal accessory, spinal root (GSE) XII—hypoglossal (GSE)

X—vagus, special sensation (SVA)

Rootlets from C1–C3

Superior ganglion, in neck, spinal trigeminal tract Inferior (or nodal) ganglion in neck, nucleus solitarius Inferior (or nodal) ganglion in neck, nucleus solitarius Dorsal motor nucleus Nucleus ambiguus

X—vagus, sensation (GSA)

X—vagus, sensation (GVA)

Nucleus ambiguus

Medulla

Inferior salivatory nucleus

Medulla

Nucleus ambiguus Medulla

Sensory to base of tongue and upper pharynx Motor to stylopharyngeus and superior constrictor mm Taste, base of tongue, baroreceptor

Medulla

Nucleus solitarius (“gustatory nucleus”)

Sensation to postauricular skin

Balance

Function

Medulla

Pons

Brainstem location

Vestibular nuclei (superior, medial, lateral, inferior) Superior ganglion, in neck, spinal trigeminal nucleus Inferior salivatory

X—vagus, motor (SVE)

IX—glossopharyngeal, special sensory (SVA) IX—glossopharyngeal, parasympathetic (GVE)

IX—glossopharyngeal, sensory (GSA) IX—glossopharyngeal, sensory (GVA) IX—glossopharyngeal, motor (SVE)

VIII—vestibular nerves

Brainstem nucleus

Cranial Nerves, Their Nuclei, Brainstem Location, and Function (Continued)

Cranial nerve

Table 3

102 Gidley

Chapter 5: Head, Neck, and Neuro-otologic Assessment of Patients with Tumors of the Skull Base

pinprick, and temperature can be tested for each division of the trigeminal nerve. The motor function of the trigeminal nerve is carried on V3 to the masticatory muscles (masseter, temporalis, medial, and lateral pterygoid) and to the accessory muscles of mastication (mylohyoid, anterior belly of the digastric, tensor tympani, and the tensor veli palatini). Motor strength is difficult to assess clinically, but the tone of the masseter and temporalis can be palpated while the patient grinds teeth. Corneal Reflex The description of the corneal reflex rightfully belongs between the discussion of trigeminal and facial nerve function since it involves both nerves. The corneal reflex arc is composed of afferents from corneal epithelium through the V1 into the brainstem, where synapses through one or two interneurons and connects to the facial nuclei to produce muscular contraction of the orbicularis oculi muscles. Normally, unilateral corneal irritation produces bilateral orbicularis oculi contraction. The test is performed by asking the patient to look slightly nasally while a wisp of cotton is placed on the temporal portion of the cornea. Care is taken to prevent the patient from seeing the cotton approach the eye. In the case of a trigeminal nerve lesion, no muscular contraction will be elicited in either eye. In the case of a facial nerve lesion, the muscular contraction will be absent on the side of the lesion but will still be present on the normal side.

Facial Nerve As the motor supply to the face, the facial nerve controls several different, wide ranging functions. Under control of the facial nerve, the buccinator muscle aids in mastication by helping to keep the food bolus on the occlusal surface of the molars and not in the gingivobuccal sulcus. The perioral muscles aid in articulation of speech (for labial and plosive sounds). The orbicularis oculi protects the eye by closing the lids and by moving a lubricating coating of tears over the cornea. Lastly, and perhaps most importantly, it allows nonverbal communication of emotion through facial muscle contractions. Like the trigeminal nerve, the facial nerve has an intricate anatomy including the longest bony course of any cranial nerve, conveyance of motor, general sensory, and special sensory function, and is the primary pathway for two parasympathetic ganglia (sphenopalatine and submandibular). Since the facial nerve has many different branches along its course, each with a testable function, a topographic method of testing had previously been used to determine the site of lesion. In this way, testing lacrimation (Schirmer test), taste (electrogustometry), salivation, stapedial reflexes, and facial muscle function can provide the examiner with the location of the lesion. However, this topographic testing has largely been supplanted by modern imaging techniques and thus is not widely used. Acoustic reflex testing is performed and will be discussed in the section on audiometric testing. Facial muscle function is tested by asking the following to the patient: “raise your eyebrows,” “close your eyes tightly” even against resistance, “wrinkle your nose,” “puff out your cheeks,” “pucker your lips,” “show me your teeth” [Fig. 6(A)–6(D)]. In case of complete paralysis, the examiner presses his thumbs on the midline of the patient’s face to prevent the unopposed normal side from distorting the examination of the paralyzed side. Facial function should be reported for each area of the face, since just one branch might be paralyzed. Single branch

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facial paralysis strongly suggests tumor (44). Any individual with progressive facial weakness should be considered to have a tumor of the facial nerve until proven otherwise (44). The American Academy of Otolaryngology has approved the House–Brackmann scale as a measure of facial function for reporting results in its publications (Table 4) (45). The constellation of cranial nerve abnormalities can be grouped along recognizable patterns. These patterns, often carrying eponyms, can help in deducing the underlying pathologic process. Several such syndromes are listed in Table 5 (41,46–52).

Gait and Balance Testing A general neurologic examination of upper and lower body strength and sensation and cerebellar function should be performed looking for light touch, vibratory sensation, fine and rapid motor skills, and finger-to-nose testing (13).

Gait Patients are asked to walk for 15 ft and to return in order to assess the gait. The observer should note the posture, the position of the head, the motion in the arms, and the gait. Foot drop or poor posture might be indicators of imbalance. One should note how the patient turns himself around: does he use a quick method without needing to stop or does he make several small steps to turn himself around? The latter might be an indication of a vestibular pathology. Next, the patient is asked to walk heel to toe (tandem gait) for 15 ft. The examiner should accompany the patient to be certain that the patient does not fall. An abnormal tandem gait is loss of balance more than three times in 15 ft.

Stance Moritz Heinrich Romberg first published his description of tabes dorsalis in 1846 (53). Romberg test is performed with eyes closed, feet together, arms folded across the chest, and head extended (54). A sharpened Romberg test is performed with feet tandem (heel to toe), eyes closed, arms folded across the chest, and head extended. A simplified Romberg is performed with feet together, arms at the side, head in a neutral position, and eyes closed. The examiner looks for increased body sway and protects the patient from falling. This can be done by asking the patient to stand between two chairs, with his back about 50 cm from the wall. Normal individuals can maintain a Romberg posture for 30 seconds with eyes closed. Romberg posture relies on normal proprioception (dorsal columns), and an abnormal Romberg often indicates disease outside of the labyrinths (54). Patients are then asked to stand on one leg with eyes open and then eyes closed. Normal patients can easily stand on one leg for 15 seconds. Inability to stand on one leg indicates imbalance and highlights the need for normal muscle and joint strength and normal proprioception to maintain balance.

Fukuda Stepping Test The Fukuda (55), also called Unterberger (56), stepping test is performed with eyes closed, arms outstretched while the patient marches in place. The examiner watches the patient’s movement during 50 marched steps. Forward movement (>1 m) or turning movement (>45 degrees, usually toward the side of the lesion) are significant findings in the Fukuda test (57). This is a test of vestibulospinal and proprioceptive contributions for balance control (58). Some reports have shown good sensitivity of this test (57), while others have discounted its usefulness (56,59).

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Figure 6 paralysis.

Gidley

(A)

(B)

(C)

(D)

Facial function (A) at rest, (B) during raised eyebrows, (C) during closed eyes, (D) while showing teeth in a patient with complete right facial

Clinical Test of Sensory Integration and Balance This series of tests uses simple objects to test static and dynamic equilibrium (54,60). Romberg postures with eyes open and closed are used to mimic the test situations 4 and 5 found in computerized dynamic posturography (54). Thick upholstery foam, a rigid cover, and lampshade are used to create the “foam and dome” test modalities. These simple clinical tasks of static and dynamic equilibrium can reliably distinguish vestibular disorder patients from normal subjects (61).

AUDIOMETRIC, VESTIBULAR, AND ELECTROMYOGRAPHIC STUDIES These tests provide valuable insight into disease process and help to measure function. The following text is not meant to describe how to perform each test. Where indicated, a rudimentary description will be given to familiarize the reader with how the test is performed, but more importantly, how to interpret in the findings and

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Table 4 House–Brackmann Facial Nerve Grading System Grade

Description

I II

Normal Slight dysfunction

III

Moderate dysfunction

IV

Moderately severe dysfunction

V

Severe dysfunction

VI

Total paralysis

Characteristics Normal facial function in all areas Gross: slight weakness noticeable on close inspection; may have very slight synkinesis At rest: normal symmetry and tone Motion Forehead: moderate to good function Eye: complete closure with minimum effort Mouth: slight asymmetry Gross: obvious but not disfiguring difference between two sides; noticeable but not severe synkinesis, contracture, and/or hemifacial spasm At rest: normal symmetry and tone Motion Forehead: slight to moderate function Eye: complete closure with effort Mouth: slightly weak with maximum effort Gross: obvious weakness and/or disfiguring asymmetry At rest: normal symmetry and tone Motion Forehead: none Eye: incomplete closure Mouth: asymmetric with maximum effort Gross: only barely perceptible motion At rest: asymmetry Motion Forehead: none Eye: incomplete closure Mouth: slight movement No movement

Source: Ref. 45.

Table 5 Cranial Nerve Syndromes Syndrome Foster Kennedy syndrome (41)

Cranial nerves involved

Orbital apex (46)

I (ipsilateral hyposmia or anosmia) II (ipsilateral optic atrophy and central papilledema) III, IV, VI, V1

Cavernous sinus (46,49)

III, IV, VI, V1 , V2 + sympathetics

Superior orbital fissure (Rochon–Duvigneaud or Foix) syndrome (46, 47) Retrosphenoidal space (Jacod) (47) Petrous apex (Gradenigo syndrome) (47)

III, IV, V1 , VI

Miller–Fisher syndrome Internal auditory canal (47)

VI, VII VII, VII

Cerebellopontine angle (47,48)

V, VII, VIII, IX, X, XI

Jugular foramen (Vernet) (47,48,50) Schmitt (48) or Collet–Sicard syndrome (50–52) Retropharyngeal syndrome of Villaret (51)

IX, X, XI IX, X, XI, XII without Horner syndrome IX, X, XI, XII with Horner syndrome

II, III, IV, V, VI V, VI

Most likely cause(s) Tumor of olfactory grove and sphenoidal ridge

Inflammatory (sarcoid, SLE, Wegener’s, Graves) Infectious (fungal, bacterial, viral) Tumors (nasopharyngeal, adenoid cystic, squamous cell, lymphoma) Iatrogenic (sinonasal or orbitofacial surgery) Vascular (carotid aneurysm, carotid cavernous fistula) Mucocele Idiopathic (Tolosa–Hunt) Thrombosis Sellar tumors Trauma Tumors of the middle fossa Chronic otitis Cholesterol granuloma Chondrosarcoma Rhombencephalitis (Herpes, Guillain–Barre) Acoustic neuroma Meningioma Epidermoid tumor Meningioma Acoustic neuroma Epidermoid tumor Neoplasm Carotid aneurysm

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place the results into the framework of the entire clinical picture. Electrodiagnostic testing is a wide field of medical practice. Audiologists, neurologists, neuromuscular specialists, and physiatrists perform one or more of these tests as part of their regular practice and are the recognized experts in performing these tests. Liberal use of these consultants is necessary in the evaluation of patients with skull base tumors. The allotted space does not permit for this chapter to be an exhaustive resource; and therefore, certain tests are eliminated though they might provide insight into disease processes (e.g., electrogustometry). The bulk of medical literature relating audiometric testing and skull base tumors concerns the diagnosis of acoustic neuroma (AN). ANs account for 5% to 10% of intracranial tumors and 80% to 90% of posterior fossa tumors (62). Since Cushing first recognized hearing loss as the presenting symptom of ANs (63), scientists and physicians have tried to develop better audiometric test to identify the presence of ANs. The history of neuro-otologic diagnosis for ANs has included reflex decay, alternate binaural loudness, and B´ek´esy audiometry (64, 65), but these modalities have been replaced by auditory brainstem response (ABR) and MRI. The following topics will primarily relate the findings of audiometry and vestibular testing to ANs. The findings of other tumors, such as meningiomas, epidermoids, etc. will be presented where significant differences are found.

Basic Audiometry The audiogram is the most fundamental element of otologic and neuro-otologic evaluation beyond the history and physical examination. A basic audiogram consists of pure tone audiometry, speech audiometry, immittance testing (e.g., the tympanogram), and acoustic reflex testing. Only a brief description of each test is permitted in this chapter;

the interested reader is directed to other reference works for an in depth discussion of the finer points of these tests (66–69). Pure tone audiometry is the measurement of the lowest threshold at which a tone is heard. A calibrated audiometer delivers sound at a specific frequency (pitch) and specific intensity (loudness). The test is performed by an audiologist in a sound proof booth using either circumaural headphones or ear inserts for air conduction levels and using a bone vibrator for bone conduction levels. Masking sound is given to the nontest ear via an ear canal insert and is the physiologic equivalent of covering one eye during a vision test. The results of pure tone tests are placed on the audiogram using conventional symbols to designate the ear, the modality (air or bone conduction), and the use of masking. The intensity levels of air conduction at 500, 1000, and 2000 Hz (and occasionally 3000 or 4000 Hz) are averaged producing a pure tone average (PTA). Hearing loss can be grouped into three different categories: conductive, sensorineural, or mixed. Conductive hearing loss indicates that the sound conducting mechanism of the ear is impaired. This condition can occur from any process that blocks the ear canal or impairs the vibration of the tympanic membrane or ossicles. Cholesteatoma, cerumen impaction, otitis media, tympanic membrane perforations, ear canal cancers (Fig. 5), and otosclerosis are common causes of conductive hearing loss (Fig. 7). Sensorineural hearing loss indicates that the defect in hearing lies either within the cochlea or the auditory nervous pathway. Common examples of sensorineural hearing loss occur in presbycusis, noise-induced hearing loss, ototoxicity, and ANs (Figs. 8 and 9) Mixed hearing loss means that both conductive and sensorineural hearing loss types are present in an ear.

Figure 7 Audiogram showing left conductive hearing loss due to cholesteatoma. The open circles denote the hearing level tested by ear canal inserts and denote the air conductive hearing level. The solid triangles denote the hearing level tested by a bone vibrator behind the left ear and masking noise in the right ear and mark the left ear cochlear hearing level.

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Figure 8 Audiogram from patient with left intracanalicular acoustic neuroma. The shaded area shows the normal hearing range. There is left sensorineural hearing loss above 1 kHz. The right ear hearing is essentially normal. The word recognition score phonetically balanced maximum (PBM) is 92% for each ear. The tympanograms are normal Type A bilaterally. The auditory reflexes are present bilaterally.

A threshold for perceiving words can be achieved by using spondaic words. The lowest level that 50% of words are perceived is called the speech reception threshold (SRT). The PTA and SRT should agree within 5 to 10 dB of each other. Speech audiometry measures word understanding. Phonetically balanced words are presented via air conduction at a presentation level 40 dB over the SRT or PTA (also called 40 dB sensation level or 40 dB normal hearing level). The percent of words that are understood is recorded as the speech discrimination score (SDS). Generally speaking, word understanding improves as the intensity is increased for cochlear or sensory hearing loss. However, retrocochlear hearing loss might demonstrate a worsening of word understanding with increased intensity, and this is called phonetically balanced rollover. A compilation of differences between sensory or cochlear hearing loss and retrocochlear or neural hearing loss is presented in Table 6 (70–74). Prior to ABR and MRI, site of lesion testing was of paramount importance in discerning patients who might have an AN; however, since up to 20% of AN patients might demonstrate a cochlear rather than a retrocochlear pattern of hearing loss, retrocochlear audiometric testing is of little benefit (75). The American Academy of Otolaryngology Committee on Hearing and Equilibrium (76) composed a classification system for reporting hearing results in AN surgery. This classification system uses PTA and SDS to stratify patients into four different classes of hearing level (Table 7). Alternatively, some authors report hearing results as “unchanged,” “serviceable,” “measurable,” or “not measurable.” In this context, serviceable is PTA ≤ 50 dB and SDS ≥ 50%, unchanged is hearing within 15 dB PTA and 15% SDS of preoperative levels, measurable is any other hearing, and not measurable is self-explanatory (77).

Immittance testing uses an impedance bridge to measure changes in tympanic membrane compliance. Compliance of the tympanic membrane is affected by perforations, middle ear fluid or tumor, and the reflex contraction of middle ear muscles. Several important findings can be discovered with this type of testing. Immittance testing gives a clue regarding the status of the tympanic membrane (intact, perforated, or floppy) and the status of the middle ear (aerated or fluid filled). These findings are denoted on a tympanogram; however, for the discussion of skull base tumors, tympanograms have little significance unless the tumor or spinal fluid invades the middle ear and produces a flat tympanogram. Acoustic reflex testing, on the other hand, has more significance for neuro-otologic diagnosis of skull base tumors. Using the impedance bridge, compliance of the tympanic membrane can be measured in response to a tone burst given either ipsi- or contralaterally. In response to loud sound (85– 110 dB), a reflex contraction of the stapedial muscle will occur bilaterally. A normal reflex requires an intact tympanic membrane, an air-filled middle ear, normal movement of the ossicles, no worse than 35 dB hearing loss, and an intact facial nerve (stapedial muscle). A defect anywhere along this pathway can produce an absent or reduced acoustic reflex. The sensitivity of acoustic reflex testing for ANs has been quoted anywhere between 21% and 90% (75,78–84). Acoustic reflex decay is defined as a 50% loss of middle ear contractility in response to a tone administered 10 dB above threshold. The sensitivity of reflex decay has been reported from 36% to 100% for ANs (75,78,79,81–85).

Acoustic Neuroma Hearing loss is found in up to 95% of patients with an AN (75). By that same token, normal hearing is reported in 3% to 12% of AN patients (75,81,86–88). The current level of

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Gidley Table 7 AAO–HNS Hearing Classification Class

PTA

SDS

≤30 dB >30 dB, ≤50 dB >50 dB Any level

A B C D

≥70% ≥50% ≥50% ≤50%

Source: Ref. 76.

(A)

(B)

Figure 9 (A) Contrast-enhanced axial MRI and (B) contrast-enhanced coronal MRI of left intracanalicular acoustic neuroma from patient whose audiogram is depicted.

clinical detection of AN is approximately 1 in 100,000 person per year (89), though vastly higher numbers of tumors must be present and escaping detection given the 1% observed rate of acoustic tumors found at autopsy (90). Indeed, a significant number of ANs are found serendipitously on MRI performed for unrelated complaints (91). In general, the degree of hearing loss is significantly linked with tumor size, so that up to 33% of intracanalicular tumors are associated with normal

hearing (83). However, there are many reports of individual large tumors (>2 cm) associated with normal hearing and small tumors (<1 cm) associated with anacusis (92). Schuknecht has calculated that 75% of nerve fibers need to be destroyed before pure tone hearing is affected, given an intact organ of Corti (93). The distribution of high-frequency nerve fibers on the periphery and low-frequency fibers centrally in the acoustic nerve accounts for high frequency hearing loss that is found in early acoustic tumors development. Hearing deteriorates by as much as 2.4 dB per year while ANs are observed (94). Speech discrimination also significantly deteriorates over time in observed ANs (94). In the series of tumors described by Selesnick and Jackler (88), high-frequency asymmetry at 4 kHz was a more sensitive indicator of an AN than difference in either SRT or SDS. While the classic presentation of an AN is a unilateral progressive sensorineural hearing loss with poor speech discrimination (95), experts have not agreed on what exactly constitutes a significant asymmetry (75,96,97). As a rule of thumb, a significant asymmetry in hearing is described as an interaural SRT difference greater than 15 dB, an interaural SDS difference greater than 12% to 20% or an interaural 4 kHz difference greater than 15 dB (75). Obholzer et al. (98) sought to define appropriate audiometric criteria for referral for MRI. They reviewed 392 MRIs performed in 1 year. Of these, 36 patients had ANs; these 36 ANs and 92 randomly selected “normals” were included for the analysis. Audiometric data and clinical histories were evaluated to look for findings that might be indicative of AN. They used the published protocols of seven different studies to analyze audiometric data. Their study supports the use of interaural asymmetry at two neighboring frequencies of >15 dB if the mean threshold in the better ear was ≤30 dB (unilateral hearing loss) and an interaural difference of 20 dB if the mean threshold is greater than 30 dB in the better ear (bilateral asymmetric hearing loss). These criteria had a 97% sensitivity and 49% specificity for AN. The most sensitive individual frequency asymmetry was a 15 dB at 2 kHz, with a sensitivity of 91% and a specificity of 60%. The most sensitive criterion was a difference of 15 dB at any frequency (sensitivity 100% and specificity 29%). Several authors have examined hearing levels as a predictor of hearing preservation in AN surgery. In a multivariate logistic analysis of preoperative hearing variables

Table 6 A Compilation of Differences Between Sensory (Cochlear) vs. Neural (Retrocochlear) Hearing Loss

Site of pathology

Pure tone audiometry (72)

Sensory or cochlear

Hair cell

Decreased

Neural or retrocochlear

Auditory nerve

Relatively unaffected

Speech discrimination (72) Preserved, until widespread cochlear damage Decreased

Secondary findings (71,73) Recruitment

Auditory fatigue or tone decay

Speech discrimination (72) Preserved, until widespread cochlear damage Decreased

ABR (70)

OAE (74)

Intact

Absent

Abnormal or absent

Intact

Chapter 5: Head, Neck, and Neuro-otologic Assessment of Patients with Tumors of the Skull Base

predictive of hearing preservation, Robinette et al. (99) examined the audiometric test results in 104 AN patients. Only word recognition score (WR40) was found to be a significant determinant after accounting for small tumor size (≤2.0 cm). Additionally, they found that patients who had hearing preserved had a higher rate of normal acoustic reflexes than in those patients who did not have hearing preserved (99).

Other Tumors In 1997, Baguley et al. (100) published their series of cerebellopontine angle (CPA) meningiomas and performed a review of the literature. In their series, 80% (20/25 patients) had abnormal pure tone testing and 50% (10/20) had abnormal SDS (i.e., <90%). Interestingly, the five patients who had normal audiometry had large tumors (two in 2.5–3.4-cm range, and three >4.5 cm); equally, 9/10 patients with normal SDS were found to have large tumors (2.5 cm and larger). When combined with the other series reviewed, 37/61 (61%) patients had abnormal PTA and 22/42 (52%) had abnormal SDS (100). Doyle and De La Cruz (101) reported audiometric results in 13 patients with CPA epidermoid tumors. Four patients had PTA greater than 30 dB; SDS was reduced out of proportion to pure tone hearing. Quaranta et al. (102) described the audiometric features in a report of 11 CPA epidermoid tumors. Their series consisted of tumors that measured 3.5 to 7 cm in maximum diameter. They found symmetric hearing in six patients. Another four had asymmetric hearing loss, worse on the tumor side. In a report on 10 epidermoid tumors, Kaylie et al. (103) found normal hearing in three, while the remainder had varying levels of hearing loss from mild to anacusis.

Auditory Brainstem Responses In the history of methods to diagnose ANs, ABR represented a giant advance and promised a much less invasive test. Prior

+ A1

I

to its development, audiologists developed many different tests to stress the auditory nerve to determine its function. But as the preceding paragraphs indicate, many of these tests lacked the specificity or sensitivity necessary to identify tumors. However, once a patient was identified as possibly having an AN, the next step would have required either an air-contrast or a pantopaque posterior fossa myelogram or polytomograms of the internal auditory canal. These tests were not only invasive, but they were extremely painful and potentially morbid. They were not recommended lightly. In 1971, when ABR was introduced, its significance for AN screening had not yet been realized (104); however, before the end of the decade, the sensitivity of ABR to identify ANs was well established (105). Unfortunately for ABR, its heyday was relatively short lived. MRI with gadolinium contrast enhancement was introduced in 1988 (96), and MRI has been nearly 100% sensitive for ANs as small as 4 mm (106,107). ABR is performed with a ground electrode on the vertex and another electrode on the earlobe or mastoid of the stimulated ear. Clicks or tone burst are given at 20/sec or faster rates. Click stimulus estimates hearing in the range of 1000 to 4000 Hz. Intensity can be varied but is generally given at 70 dB; however, with lower intensities the amplitude response decreases and latency increases. Bandpass filters are set from 30 or 100 to 3000 Hz and are used to encompass the spectrum of response while reducing undesirable activity. ABR is influenced by age, gender, and body temperature, but it is not affected much by state of arousal or sedative medications (108). By convention, ABR waveforms are number I through V. Each numeral indicates a positive waveform. These waveforms have been correlated with structures within the auditory pathway: I for the distal eighth nerve, II for the proximal eighth nerve, III for the cochlear nucleus, IV for the olivary complex, and V for the lateral lemniscus (Fig. 10).

V III

Left 80 dB

.25 µV V

III A2

Left 70 dB

.25 µV

III I A3

109

V

Right 80 dB

.25 µV V I

A4

III Right 70 dB

.25 µV

Latency 1.00 ms/div Latency Offset –.80 ms

Figure 10 ABR of same patient with left intracanalicular acoustic neuroma. Click stimulus was performed at 70 dB and 80 dB for each ear. Note that latency increases with lower intensities. In this patient, the absolute latency of wave V is 5.96 for the left ear and 5.84 for the right ear (within normal limits). The interpeak latencies I to V are 4.00 for the left and 4.04 for the right (within normal limits).

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Table 8 Probability of an Acoustic Neuroma Based on Symptoms and Signs Probability Low probability (<5% chance)

Moderate probability (5–30% chance) High probability (>30% chance)

Factors Isolated vertigo Symmetrical hearing loss Historically explainable unilateral hypoacusis or tinnitus Sudden SNHL Unexplained tinnitus Combination of “classic symptoms and findings:” unilateral SNHL tinnitus decreased speech discrimination

Source: Refs. 62,75,96.

Acoustic Neuroma ABR’s place in the diagnosis of acoustic tumors still provokes debate among neuro-otologists. While some use ABR to screen all patients with asymmetric hearing loss, others reserve ABR for patients who have only a low probability of tumor (Table 8) (62,75,96), preferring to use MRI for patients who have a higher probability of having a tumor (96). Certainly, one could use MRI for all suspicious cases if availability and costs were not considerations, yet this is not the case in today’s healthcare environment. These arguments are largely based on the sensitivity of ABR to diagnose an AN. In large retrospective series of tumor patients, normal ABR can be seen in 2% to 18% of patients (105,109,110). In their series of 309 CPA tumors, Marangos et al. (110) found normal ABR in 50/261 sporadic ANs, 3/29 ANs due to NF-2, and 4/17 meningiomas. Their study further demonstrates quite elegantly the impact of MRI and the steady decrease in average tumor size by year of initial diagnosis. In their study population, in 1986 the average tumor size was 36 mm (+/– 10 mm); while in 1999, the average decreased to 16 mm (+/– 5 mm). ABR as a screening tool has been examined in prospective studies. Ruckenstien et al. (97) performed a prospective study of patients with asymmetric hearing loss examined with both ABR and MRI to determine the sensitivity, specificity, positive predictive value, and negative predictive value of ABR. Their small study included only 47 patients who met the inclusion criteria. Eight patients had significant pathology on MRI, five of which were ANs. However, ABR was normal in three of these patients; and all three had tumors smaller than 1.5 cm. Fourteen patients had an abnormality in ABR testing that was not demonstrable by MRI. In this preliminary study, the sensitivity of ABR to diagnose significant retrocochlear pathology was 63%, its specificity was 64%, the positive predictive value was 26% for AN, and its negative predictive value was 89% (97). Similar results were published by Ferguson et al. (106), though their protocol used contrast enhanced CT as a prerequisite prior to MRI imaging. Cueva (111) published a follow-up study to that of Ruckenstein et al. (97) and examined 312 adult patients with asymmetric hearing loss with ABR and MRI prospectively. He found 31 patients with retrocochlear pathology by MRI: 24 ANs and a collection of other pathologies (including 2 glomus jugulares and 1 petrous apex cholesterol granuloma). The ABR was abnormal in 22 of these 31 patients, thus nine patients had normal ABR, seven of which had an AN and all seven tumors were 16 mm or smaller. It should be noted that tumors as small as 5 mm were the cause of an abnormal ABR by these criteria. By his calculations, the sensitivity for ABR

was 71% and specificity was 74%. He recommends use of MRI for patients with asymmetric hearing loss, noting that if ABR is relied on as a screening test, 29 patients of 1000 screened will be missed (111). Overall sensitivity rates of ANs by ABR range from 88% to 95% (62,97,109,112–116). There are several reasons to account for such a wide range of positive findings: (i) testing parameters, (ii) tumor size, (iii) tumor location (intracanalicular versus extracanalicular), and (iv) involved nerve (superior versus inferior vestibular nerve). Waveform latencies and waveform morphologies have been studied by various authors. The most common indicators of pathology have been (i) an interaural wave I to V latency difference (IT5 or ILD I–V) >0.2 msec, (ii) a wave I–V interpeak latency (I–V IPL) >4.4 msec, and/or (iii) poor waveform morphology with either absent wave or no response. Absolute latencies are not considered as useful as interpeak latencies for the diagnosis of ANs because the absolute latency is affected by many factors, such as click intensity, hearing loss, and age (117). Some authors have not used interpeak latencies since wave I or II is difficult to identify even in normal listeners (112). Additionally, waveform amplitude is not used as a criterion since it is highly variable (112). A compilation of criteria used by several authors is presented in Table 9. Many different studies have examined the sensitivity of ABR by tumor size (Table 10), and a statistically significant positive correlation between tumor size and wave V latency has been reported (92). Additionally, when ABR waveforms from the contralateral ear are abnormal (e.g., a delayed wave V or prolonged wave I–V interval), a tumor larger than 2 cm should be suspected (118). Thus, it is concluded that ABR is nearly 100% sensitive for tumors larger than 2 cm (62,116,119). For this reason, ABR is a desirable screening test in the elderly and poor surgical risk patients for whom surgery may be indicated only for a symptomatic, large tumor (61,111). However, to have a reasonable chance of hearing preservation, tumors should be diagnosed as early (small) as possible, where small is defined as 2 cm or smaller (99,120). ABR sensitivity rates for tumors smaller than 1 cm range from 63% to 93% (62,97,113–116). Healthy patients with unilateral symptoms (hearing loss, poor discrimination, and tinnitus) should have MRI with gadolinium enhancement to find an AN. ABR still provides excellent insight into the physiology of the acoustic nerve, and this may have important implications for hearing preservation. Matthies and Samii (121) found that preoperative ABR was more important than the preoperative hearing quality for the chances of hearing preservation. They found that the presence of wave III correlated with better postoperative results, especially SDS (121). Robinette et al. (99) found similar results regarding the presence of waves I, III, and V when looking at preoperative predictors of hearing preservation. They reported that when these three waves are present, 61% of patients had hearing preservation, while only 27% of patients with one or more waves absent had hearing preserved (99). One can find papers that dispute any relationship between ABR waveforms and hearing preservation as well (120,122,123). It should be noted that poor ABR waveforms should not be used as a criteria to exclude the possibility of hearing preservation. Stidham and Roberson (124) reported a series of 30 patients undergoing middle fossa craniotomy for hearing preservation. They described seven patients with hearing improvement, classified as an increase in PTA ≥ 5 dB and/or an improvement in SDS by ≥ 12%. Interestingly, no patient with normal preoperative ABR experienced a hearing

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Table 9 Definitions of Abnormal ABR Interaural wave V latency difference, msec (ILD-V) (a.k.a. IT5)

Authors

Absolute wave V latency, msec

Interaural latency difference of I–V, msec (ILD I–V)

I–V interpeak latency, msec (I–V IPL)

Waveform morphology

House and Brackmann, 1979 (125) Bauch, 1982 (112)

>0.2

>6

Absence of wave V

>0.2

>6.1

Josey, 1988 (169)

>0.4

No response or poor overall waveform at high intensities Absence of V despite good hearing

Weiss, 1990 (170) Wilson, 1992 (113)

≥0.4 ≥0.4

>6.03

Dornhoffer, 1994 (114) Chandrasekhar, 1995 (115)

≥0.4 >0.2

>5.9

Gordon and Cohen, 1995 (62) Berrettini 1996 (83)

Ferguson, 1996 (106) Ruckenstein, 1996 (97)

>0.2

Saleh 1996 (95) Zappia, 1997 (116)

>0.3 >0.2

Godey, 1998 (84)

>0.2

Noguchi, 1999 (171) El Kashlan, 2000 (61)

≥0.3 >0.4

Haapaniemi, 2000 (144) Marangos, 2001 (110) Rupa, 2003 (119)

≥0.4 >0.3 ≥0.3

Cueva, 2004 (111)

>0.2

>4.4 ≥0.4

“abnormally prolonged” (>2 SD above normal limit for patient’s age and gender) >6.10 (male) >5.97 (female) Abnormal absolute wave V latency >6

≥4.45 ≥4.4

Abnormal ipsilateral or contralateral waveforms Abnormal or absent waveform morphology

>0.2 >0.3

>4.3

>0.3

>4.58 (male) >4.34 (female) ≥4.4

>0.2

>4.4 ≥4.4 >4.4

>7.75 >=0.4 >0.2

≥4.4 >4.4 ≥4.4

Abnormal absolute wave V latency

improvement. Of course, ABR is the most common technique used to monitor hearing intraoperatively (Chap. 6).

Other Tumors ABR results for posterior fossa meningiomas have similar rates of sensitivity as is found for ANs. In the pre-MRI era, House and Brackmann (125) found that only 75% of patients

Poor morphology in spite of adequate hearing

Absent or poor waveform morphology Absent waves, if adequate PTA Absent or abnormal waveform morphology Absent or abnormal waveforms Complete absence of waves if adequate PTA or absence of waves beyond wave I Abnormal or absent Absence of one or more waves, poor waveform morphology Absent or distorted waveform morphology

with non-AN pathology had abnormal ABRs. In their paper, 3 out of 10 meningiomas had normal ABR (125). Laird et al. (126) and Granick et al. (127) each found six out of six posterior fossa meningiomas had abnormal ABR. Aiba et al. (128) reported abnormal ABR in 8/10 cases; and Hart and Lillehie (129) reported abnormal ABR in 5/7 cases. Baguley contributed another 25 cases of CPA meningiomas, and found

Table 10 ABR Sensitivity with Respect to Tumor Size Study

No. of patients

Gordon and Cohen, 1995 (62) Chandrasekhar, 1995 (115) Bauch, 1996 Zappia, 1997 (116)

105 197

Marangos, 2001 (110)

309

Wilson, 1992 (113) Godey, 1998 (84)

111

40 89

≤10 mm

11–20 mm

>21 mm

69% 83% 82% 89% <15 mm 59.3%

88% 97%

100% 100%

98% 16–25 mm 82.7%

100% >25 mm 96.7%

Intracanalicular 66% 77%

Extracanalicular 96% 94%

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abnormal ABR in 100% of their tumors (100). Marangos et al. (110) found that 23.5% of meningiomas had normal ABR. Clearly, MRI is required to make the diagnosis of this tumor as well. Epidermoid tumors generally present at an advanced stage with multiple cranial nerve deficits and cerebellar signs (102,103). In the series by Quaranta (102), tumors ranged from 3.5 to 7 cm in maximum diameter. They found that ABR was normal in just one case. Absent or delayed waves were present in five cases, ipsilateral to the tumor. Four cases had bilateral abnormalities on ABR. Thus, 90% of their patients had abnormalities on ABR (102).

Stacked ABR Don et al. (130) described a new technique of ABR they called “stacked ABR.” In this test, ABR is obtained using 63 dB normal hearing level clicks in a high-pass noise-making procedure. The wave V amplitude is constructed by temporally aligning wave V of each derived-band ABR and summing the time-shifted responses. Using this technique, they found significantly lower wave V amplitudes in five AN patients who were missed by conventional ABR technique. These five tumors were all less than 1 cm in greatest dimension. They propose this technique as a cost-effective approach for AN screening. In a further study of stacked ABR, Philibert et al. (131) noticed that stacked ABR required a masking technique that might not be readily available. Additionally, they found that the relatively high intensity of the test might be annoying to the patient. Instead, they propose using tone burst to obtain a frequency-specific ABR.

Otoacoustic Emissions The phenomenon of sound being produced by the ear was first described in 1948 (132), and the definitive paper on otoacoustic emissions (OAEs) was published in 1978 (133). However, it was not until the 1990s that OAE testing became clinically widespread (134). OAE testing has enjoyed a significant increase in usage as part of a neonatal hearing screening strategy, monitoring ototoxicity or noise-induced hearing loss, and in suspected cases of functional hearing loss (134). OAEs are generated by outer hair cells of the cochlea (135). While OAEs are not useful as a screening test for ANs or other skull base tumors, they are measures of “cochlear reserve” and have been examined as possible predictors of hearing preservation (77,99,136). OAEs are divided into two groups: spontaneous and evoked. Spontaneous emissions are present in roughly 60% of normal ears (137). Evoked emissions are present in virtually 100% of normal ears (134). Evoked emissions are divided into distortion product (DPOAEs) and transient evoked (TEOAEs) emissions [Fig. 11(A) and 11(B)]. In a literature review, Robinette et al. (99) examined five studies describing 236 AN patients and reported that TEOAEs were present in at least one frequency in 47% of tumor ears. Brackmann et al. (77) described 333 AN patients considered for hearing preservation, 56 of these patients had DPOAEs measured. Normal DPOAEs were found in 91% (77). Ferber-Viart et al. (138) examined 168 AN patients with TEOAEs; (21%) had normal preoperative TEOAEs. They did not find an association with tumor size, functional symptoms, PTA, ABR, or electronystagmography (ENG) response with TEOAEs. Patients with TEOAEs tended to be younger, on average six years younger than those without TEOAEs.

In the subpopulation of 63 patients who underwent hearing conservation surgery, TEOAEs were present in 28% and absent in 72%. Sixty-six percent of those with TEOAEs present had hearing preserved, while only 44% with absent TEOAEs had hearing preserved. This difference was not statistically significant (138). In a more recent study, Kim et al. (136) examined 93 patients with AN that were candidates for hearing preservation. Fifty-one patients had hearing preserved. Eleven (22%) of these 51 patients had TEOAEs present in all five frequencies tested (1–4 kHz), while 40 (78%) had TEOAE responses anywhere from 0 to 4 of the frequencies tested. In the 42 patients who did not have hearing preserved, only three (7%) had positive TEOAEs in all five frequency bands, and 39 (93%) had TEOAEs from 0 to 4 frequency bands (p < 0.05). Other positive factors for hearing preservation in their series were small tumor size, tumor within the IAC, better hearing, and shorter latencies on ABR. Their conclusion was that a robust preoperative TEOAE pattern may be used as a favorable indicator for hearing preservation, especially when combined with the other positive factors listed above (136).

Electronystagmography Since its introduction in the 1960s, ENG (or more commonly now videonystagmography) has established itself as the most common test performed in evaluating patients with complaints of dizziness and vertigo (139). This test combines positional testing, optokinetic testing, random saccades and visual pursuit tests, and caloric stimulation to evaluate the vestibular ocular reflex and visual tracking centers of the brain. Findings on ENG for peripheral lesions are well described (140). ENG is an extremely valuable tool for examining the anatomic and functional integrity of the central and peripheral vestibular systems (141). The sensitivity of caloric testing for acoustic tumors ranges from 44% to 95% (83,140,142–144). Reduced or absent caloric response is the most frequent finding in AN patients (140,145,146). The amount of caloric weakness is proportional to the size of the tumor (140,145,146), although this has been disputed by others (92). Different authors use various criteria to describe a significant weakness; this can range from 20% (84) to 25% (77,147) and have a significant impact on the sensitivity and specificity of the test. The incidence of diminished caloric response by ENG for AN patients is presented in Table 11. More recently, head-shaking nystagmus (HSN) has been studied as a possible screening test for ANs. Humphriss et al. (27) studied 102 AN patients seen preoperatively. They used a passive head-shaking maneuver (1–2 Hz) and recorded eye movements with an ENG system. A significant response was five or more beats of nystagmus with a slow phase of at least 3 degrees/sec. In their study, significant caloric paresis was ≥ 25%. All patients had tumors confirmed by MRI and surgery. They found HSN in only 22 patients (i.e., sensitivity 22%). HSN was contralaterally beating in 19 patients (86%), ipsilaterally beating in three patients (14%), but absent in the remaining 80%. HSN was found more often in patients with either a greater canal paresis or have central vestibular signs than patients without HSN; however, the sensitivity still remains low [only 36% sensitivity even with severe (75–100%) canal paresis] (27). A low sensitivity rate (47.6%) for HSN was also reported by Asawavichiangianda et al. (148) for ANs. The range of reported sensitivity and specificity of HSN has been tabulated by Humphriss et al. (27). Sensitivity ranges from 22% to 95%; and specificity for a unilateral vestibular

Chapter 5: Head, Neck, and Neuro-otologic Assessment of Patients with Tumors of the Skull Base

(A)

30

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Figure 11 (A) Distortion product otoacoustic emissions (marked with Xs) from left ear of same patient with ipsilateral intracanalicular acoustic neuroma. Emissions are diminished but present from 1 to 3 kHz, and absent for higher frequencies, consistent with the audiometric findings. (B) Distortion product otoacoustic emissions (marked by circles) from right ear from same patient with left intracanalicular acoustic neuroma and are normal from 1 to 4 kHz.

disorder ranges from 53% to 92%. Across the 10 studies reviewed, many different criteria are used for the “gold standard” with ENG canal paresis definitions ranging from greater than 13% to greater than 30% difference. Additionally, the methods (active vs. passive) and nature of HSN (e.g., >3 beats, >5 beats, >2.5 degrees/sec, >6 degrees/sec) differed

across these different studies, which points out the variable nature of definitions used for HSN. Optokinetic and smooth pursuit abnormalities, when present, are reliable signs of brainstem compression (140). Berrettini (83) found a higher frequency of central findings in tumors greater than 3 cm.

Table 11 Incidence of Diminished Caloric Response by ENG Study Linthicum, 1979 (142) Haapaniemi, 2000 (144) Berrettini, 1996 (83) Naessens, 1996 (143) Godey, 1998 (84)

Small 43% Intracanalicular 55% Small tumors (<1 cm) 4/5 Overall 62.5% Overall 86%

Medium (1.1–3 cm) 16/18

Large 95% Extracanalicular 67% Large tumor (>3 cm) 16/16

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Caloric testing has been examined as a predictor of hearing preservation. The horizontal semicircular canal is stimulated through caloric testing, and thus an insight is gained regarding the superior vestibular nerve (144). Small superior vestibular nerve tumors have a more favorable prognosis for hearing preservation (77,113,149). Thus, it is reasoned that patients with reduced or absent caloric responses have a better chance of hearing preservation, since the superior vestibular nerve is involved. However, in practice, caloric results are not so clear cut. Linthicum (142) showed that 97.2% of superior nerve tumors had a caloric weakness, while only 60% of inferior vestibular nerve tumors had a caloric weakness. Holsinger et al. (150) examined 47 AN cases with planned hearing preservation. Their overall rate of measurable hearing postoperatively was 60%. ENG was obtained on 36 patients. Twenty-five patients demonstrated a significant unilateral weakness and measurable hearing was preserved in 14 (56%). Eleven patients had no caloric weakness and five had hearing preservation (45%). Brackmann et al. (77) published their series of 333 patients with tumors less than 2 cm considered candidates for hearing preservation. ENG was performed in 261 patients: 49% had “normal reduced response” (i.e., ≤25% weakness) and 51% had a reduced vestibular response (i.e., >25% weakness). They found similar rates of reduced responses across all hearing categories and that no significant difference existed between the preserved hearing groups and the no measurable hearing group (77). Despite its lack of sensitivity and its inability to discern superior from inferior nerve of origin, ENG might be helpful in identifying patients preoperatively that will have prolonged imbalance postoperatively. Driscoll et al. (151) found that central signs seen on ENG in AN patients portended a higher incidence of persistent (>3 mo) disequilibrium than those without central signs. Age greater than 55.5 years, female gender, constant preoperative disequilibrium present for >3.5 months were also associated with prolonged postoperative disequilibrium in their study.

Other Tumors The literature regarding ENG findings in meningioma is scant compared with that for ANs. Baguley et al. (100) compared the results of 18 of their patients with the tabulated results of caloric testing performed in four previous studies. Overall, abnormal caloric results were found in 55/67 (82%) patients; and the incidence of abnormal ABR ranged from 66% to 95% among the five studies. Marangos et al. (110) examined 309 CPA tumors, including 17 meningiomas, found on either CT or MRI. In the four meningiomas with normal ABR, ENG was normal in three. The article does not reveal the ENG results of the other 13 cases of meningiomas.

Rotatory Chair Testing Rotatory chair testing uses a computer controlled rotational stimulus of the horizontal VOR (usually from 0.01–0.64 Hz). Rotational stimuli produce a reflex, slow eye movement in the opposite direction of rotation with a rapid corrective saccade contralaterally (147). Gain, phase, asymmetry, and failure of visual fixation can be calculated at each test frequency and compared to age-specific normative data. The definition of abnormal findings varies from center to center, but a generally accepted rule is an abnormality of gain, phase, or symmetry seen in two frequencies (147). As with most balance tests, a “gold standard” is lacking with which to compare sensitivity and specificity. Most

Table 12 Test Conditions in Computerized Dynamic Posturography Sensory Organization Test Test 1 2 3 4 5 6

Condition Eyes open, fixed support Eyes closed, fixed support Visual surround referenced to sway, fixed support Eyes open, force plate referenced to sway Eyes closed, force plate referenced to sway Force plate and visual surround referenced to sway

reports on dizziness evaluation rely on history and physical findings to indicate “normal” and “abnormal”. Since the examining physicians are also the interpreting physicians of the balance test, there are no blinded comparison reviews. Rotary chair has been compared with ENG for sensitivity and specificity in identifying patients with vestibulopathy. In this regard, rotary chair has a higher sensitivity for peripheral vestibular pathology than ENG, but the specificity of ENG is higher than rotary chair (147).

Computerized Dynamic Posturography Computerized dynamic posturography (CDP) has been clinically available since 1986 (152). This test has two distinct parts: motor control test (MCT) and somatosensory organization test (SOT). MCT is a technique used to measure the functional ability of the subject to create adequate motor responses to changes in the pitch plane (58). Three trials are made of small, medium, large forward and backward movement and the latency, amplitude and symmetry of neuromuscular response to this movement (152). Electromyography (EMG) and biomechanical measures can be used to track the patient’s responses to each balance perturbation. The commercially available Neurocom MCT uses a strain gauge in the support surface, and not EMG, to track ankle-torque corrections during balance-correction. Normal latencies range between 130 and 160 msec for medium and large perturbations. The SOT measures the relative contributions from the vestibular, proprioceptive, and visual systems to maintain balance. This test uses a force platform, which can be stable or referenced to sway (move in a horizontal plane or pitch back and forth), and a visual surround, which can be stationary or referenced to sway, to determine the relative importance of visual, somatosensory, and vestibular input (153,154). Six different testing situations are created by combinations of stationary or moving force plate and stationary or moving visual surrounds (Table 12). The computer can change the position of the force plate or visual surround so that it remains in the same position relative to the patient’s sway (“sway referenced”). The interested reader is encouraged to read Allum and Sheperd’s (58) excellent review of this topic. The most commonly recognized pattern with vestibular lesions is abnormalities in situations five and six. Although CDP does not help in localizing a lesion, it does provide a functional measure of a patient’s ability to use properly the various input systems to maintain balance (153–155). Sensitivity of CDP to pick up vestibular pathology, in comparison to ENG, has been evaluated (141); however, these two modalities provide different types of information. Since not all imbalances are due to a vestibular lesion, CDP might certainly be abnormal in a patient with a normal ENG. Nonetheless, CDP gives information that is helpful regarding the functional status of the patient and might help to tailor a rehabilitation program for that patient (152).

Chapter 5: Head, Neck, and Neuro-otologic Assessment of Patients with Tumors of the Skull Base

Levine et al. (156) used preoperative CDP to determine the nerve of origin for ANs less than 1.5 cm. In a small series, they found that patients with an inferior vestibular nerve tumor had abnormalities on SOT in conditions five and six, while patients whose tumors were from the superior vestibular nerve had normal CDP findings. Bergson and Sataloff (157) examined 21 patients with AN using CDP. They found abnormal test results in 81%, usually in conditions five and six. They found no correlation between the presence or severity of preoperative CDP results and postoperative balance function. Similar findings were reported by El-Kashlan et al. (155). Collins et al. (158) examined changes in balance following AN resection using balance posturography. They found patterns of abnormal sway and prolonged recovery times both pre- and postoperative, and these were most marked one month postoperatively. The limitations of CDP are that it does not provide lateralizing information or any information regarding cause (153). However, CDP does provide insight into how well patients can use their balance and how imbalance affects their activities of daily living.

Vestibular Evoked Potentials Vestibular evoked myogenic potentials (VEMPs) are shortlatency potentials recorded from surface electrodes over the tonically contracted SCM muscle evoked by high-level acoustic stimuli (159). The test subject is seated upright and asked to turn the head to the opposite side of the tested muscle. Surface electrodes are placed over the upper half of the SCM, while a ground electrode is placed on the forehead or sternum. Click stimuli sounds are delivered to the ipsilateral ear at intensities of 85 to 100 dB, and EMG is measured. The source of these responses is thought to be saccule. Matsuzaki et al. (160) described two patients with AN that had normal ABR results but abnormal VEMP. The tumors were 8 and 10 mm in size. They concluded that VEMP might be useful in the early diagnosis of ANs in patients with normal ABR. In a follow-up study, they review their experience with 87 AN patients, 79% of whom had decreased or absent VEMPs (161). Murofishi et al. (162) examined 21 patients with AN. They found abnormal or diminished VEMP ipsilateral to the tumor in 80% of patients, while all contralateral VEMPs were normal. Takeichi et al. (163) studied 18 patients with AN. They found diminished VEMP on the affected side in 13 patients (72%). They did not find any correlation with disequilibrium, spontaneous nystagmus, canal paresis, or pure-tone hearing. Tsutsumi et al. (164) examined 28 patients with AN and VEMP. They found no correlation between VEMP and caloric response, nerve of origin, audiometric threshold, or size of tumor. In a larger study of 170 patients with AN, Patko et al. (165), found abnormally low or absent VEMPs in 78.8% of patients. They did not find any correlation with horizontal canal weakness. Rauch has shown that VEMP has usefulness in the diagnosis of superior semicircular canal dehiscence syndrome and Meniere disease (166). Additionally, VEMP might provide some insight into brainstem pathology from stroke (167) or multiple sclerosis (168); however, at the time of this writing, their utility with AN or other skull base tumors is limited.

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CONCLUSION The evaluation of patients with skull base tumors requires a rigorous history and physical examination. Careful evaluation of cranial nerve function is demanded. The examining physician should be aware of nontumor conditions that can mimic the findings of a skull base tumor. Judicious use of ancillary tests of neuro-otologic function helps in determining the extent of disease and plays an important role in deciding treatment methods. Some of these tests can be used to predict postoperative hearing and balance function.

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109. Josey AF, Jackson CG, Glasscock ME 3rd. Brainstem evoked response audiometry in confirmed eighth nerve tumors. Am J Otolaryngol. 1980;1(4):285–290. 110. Marangos N et al. Brainstem response in cerebellopontine angle tumors. Otol Neurotol. 2001;22(1):95–99. 111. Cueva RA. Auditory brainstem response versus magnetic resonance imaging for the evaluation of asymmetric sensorineural hearing loss. Laryngoscope. 2004;114(10):1686–1692. 112. Bauch CD, Rose DE, Harner SG. Auditory brain stem response results from 255 patients with suspected retrocochlear involvement. Ear Hear. 1982;3(2):83–86. 113. Wilson DF et al. The sensitivity of auditory brainstem response testing in small acoustic neuromas. Laryngoscope. 1992;102(9):961–964. 114. Dornhoffer JL, Helms J, Hoehmann DH. Presentation and diagnosis of small acoustic tumors. Otolaryngol Head Neck Surg. 1994;111(3 Pt 1):232–235. 115. Chandrasekhar SS, Brackmann DE, Devgan KK. Utility of auditory brainstem response audiometry in diagnosis of acoustic neuromas. Am J Otol. 1995;16(1):63–67. 116. Zappia JJ et al. Rethinking the use of auditory brainstem response in acoustic neuroma screening. Laryngoscope. 1997;107(10):1388–1392. 117. Burkey JM et al. Acoustic reflexes, auditory brainstem response, and MRI in the evaluation of acoustic neuromas. Laryngoscope. 1996;106(7):839–841. 118. Musiek FE, Kibbe K. Auditory brain stem response wave IVV abnormalities from the ear opposite large cerebellopontine lesions. Am J Otol. 1986;7(4):253–257. 119. Rupa V et al. Cost-effective initial screening for vestibular schwannoma: Auditory brainstem response or magnetic resonance imaging? Otolaryngol Head Neck Surg. 2003;128(6):823– 828. 120. Nadol JB Jr et al. Preservation of hearing and facial nerve function in resection of acoustic neuroma. Laryngoscope. 1992;102(10):1153–1158. 121. Matthies C, Samii M. Management of vestibular schwannomas (acoustic neuromas): The value of neurophysiology for intraoperative monitoring of auditory function in 200 cases. Neurosurgery. 1997;40(3):459–466; discussion 466–468. 122. Nadol JB Jr et al. Preservation of hearing in surgical removal of acoustic neuromas of the internal auditory canal and cerebellar pontine angle. Laryngoscope. 1987;97(11):1287–1294. 123. Kemink JL et al. Hearing preservation following suboccipital removal of acoustic neuromas. Laryngoscope. 1990;100(6):597– 602. 124. Stidham KR, Roberson JB Jr. Hearing improvement after middle fossa resection of vestibular schwannoma. Otol Neurotol. 2001;22(6):917–921. 125. House JW, Brackmann DE. Brainstem audiometry in neurotologic diagnosis. Arch Otolaryngol. 1979;105(6):305–309. 126. Laird FJ et al. Meningiomas of the cerebellopontine angle. Otolaryngol Head Neck Surg. 1985;93(2):163–167. 127. Granick MS et al. Cerebellopontine angle meningiomas: Clinical manifestations and diagnosis. Ann Otol Rhinol Laryngol. 1985;94(1 Pt 1):34–38. 128. Aiba T et al. Clinical characteristics of rare cerebellopontine angle tumours: Comparison with acoustic tumors. In: Proceedings of the First International Conference on Acoustic Neuroma. New York, NY: Kugler, 1992. 129. Hart MJ, Lillehei KO. Management of posterior cranial fossa meningiomas. Ann Otol Rhinol Laryngol. 1995;104(2):105– 116. 130. Don M et al. Successful detection of small acoustic tumors using the stacked derived-band auditory brain stem response amplitude. Am J Otol. 1997;18(5):608–621; discussion 682–685. 131. Philibert B et al. Stacked tone-burst-evoked auditory brainstem response (ABR): Preliminary findings. Int J Audiol. 2003;42(2):71–81. 132. Gold T. Hearing II. The physical basis of the action of the cochlea. Proc Royal Soc Britain. 1948;135:492–498. 133. Kemp DT. Stimulated acoustic emissions from within the human auditory system. J Acoust Soc Am. 1978;64(5):1386–1391.

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134. Hall J. Handbook of Otoacoustic Emissions. San Diego, CA: Singular, 2000. 135. Brownell WE et al. Evoked mechanical responses of isolated cochlear outer hair cells. Science. 1985;227(4683):194–196. 136. Kim AH et al. Transient evoked otoacoustic emissions pattern as a prognostic indicator for hearing preservation in acoustic neuroma surgery. Otol Neurotol. 2006;27(3):372–379. 137. Burns EM, Arehart KH, Campbell SL. Prevalence of spontaneous otoacoustic emissions in neonates. J Acoust Soc Am. 1992;91(3):1571–1575. 138. Ferber-Viart C et al. Is the presence of transient evoked otoacoustic emissions in ears with acoustic neuroma significant? Laryngoscope. 1998;108(4 Pt 1):605–609. 139. Jongkees LB, Philipszoon AJ. Electronystagmography. Acta Otolaryngol Suppl. 1964;189. 140. McGee ML. Electronystagmography in peripheral lesions. Ear Hear. 1986;7(3):167–175. 141. Amin M et al. A comparison of electronystagmography results with posturography findings from the BalanceTrak 500. Otol Neurotol. 2002;23(4):488–493. 142. Linthicum F, Khalessi M, Churchill D. Electronystagmographic caloric bithermal vestibular test (ENG): results in acoustic tumor cases. In: House and Luetje C eds. Acoustic Tumors. Baltimore: University Park Press, 1979 pp 237–240. 143. Naessens B et al. Re-evaluation of the ABR in the diagnosis of CPA tumors in the MRI-era. Acta Otorhinolaryngol Belg. 1996;50(2):99–102. 144. Haapaniemi JJ et al. Audiovestibular findings and location of an acoustic neuroma. Eur Arch Otorhinolaryngol. 2000;257(5):237– 241. 145. Bergenius J, Magnusson M. The relationship between caloric response, oculomotor dysfunction and size of cerebello-pontine angle tumours. Acta Otolaryngol. 1988;106(5-6):361–367. 146. Guyot JP et al. Diagnosis of cerebellopontine angle tumors. ORL J Otorhinolaryngol Relat Spec. 1992;54(3):139–143. 147. Arriaga MA, Chen DA, Cenci KA. Rotational chair (ROTO) instead of electronystagmography (ENG) as the primary vestibular test. Otolaryngol Head Neck Surg. 2005;133(3):329–333. 148. Asawavichiangianda S et al. Significance of head-shaking nystagmus in the evaluation of the dizzy patient. Acta Otolaryngol Suppl. 1999;540:27–33. 149. Shelton C et al. Acoustic tumor surgery. Prognostic factors in hearing conversation. Arch Otolaryngol Head Neck Surg. 1989;115(10):1213–1216. 150. Holsinger FC, Coker NJ, Jenkins HA. Hearing preservation in conservation surgery for vestibular schwannoma. Am J Otol. 2000;21(5):695–700. 151. Driscoll CL et al. Preoperative identification of patients at risk of developing persistent dysequilibrium after acoustic neuroma removal. Am J Otol. 1998;19(4):491–495. 152. Voorhees RL. The role of dynamic posturography in neurotologic diagnosis. Laryngoscope. 1989;99(10 Pt 1):995–1001. 153. Furman JM. Role of posturography in the management of vestibular patients. Otolaryngol Head Neck Surg. 1995;112(1):8–15.

154. Monsell EM et al. Computerized dynamic platform posturography. Otolaryngol Head Neck Surg. 1997;117(4):394– 398. 155. El-Kashlan HK et al. Disability from vestibular symptoms after acoustic neuroma resection. Am J Otol. 1998;19(1):104– 111. 156. Levine SC, Muckle RP, Anderson JH. Evaluation of patients with acoustic neuroma with dynamic posturography. Otolaryngol Head Neck Surg. 1993;109(3 Pt 1):392–398. 157. Bergson E, Sataloff RT. Preoperative computerized dynamic posturography as a prognostic indicator of balance function in patients with acoustic neuroma. Ear Nose Throat J. 2005;84(3):154–156. 158. Collins MM et al. Dynamic assessment of imbalance in acoustic neuroma patients by sway magnetometry. Clin Otolaryngol. 2000;25(6):570–576. 159. Akin FW, Murnane OD. Vestibular evoked myogenic potentials: Preliminary report. J Am Acad Audiol. 2001;12(9):445-452; quiz 491. 160. Matsuzaki M, Murofushi T, Mizuno M. Vestibular evoked myogenic potentials in acoustic tumor patients with normal auditory brainstem responses. Eur Arch Otorhinolaryngol. 1999;256(1):1– 4. 161. Ushio M et al. Click- and short tone burst-evoked myogenic potentials in cerebellopontine angle tumors. Acta Otolaryngol Suppl. 2001;545:133–135. 162. Murofushi T, Matsuzaki M, Mizuno M. Vestibular evoked myogenic potentials in patients with acoustic neuromas. Arch Otolaryngol Head Neck Surg. 1998;124(5):509–512. 163. Takeichi N et al. Vestibular evoked myogenic potential (VEMP) in patients with acoustic neuromas. Auris Nasus Larynx. 200128 Suppl:S39–S41. 164. Tsutsumi T et al. Prediction of the nerves of origin of vestibular schwannomas with vestibular evoked myogenic potentials. Am J Otol. 2000;21(5):712–715. 165. Patko T et al. Vestibular evoked myogenic potentials in patients suffering from an unilateral acoustic neuroma: A study of 170 patients. Clin Neurophysiol. 2003;114(7):1344–1350. 166. Rauch SD. Vestibular evoked myogenic potentials. Curr Opin Otolaryngol Head Neck Surg. 200614(5):299–304. 167. Chen CH, Young YH. Vestibular evoked myogenic potentials in brainstem stroke. Laryngoscope. 2003;113(6):990–993. 168. Alpini D et al. Vestibular evoked myogenic potentials in multiple sclerosis: Clinical and imaging correlations. Mult Scler. 2004;10(3):316–321. 169. Josey AF, Glasscock ME 3rd, Musiek FE. Correlation of ABR and medical imaging in patients with cerebellopontine angle tumors. Am J Otol. 1988;9 Suppl:12–16. 170. Weiss MH, Kisiel DL, Bhatia P. Predictive value of brainstem evoked response in the diagnosis of acoustic neuroma. Otolaryngol Head Neck Surg. 1990;103(4):583–585. 171. Noguchi Y, Komatsuzaki A, Nishida H. Cochlear microphonics for hearing preservation in vestibular schwannoma surgery. Laryngoscope. 1999;109(12):1982–1987.

6 Anesthesia and Intraoperative Monitoring of Patients with Tumors of the Skull Base Walter S. Jellish and Steven B. Edelstein

INTRODUCTION

for posterior fossa surgeries, with some modifications. The prone position is particularly useful for accessing lesions at or near midline and the fourth ventricle (3). Prone positioning is associated with numerous hemodynamic and respiratory changes that must be monitored closely. Significant V/Q mismatching is present in the prone position and access to the airway is compromised. Vigilance by the anesthesiologist is required when positioning the patient since dislodging of the endotracheal tube will require emergency re-intubation in suboptimal conditions. When transferring patients from supine to prone, significant hemodynamic changes can occur, secondarily to acute changes in preload from either abdominal compression or thoracic impedance. Cardiac dysrhythmias may occur from changes in preload as a result of this compression, thus electrocardiographic monitoring is essential (4). Several items, such as chest rolls and orthopedic frames, have been developed to help decrease these side effects. Some of the frames include: the Jackson spine table, simple chest and abdominal rolls composed of fabric or gel, and padded square frames that have a large opening for the abdominal contents. Each frame or support device is associated with its own series of risks and benefits that is beyond the scope of this article. Other than hemodynamic and respiratory problems associated with the prone position, if a slight head-up position is used, the patient is at risk for venous air embolism (VAE). VAE is a significant concern during skull base procedures and this will be discussed in further detail later in this chapter. Prolonged prone positioning has also been associated with significant facial edema, orbital/facial swelling, central venous retinal thrombosis, and posterior ischemic optic neuropathy—a disastrous condition that can result in permanent blindness.

Many issues surround the administration of anesthesia for patients undergoing surgery of the skull base. Not only are there the difficulties surrounding exposure of deeply seated anatomic structures, but there are also issues regarding positioning, prevention of iatrogenic nerve injury, and blood loss. This chapter describes many of the issues surrounding the delivery of anesthesia for skull base surgery and will touch on some of the neurophysiological monitors that can be used to improve the outcome. The review of this subjective matter is by no means exhaustive, but is meant to give some insight into the multiple and complex problems faced by the operative team during these procedures.

POSITIONING One of the challenges of skull base surgery has to do with positioning. The exact approach will depend on patient’s anatomy, clinical status, and tumor size. These approaches relate to the bone routes the surgeon will take in order to reach the neoplasm. These approaches include craniofacial, orbitocranial, infratemporal, and suboccipital (transcondylar). Lateral approaches include retrosigmoid, translabyrinthine, and orbitocranial zygomatic (1). Each of these approaches is associated with particular positions that have specific morbidities. Some of these morbidities and concerns will be discussed in further detail.

Supine Position Anterior skull base lesions can be quite difficult to surgically approach, though the physical position of the patient is that of supine. Supine position is, for the anesthesiologist, the easiest one to manage. Access to the airway is simple, though the patient may be rotated 180 degrees. There are limited changes in the patient’s hemodynamic profile, but there are significant changes in the pulmonary system, especially those related to diaphragmatic elevation. This altered diaphragmatic elevation ultimately promotes atelectasis and ventilation-to-perfusion (V/Q) mismatching. Posterior fossa lesions can also be accessed via the supine position, but require the head be laterally rotated and flexed. This flexion is sometimes impossible, especially in the elderly population and may be associated with venous obstruction (2).

Park-Bench Position The park-bench position (lateral oblique position) is commonly used in skull base procedures involving the posterior fossa. It is a semiprone lateral position with the head flexed and slightly elevated—5 to 10 degrees. It is quicker than the true prone and allows both lateral and midline approaches to the posterior fossa (3). The flexion of the neck may impinge on the venous circulation and an obstruction may not always be recognized by examination of the external position (5). This position has less hemodynamic and respiratory effects than the full prone position, but the neck flexion may be associated with brachial plexus injuries if care is not taken when final position is achieved. Extreme flexion may compromise spinal cord perfusion and has been associated with quadriplegia (5).

Prone Position The prone position is one of the most frequently used positions for spine surgery, though it is sometimes used 119

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Lateral Position This position is frequently used for intracerebellar procedures involving lateral or cerebellar hemispheric lesions, lesions of the clivus, petrous ridge, anterior and lateral foramen magnum. Typically the retromastoid, transtentorial, and transcondylar surgical approaches require this position. Again, there are some significant hemodynamic and pulmonary implications to the position. Significant V/Q mismatching takes place, though to a much less degree than the prone position. Some of the disadvantages of this position include the potential for lateral popliteal nerve palsy in the dependent leg, compression of the inferior shoulder and axillary structures, and the superior shoulder being in the line of sight of the surgeon (3). As such, it is important that the anesthesiologist confirms that the final position of the patient is appropriate. Devices such as axillary rolls (designed to decompress dependent axillary neurovascular structures) must be correctly placed and leg positions be padded.

Sitting Position Of all positions used by surgeons involved with skull base procedures, the sitting position has undergone the most scrutiny. The theoretical advantage of the sitting position is that it allows for improved cerebral relaxation and promotes gravity drainage of blood and cerebral spinal fluid (7). However, the complications are numerous and include hemodynamic instability, VAE with the possibility of paradoxical air embolism, pneumocephalus, quadriplegia (especially in the presence of extreme neck flexion), and compressive neuropathy (8,9). Another potential complication includes inadequate cerebral perfusion after assuming the sitting position, but may be balanced by a reduction in cerebral rate of metabolic oxygen consumption (10). Early physiological studies reveal significant changes when a patient assumes the upright position. A change in cardiac and systemic vascular resistance is known to increase 19% and 10%, respectively. In addition, stroke volume and cardiac index may decrease as much as 21% and 10%, respectively (11). In the presence of inhalational anesthetic agents, arterial hypotension may be profound, especially since these agents may cause vasodilation, venous pooling in the lower extremities, and dose-dependent cardiovascular depression (12). It is essential that the anesthesiologist carefully monitor systemic blood pressure as the patient assumes the sitting position. Interventions to maintain blood pressure may include fluid administration, decreasing inhalational agent concentration, compression of distal extremities, and short-term infusions of phenylephrine or other vasoactive drugs. There is a perceived advantage of the sitting position from the point of view of the respiratory system. In this position, access to the chest wall and the airway is obtained, while ventilation is unimpeded because diaphragmatic excursion is greater than in the horizontal position and consequently airway pressure is lower (13). It is important to keep in mind these potential complications when performing skull base procedures in sitting positions. A vital role for the anesthesiologist who is taking care of the sitting patient is to assure that the entire care team participates in the careful positioning of the patient. Goals are to avoid large changes in blood pressure, impairment of ventilation, and avoidance of potential nerve compression and entrapment. Recent reviews have gone as far as to list contraindications for assuming this position, including advanced age, hypertonia, chronic obstructive lung disease, and diagnosed patent foramen ovale (13).

Table 1 Four Grades of Intensity of Venous Air Embolus (VAE) Grade I: characteristic changes in Doppler sounds Grade II: changes in the Doppler sound plus fall of end-expiratory CO2 concentration by more than 0.4% Grade III: changes in Doppler sounds, fall in end-expiratory CO2 concentration, plus aspiration of air through the atrial catheter Grade IV: combination of above signs with arterial hypotension over 20% and/or arrhythmia or other pathological ECG changes Source: From Ref. 14

COMPLICATIONS DURING SKULL BASE PROCEDURES Venous Air Embolism VAE is one of the complications that concern most physicians during skull base surgery. Since skull base procedures commonly deal with venous structures that do not collapse and typically are held open by a bone, it is easy to see that venous air can be entrained via one or several of these open venous plexuses. The occurrence of VAE is especially concerning in patients with patent foramen ovale (present in 10–30% of the population), in which the potential for paradoxical venous air embolus is high. The concern is that changes in hemodynamics may result in right atrial pressures rising higher than left atrial pressures, leading to significant systemic complications such as cerebral infarction. Matjasko and colleagues have described four grades of VAE seen during sitting craniotomies. These grades (I–IV) relate to changes in precordial Doppler sounds, changes in end-tidal carbon dioxide (ETCO2 ) levels, the ability to aspirate air, and the presence of hemodynamic instability (Table 1) (14). Factors that play a role in the development of VAE include the pressure gradient between the surgical field and the right atrium, the surgical technique, and the amount of air entrained. In addition, many neurosurgical patients are hypovolemic, which reduces central venous pressure and further increases the risk of a VAE. Although frequently detected [there was a 72% incidence of VAE detected by transesophageal echocardiography (TEE) in one study (15)], the overall morbidity of VAE is currently low at less than 0.36%. Monitoring for VAE has been extensively described and usually consists of one or more of the following devices (in descending order of sensitivity): TEE, precordial Doppler (in the right third to sixth intercostal space), pulmonary artery pressure, ETCO2 /end-tidal nitrogen, right atrial pressure, electrocardiography (ECG), and esophageal stethoscope (13). Although many clinicians have used a transesophageal echo for detection of VAE because of increased sensitivity, this increase in sensitivity produces too many false positives reducing the specificity as a monitor to detect air entrainment (16). In addition, TEE is expensive and requires trained personnel to be available for interpretation. TEE has also been associated with vocal cord paralysis from recurrent laryngeal nerve palsy after prolonged use. Recommended therapeutic measures in the event of air entrainment include bilateral compression of the jugular veins, having the surgeon flood the wound with saline, discontinuation of nitrous oxide, aspiration of air from a central catheter, and downward tilt of the surgical table (17). The purpose of the atrial catheter is to allow efficient aspiration of trapped air. As such, it is essential that the right atrial catheter be multiorificed in nature. The catheters can be difficult to place, since it is necessary that the catheter tip be in the right atrium, a position that is hard to confirm unless one uses radiographic imaging or ECG tracing (biphasic P-wave morphology). A recent prospective trial regarding the placement

Chapter 6: Patients with Tumors of the Skull Base

of right atrial air aspiration catheters noted that the intravenous ECG P-wave morphology that correlated with the right atrial superior vena cava junction, identified by TEE, was the largest monophasic negative P wave without any biphasic component (18). We prefer the use of an angiographic catheter (Swan-Ganz Angiographic Catheter, Baxter Healthcare Corp, Irvine, CA). This multiorifice catheter is placed in a similar fashion to that of a Swan-Ganz and requires the use of a small pilot balloon at the tip to float the catheter into the right ventricle. Once an right ventricular (RV) waveform is observed, the catheter is withdrawn 1 to 2 cm until the trace disappears. This places the tip in the proper position in the right atrium. Another common practice is changing the position of the patient to left lateral recumbent; however, this has been refuted by Geissler and colleagues (19), who noted that body position had no effect on hemodynamics, nor did the occurrence of right heart failure appear to be related to outflow obstruction. Hypotension and a decrease in coronary perfusion pressure appeared to play more of a role in explaining the cardiovascular effects of air emboli. The role of positive end-expiratory pressure (PEEP) has also come into question. Schmitt and colleagues (15) noted that when PEEP was released, there was a significant occurrence of air emboli as documented by TEE. The group postulates that a sudden decrease of moderate PEEP might decrease right atrial pressure and subsequently increase venous return from cerebral veins. This would result in an increase in air entrainment and possibly an increase in the detectable number of VAE.

Pneumocephalus Another complication associated with skull base surgery is pneumocephalus, defined as the presence of intracranial air. In a retrospective review that compared sitting, park-bench, and prone positioning, 100% of the patients in sitting, 73% of the patients in park-bench, and 57% of the patients in prone positioning had evidence of intraventricular air (20). This has been attributed to the large amount of cerebrospinal fluid (CSF) drained due to gravitational effect. A patient in the sitting position is subject to the effects of gravity more than other positions. Ultimately, more CSF is drained, leading to the high incidence of pneumocephalus seen in the sitting patient. Not every case of intracranial air results in tension pneumocephalus. Historically, approximately 3% of sitting posterior fossa cases are noted to have developed tension pneumocephalus (8). Postoperative care and length of surgery play a role in the development of tension pneumocephalus; however, single contributing factors such as preexisting ventriculo-peritoneal shunts, the utilization of nitrous oxide, or intraoperative diuretics do not appear to play a solitary role (20).

Macroglossia/Facial Swelling A rare, but potentially catastrophic complication of skull base surgeries includes the development of macroglossia. Several case reports describe the occurrence of macroglossia in the immediate postoperative period, but the overall incidence is around 1% (21). Venous drainage of the face, tongue, larynx, and orbits enters the internal jugular system, which, when the neck is maximally flexed, may kink and lead to partial or complete obstruction of the system. In the worse case scenario, this may lead to thrombosis of the internal jugular vein (22). Other theories regarding the etiology of macroglossia also exist, including arterial compression, a neurogenic event,

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reperfusion injury, and impaired lymphatic drainage (5,23). Lam and colleagues (5) believe that there is a significant role for reperfusion injury since many of the cases are not associated with cerebral swelling and edema, a condition one would expect if obstruction of venous drainage of the internal jugular system was present. The risk factors of obesity, neck flexion, local compression, and long surgical duration have been identified and should be kept in mind when patients present for skull base procedures. Regardless of the specific etiology of macroglossia, careful positioning of the head and neck is essential. As a rule of thumb, the authors assure a space of approximately 2 fingerbreadths between the mandible and the clavicle to prevent venous occlusion.

Cerebrovascular Complications Fortunately, cerebrovascular accidents and complications are rare during skull base procedures. Injury to the carotid artery is one of the most feared complications and may lead to stroke and other brain injuries. Repair of the carotid may be required and may include: saphenous vein bypass graft from the extracranial carotid artery to the petrous carotid artery and superficial temporal to middle cerebral artery bypass (26). Usually, preoperatively, when the carotid artery is affected by tumor, a balloon-occlusion test will be performed. This will help to identify those patients who would tolerate the sacrifice of the carotid artery if it became necessary during the procedure. “Blowout injury” is another carotid vascular complication that may occur. This situation is caused when the carotid artery is inadvertently lacerated as a bone spur is being removed. Blood loss may be brisk at the time of the injury and interventions include packing and urgent angiography with balloon occlusion (27). Delayed blowout injury can also occur if the carotid artery is exposed in the nasopharynx; however, this potentially can be prevented with muscle flap coverage (26). Vasospasm has also been reported and may result in stroke. Vasospasm tends to be seen in younger patients and felt to be due to a myogenic reaction in the vessel wall. It may result from arterial contact with fresh blood or arterial traction. Treatment usually consists of topical vasodilators, such as papaverine, though systemic drugs may have a role (28).

Arrhythmias Since many skull base procedures are in the area of the trigeminal and vagus nerves, as well as the brain stem, arrhythmias during the surgical procedure are common. Direct stimulation of the vagus may lead to negative chronotropy and inotropy manifested as sinus bradycardia, bradycardia terminating in asystole, asystole with no bradycardia, and arterial hypotension. When the trigeminal nerve is involved, sensory nerve endings of the trigeminal send signals to the sensory nuclei at the Gasserian ganglion. These signals ultimately continue along the short internuncial nerve fibers to connect with the efferent pathway in the motor nuclei of the vagus nerve. Again, the effects of stimulation of the cardioinhibitory efferent fibers of the vagus are seen (29). In this situation, the anesthesiologist should alert the surgeon and may request that the surgeon release traction or may choose pharmacologic intervention with a vagolytic substance, such as glycopyrrolate or atropine. Atropine, due to its quick onset, may be the drug of choice; however, the duration of action is shorter than that of glycopyrrolate. Over time, the reflex tends to decrease in its intensity. If the skull base surgery involves resection of a glomus jugulare tumor, one needs to be aware if the tumor is

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catecholamine secreting. Glomus jugulare tumors may be considered arteriovenous malformations, may be giant in size, and may be associated with multiple paragangliomas or adrenal tumors. The incidence of catecholamine secretion is around 4% and can be associated with tachyarrhythmias, hypertension, sweating, myocardial infarction, and cardiovascular collapse, which reflects catecholamine excess. It is important for the anesthesiologist to be prepared to treat any hypertensive crises arising from manipulation of a catecholamine secreting glomus jugulare tumor. Appropriate invasive arterial monitoring is essential and utilization of fast- and short-acting vasodilators, such as nitroglycerin, nitroprusside, and to a lesser extent phentolamine. As seen in the surgical cases involving resection of catecholaminesecreting pheochromocytomas, significant hypotension may occur once the output of norepinephrine has been interrupted. As such, short-term utilization of direct arterial vasopressors (such as phenylephrine or norepinephrine) may be needed to maintain adequate cerebral and coronary perfusion pressures. The resection of glomus jugulare tumors may also result in new cranial nerve injuries of up to 7.1%, with the highest being cranial nerve VII and IX (30).

Blood Loss Blood loss during resection of skull base tumors may be significant and the appropriate preoperative measures for such an event are essential. Many of the tumors are highly vascular in nature and preoperative assessment is necessary to delineate involvement of the cavernous sinus and jugular bulb. Of particular note, meningiomas have been shown to produce tissue plasminogen activator and may lead to increased fibrinolysis during resection (31). Other skull base lesions, known for their vascularity, include jugular paragangliomas, vagal paragangliomas, and nasopharyngeal angiofibromas. Preoperative embolization of feeding vessels may lead to decrease blood loss via a decrease in blood flow and pressure through the tumor (26). Maintenance of normovolemia is essential in skull base operations. When to transfuse will depend on the patient’s coexisting disease processes and is always indicated when there are signs of inadequate oxygen delivery to the tissues. Numerous blood conservation techniques are available including utilization of cell salvage devices in the presence of benign tumors, induced hypotension, acute normovolemic hemodilution, and antifibrinolytic therapy. Risks and benefits of each of the conservation techniques must be assessed prior to institution of therapy.

Peripheral Nerve/Cranial Nerve Injuries Protection from peripheral nerve injuries is of major concern during skull base procedures. The peripheral nerves are at particular risk given the multitude of positions assumed during surgery. All positions from supine to seated have been at one time or another associated with nerve injuries. Varying degrees of injury have been described and the Seddon Classification describes three broad classifications of nerve injury. These include neurapraxia, axonotmesis, and neurotmesis. Neurapraxia is a mild insult that results in conduction failure across an affected segment. This is reversible and tends to be the type of injury most seen during surgical procedures. Axonotmesis is when the axon is physically disrupted but the epineurium and perineurium are preserved. Recovery depends on the speed of neural regeneration. The worst injuries are those in which neurotmesis has taken place. In this situation, there is a complete disruption of the nerve and sup-

port structures and the prognosis for recovery is exceedingly poor (32). Although brachial plexus injuries have been described and felt to be secondary to cervical contralateral flexion rotation and lateral rotation of the shoulder and fixation of the shoulder girdle in a neutral position (33), other injuries have been noted including common peroneal nerve injuries leading to footdrop (34). Ulnar nerve injuries may also occur, but the complete etiology of their occurrence has yet to be determined. The role of extension, rotation, obesity, preexisting disease states, such as diabetes mellitus, have been mentioned as possible contributing factors for ulnar nerve injury. Whatever the etiology, meticulous documentation of appropriate intraoperative padding and the awareness of the existence of preexisting neurological defects is essential when taking care of these patients. Peripheral nerves are not the only nerves at risk during skull base procedures. It is well known that cranial nerve injuries are possible, especially when the operation is close to nerve origin. As mentioned earlier, anosmia is a complication of anterior craniofacial resections and may also lead to changes in taste. Transphenoidal approaches for tumor resection may lead to ocular and oculomotor nerve injuries. This may result in the loss of vision or the development of diplopia. Another major cranial nerve injury encountered during skull base procedures involves the vagus. Vagal injuries result in problems with dysphagia and the potential for aspiration. High vagal nerve paralysis can manifest as true vocal cord paralysis, palate paralysis, loss of pharyngeal muscle function, loss of pharyngeal sensation, and failure of cricopharyngeus to relax (26). Postoperative swallowing evaluation and laryngoscopy is indicated to assess these patients prior to allowing oral intake.

MONITORING AND ANESTHESIA Monitoring for skull base procedures depends on the type of procedure to be performed, the vascular and nerve structures that are involved, and the position in which the patient will be placed for the surgery. In all instances, the patient will have standard routine monitoring, such as ECG, noninvasive blood pressure, pulse oximetry, capnography, and temperature. Other monitors are added as the complexity, blood loss, surgical trauma, and comorbidities of the patient are also factored. Monitoring for skull base procedures must assure for adequate central nervous system perfusion, maintenance of cardiovascular stability and the integrity of the neurologic pathways that are being manipulated. Arterial line placement is the standard for most intracranial and extracranial procedures of the skull base. Invasive blood pressure monitoring provides for closer control of blood pressure and better titration of hyperventilation and blood pH. In addition, hemoglobin levels and electrolyte abnormalities can be easily detected by following serial arterial blood samples obtained from this catheter. Central access with either large-bore single lumen or double lumen catheters is contingent on the length of the surgery, anticipated blood loss, need for estimation of central vascular volume, and position of the patient. Depending on tumor type and location, neurophysiologic monitoring may also be employed to detect disruption of neural tracts or trauma to cranial nerves that may be near the site of surgery. Cranial nerve monitoring has markedly decreased postoperative morbidity after skull base surgery. Electromyography (EMG) of the facial nerve, vagus

Chapter 6: Patients with Tumors of the Skull Base

or trigeminal nerve is used during surgical resection to identify the nerve and preserve neurologic integrity, especially if the nerve is surrounded by a tumor (35). EMG of cranial nerves provides early recognition of surgical trauma, facilitates tumor excision, identifies nerve dysfunction, and confirms nerve function after the tumor is removed. The use of muscle relaxants in conjunction with facial nerve monitoring may be problematic. Muscle relaxants prevent movement and reduce the amount of anesthetic agents needed. At any given level of neuromuscular blockade, a facial muscle response is more resistant to neuromuscular blocking agents than a peripheral muscle (36). This is due to larger motor unit size and the increased number of neuromuscular junctions in the facial muscles. Several studies have demonstrated that neuromuscular blockade, titrated to a T1 of 25%, still allows adequate response from compound motor action potentials of facial muscles to adequately monitor nerve function (37). Nerve irritation and tumor infiltration, however, can lead to reduced or blocked conduction. Preoperative partial facial paralysis may make the monitoring difficult. In addition, external or mechanical noise artifacts could mask muscular contraction and if high-dose inhalational agents are used, muscle activity with nerve stimulation can be further reduced. If muscle relaxants must be used to facilitate surgical resection, alternative methods to monitor the facial nerve may be used. The first method stimulates the nerve at the stylomastoid foramen (38). Antidromic responses are recorded in the operative field. However, this method is awkward to use and does not provide the information obtained by continuous recording. Nerve action potentials can also be recorded at the stylomastoid junction; however, this technique is an evoked response. There is no audible feedback compared to EMG and no information concerning this method’s sensitivity in detecting injury. The final method that may be used to determine facial nerve integrity in the presence of muscle relaxants is the brain stem facial evoked response (39); this nerve monitoring method is based on cross auricular responses to sound that controls ear movement. The facial nerve response is recorded at the mastoid after sound stimulation of the contralateral ear. This technique is technically challenging because of the need for digital computer filtering. The best conditions for monitoring cranial nerve function would be with an anesthetic technique that avoids muscle relaxants. Newer inhalational agents such as sevoflurane and desflurane have low blood gas partition coefficients and reduced fat solubility. These agents produce a rapid induction and emergence with minimal accumulation of anesthetics even after prolonged anesthesia. In addition, short-acting opioids such as remifentanil are extremely potent and have minimal accumulation when given as an infusion. The half life is three to eight minutes and metabolism is produced by nonspecific esterases. The anesthetic technique that produces the best operating conditions for surgery and cranial nerve monitoring uses an anesthetic induction with propofol and fentanyl coupled with an intermediate acting muscle relaxant to facilitate intubation. Maintenance of anesthesia is provided with low-dose desflurane or sevoflurane administered in a 50:50 air/O2 mixture with a background infusion of either fentanyl 2 µg/kg/hr or remifentanil 0.25–0.35 µg/kg/min. No further muscle relaxants are administered as the initial dose is reversed by the time surgery begins. Brain stem auditory evoked potentials (BAEPs) and somatosensory evoked potential (SSEP) monitoring may also be used during resection of skull base tumors, especially if there is possible vascular compromise or ischemia due to temporary occlusion of vascular structures or manipulation

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of the brain stem. Recording short-latency auditory responses by electrocochleography determines the status of the cochlea and nerves peripheral to the tumor while BAEPs monitor activity central to the tumor (40). Headphone stimulators are unacceptable in the operating room because of their size. Small electrodes are used, the most important of which is placed near the mastoid, on or in the ear. The reference electrode is placed at the top of the head and the ground electrode is placed on the forehead. In general, anesthetic affects on the brain stem auditory evoked response are not dramatic. Slow shifts may be seen as the concentration of inhalational agents increase. Since these recordings are of small amplitude, thousands of responses must be recorded to acquire an adequate average. Frequently, the responses are abnormal and smaller than normal due to the effects of the tumor. Also the time interval required to acquire sufficient responses may reduce the sensitivity of this technique in determining neural injury during tumor removal. Of primary importance for intraoperative monitoring are waves I, III, and V. The interpeak latency I–III provides information regarding the integrity of the peripheral component of the auditory pathway. Shortlatency BAEPs are usually resistant to both intravenous and inhalational agents. Increasing blood levels of barbiturates and ketamine will increase interpeak latency. Propofol however, given at 2 mg/kg/bolus followed by an infusion will increase the latency of I, III, and V waves by <5% without changes in amplitude (41). Inhalational agents such as isoflurane, sevoflurane, and desflurane also increase the latency of the waveform without an appreciable change in amplitude. Hypercapnia does not change BAEP’s waveforms but hypoxia in the presence of normal perfusion will depress waveform amplitude (42). If a decrease in perfusion pressure accompanies hypoxia, all evoked responses become depressed or isoelectric. Body temperature will also affect BAEP with reduced temperature prolonging latency of the observed waveform. Brain stem auditory evoked response amplitude is variably affected by hypothermia. In some studies, amplitude increased with progressive hypothermia reaching a maximum at 28–38 ◦ C (43). At a temperature below 23 ◦ C, however, BAEP waveforms disappeared. In most instances where changes in waveform were due to anesthetics, the observations will occur bilaterally. Unilateral decreases in waveform activity would be indicative of nerve damage secondary to surgical manipulation. The major advantage of intraoperative monitoring with electrocochleography is the detectability of the response. Electrocochleography has a much larger amplitude and these responses can be detected clearly within a few seconds, while detection of BAEP requires minutes. The two recording techniques compliment each other in terms of the regions of the auditory system monitored. There are a number of technical problems that must be overcome with electrocochleographic monitoring. It is necessary to position a recording electrode against the promontorium of the middle ear. As such, this electrode could damage the eardrum or become easily dislodged. The N1 wave is exceedingly large and its loss inevitably predicts postoperative deafness. Both electrocochleography and Brainstem Auditory Evoked Responses (BAER) are considered short-latency responses and, as such, are not markedly affected by inhalational anesthetics. Anesthetic techniques utilizing 1 minimum alveolar concentration (MAC) or less of inhalational anesthetic with or without the addition of nitrous oxide (N2 O) combined with an opioid infusion provide optimum conditions for monitoring these responses to assess cochlear activity.

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Jellish and Edelstein Table 2 Effect of Inhaled Anesthetics on Somatosensory Evoked Potentials Early cortical waveform Anesthetic drug/concentration Halothane (24, 26, 34) 0.5 MAC + 60% N2 O 1.0 MAC + 60% N2 O 1.5 MAC + 60% N2 O 1.5 MAC (alone) Isoflurane (23–28,31,35,36) 0.5 MAC + 60% N2 O 0.5 MAC (alone) 1.0 MAC + 60% N2 O 1.0 MAC (alone) 1.5 MAC + 60% N2 O∗ 1.6 MAC (alone)∗ Enflurane (24–26) 0.5 MAC + 60% N2 O 0.2–0.6 MAC (alone) 1.0 MAC + 60% N2 O∗ 1.5 MAC + 60% N2 O 1.5 MAC (alone)∗ Sevoflurane (32,33) 0.5 MAC + 66% N2 O 1.0 MAC + 66% N2 O 1.5 MAC + 66% N2 O 1.7–2.5 MAC Desflurane (38,39) 0.5 MAC 1.0 MAC 1.5 MAC Any with 65% N2 O† Nitrous oxide (39,41,47) 60–65%

Latency

Amplitude

Subcortical waveform

<10% ↑ <10% ↑ 10–15% ↑ 10–15% ↑

≈60% ↓ ≈70% ↓ ≈80% ↓ ≈70% ↓

Negligible Negligible Negligible Negligible

<10% ↑ <15% ↑ 10–15% ↑ 15% ↑ >15% ↑ 15–20% ↑

50–70% ↓ <30% ↑ 50–75% ↓ ≈50% ↓ >75% ↓ 60–70% ↓

Negligible Negligible Negligible Negligible 5% ↑ in latency 5% ↑ in latency 20% ↓ in amplitude

<10% ↑ <10% ↑ 20% ↑ Not recordable >25% ↑

≈50% ↓ <20% ↓ ≈85% ↓ Not recordable ≈85% ↓

Negligible NA Negligible Negligible Negligible

<5% ↑ <10% ↑ <10% ↑ 10–15% ↑

38% ↓ ≈45% ↓ ≈50% ↓ ≈100% ↑

Negligible Negligible Negligible NA

<5% ↑ 3–8% ↑ ≤10% ↑ ≥15% ↑

<20% ↓ 30–40% ↓ <50% ↓ >60% ↓

Negligible Negligible Negligible Negligible

No effect

50–55% ↓

Negligible

NA = data not available; negligible = less than 5% change in latency; ↑ = increase; ↓ = decrease. All data are from humans. ∗ In a substantial fraction of patients, waveforms were not attainable at this concentration. † Complete loss of waveform observed only with 1.5 minimum alveolar concentration (MAC) desflurane plus 65% nitrous oxide (N2 O). Source: From Ref. 45.

Finally, somatosensory evoked responses may also be used to assess the integrity of the brain stem and other subcortical structures during surgical procedures involving the skull base. SSEP represents reproducible electrical activity of cortical and subcortical structures locked to a peripheral nerve stimulus. Diagnostic criteria to evaluate intraoperative waveform changes, diagnostic of spinal cord or brain stem dysfunction, are difficult to establish. A decrease in amplitude of 50% or greater and an increase in latency of 10% or greater constitute a significant change that should be investigated (44). Because SSEP has a central component to its measurement, it is very sensitive to the effects of anesthetic agents. All volatile anesthetics produce a dose-dependent increase in SSEP latency, an increase in central conduction time, and a decrease in amplitude (Table 2) (45). Satisfactory monitoring of early cortical SSEPs is possible with 0.5 to 1.0 MAC of halothane, enthrane, and isoflurane. With deep inhalational anesthesia (1.6 MAC), the early cortical N-20 waveform was reproducible but the amplitude was severely decreased (46). The effect of volatile agents on cortical SSEP amplitude is compounded by N2 O. In the presence of 1 MAC isoflurane and N2 O, cortical SSEP demonstrated a 75% decrease in waveform amplitude (47). The newer volatile anesthetics, desflurane and sevoflurane, affect SSEPs like isoflurane but

permit the use of higher inhaled concentrations (upwards of 1.5 MAC). How volatile anesthetics differ quantitatively is still not totally known, but sevoflurane and desflurane are associated with less amplitude reduction than isoflurane at a MAC range of 0.7 to 1.3 (48). Intravenous anesthetics generally affect SSEPs less than inhaled anesthetics. SSEP waveforms are preserved even at high doses of narcotics and barbiturates. Intravenous agents only modestly affect early and intermediate SSEP components. Most authors report clinically unimportant changes in SSEP latency and amplitude with the administration of opioids given in either anesthetic or analgesic doses. McPherson et al. found minimal SSEP changes after 25 µg/kg fentanyl (49). They noted a small increase in cortical median nerve SSEP latency and a variable decrease (0–30%) in amplitude after 36 to 71 µg/kg fentanyl was administered. This makes opioids useful as part of the anesthetic technique when intraoperative neurophysiologic monitoring is used. Propofol affects the SSEP waveform by increasing latency and decreasing central amplitude in a dose-dependent manner. This drug affects synaptic transmission more than axonal conduction. However, when given as either a bolus or an infusion, it can still be used to monitor central SSEP. When used as a sedative hypnotic along with opioids, propofol reduces SSEP amplitudes less than N2 O or

Chapter 6: Patients with Tumors of the Skull Base

midazolam. Anesthetics that result in latency prolongation or amplitude depression may confuse the interpretation of SSEP changes and potentially risk either not detecting a critical event or providing excessive false positive interpretations. These anesthetic regimens should be avoided. Anesthetic techniques where high-dose inhalational agents, at greater than 1 to 1.3 MAC, in combination with N2 O are problematic. The substitution of propofol for N2 O increases cortical SSEP amplitude up to 100% during an opioid based anesthetic. Substituting remifentanil for fentanyl and N2 O, during a low-dose isoflurane anesthetic, decreases SSEP waveform variability, which should improve reliability. The effect of anesthetics on evoked potentials can be greater in neurologically impaired patients than in those without preoperative deficits. Thus the anesthetic regimen must be adjusted to carefully limit the concentration of volatile anesthetics to less than 1 MAC or avoid N2 O. If neurophysiologic monitoring will include electrocochleography or SSEP, volatile anesthetics with N2 O should be limited to 0.5 MAC concentrations. Without N2 O, 1 MAC concentrations may be used. Newer volatile anesthetics such as desflurane or sevoflurane seem to allow neurophysiologic monitoring at higher concentration but may produce baseline nerve firing with facial nerve monitoring. The use of continuous infusion of intravenous anesthetics (propofol) and opioids with low concentration of background inhalational anesthetics is ideal and recommended for intraoperative neurophysiologic monitoring during skull base procedures.

ANESTHETIC CONCERNS WITH VASCULAR LESIONS Skull base surgeries that have a vascular component may present many problems concerning intraoperative anesthetic management. Complete resection to alleviate symptoms or affect cure while minimizing neurologic complications may be difficult. Vascular bypass procedures may be done for many pathologic entities including aneurysms that encompass the internal carotid or tumors that involve the artery at the skull base or cervical region. Aneurysms may form in the petrous cavernous portion of the skull base where repairs and access to the lesion are difficult. In other situations, paragangliomas may also involve the carotid artery, both in the cervical and in skull base region. If the carotid artery is to be occluded during the surgery, some form of assessing cerebral perfusion may be necessary. In addition, if the possibility of cerebral hypoperfusion exists, methods to provide cerebral protection must be incorporated into the anesthetic plan. As mentioned earlier, cerebrovascular complications during and after these procedures may occur. After resection of tumor, involving the carotid, complications are thought to occur by two mechanisms: the first is by acute infarction after interruption of blood flow; the second is infarction as a result of clot propagation or embolic phenomenon from static blood. Despite advances in surgical techniques and preoperative assessment, patients are still at risk for transient or permanent stroke, coma, or death from thromboembolic phenomenon or sustained hypoperfusion. For these reasons, use of perioperative anticoagulation and antiplatelet therapy, plus careful intraoperative blood pressure control with brain protection measures is important. If the skull base procedure is likely to cause interruption of cerebral blood flow, the intraoperative anesthetic management can be tailored to produce optimal perfusion to the areas affected by the interruption of blood flow. The patient should be hemodiluted prior to interruption of perfusion to reduce blood viscosity and to increase

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blood flow (50). The optimal hematocrit should approximate 30% to provide the best oxygen transport and cerebral oxygen metabolism. Glucose concentrations are also important if there is a risk of cerebral ischemia. High plasma glucose levels induce anaerobic glycolysis and lactic acidosis, which results in brain edema and microcirculatory dysregulation (51). In addition, insulin protects against ischemicinitiated excitatory damage, protects mitochondrial oxidation capacity, decreases serum K+ levels and glucose utilization, and directly stimulates Na+ /K+ -ATPase (52). Tight control of plasma glucose is warranted for perioperative outcome. Plasma glucose should be maintained between 95 mg/dl and 105 mg/dl throughout the intraoperative period.

Anesthesia and Neuroprotection If temporary vascular occlusion is anticipated, the anesthetic technique should incorporate strategies to augment systemic blood pressure. Cerebral ischemia impairs autoregulation of the cerebral vasculature resulting in resistance blood vessels that are maximally dilated. Blood flow to the ischemic region becomes pressure dependent. Increasing perfusion pressure improves cerebral blood flow and may reduce cell death in the compromised vascular territory by improving collateral circulation (53). Phenylephrine, norepinephrine, and dopamine are the most commonly used agents. Phenylephrine does not cause direct cerebral vasoconstriction and is often the drug of choice. The ability of phenylephrine to augment cerebral blood flow is probably due to a systemic effect. The tendency for a reflex decrease in heart rate makes the use of phenylephrine, particularly, useful in patients with coronary artery disease. Another simple yet effective measure to reduce cerebral ischemia during temporary disruption of blood flow is to elevate the inspired fraction of oxygen. This results in higher tissue levels than expected on dissolved oxygen in blood. Increasing numbers of studies support the use of normobaric 100% O2 in the setting of transient focal ischemia (54). The neuroprotective effects of hypothermia are not precisely known, but probably relate to reduced cerebral oxygen demand (7–8% per 1 ◦ C), decreased release of excitatory neurotransmitters, and increased release of inhibitory neurotransmitters (55). Evidence indicates that the relationship between brain protection and the degree of hypothermia is not linear and mild hypothermia (34 ◦ C) may provide protection against cerebral ischemia (56). Deliberate hypothermia to 34 ◦ C is easily achieved intraoperatively by passive cooling and can be reversed after the restoration of blood flow by conventional methods (convection heaters, circulatory water blankets, forced-air warners, etc.). Besides the physiologic manipulations that can be used to preserve the brain during temporary interruption of blood flow, pharmacologic agents may also be used to decrease neuronal activity and metabolic demand. The use of thiopental to protect the brain has been demonstrated during cardiac bypass (57). Thiopental, at doses capable of producing electroencephalogram (EEG) burst suppression, should offer protection during short occlusion times and longer with the use of continuous infusions of the drug. Barbiturates are also thought to enhance gamma-aminobutyric acid activity and antagonize the N-methyl-D-aspartate receptor which reduces ischemic excitotoxicity (58). Propofol, like barbiturates, will induce burst suppression in a dose-dependent fashion. Furthermore, it is metabolized quickly and therefore does not accumulate. Although propofol has been shown to be of some benefit, results of animal studies have been inconclusive compared with thiopental (59). Etomidate has also been shown to prevent increases in excitatory neurotransmitters

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during cerebral ischemia; however, its protective role compared to other anesthetics is unclear. Recent studies have demonstrated that etomidate administration, prior to cerebral ischemia, produces a 30% reduction in PaO2 levels and a 23% increase in PaCO2 concentrations in the cerebral cortex (60). These changes were thought to be due to etomidate associated vasoconstriction and a reduction in cerebral blood flow prior to a drop in cerebral metabolic rate. This reduces etomidate’s effectiveness as a neuroprotectant, even though its short half life and hemodynamic stability is superior to barbiturates. Volatile anesthetics can also be used to reduce cerebral metabolism, but their ability to dilate arteries and reduce blood pressure makes them a less than optimal choice when attempting to maintain cerebral perfusion to ischemic areas. Other agents such as calcium channel blocker and local anesthetics may provide some added benefit through their ability to block ion channels and reduce Na+ /K+ transmembrane flux which reduces basal energy expenditures (61). Most effective neuroprotective techniques used today involve some combination of pharmacologic therapy coupled with some level of hypothermia or other physiologic manipulation. If neuroprotection is needed or anticipated, EEG monitoring may be helpful for detection of cerebral ischemia or for titration of anesthetic agents used to produce burst suppression. In addition to EEG, SSEP monitoring of cerebral function has been advocated (62). Although there is a clearly documented relationship between electrophysiologic changes and decreased blood flow, scalp electrodes placed at a distance to the ischemic area are relatively insensitive. The electrical signal is further attenuated by CSF drainage and osmotherapy, which introduces air between the scalp electrodes and the underlying cerebral cortex. SSEP monitoring for cerebral ischemia during temporary vessel occlusion is limited by its inability to detect ischemia in the motor cortex, subcortical structures, and sensory regions not topically represented by the stimulated peripheral nerve. In many instances, brain stem auditory evoked potential monitoring may also be beneficial, especially if the posterior circulation is involved. Whatever the monitoring technique used, the anesthetic method must be adjusted to provide the best conditions for monitoring.

ANESTHESIA FOR ENDOSCOPIC SKULL BASE SURGERY As in most fields of medicine, there has been a movement toward less invasive procedures. As new imaging devices and surgical techniques have developed, there has been an explosive growth in the area of minimally invasive neurosurgical techniques. One area that has seen this development is endoscopic skull base surgery, especially with acoustic neuromas and pituitary tumors. The traditional translabyrinthine approach to acoustic neuromas results in the sacrifice of hearing during the course of the procedure and other complications, including stroke, hemorrhage, neuropathies, CSF leaks, and cranial nerve injuries. Much as the lateral approach to the skull improved the ability to access certain skull base tumors and reduce postoperative morbidity, endoscopic skull base surgery has become a popular technique to access skull base pathology and resect the lesion with minimal operative trauma and an improved postoperative course. The endoscopic approach requires an image guidance system that may either be computer tomography or magnetic resonance based. The imaging system helps to map the

area of interest and guide in the resection of the tumor in an efficient manner. In addition, specific instruments have been created to maximize efficiency in a tight space (63). The patient is usually in a semi-sitting position and rotated away from the anesthesia team, thus the airway is removed from the immediate proximity of the anesthesiologist. Endoscopic endonasal approaches to the anterior, clival, and posterior skull base have reduced the need for postoperative analgesia therapy and the surgical trauma that accompanies these procedures. Endoscopic resections of pituitary, craniopharyngiomas, chordoma, and other tumors have been done in recent years through small incisions through the nostril, glabella, and orbital roof by incisions in the eyebrow, superolateral orbit, and subtemporal regions. Since there is reduced blood loss and surgical trauma, anesthetic techniques have been modified to adjust to this new emerging surgical technology. The general aims of the anesthesiologist are to provide hemodynamic stability, maintain cerebral oxygenation, provide favorable conditions for surgical exposure, and facilitate a rapid emergence. If the pituitary is involved, hormone replacement therapy should be continued into the operative period. In all instances, a careful airway evaluation should be performed, especially if the patient has a pituitary tumor and is secreting abnormal amounts of growth hormone. Acromegalics have particularly problematic airways and depending on the amount of soft tissue overgrowth of the mandible and the amount of tongue enlargement, these patients could be exceedingly problematic to intubate. If awake, fiber-optic intubation cannot be safely performed; a tracheostomy may be done to facilitate control of the airway. With the exception of pituitary tumors, airway control for other endoscopic skull base procedures is routine. The endotracheal tube is secured without tape to the upper lip. For a transnasal endoscopic approach, the surgeon may want to introduce a vasoconstricting agent into each nostril to prevent bleeding. Traditionally, a mixture of cocaine and epinephrine is used. Although the addition of epinephrine limits systemic absorption, the use of cocaine-containing preparations continues to be associated with a risk of arrhythmia and myocardial infarction. We routinely place an arterial line in all patients who will be administered nasal cocaine to monitor blood pressure and heart rhythm during systemic absorption. Most endoscopic approaches to the skull base are done with the patient in the supine head-up position with the head tilted or turned to improve access. The operating room (OR) table could be at 90 degrees from the anesthesia provider or turned to 180 degrees, depending on surgical preferences. In most instances, the trachea is intubated to control respirations and ETCO2 . However, with some endoscopic approaches, a laryngeal mask airway may be used with the patient spontaneously ventilating. Any anesthetic technique is suitable since most of these cases are done without neurophysiologic monitoring. However, if intraoperative neurophysiologic monitoring is to be used, the anesthetic technique must be adjusted to provide optimal conditions for monitoring. The choice of anesthetic technique for these procedures is usually determined by personal preference. A total intravenous technique with propofol and remifentanil provides ideal intraoperative conditions with rapid emergence and extubation. Short-acting inhalational agents can also be used in conjunction with remifentanil. Since postoperative pain is minimal, longer half-life analgesics are not necessary and anesthetic techniques are modified to produce a rapid emergence with minimal hangover effect. With some of the endoscopic approaches, there may be periods of intense stimulation. The short-acting opioids should be titrated against

Chapter 6: Patients with Tumors of the Skull Base

blood pressure. At the end of the endoscopic procedure, the patient should emerge rapidly and have no overt bleeding. If hemodynamically stable, breathing spontaneously, and following commands, the patient may be extubated. Recently, in a study that compared the sublabial transeptal hypophysectomy to the endoscopic approach, there was a significant reduction in the rate of nasal complications and CSF leaks (64). Others have revealed that endoscopic procedures result in less postoperative pain and less blood loss when compared to standard nonendoscopic approaches (65).

POSTOPERATIVE MANAGEMENT After the completion of the skull base procedure, depending on blood loss and surgical length, the patients who have sufficiently recovered from anesthesia to follow commands and maintain oxygenation while spontaneously breathing are usually extubated. Recovery from anesthesia is expedited by the use of short-acting, low solubility inhalational agents and infusions of potent opioids. Cranial nerve deficits, including injury to the vagus nerve producing vocal cord paralysis, may occur after skull base surgery. Even though this would produce unilateral vocal cord paralysis, the patient should be awake and able to handle secretions to avoid the risk of aspiration. Nausea, vomiting, and pain are important aspects for consideration in the immediate postoperative period. The incidence, magnitude, and duration of acute pain experienced after craniotomy are not well known. Pain after acoustic neuroma surgery, with a posterior fossa approach, has been noted to be severe in 67% of patients and was thought to be due to either nuchal dissection or traction on the dura by nuchal musculature (66). Evidence shows that patients who undergo skull base surgeries experience varying degrees of postoperative pain. Some of this variability may be explained by the different anatomical approaches to the brain and meninges. The proximity of cranial nerves and the chemoreceptor trigger zone to the surgical field may increase the risk of pain and nausea after posterior fossa and skull base surgery. Pain from the infratentorial structures is transmitted by efferent fibers in cranial nerve V, IX, and X and the upper three cervical nerves. There is evidence that neurosurgical patients receive inadequate analgesia from currently available regimens (67). The desire to avoid respiratory depression with CO2 retention and preservation of pupillary responses has reduced the use of strong opioid analgesics in this patient population. De Beneditis et al. demonstrated that patients undergoing surgery by the subtemporal and suboccipital routes have the highest incidence of postoperative pain (68). Approximately 90% of these patients experienced pain in the first 12 hours after surgery. The pain that occurred was influenced by surgical route and was defined as pulsating or pounding, steady, and sometimes stabbing in nature. Although no ideal analgesic exists, all believe patient controlled analgesia (PCA) is extremely valuable after skull base procedures (68). PCA has been found to be subjectively better for patients and leads to overall lower doses of opioid. It produces a mechanism to titrate drug administration, allows the patients to control their pain, and may alleviate the psychological stress of pain. Morphine in a dose regimen of 1.5 mg/dose with an eight-minute lockout and a maximum dose of 40 mg at four hours has not been observed to cause respiratory depression requiring reintubation. The most common associated morbidity and reason for dissatisfaction with PCA is the development of nausea and vomiting. This may be due to the type of surgery and

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anesthetic agents used, but could also be due to blood opioid concentrations that change with PCA administration (69). Although nausea and vomiting may have evolved as protective reflexes, they are undesirable side effects that can lead to significant morbidity such as increased intracranial pressure, loss of fluids/electrolytes, alkalosis, and worsening respiratory function. Physiologic evidence suggests that vomiting may be associated more with infratentorial surgery (67). Since pain is controlled, in most instances, by the judicious use of opioids, subsequent nausea and vomiting is controlledby antiemetics. Several methodologies are employed to provide relief from nausea or vomiting with the antiemetic given as a rescue agent. Droperidol, a dopamingeric antagonist, given in a dose of 0.625 mg IV has been noted to be effective in reducing nausea and the incidence of vomiting (70). However, it may cause extensive extrapyramidal side effects and synergistically increase the sedation associated with opioids. Thus, it is not the ideal antiemetic. Ondansetron, a serotonin receptor antagonist, has also been used with some limited success in reducing the incidence and severity of nausea and vomiting. Finally, the addition of dexamethasone (decadron) to antiemetic regimens seems to reduce the incidence of nausea and vomiting (71). Dexamethasone has been demonstrated to be effective for prophylaxis of postoperative nausea and vomiting secondary to prostaglandin metabolism (72). Others have suggested that the dexamethasone’s effectiveness may be due to a release of endorphins resulting in mood elevation, a sense of well-being, and appetite stimulation. Dexamethasone has also been used in combination with 5HT3 receptor antagonists. Corticosteroids may reduce levels of 5-hydroxytryptophan in neural tissue by decreasing tryptophan, its precursor. Secondly, the anti-inflammatory portion of dexamethasone may prevent release of serotonin in the gut. Lastly, dexamethasone may potentiate the main effects of the antiemetics by sensitizing pharmacological receptors. Antiemetics have also been added to PCA solutions to administer antiemetics simultaneously in conjunction with opioids. Our group demonstrated that patients who undergo craniotomy, especially in the skull base region, have significant postoperative pain (73). The combination of ondansetron with PCA morphine reduced pain scores in the immediate 24 hours post surgery, but had little effect on the incidence of nausea and vomiting, and should not be used in combination with PCA morphine. R Ondansetron ODT
oral treatment given prior to surgery with intraoperative IV dexamethasone plus IV ondansetron was associated with less frequent rescue therapy on the first postoperative day compared with patients receiving IV dexamethasone plus placebo (71). This multimodal treatment of nausea and vomiting after skull base procedures may be more effective in reducing nausea and vomiting associated with pain or opioid administration than single therapy regimens. Multimodal analgesic therapies should also be used to reduce pain. Besides aggressive PCA therapy, local anesthetics can be used to infiltrate the surgical wound during closure. Lidocaine 2% with 1:200,000 epinephrine prolongs the analgesic half life while reducing bleeding from the incision site. Other anti-inflammatory agents such as ketorolac or indomethacin may be added to reduce the narcotic demand secondary to musculoskeletal trauma. In conclusion, the anesthesia technique used for skull base surgery is instrumental in providing optimum conditions for intraoperative monitoring while enabling the surgeon to accomplish the surgical procedure in a hemodynamically stable patient. The anesthesiologist can also improve postoperative outcomes and reduce morbidity provided he

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or she is given the information concerning surgical approach, tumor type, and involved vital structures. It is imperative that the neuroanesthesiologist discuss the procedure with the skull base surgical team and be involved in the decisions concerning perioperative management to produce an optimal outcome.

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7 Minimally Invasive Techniques: Endonasal Endoscopic Skull Base Surgery Allan D. Vescan, Ricardo L. Carrau, Carl H. Snyderman, Amin B. Kassam, Arlan Mintz, and Paul Gardner

INTRODUCTION

achieved, either by an “en bloc” resection or by a piecemeal removal, as long as the microscopic analysis of all margins is negative. Our opinion is based on our experience with open skull base approaches in which the “en bloc” removal of tumor is rarely achieved and ultimately the tumor is removed in multiple small pieces. Third, every attempt should be made to preserve major neurovascular structures. As a result of this principle, when approaching tumors via an endoscopic endonasal approach, one of the critical determinants of feasibility and safety of the resection is the relationship of critical neurovascular structures. If a lesion is located in a line of sight that is distal to the internal carotid artery (ICA) or the optic nerve, then one must consider alternate approaches. Fourth, the skull base reconstruction must separate the cranial cavity from the sinonasal tract. In our experience, this has been one of the most challenging and dynamic areas of endonasal approaches to the skull base. We will discuss this issue in detail later in this chapter. The final tenet to be considered when choosing an approach is to be able to minimize morbidity, preserve function and quality of life, and preserve or reconstruct optimal cosmesis (Table 1).

Skull base surgery is a relatively new subspecialty. Since the seminal paper by Ketcham et al. in the early 1960s the anterior craniofacial resection became the standard approach to treat tumors of the anterior cranial base (1). Halstead used the transnasal approach to access the sella turcica for the treatment of pituitary tumors in the early 1900s (2), an approach that was later popularized by Cushing (3). Jules Hardy introduced the microscope as a visualization tool and ultimately standardized the transnasal transseptal approach as the optimal technique to extirpate tumors of the sella (4). With the advent of rod lens telescopes in the late 1970s, numerous pioneering otolaryngologists, including Messerklinger, Stammberger, Wigand, Kennedy, and others, successfully applied endoscopic techniques to treat disorders of the paranasal sinuses (5–8). The logical progression, as otolaryngologists became familiar with the use of endoscopic techniques to treat a wide array of inflammatory and infectious disorders of the paranasal sinuses, was to expand their indications to treat other pathologies. These included cerebral spinal fluid fistulas, traumatic optic neuropathies, Grave exoophthalmopathy, refractory epistaxis, and ultimately benign and malignant tumors of the paranasal sinuses and skull base. In fact, one of the most dramatic changes in the practice of skull base surgery over the past decade has been the introduction of endoscopic techniques to approach selected tumors of the anterior cranial fossa and ventral skull base. This has been made possible by parallel advances in surgical instrumentation, hemostatic techniques and materials, image guidance systems, and most importantly collaboration between both neurosurgeons and otolaryngologists. The purpose of this chapter is to describe and highlight critical principles and philosophies that the surgeon should consider when selecting approaches to the skull base. In addition, various endoscopic approaches to the skull base from the crista galli to the odontoid will be discussed. This will be complemented by a discussion about reconstruction dilemmas and surgical complications.

MINIMAL ACCESS SKULL BASE APPROACHES The expanded endonasal approaches to the skull base can be divided into specific “modules” based on the anatomic area that needs to be accessed in addition to the extent of the tumor (9–11). This modular system is based on the control and exposure of key neurovascular structures such as the ICA and optic nerve. The modules fall under two main categories. The first includes access to the skull base from a rostral to a caudal direction, beginning at the posterior wall of the frontal sinus or crista galli and extending to the foramen magnum and odontoid. The second set of modules involves the coronal plane and represents the incremental expanded exposure and access to critical areas of the middle and posterior skull base from a medial to a lateral direction. The rostral–caudal axis involves the transcribriform, transplanum/transtuberculum, transsellar/parasellar, clivus, and odontoid/foramen magnum approaches. The coronal axis refers to exposure of structures centered on the middle third of the clivus and the key anatomic structure, which divides the coronal axis into separate modules, is the petrous ICA. The coronal plane is divided into zones based on the relationship to the petrous ICA and whether the location is suprapetrous, above the ICA or infrapetrous, below the ICA. There are two infrapetrous approaches consisting of the medial petrous apex approach (zone 1) and the petroclival approach (zone 2). The suprapetrous approaches consist of quadrangular space

PRINCIPLES AND PHILOSOPHY We believe that before one embarks on removing a tumor of the skull base, the surgeon must decide which approach best fulfills key criteria, irrespective of whether it is a conventional, external or an endoscopic approach. The first key element is that the approach should provide adequate visualization of the tumor. The second element is that the tumor be completely extirpated in adherence with oncologic principles. We believe that a complete tumor removal may be 131

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Table 1 Summary of the Five Key Principles of Minimal Access Endoscopic Skull Base Surgery Principles of minimal access endoscopic skull base surgerya 1. Approach provides adequate visualization of tumor. 2. Tumor is removed respecting oncologic principles. 3. Preservation of major neurovascular structures. 4. Separation of sinonasal tract from intracranial contents. 5. Optimize cosmesis, minimize morbidity, and preserve quality of life. a

If one or more of these principles cannot be adhered to, an alternate approach should be considered.

approach (zone 3), superior cavernous sinus approach (zone 4), and the transpterygoid/infratemporal fossa approach (zone 5) (Fig. 1). When considering the optimal endoscopic approach for any pathology of the skull base, a detailed review of preoperative CT and MRI scans by both the otolaryngologist and the neurosurgeon is critical to plan a safe and efficient access. As a team, we routinely discuss which modules will be required, in both the coronal and the rostral–caudal plane, before each case. For the purposes of this chapter, we will discuss the most commonly employed approaches.

General Preparation: The Nasal Corridor There are certain steps and maneuvers that are common to all endonasal endoscopic approaches (EEA), irrespective of which modules will be needed for the tumor removal. Routinely, patients are positioned supine on the operating table and an orotracheal airway is secured. The head is fixed in a three-point Mayfield holder with either a slight amount of flexion (to enhance the visualization of posterior structures) or a slight amount of extension (to facilitate the visualization of anterior areas), depending on the area of the skull base that needs to be exposed. We then obtain an appropriate

image guidance registration with the aid of an optical tracking system, using surface fiducials markers that were placed prior to imaging or an LED (light emission diode)-based face mask. Once this has been completed, the nose is topically decongested with cottonoids soaked in 0.05% oxymetazoline. The middle turbinate, lateral nasal wall, and posterior nasal septum are then sequentially infiltrated with 0.5% Xylocaine, with 1:100,000 epinephrine. Resection of the middle turbinate increases the space for instrumentation and improves the visualization. Inferior turbinates are out-fractured in a two-step fashion: first by placement of blunt instrument on its undersurface displacing the turbinate medially, and second by lateral displacement of the turbinate applying pressure in a medial-to-lateral direction.

Transsellar/Transplanum This is the most commonly used skull base exposure. It is the building block for most of the extended approaches and its initial steps provide a platform and foundation for more complex and technical steps. If a vascularized septal flap is required for the reconstruction, it is harvested first to avoid devascularization and severing of the pedicle during the sphenoidotomy and posterior septectomy (see reconstruction section). Following preparation of the nasal corridor, approximately 2 cm of the posterior septum is resected to facilitate bimanual, four hand surgery. The sphenoidotomy is then widened bilaterally, using the Kerrison rongeurs. The final rectangular opening should have the lateral walls in plane with the lamina papyracea and the roof is in plane with the cribriform plate. Due to the variable pneumatization of the lateral recess of the sphenoid, it may be necessary to drill the inferolateral aspect of the sphenoidotomy over the base of the medial pterygoid plates. Superiorly, the opening is extended to the junction with the planum to allow for identification of the skull base. Inferiorly, the rostrum of the sphenoid is removed and the floor drilled posteriorly to enhance access for instrumentation. At this point, there is unencumbered visualization of the sella, medial and lateral optico-carotid recesses, clival recess, optic nerves, and ICA canals. In order to facilitate the identification of these landmarks, we remove the mucosa from the sphenoid sinus walls. This will create a moderate amount of venous bleeding, which can be controlled with warm water irrigation and the application of bone wax to high-flow areas. Paramedian septations within the sphenoid sinus require removal; however, one must be careful as these often insert directly on the carotid artery canal. A sellotomy follows removing bone from the medial aspect of the cavernous sinus on one side to medial aspect of the cavernous sinus on the other, and from the superior intercavernous sinus to inferior intercavernous sinus. This is critical to achieve an adequate sellar access for tumor removal and thus facilitates the extirpation of tumor from the lateral gutters and superoanterior areas without having to use a blind dissection technique (i.e., blind curettage). The decision of whether to remove bone over the medial opticocarotid recess or the tuberculum depends on the lateral and superior extent of tumor, respectively. Preoperative discussion between the neurosurgeon and the otolaryngologist is invaluable to plan the approach adequately.

Transcribriform Figure 1 Schematic illustration of the coronal plane containing five zones. Zone 1—medial petrous apex approach. Zone 2—petro-clival approach. Zone 3—quadrangular space approach. Zone 4—superior cavernous sinus approach. Zone 5—transpterygoid/infratemporal fossa approach.

EEA to the skull base can be divided into extradural and intradural segments. The key principle is that all dissection and visualization during the intradural portion of the case is dependent on the extradural component of the exposure. The transcribriform approach involves exposure of the anterior skull base from the posterior wall of the frontal sinus

Chapter 7: Minimally Invasive Techniques: Endonasal Endoscopic Skull Base Surgery

Figure 2 Endoscopic basal view of boundaries for an endoscopic anterior craniofacial resection. Dotted line represents the area to be resected. Source: Published with permission from Carrau RL, Kassam AB, Snyderman CH, et al. Endoscopic Transnasal Anterior Skull Base Resection for the Treatment of Sinonasal Malignancies. OperTech Otolaryngol. 2006;17:102–110.

anteriorly to the planum sphenoidale posteriorly and from the medial wall of the orbit (lamina papyracea) laterally to crista galli medially in a unilateral approach and medial orbit to medial orbit in the more commonly employed bilateral approach (Fig. 2). The nasal corridor is prepared as described above. Sometimes, it may be necessary to debulk the pedunculated aspect of the tumor first in order to be able to introduce instrumentation. The nasal septum is then disarticulated by a series of three incisions. The first is via a vertical transfixion incision at the junction of the septum and rostrum of the sphenoid. The second is an anterior vertical transfixion incision at the level of the anterior aspect of the middle turbinate or the posterior wall of the frontal sinus. This latter incision may be adapted according to the anterior extent of tumor. The two vertical incisions are then connected via a third horizontal incision parallel to the floor of the nose. By creating a septectomy defect, bimanual dissection becomes feasible. An uncinectomy, wide antrostomy, and anterior and posterior ethmoidectomy are sequentially performed. A sphenoidotomy is often performed to identify the planum sphenoidale as the posterior limit of dissection, therefore identifying the skull base. One then can proceed with the removal of all air cells in a posteroanterior direction with the skull base under direct visualization to avoid inadvertent CSF (cerebrospinal fluid) fistula. The nasofrontal recess is then widened accordingly and a Draf IIb or Draf III dissection is carried out in order to define the anterior limit of dissection (12). The lamina papyracea is then removed to provide access to the medial orbital wall. This is necessary to facilitate the control of the anterior and posterior ethmoidal arteries and serves as the lateral margin of the tumor resection. In addition, at this time the posterior wall of the maxillary sinus can be removed to access the pterygopalatine fossa. If necessary, the terminal branches of the internal maxillary artery, namely the posterior septal artery and the sphenopalatine artery, can be coagulated or clipped as needed. At this point, the mu-

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Figure 3 Endoscopic basal view attained once osteotomies have been completed. Source: Published with permission from Carrau RL, Kassam AB, Snyderman CH, et al. Endoscopic Transnasal Anterior Skull Base Resection for the Treatment of Sinonasal Malignancies. OperTech Otolaryngol. 2006;17:102–110.

coperiosteum is stripped from both olfactory sulci leaving exposed bone. This bone is then thinned using a 3-mm hybrid cutting/diamond bur. The exposure now comprises the frontal sinus anteriorly, the planum sphenoidale posteriorly, and both orbits laterally. A rectangular area comprising the anterior skull base is then osteotomized. This comprises two paramedian osteotomies running in a rostral to caudal direction, at the junction of the orbit and the roof of the ethmoid sinuses, and two transverse osteotomies one slightly anterior to the rostrum of the sphenoid and the second rostrally, just behind the posterior wall of the frontal sinus. This allows the mobilization of the rectangular area that encompasses most of the anterior skull base (Fig. 3). It should be noted that the crista galli extends intracranially and must be thinned in an inside out fashion before being fractured or removed with a cutting punch. The intradural component of the dissection now commences with bipolar cauterization and resection of the olfactory nerves, followed by thorough cauterization of the dura. This achieves maximum vascular control outside the anterior falcine artery and controls any parasitized blood supply from the cortical circulation. Dural incisions are then performed using the previously performed osteotomies as a template and the intradural dissection proceeds from anterior to posterior. Margins are sent for frozen section to confirm histologically negative margins of resection. Histological confirmation of adequate margins is a critical and an absolute requirement during the resection of malignant tumors of the anterior cranial base regardless of the approach.

Transpterygoid/Infratemporal Fossa This approach provides access to the lateral recess of the sphenoid sinus, middle cranial fossa, pterygopalatine space, infratemporal fossa, and the lateral aspect of the middle third of the clivus for identification of the anterior genu of the petrous ICA. The nasal corridor is prepared as previously

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rounding neurovascular structures, thus facilitating the dissection. Image guidance and specific instrumentation such as an endoscopic bipolar electrocautery and angled endoscopes are essential.

Panclival Approach

Figure 4 Axial CT Scan without contrast demonstrating prominent vidian canals leading from the pterygopalatine fossa to the apex of the petrous ICA. Drilling of the bone medial and inferior the vidian canal will allow for safe identification of the anterior genu of the ICA. Abbreviations: VC, vidian canal; ICA, internal carotid artery; Cl, Clivus.

described. The initial exposure requires an uncinectomy and a wide maxillary antrostomy that extends posteriorly until it is flush with the back wall of the antrum. Anterior and posterior ethmoidectomies and a wide sphenoidotomy widen the exposure and a posterior septectomy allows binarial and bimanual dissection techniques. In addition, it may be necessary to resect part or all of the middle turbinate for access. The crista ethmoidalis and sphenopalatine foramen can now be visualized and the posterior wall of the maxillary sinus is removed with Kerrison rongeurs. Control of the terminal vessels of the internal maxillary artery can be attained with either vascular clips or bipolar cauterization. The mucosa over the posterior wall of the sinus can be lateralized and preserved if the disease process does not involve the back wall of the maxillary sinus. Similarly, the contents of the pterygopalatine space can be lateralized to expose the base of the pterygoid plates. The vidian canal and foramen rotundum can be seen as one proceeds from medial to lateral along the back wall of the pterygopalatine fossa. Dissection can now proceed laterally to access lesions that extend through the pterygomaxillary fissure into the infratemporal fossa or posteriorly by drilling the base of the pterygoid plates. The vidian canal is a critical landmark and will lead to the second genu of the petrous ICA (Fig. 4). The vidian nerve that travels within the canal, often accompanied by the vidian artery, originates at the pterygopalatine ganglion, which is located on the superior aspect of the pterygopalatine fossa. In general, the vascular structures within the pterygopalatine space lie superficial to the neural structures. By sequentially drilling bone on the inferomedial aspect of the vidian canal, one can localize the ICA before it turns up on its vertical paraclival course. Identification of the petrous ICA is not a required component of the trans-pterygopalatine fossa approach; however, this approach is often used when further dissection and exposure necessitates identification of the artery. It should be noted that slow-growing pathologies that involve the pterygopalatine space, such as juvenile angiofibromas or schwannomas, might enlarge this corridor significantly and displace sur-

A panclival approach involves the standard initial approach that is required for a transsellar module, which will be extended inferiorly. The key principle during the clival approach is knowing the location of the petrous ICA at all times and in fact removing its bony canal in order to create the widest corridor possible for intradural dissection. Subsequent to a wide sphenoidotomy, the floor of the sphenoid sinus is drilled down until flushed with the clival recess (posterior wall of the sphenoid sinus). The inferior extent of the dissection is the level of the soft palate and the superior extent is the sella. In order to expose the lower third of the clivus, the basopharyngeal fascia needs to be dissected. This fascia is extremely resilient and a combination of techniques may be necessary for its removal. The lateral limits of the dissection are the fossae of Rosenmuller. As mentioned during the transpterygoid approach, the key element for safe identification of the anterior genu of the petrous ICA is the vidian canal and its contents. Once the vidian canal is identified in the posterosuperior aspect of the pterygopalatine, space drilling can proceed on the inferomedial aspect of the canal until it reaches the ICA at the foramen lacerum. Once this is achieved, drilling can proceed on the superior lateral aspect of the canal, thus maintaining safe depth perception of the anterior genu of the petrous ICA (Fig. 5). The exposure of the contralateral carotid artery is undertaken in the same manner followed by removal of clival bone between both paraclival carotids as they ascend vertically. During the removal of the cancellous bone within the clivus, it is common to encounter a significant amount of bleeding; this can be controlled with bone wax or, alternatively, the surgeon works through the bleeding using high-flow suction in the nondominant hand to maintain visualization. Once all of the bone work is completed, the intradural exposure is possible, thus providing access to the vertebrobasilar junction, cranial nerves V–X, pons, and the posterior circulation.

Figure 5 Intraoperative picture demonstrating the vidian nerve originating from the pterygoid wedge of the sphenoid bone. Drilling inferomedial to the vidian will allow for identification of the correct depth of the ICA.

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RECONSTRUCTION Skull base surgery is a rapidly evolving field with new approaches and techniques continually under development. The recent advances in endoscopic and minimal access approaches have produced complex defects that communicate the subarachnoid space and the nasal cavity. This has required ingenuity and novel techniques for the repair of these defects. There are two main options for the repair of skull base defects, the use of vascularized tissue and of nonvascularized tissue. Repair with vascularized tissue after traditional skull base approaches is well documented and widely accepted and includes regional flaps such as pericranial, galeal, and temporoparietal flaps (13–15); free flaps such as the radial forearm, latissimus dorsi, and rectus abdominis flaps (16–21). Until recently, the options for the endoscopic reconstruction of the skull base were limited to the use of nonvascularized tissue. This yielded CSF leak rates of 20–30% and became a major obstacle for the widespread acceptance of these techniques. Recently, the Haddad-Bassagasteguy flap (HBF) or nasoseptal flap has proven to be a versatile, robust vascularized flap for the reconstruction of EEA defects (22). Since its adoption, we have seen our CSF leak rates drop to numbers that compare with those of traditional techniques (around 5%). The advantage of this flap as a reconstructive option is that a second approach or incision is not necessary and the flap can be harvested endoscopically. The major drawback of the HBF is that its need must be anticipated prior to embarking on the resection as the vascular pedicle to this flap is frequently compromised during the sphenoidotomy and posterior septectomy portion of the procedure. In addition, if a revision procedure is necessary, the flap may have been used previously or the pedicle previously damaged. This leads to the second option for vascularized endoscopic skull base reconstruction, the pedicled temporo-parietal flap. The main drawback of this option is the need for a hemicoronal incision and the morbidity associated with it. However, its use in skull base surgery and other areas of head and neck surgery is well proven and its novel incorporation into endoscopic skull base reconstruction will be described below.

Vascularized Nasoseptal Flap The nose is topically decongested with 0.05% oxymetazolinesoaked cottonoids. Infiltration with 0.5% lidocaine with 1:100,000 epinephrine is undertaken, with care taken not to inject the area of the pedicle over the anterior face of the sphenoid. The flap can then be designed based on the expected size of defect. This point is counterintuitive to most reconstructive surgeons, as the flap is harvested before the resultant defect is created, thus one can be left with a flap that is inadequate. Due to this potential flaw, we tend to harvest a larger flap. The first incision is the most critical and involves use of electrocautery along the free edge of the choana from the lateral nasal wall toward the nasal septum. This incision is exceedingly difficult to perform once the flap has been elevated; extra time and patience is warranted to ensure a full incision down to the level of the sphenoid floor is performed. Two longitudinal incisions are then created from posterior to anterior. The most inferior incision is placed along the maxillary crest; however, it can be extended inferiorly and laterally to harvest the mucoperiosteum of the nasal floor. The superior incision is created 1- to 1.5-cm inferior to the cribriform plate in order to preserve olfactory function. It then crosses the rostrum of the sphenoid at level of the sphenoid sinus os.

Figure 6 Dotted lines illustrating the incisions required for harvesting a right-sided septal mucosal flap.

This leaves approximately a 1- to 2-cm width of pedicle across the anterior face of the sphenoid. Both of these incisions are joined anteriorly with a vertical incision at the level of the anterior end of the inferior turbinate (Fig. 6). Once all of the incisions are completed, the flap is elevated in a subperichondrial and subperiosteal plane back to its pedicle on the sphenopalatine foramen. The flap can then be “stored,” for the duration of the resection, in the nasopharynx or inside the antrum through a wide maxillary antrostomy. The “best” reconstruction is a constantly evolving technique. We currently employ a subdural inlay graft using a collagen matrix compound (DuraGen: Integra LifeSciences, Plainsboro, New Jersey, U.S.). This is often followed by overlay fascial acellular dermis graft (Alloderm, LifeCell Corporation, The Woodlands, Texas). Depending on the bony defect, we then lay the HBF flap directly on the denuded bone or we obliterate the dead space with a free abdominal fat graft. This is followed by fibrin glue (Tisseel, Baxter Healthcare Corporation, Deerfield, Illinois, U.S.) and Gelfoam (Johnson & Johnson, Somerville, New Jersey, U.S.). Depending on the geometry of the defect, grafts and flaps are supported with a 14 Fr Foley catheter balloon filled with saline or using an expandable sponge packing.

Transpterygoid Temporoparietal Flap The temporoparietal flap has been used extensively in head and neck reconstruction and in the repair of skull base defects. Its use as a reconstructive option during endoscopic approaches to the skull base is a novel application. The flap is based on the superficial temporal artery and its harvest necessitates a hemicoronal incision. Once the flap is harvested an endoscopic trans-antral transpterygoid approach is performed as described previously. The main reason for this approach is to create a wide tunnel for the pedicled T-P flap and to avoid any unnecessary strain on the vascular pedicle. A longitudinal incision is then fashioned in the superficial layer of the deep temporal fascia. This achieves two goals: first is to protect the frontal branch of the facial nerve and second is to gain access to the deep aspect of the zygoma for tunneling of the flap. A lateral canthotomy incision is then performed to separate the temporalis muscle from the pterygomaxillary fissure. We then employ a Seldinger technique

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Subdural inly graft Extradural onlay graft Brain

Fat Fibrin glue

Balloon stent

struction is placed. We have found that the tissue sealant can interfere with the “take” of the grafts. In order to prevent migration of the onlay acellular dermal graft, we have used nitinol U-clips (Medtronic U-Clips, Memphis, Tennessee, U.S.) in selected situations where there is enough free dural edge to suture the graft. The application of the endoscopic sutures is a technically challenging endeavor and the nitinol U-clips are a self coiling device which we have found decreases the effort and time required for suturing. As mentioned above, the final step involves placement of either a 14 Fr Foley catheter balloon filled with approximately 10 cc of saline or expandable sponge packs. This should be done under direct visualization to avoid overinflation and compression of neural structures such as the optic nerve or shifting of the grafts.

COMPLICATIONS

Figure 7 Sagittal schematic illustrating the multilayered nonvascular reconstruction of a skull base defect. Source: Published with permission from Carrau RL, Kassam AB, Snyderman CH, et al. Endoscopic Transnasal Anterior Skull Base Resection for the Treatment of Sinonasal Malignancies. OperTech Otolaryngol. 2006;17:102–110.

using a percutaneous tracheostomy set. Concomitant endoscopic visualization is needed to confirm the passage of the guidewire into the pterygopalatine space. Once the tunnel is dilated, the external portion of the guidewire is ligated to the flap and the nasal end of the guidewire is used to pull through the flap. It is important for one surgeon or assistant to monitor the T-P flap, as it is pulled through avoiding any kinking of the pedicle. Once the flap is in the nasal cavity, it can be placed over the skull base defect and secured much the same way as with an H-B nasoseptal flap.

Nonvascularized Our technique for nonvascularized reconstruction of the skull base stems from the experience that we and others have accumulated with reconstruction of more limited defects of the skull base. The literature supports that an endoscopic repair using a variety of techniques and materials yields a success rate exceeding 95% (23–26). Our nonvascularized repair has undergone multiple changes and is constantly evolving, mainly due to the high rate of postoperative CSF fistulas we have encountered after EEA. The main premise is the use of a multilayered technique (Fig. 7). In our early experience, the first layer of reconstruction was in the epidural space between the bone and the dura. This often proved to be a technical challenge if not an impossibility due to the nature of some of the defects that were created. Our current technique involves the placement of a subdural graft of a collagen matrix compound (DuraGen: Integra LifeSciences, Plainsboro, New Jersey, U.S.). This graft is easy to manipulate due to its pliability, the goal is to overlap the dural edges by 5 mm. The next layer is an onlay graft of acellular dermis, which is placed on the bare bone. This is followed by a layer of fibrin glue. In situations where there is a need for a decrease in dead space, we use a free abdominal fat graft harvested from a periumbilical incision. An important point is that the tissue sealant should not be applied until the final layer in the multilayer recon-

Complications that result from EEA to the skull base can be divided into major and minor categories. Within the context of major complications, many are the same as those encountered during open skull base surgery; however, their incidence and severity vary as a result of the approach. Major complications include ICA and other vascular injury, CSF leak, tension pneumocephalus, cerebrovascular accidents, and intracranial infectious complications. Unique to the minor category of complications associated with EEAs are complications such as alar burns, crusting, sinusitis, dry eyes, and hypoesthesia of sensory nerves in the maxillary and mandibular distribution.

Major Complications Vascular Injuries Vascular injuries related to the expanded endonasal approach comprise capillary, venous, and arterial bleeding. Arterial bleeding can be classified as either high flow or low flow. Most of the capillary and venous bleeding that arises from bone and mucosa can be controlled with warm water irrigation. In fact, warm water irrigation (40◦ C) is used repeatedly during the case not only to stop active low-flow bleeding but also to clear the field of clotted blood which tends to absorb much of the light and affects clarity of the working picture. When focal venous bleeding is encountered from areas such as the cavernous sinus or superior and inferior intercavernous sinus, the use of microfibrillar collagen folded on a half inch by half inch cottonoid in a “sandwich” is pressed over the site to achieve hemostasis. Often, it is necessary to exchange one sandwich numerous times until venous bleeding is controlled. Arterial injury, specifically ICA injury, is the most feared complication during EEA. Injury to the ICA and its management have been described by numerous authors (27– 30). Localization and constant identification of the carotid artery is the focus of most of the dissection. Avoidance of injuries to the ICA is the best way to avoid undue morbidity to the patient. Despite extensive preoperative planning and image-guided surgery, injuries to the ICA can still occur. This is the scenario where having a two-surgeon team becomes critical. An algorithm for control of these injuries is important and all members of the surgical team should know what steps need to be instituted for prompt management. The tenets of management involve avoiding hypoperfusion of the brain, while at the same time correcting hypovolemia and maintaining controlled hypertension for brain perfusion. Oxygen (100%) can also be administered to optimize oxygenation. During this initial phase, communication between the skull

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base surgeon and the anesthesiologist is paramount. For most injuries to the ICA during endoscopic skull base surgery, the safest method of controlling the vessel is probably sacrifice of the vessel via angiography and embolization with internal coiling. Before one can proceed to the interventional radiology suite, the hemorrhage must be controlled. This can be done through a variety of techniques: packing, muscle and fascia onlay grafting, and clipping and bipolar cautery(31). It is important to do a follow-up angiogram 5 to 14 days following the injury to rule out formation of a pseudo aneurysm.

Cerebrospinal Fluid Leak CSF leak is the most commonly encountered complication of EEA approaches to the skull base. With the recent introduction of the H-B nasoseptal flap, we have seen dramatic reductions in the incidence of CSF fistulas. There are numerous factors that predispose to development of a CSF leak following endoscopic skull base surgery. These include, size of the defect, extent of intracranial dissection, opening of an arachnoid cistern or ventricle, prior radiation therapy, patient body mass index, and, ultimately and most importantly, the technique of repair. The diagnosis of a CSF leak is a combination of clinical findings of clear rhinorrhea and a positive “halo” sign in addition to a positive beta-2 transferrin test. At our institution, we are able to obtain a beta-2 test in less than 24 hours; however, this is not always possible. Routine use of lumbar drainage is not necessary and we recommend selectively employing lumbar drainage in patients with elevated CSF pressures or in those patients that an arachnoid cistern or ventricle was opened (25). We found that once the leak has been documented, the majority of these patients will require an exploration and repair of the leak. The patient is taken to the operating room, no preoperative localization studies are performed, and the reconstruction is taken down until the site of leak is identified. Once this is done, we then employ a variety of reconstructive techniques depending on vascularized tissue available and size of the defect, as described previously in this chapter. In a small percentage of patients, conservative treatment with a lumbar drain and the usual CSF leak precautions achieves a complete closure. Tension Pneumocephalus This is an uncommon complication following endoscopic approaches to the skull base. There are numerous theories as to why this is not as common during endoscopic approaches as compared with open approaches. One of them being that we tend to completely occlude the posterior nasopharynx, thus preventing any airflow to the skull base with our reconstructive techniques, either using a Foley catheter or a merocel pack. Another theory is that the reconstruction involves some sort of overlay technique from below which can act as a physical barrier and prevent any ball valving of the skull base. The management of tension pneumocephalus after an EEA involves the removal of all packing materials and potentially aspiration of air via a burr hole, needle, or ventriculostomy, in addition to the administration of 100% oxygen. Close neurologic monitoring is necessary.

Infectious Complications The main infectious complication to be concerned with is bacterial meningitis. Our incidence of culture proven bacterial meningitis is very low and is a mirror image of our open skull base experience. Ascending meningitis can occur secondary to direct spread via a breakdown in the reconstruction; it can also occur secondary to extensive crusting and sinusitis in the absence of a CSF fistula. Active bacterial sinusitis associated

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with mucopurulent secretions is a contraindication to proceeding with intradural work. If this is encountered during the approach, the operation must be staged with the patient receiving treatment for sinusitis in the interim. The meningitis can be treated with culture-directed antibiotics in addition to reversal of the underlying etiology.

FUTURE DIRECTIONS Since the inception of skull base surgery as a discipline in the 1960s, dramatic changes have occurred with respect to the surgical management of the wide variety of pathologies that can be found in this anatomic area. The advancement of the field has been directly related to collaboration both between skull base surgeons and between physicians and the biomedical industry that supports them. Future directions include advancement of imaging technology such that it will be possible to acquire fast and precise imaging during the actual procedure. Current image guidance technology is based on a preoperative scan and does not account for tissue shift or surgical resection during the procedure. The advent of fast and portable CT scanning will allay many of these problems. In addition, the endoscopic skull base surgeon is inundated with information and data during the procedure. Future developments would consist of new ergonomically designed displays and information feedback mechanisms that would allow seamless synchronization of data for the primary surgeon. It is also the responsibility of the leading endoscopic and other minimal access skull base surgeons to provide good outcomes data to justify a variation from the traditional methods. Despite clear improvement in patient morbidity with minimal access procedures, what remain to be defined are the long-term outcomes. This will be a key element to forwarding the specialty. Future development and implementation of robotassisted surgery could aid in technically challenging maneuvers. This will complement new biological glues and chemotherapeutic delivery systems. As with the introduction of any new procedures, training of future generations will be a requisite. Surgical simulators and novel teaching techniques will be instrumental in acquiring minimal access skill sets to shorten the learning curve for these approaches. In summary, the future of minimal access skull base surgery is exciting. There are many areas for advancement and refinement and the future is full of opportunity.

REFERENCES 1. Ketcham AS, Wilkins RH, Van Buren JM, et al. A combined intracranial facial approach to the paranasal sinuses. Am J Surg. 1963;106:698–703. 2. Cohen-Gadol AA, Liu JK, Laws ER. Cushing’s first case of transphenoidal surgery: The launch of the pituitary surgery era. J Neurosurg. 2005;103(3):570–574. 3. Carrau RL, Kassam AB, Snyderman CH. Pituitary Surgery. Otolaryngol Clin North Am. 2001;34(6):1143–1155. 4. Hardy J. Transsphenoidal hypophysectomy. J Neurosurg. 1971;34(4):582–594. 5. Stammberger H, Posawetz W. Functional endoscopic sinus surgery. Concept, indications and results of the Messerklinger technique. Eur Arch OtorhinoLaryngol. 1990;247(2):63–76. 6. Messerklinger W. Background and evolution of endoscopic sinus surgery. Ear Nose Throat J. 1994;73(7):449–450.

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7. Hosemann W, Gode U, Wigand ME. Indications, technique and results of endonasal endoscopic ethmoidectomy. Acta Otorhinolaryngol Belg. 1993;47(1):73–83. 8. Kennedy DW. Technical innovations and the evolution of endoscopic sinus surgery. Ann Otol Rhinol Laryngol Soppl. 2006;196:3–12. 9. Kassam A, Carrau RL, Snyderman CH, et al. Expanded endonasal approach: Fully endoscopic, completely transnasal approach to the middle third of the clivus, petrous bone, middle cranial fossa and infratemporal fossa. Neurosurg Focus. 2005;19(1): E6. 10. Kassam A, Snyderman CH, Carrau RL, et al. Expanded endonasal approach: The rostrocaudal axis. Part I. Crista galli to the sella turcica. Neurosurg Focus. 2005;19(1):E3. 11. Kassam A, Snyderman CH, Carrau RL, et al. Expanded endonasal approach: The rostrocaudal axis. Part II. Posterior clinoids to the foramen magnum. Neurosurg Focus. 2005;19(1):E4. 12. Weber R, Draf W, Kratzsch B, et al. Modern concepts of frontal sinus surgery. Laryngoscope. 2001;111(1):137–146. 13. Snyderman CH, Janecka IP, Sekhar LN, et al. Anterior cranial base reconstruction: Role of galeal and pericranial flaps. Laryngoscope. 1990;100:607–614. 14. Neligan PC, Mulholland S, Irish J, et al. Flap selection in cranial base reconstruction. Plast Reconstr Surg. 1996;98:1159–1166. 15. Urken ML, Catalano PJ, Sen C, et al. Free tissue transfer for skull base reconstruction: Analysis of complications and a classification scheme for defining skull base defects. Arch Otolaryngol Head Neck Surg. 1993;119:1318–1325. 16. Funk GF, Laurenzo JF, Valentino, et al. Free tissue transfer reconstruction of midfacial and cranio-orbital-facial defects. Arch Otolaryngol Head Neck Surg. 1995;121:293–303. 17. Izquierdo R, Leonetti JP, Origitano TC, et al. Refinements using free-tissue transfer for complex cranial base reconstruction. Plast Reconstr Surg. 1993;92:567–575. 18. Jackson IT, Adham MN, Marsh WR, et al. Use of galeal frontalis myofascial flap in craniofacial surgery. Plast Reconstr Surg. 1986;77:905–910.

19. Jackson IT, Marsh WR, Hide TA. Treatment of tumors involving the anterior cranial fossa. Head Neck Surg. 1984;6:901–913. 20. Johns ME, Winn HR, McLean WC, et al. Pericranial flap for the closure of defects of craniofacial resection. Laryngoscope. 1981;91:952–959. 21. Jones NF, Schramm VL, Sekhar LN. Reconstruction of the cranial base following tumor resection. Br J Plast Surg. 1987;40:155–162. 22. Hadad G, Bassagasteguy L, Carrau RL, et al. A novel reconstructive technique after endoscopic expanded endonasal approaches: Vascular pedicle nasoseptal flap. Laryngoscope. 2006;116:1882– 1886. 23. Zweig JL, Carrau RL, Celin SE, et al. Endoscopic repair of CSF leak to the sinonasal tract: Predictors of success. Otolaryngol Head Neck Surg. 2000;123:195–201. 24. Hegazay HM, Carrau RL, Snyderman CH, et al. Transnasal endoscopic repair of cerebrospinal fluid rhinorrhea: A meta-analysis. Laryngoscope. 2000;110:1166–1172. 25. Carrau RL, Snyderman CH, Kassam AB. The management of the CSF leaks in patients at risk for high pressure hydrocephalus. Laryngoscope. 2005;115:205–212. 26. Zweig JL, Carrau RL, Celin SE, et al. Endoscopic repair of acquired encephaloceles, meningoceles, and meningoencephaloceles: Predictors of success. Skull Base Surg. 2002;12:133–139. 27. Oeken J, Bootz F. Severe complications after endonasal sinus surgery: An unresolved problem. HNO. 2004;52:549–553. 28. Weber R, Draf W. Complications of endonasal microendoscopic ethmoid bone operation. HNO. 1992;40:170–175. 29. Rauchfuss A. Complications of endonasal surgery of the paranasal sinuses. Special anatomy, pathomechanisms and surgical management. HNO. 1990;38:309–316. 30. Kassam A, Snyderman CH, Carrau RL. Endoneurosurgical hemostasis techniques: Lessons learned from 400 cases. Neurosurg Focus. 2005;19(1):E7. 31. Weidenbecher M, Huk WJ, Iro H. Internal carotid artery injury during functional endoscopic sinus surgery and its management. Eur Arch Otorhinolaryngol. 2005;262:640–645.

8 Reconstruction of Skull Base Defects Peter C. Neligan, Christine B. Novak, and Patrick J. Gullane

The pedicled myocutaneous flap, including the pectoralis major and the latissimus dorsi flaps, introduced another reconstructive option for patients following tumor ablation in the head and neck region. Ariyan (20), in 1979, used the pectoralis major flap and then described a variation that included externalizing the flap to repair defects as far as the orbital region (21). Quillen et al. (22), in 1978, described the latissimus dorsi myocutaneous flap for reconstruction of head and neck defects. This flap provided a number of advantages over previously described flaps, including a large arc of rotation, which allowed the flap to be extended to the floor of the middle fossa. However, because of the anatomic location of the latissimus dorsi muscle, the patient must be repositioned to elevate this flap. In general, this myocutaneous flap is rarely used for primary reconstruction in the skull base. The free tissue transfer has transformed and improved skull base reconstruction. The free flap provides an abundant source of well-vascularized tissue for repair of large cranial base defects (23). Unlike pedicled flaps, design and placement are not limited by the attachment of the pedicle and the arc of rotation and therefore dependent on the requirements of the reconstruction multiple flap designs may be considered. Free tissue transfer also provides the option of using two surgical teams which can decrease anesthesia time by having one team continue with tumor ablation while the second team proceeds with the flap harvest. While excellent patient outcome depends on many factors including microvascular expertise and correct patient selection, success with free tissue transfer is reported to be greater than 95%. The multidisciplinary surgical team has expanded the surgical options for treatment of skull base tumors by providing expertise from the head and neck surgeon, the plastic reconstructive surgeon and the neurosurgeon.

INTRODUCTION Lesions located in the skull base create a challenge for the reconstructive surgeon. Ablation of neoplasms in this region often requires extensive resection and this results in a large defect that often requires complex reconstruction. Because of the anatomic location of the skull base and the potential for postoperative complications, this region has a unique complexity that requires a comprehensive approach. The management of patients with skull base tumors has advanced with the improvement of operative technique, diagnostic and interventional radiology, and the introduction of the multidisciplinary surgical and medical teams. This has provided the opportunity for successful surgical treatment of most cranial base tumors, which were previously deemed inoperable.

HISTORY Crile (1), in 1906, introduced the radical neck dissection and prior to the use of this approach the prognosis was poor for patients with head and neck cancer who were treated with surgery (2). Early in the 20th century, only a limited number of reconstructive options were available and therefore skin grafts were commonly used for coverage and these grafts were often put directly on to the dura or cranial bone (3– 5). This resulted in many reconstruction failures. In patients where reconstruction of the orbit was required, tubed pedicles were used in multiple staged procedures (6). Golovine (7)and then Gillies (8) popularized the temporalis muscle flap for soft tissue orbital reconstruction; the temporalis flap remains a popular reconstructive option for other defects in the skull base region (6,9–12). For orbital reconstruction, Thomson (13) described using the ipsilateral forehead flap. Expanding the use of the forehead flap, McGregor described this flap for reconstruction of intraoral lining (14). In 1965, Bakamjian (15) described the deltopectoral flap for oropharyngeal reconstruction. This was followed by a modification by McGregor and Jackson (16) that allowed the flap to be lengthened so that it could be extended to the ear. Fisch et al. (17) broadened the use of this flap by suggesting that the flap could be internally tunneled to reconstruct the nasopharynx and also if the flap was transferred externally, it could be extended to the orbital and zygomatic regions. Historically, the temporalis and deltopectoral flaps were the workhorse flaps for reconstruction in the head and neck region (2). While these flaps do provide good soft tissue coverage, the donor site morbidity is considerable. With defects that are located superior to the palate, the reported complication rate is between 40% and 50% when the deltopectoral flap is used (18,19) and this is likely due to the failure of these flaps to provide a watertight seal of the oral cavity.

ANATOMY The intracranial surface of the skull base is created by the floor of the posterior, middle, and anterior cranial fossae, and the extracranial component provides structure to the orbital roof, sphenoid sinus, nasopharynx, and infratemporal fossa. This area of the cranial base has many critical anatomic structures that transverse the cranium via foramina and canals. The unique function and complex location of the skull base makes the management of any pathologic lesion in this region challenging. To assist in the evaluation and treatment of skull base lesions and because of the complexity of the cranial base, this area has been classified into different regions or zones (17,24,25). The skull base was divided into the anterior and posterior areas by Jackson and Hide (17) to describe the 139

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Skull base defect

Region I

Small size defect

Watertight dural seal

Region II

Local vascularized flap

Large size defect

Watertight dural seal

Free tissue transfer

Region III Midline zone 1 defect

Figure 1 The skull base is divided into 3 regions based upon the anatomic location and growth pattern of the tumors. Source: Reproduced with permission from Ref. 23.

requirements for operative reconstruction; the anterior area is associated with the anterior cranial fossa and the posterior area was subdivided into the posteroanterior, posterior– central, and posterior–posterior segments. Jones et al. (25) separated the skull base into the anterior, middle, and posterior regions, which corresponded to the anterior, middle, and posterior cranial fossae. Irish et al. (24) reviewed 77 patients with skull base neoplasms and divided the skull base into three regions (Fig. 1) based upon the anatomic boundaries and tumor growth patterns within the different regions of the skull base. As described by Irish et al. (24), Region I tumors arise from the sinuses, orbit, and other anterior structures and may involve lesions extending into the anterior cranial fossae. In addition, Region I tumors include those lesions that originate from the clivus and those that extend posteriorly to the foramen magnum. These tumors were included in Region I because of the similarity to other Region I tumors and also they are surgically accessed using an anterior approach. Tumors that are classified in Region II originate in the lateral skull base and may have extension to the middle cranial region but primarily involve the infratemporal and pterygopalatine fossa. Region III lesions occur in the area around the parotid and temporal bone and ear and these tumors extend intracranially to involve the posterior cranial fossae (24). The patient sample evaluated by Irish et al. (24) included only patients with neoplasms that entered the skull base and did not include tumors that projected only to the skull base. Outcome data reported in other studies vary significantly because many reports include patients with extracranial tumors and tumors with bony invasion. One of the difficulties when comparing outcome in patients with skull base neoplasms is the inclusion of patients with tumors in different locations within the skull base and varying pathologies. Skull base tumors for this review are defined as those neoplasms that require both an intracranial and an extracranial approach for ablation.

RECONSTRUCTION OF THE SKULL BASE In general, head and neck reconstruction requires consideration of postoperative function and cosmesis and must pro-

Galea-frontalis flap Pericranial flap

Lateral zone 1 defect

Zone 2 or zone 3 defect

Galea –frontalis flap Temporalis flap Pericranial flap Regional pedicled flap Temporalis flap e.g., trapezius Temporoparietal fascial flap

Figure 2 Algorithm for management of skull base defects. Source: Reproduced with permission from Ref. 61.

vide structural support and soft tissue bulk. The additional unique challenges of reconstruction of skull base defects is the need to ensure a watertight dural seal, to fill dead space, and to provide coverage with well-vascularized tissue. Adherence to these reconstructive goals will provide the best opportunity for optimal patient outcome with the least risk of postoperative complications. The specific reconstructive procedure that is required will be selected based upon several key factors, including the exact location of the defect, the defect size, the tissue involved, and if there has been exposure of the dura (Fig. 2). In this review of reconstruction of skull base defects, we have utilized the regional classification system based on the classification described by Irish et al. (24).

Skull Base Zone I Zone I is compatible with the anterior skull base defects described by Jackson and Hide (17) and Jones et al. (25) and extends from the midline anteriorly to the posterior wall of the orbit and also includes an extension to the foramen magnum. Zone I tumors originate in the anterior sinuses, midfacial skin, and also may extend to the cribriform plate, the dura and brain tissue. In the patients described by Irish et al. (24), the most common location of the tumors was in Zone I (44%) and 6% of patients had lesions in Zone I and II. Surgery in the skull base requires a direct operative approach, which will provide access to the entire tumor. While the location of the tumor is important in selection of the surgical approach, consideration must also be given to the size and characteristics of the lesion. In Zone I, a lateral rhinotomy or maxillotomy approach is most commonly used and in some cases a partial or total maxillectomy may be necessary. Tumors extending into the region of the clivus can be accessed by combining a Le Fort I maxillary osteotomy and mandibulotomy with midline split of the soft and hard palates (26). To provide complete exposure for tumor excision and to protect vital neural and vascular structures, a bicoronal incision and frontal craniotomy may also be necessary.

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Figure 3 (A–F) (A) Patient is seen preoperatively with proptosis due to a Region I tumor. (B) The anterior skull base tumor is seen on MRI. (C) The rectus abdominus free tissue transfer is prepared. (D) The flap is inset. (E, F) The patient is seen with excellent outcome six years following surgery. Source: Reproduced with permission from Patrick J. Gullane, MB & Peter C. Neligan, MB.

Following tumor ablation, the reconstructive options available will be determined by the type of tissue required, the size and the position of the defect, and if there was exposure of the dura. Preceding the development of myocutaneous flaps, the reconstruction consisted of coverage using split thickness skin grafts and this was utilized even in patients where the dura was exposed. The use of skin grafts in many cases was unsuccessful and similarly, when tensor fascia lata grafts were used to repair the dura, these efforts proved ineffective. Ketcham et al. (3) in their review, found that approximately 50% of these patients developed cerebrospinal fluid leaks. Because of the failed experience of using a nonvascularized skin graft to cover a nonvascularized tensor fascia lata graft, vascularized tissue was introduced for these repairs. There are numerous local soft tissue flaps which have been reported for use with skull base defects, including forehead flaps (13,27,28) and glabellar flaps (29). In patients where a bicoronal incision was necessary, the pericranial flap (30,31) and the galeal flap (32,33) have also been described. The pericranial and galeal flaps may be used when there is a small midline defect and they provide good soft tissue coverage with minimal donor site morbidity. In patients with defects that are located more laterally in the region of the anterior cranial fossa, the temporalis muscle can be used. This flap is not as dependable when it is medially transposed, due to decreased vascularity. The most distal portion of the flap is most vulnerable to vascular compromise and it is often this distal area that is vital for successful closure. Therefore, if there is necrosis of the flap and/or wound dehiscence in this region, the risk of failure of the reconstruction increases. Donor site morbidity and patient dissatisfaction may also be a problem with the temporalis flap. With transposition of the temporalis muscle, a concave deformity will occur at the donor site and this may not be acceptable to all patients. If the temporalis muscle has been devascularized by tumor ablation or neck dissection, then this muscle may not be available

and other sources of soft tissue must be considered for the reconstruction. Myocutaneous or muscle flaps provide vascularized soft tissue bulk and this is helpful to cover an area that may require postoperative radiation or may have been irradiated preoperatively. These muscle flaps provide good soft tissue contour and can minimize the risk of postoperative complications by filling dead space in the skull base region. The trapezius, the latissimus dorsi, and the pectoralis major muscles have been used as pedicled myocutaneous flaps for the management of these defects (34). Rosen (35) described the extended trapezius flap to reconstruct defects that are located more anterior in the skull base. Although pedicled flaps can reach the defect in many cases and have been historically used for reconstruction in this region, they have been become obsolete in favor of free tissue transfers and are no longer the first choice for skull base reconstruction. However, pedicled flaps may be used as a secondary procedure in patients who have had a failure of a free flap reconstruction. When large defects remain following tumor ablation, free tissue transfer is the best reconstructive option for the majority of patients (34,36–38). It provides well-vascularized tissue and because a free flap does not have the attachment of a pedicle, it can be designed and placed in the desired position and it provides well-vascularized tissue. With a pedicled flap, the design is such that the most distal portion of the flap is usually the aspect that is essential for successful soft tissue coverage. In most pedicled flaps, this distal region is the least reliable in terms of vascularity and therefore in cases where distal flap necrosis occurs, the whole reconstruction may fail. Free tissue transfer flaps can be designed to provide well-vascularized tissue in the best position to effectively seal the defect (Fig. 3A–3F). Because a microvascular free tissue transfer may be harvested at the same time as the tumor ablation, it is possible to utilize a two-team approach; one team performing the tumor ablation and the second team

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performing the flap harvest. This two-team approach minimizes patient anesthesia time and thus decreases the risk of anesthesia-related complications. When the dura and aerodigestive tracts have been exposed during tumor ablation, it is necessary to provide a barrier between these two tracts, and myocutaneous flaps are particularly useful in this role because of their capability for resistance of infection. Numerous muscle flaps have been described for soft tissue reconstruction and the rectus abdominis myocutaneous flap is often used to repair large defects in this area of the cranial base (34,39). It is a well-vascularized flap that can provide good soft tissue coverage for large defects and thereby provides an excellent barrier between the aerodigestive and dura tracts. In Zone I, reconstruction of small defects may be accomplished with a local vascularized flap, such as the pericranial or galeo-frontalis flap and this type of flap will provide sufficient soft tissue. When a large muscle flap is required in cases of more extensive Zone I defects, the rectus abdominous flap is the flap of choice in our unit.

topectoral flap (42) have been used for repair of soft tissue defects located in Zone II. For smaller defects that are located in a more lateral region, a temporalis muscle flap may be used. Other muscle flaps including the pectoralis major flap and the trapezius flap have also been described for reconstruction in Zone II defects. These flaps have not proven to be consistently reliable and therefore are used less often. Other alternatives include a free tissue transfer such as the rectus abdominis muscle, which provides ample soft tissue bulk, a long pedicle and reliable vascularity. The rectus abdominus muscle flap can also be designed to provide muscle extensions. When necessary, these extensions are useful to obliterate the sphenoid sinus and to provide coverage in the neck region, particularly when a saphenous vein graft has been used to reconstruct the carotid artery. The use of the free tissue transfer also provides the opportunity to utilize separate surgical teams for the tumor extirpation and for the reconstruction, which will significantly reduce operative time.

Skull Base Zone III Skull Base Zone II Zone II (24) is formed by the infratemporal and pterygomaxillary fossae and a segment of the middle cranial fossa and it extends from the posterior aspect of the petrous temporal bone to the posterior orbital wall. There are several neural and vascular structures that traverse this zone to the middle cranial fossa. The foramen lacerum is positioned on the skull’s under surface and the internal carotid artery passes through this foramen to the carotid groove on the sphenoid bone. The mandibular and maxillary branches of the trigeminal nerve are also found in this zone; the mandibular nerve traverses through the foramen ovale and the maxillary nerve through the foramen rotundum. The facial nerve (cranial nerve VII) and the auditory nerve (cranial nerve VIII) pass through the petrous temporal bone. Neoplasms, which originate within Zone II, include nasopharyngeal tumors, glomus jugulare neoplasms, clival chordomas, and meningiomas. Common tumors that occur external to Zone II but extend into the middle cranial base include basal and squamous cell carcinomas of the external and middle ear and scalp and parotid tumors. In the review by Irish et al., only 9% of the patients had tumors that were isolated to Zone II and 43% of these neoplasms had dural involvement (24). As compared to Zone I and III, tumors involving Zone II are not as common but are associated with the worst prognosis (24). Tumors that are located within the middle skull base region may be surgically removed through an infratemporal approach (40) using a hemicoronal incision and preauricular extension. This approach provides surgical access to the mandibular condyle and if necessary allows inferior displacement of the zygomatic arch following dissection of the facial nerve from the stylomastoid foramen to the parotid gland. If an increased surgical exposure is necessary, the infratemporal approach may be combined with a mandibulectomy, a lateral mandibulotomy or an anterior mandibulotomy with anterior displacement of the mandible. A transtemporal approach (41) has also been utilized for ablation of neoplasms within Zone II. This approach necessitates a hemicoronal incision with a postauricular extension with transection of the external auditory canal. If exposure of the intradural component of middle cranial fossa is necessary, a frontotemporal craniotomy can also be used. The reconstructive options that are available will vary and are based upon the size and location of the defect following tumor ablation (Fig. 2) and patient factors. Historically, pedicled flaps such as a rotational scalp flap (28) and del-

Zone III (24) consists primarily of the posterior cranial fossa and includes some of the posterior segment of the middle cranial fossa. This zone includes the internal jugular vein, the glossopharyngeal nerve, the vagus nerve, and the accessory nerve as they traverse the jugular foramen from the posterior cranial fossa. The hypoglossal nerve is also in Zone III but passes through the anterior condylar canal. As reported by Jones et al. (25), the most common tumors occurring in Zone III were schwannomas and glomus tumors. The occurrence of this type of neoplasm was not consistent with the study by Irish et al. (24), where they noted 14 of 25 Zone III tumors were squamous cell carcinomas. The variation in the pathology reported in these two studies may signify a difference in the patients that are referred to different surgical specialties. Zone III tumors are commonly exposed using a transtemporal approach and in some cases bony resection around the carotid artery and sigmoid sinus is necessary. Following tumor ablation, small defects may be reconstructed using local muscle flaps such as the temporalis or the sternocleidomastoid muscle or the temporoparietal pedicled flap. If a radical neck dissection is necessary, then in many cases these muscles will be devascularized or excised in the resection and therefore the local muscles are not available for reconstruction. The latissimus dorsi muscle flap has been described for use in Zone III defects. However, the use of this flap requires that the patient be repositioned for flap harvest. Also the latissimus dorsi muscle flap is not as reliable as other free tissue transfers and therefore this flap is not the flap of choice for use with primary reconstruction. In patients where a large defect remains following tumor excision, a free tissue muscle flap such as the rectus abdominis is our choice. This flap provides a well-vascularized soft tissue coverage and is very reliable for reconstruction of complex defects in this region (Fig. 4A–4G ). The variety of pathologies of skull base lesions and variation in the exact location contribute to the difficulties in interpreting studies that have reported outcome and patient prognosis. It appears that squamous cell carcinomas are the most frequently reported tumors in the skull base (24,43). Irish et al. (24) reported that 29% of their patients had a diagnosis of squamous cell cancer and these tumors were most commonly located in Regions I and III. However, basal cell carcinomas, chordomas, chondrosarcomas, and esthesioneuroblastomas were most frequently found in Region I (24). Tumors that invaded both Regions II and III usually originated in the salivary gland and typically went from

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Figure 4 (A–G)(A) Patient is seen preoperatively with large mass. (B) Region III squamous cell carcinoma is shown on MRI. Source: Reproduced with permission from Patrick J. Gullane, MB & Peter C. Neligan, MB. (C) Region III squamous cell carcinoma is shown on CT scan. Source: Reproduced with permission from Ref. 61. (D) The area of resection, including the dural patch, is illustrated. Source: Reproduced with permission from Ref. 61. (E) Preparation of the area to be resected. Source: Reproduced with permission from Ref. 61. (F) Resected specimen. Source: Reproduced with permission from Ref. 61. (G) Patient presents postoperatively following a reconstruction using a rectus abdominis myocutaneous free tissue transfer. Source: Reproduced with permission from Ref. 61.

Region II into Region III (24). In the series reported by Irish et al. (24), there was better survival at two and four years in patients with Region I and III tumors and no patients with Region II tumors survived for four years (24). Prognosis not only depends on tumor pathology but also depends on patient comorbidities. In the collaborative review by Patel et al. (43), the extent of intracranial involvement and comorbid medical conditions significantly influenced patient survival.

TECHNICAL CONSIDERATIONS Because of the location of the skull base and vital anatomic structures that are located in this region, it is important to minimize the risk of complications because of the potential for life-threatening consequences. Therefore, there are aspects of skull base reconstruction that necessitate special attention and meticulous technique to avoid any preventable complications. It is important to appreciate the goals of the reconstruction and then the technical considerations become more evident. Obliteration of the dead space is essential for a successful reconstruction and therefore muscle and myocutaneous flaps are often utilized. Muscle is well vascularized and very malleable and therefore it can be packed into cavities and fills spaces within the skull base. In cases where the dura has been breached, successful reconstruction also depends on a watertight dural seal. The anatomy of the skull base is such that there is a downward gravitational pull on any reconstructive

flaps. This likely contributes to the separation of the dural repair and therefore makes it difficult to maintain a tight seal of the repair and thus creates more dead space. To solve this problem and to maintain the dural seal, the flap can be maintained in position by attaching it to the surrounding bony structures. It is secured by drilling holes in the bone and the sutures are placed through these holes (Fig. 5A and 5B). The flap may then be pulled up into the defect and further secured with fibrin glue. This will provide a more effective watertight seal between the flap and the dura. Reconstructions that utilize a free tissue transfer require optimal donor blood vessels to increase the likelihood of a successful reconstruction. The superficial temporal vessels are reliable donor vessels for most Zone I reconstructions (44,45). In cases where the superficial temporal vessels do not appear to be optimal or are not available, the pedicle can be extended to the neck and the facial or superior thyroid vessels may be used. Reconstruction in Zones II and III often utilizes vessels located in the neck and when selecting these vessels, consideration is given to several factors including the vessel caliber, pedicle length, and pedicle geometry. In most cases, vein grafts are unnecessary. Because the location of the skull base is not superficial, the reconstructive flap is often deep and therefore clinical monitoring of perfusion is not possible. In these patients, venous pedicle patency may be monitored with an implantable Doppler probe. In patients who are treated with postoperative radiation therapy, there is an increased risk of osteoradionecrosis or

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Similar to bone, appropriate vascularized soft tissue coverage must also be included in the reconstruction to minimize the risk of postoperative complications (46).

COMPLICATIONS Because of the location of the skull base and the close proximity of vital neural and vascular structures, postoperative complications can quickly develop into life-threatening conditions. Therefore, it is essential to minimize the risk of postoperative complications and this is achieved by selecting the most optimal reconstructive procedure based upon the site and size of the surgical defect and associated patient factors. The complication rate following skull base reconstruction that has been reported in previous studies varies from 11.5% to 63% and there has been a decrease in the rate in the more recent patient studies (43,47). There are several factors that have likely contributed to the decrease in complications and these include improved surgical technique, enhanced postoperative patient care, and the use of the free tissue transfer. Complications that occur in the early perioperative period may compromise the reconstruction. These early complications include infection, dural exposure, cerebrospinal fluid leak, and ascending meningitis. The occurrence of the majority of the early complications is usually related to a poor dural repair and/or persistent communication between the dura and the aerodigestive tracts. Late complications are not life threatening but will certainly impact on patient morbidity, satisfaction, and quality of life. Late complications are often the result of a lack of structural support, soft tissue atrophy, or postoperative radiation fibrosis.

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Early Complications Wound Infection The most common early complication is wound infection (43). Because of the location of the skull base, this is a potentially fatal complication that requires prompt treatment. In cases where the oral and/or nasal cavities have been breached, prophylactic antibiotics such as cephalosporin with an anaerobic agent may be instituted. Otherwise, treatment of a wound infection should include wound cultures and based on the laboratory results, the appropriated antibiotic treatment can be commenced.

Flap Compromise (B)

Figure 5 (A) To facilitate suspension of the flap, suspension sutures are passed through drill holes in the bone following resection of the temporal bone. (B) The rectus abdominus muscle free tissue transfer (within white line) is inset and it is suspended from the temporal bone defect using suspension sutures. Source: Reproduced with permission from Ref. 61.

infection when avascular bone is used in the reconstruction. Therefore, the use of avascular bone should be avoided and in most cases, a soft tissue reconstruction is preferential to bony reconstruction in the skull base region. When bony reconstruction is deemed to be necessary, avascular bone should not be used and vascularized bone should be selected. The scapular graft is a good choice to be used for the donor. A simpler alternative, such as titanium mesh, may also be used to provide structural support (46). If allograft material is selected, then titanium is an excellent choice because it is an inert nonallergenic metal and follow-up radiologic studies, including CT and/or MR imaging are not contraindicated.

As reported by Califano et al. (36), there are more free tissue transfers now used for reconstruction of skull base defects. Compared to a historical cohort who did not have free flaps, the authors reported a similar complication rate in patients who had free flaps, although these patients involved more complex resections and reconstructions. Neligan et al. (34) reported a decrease in postoperative complications in patients with free tissue transfers compared to patients with pedicled flaps. In those patients who had a free flap, there were only 10% of cases with compromised wound healing and 5% of patients had a cerebrospinal fluid leak (34). With improved surgical technique and perioperative care, the complications associated with free tissue transfers have decreased and therefore this is the reconstructive option recommended for most patients with large skull base defects following tumor ablation.

Cranial Nerve Dysfunction Because of the location of the skull base and the close proximity of the cranial nerves, postoperative dysfunction in one or more cranial nerves is not unexpected. In cases where the

Chapter 8: Reconstruction of Skull Base Defects

cranial nerve is included in the resection of the neoplasm, reconstruction of the nerve using direct nerve coaptation or a nerve graft should be attempted. In patients where the nerve has not been resected or transected, patients should be followed for reinnervation and appropriate intervention should be instituted. In patients with skull base pathology, dysfunction of the muscles innervated by the facial nerve may occur from tumor pathology, growth, ablation, or operative trauma. Injury to the facial nerve can result in significant morbidity associated with decreased self-image, function, and socialization. Therefore, facial nerve reconstruction to achieve symmetry and/or reanimation is recommended to minimize patient morbidity and to improve patient outcome. Although a complete facial palsy may be present, the absence of facial movement does not indicate the severity or degree of facial nerve injury. A neurapraxic (48) or a Sunderland first degree (49) injury may occur as a result of operative trauma, such as retraction and complete recovery would be anticipated following neural remyelination. Increased neural trauma may cause a more severe degree of nerve injury; however, reinnervation of the facial muscles and complete recovery may still occur following an adequate time for nerve regeneration (1 mm/day) (49). Because the nerve is intact and the nerve injury is not severe enough to preclude nerve regeneration, these patients will not require any operative intervention to regain facial function. In patients with no evidence of recovery, postoperative electromyography (EMG) should be performed approximately four weeks following surgery to determine the severity of nerve injury and the potential for recovery. EMGs performed before this time may not adequately assess the degree of nerve injury. Because of the inability for complete eyelid closure in some cases of facial nerve palsy, these patients should be evaluated for corneal injury. Patients with reduced eyelid closure and at risk for corneal abrasion should be considered for insertion of a gold weight to achieve eye closure. In patients where the nerve has been transected or resected, reconstruction of the facial nerve at that time should be considered when possible. If the proximal and distal nerve stumps are available, the nerve may be repaired with direct nerve coaptation at the time of tumor extirpation. If the repair cannot be achieved without tension, then an interpositional cable nerve graft or nerve transfer should be utilized. For the donor nerves, small diameter sensory nerves are commonly used, including the medial antebrachial cutaneous nerve, the sural nerve, and in some cases of facial nerve reconstructions, the greater auricular nerve (49–51). The donor nerves selected with depend on the length of the nerve deficit, the number of cables required, and the sensory deficit at the graft site. In some cases, the proximal or distal stump of the nerve may not be available and therefore nerve repair or graft may not be possible. However, nerve transfers such as the partial hypoglossal (52,53) to facial nerve or muscle transposition of the temporalis or masseter muscle are excellent alternatives and may be performed primarily (51,54–56). While controversy remains regarding postoperative radiation and nerve regeneration, several studies have documented no adverse effects (57–59). Gullane et al. (59) reported excellent function in four of six patients following facial nerve grafts and postoperative radiation after extensive resection of parotid cancers. It is our recommendation that patients who may undergo postoperative radiation should not be denied repair of the facial nerve. When facial nerve resection extends intratemporally or intracranially, it may not be possible to restore nerve continuity and other reconstructive options for facial reanimation should be considered. Delayed reconstruction may include a

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free muscle transfer innervated by the trigeminal nerve motor branch to the masseter muscle, a cross facial nerve graft with a secondary free muscle transfer or muscle transposition of the temporalis or masseter muscle (51,54,55,60). Procedures that utilize a free tissue muscle transfer and do not involve reinnervation of the facial muscles may be performed even after long periods of facial nerve injury (51,54,55,60). In patients with a poor survival prognosis or who choose not to undergo a complex reconstruction, static facial slings may be a good alternative to restore facial symmetry at rest.

Cerebrospinal Fluid Leak A cerebrospinal fluid leak can have significant consequences with regard to flap compromise, flap loss, and patient morbidity. With increased exposure of the dura, there is an increased risk of a postoperative cerebrospinal fluid leak. Therefore, to minimize the risk of this complication, it is important to attain a watertight dural seal and this is best accomplished with the use of vascularized tissue for the reconstruction and meticulous closure of the repair.

Intracranial Infections The incidence of intracranial infections has decreased with the introduction of free flaps. However, if an intracranial infection does occur, it is important that broad-spectrum antibiotics are instituted promptly.

Late Complications Late complications are not life threatening and therefore are often underestimated in terms of patient morbidity. These complications include diplopia, malocclusion, trismus, nasal obstruction, and facial abnormality and often result from soft tissue atrophy, radiation fibrosis, and/or bony support. Correction of these deformities may be helpful to decrease patient morbidity and to improve health-related quality of life.

CONCLUSION Local and regional flaps have been used in the reconstruction of the skull base but these flaps are less frequently used for large defects. Because of the advantages of the free tissue transfer, our reconstructive method of choice for these defects in the skull base region is a free flap. The increased use of vascularized free flaps in these reconstructions has provided a significant decrease in postoperative complications and improved patient outcome (34,37). Skull base neoplasms often result in extensive ablation, which often produces large soft tissue defects with dural exposure and this will increase the risk of postoperative complications. A successful reconstruction in the skull base requires a watertight dural seal and obliteration of all dead space. This will effectively separate the intracranial contents from the upper aerodigestive tract and all potential infective sources. The use of a well-vascularized tissue will provide an excellent dural barrier and seal, in addition to obliterating potential sources of infection. At one time, skull base tumor ablation and reconstruction were considered too risky to even attempt but now this surgery is routine, reliable, and predictable in many patients. Advancements in diagnosis, imaging, and surgical technique, both for tumor resection and for reconstruction, have made this method of management achievable. The location of the tumor and the size of the skull base defect are two of the factors that will help to determine the optimal reconstruction. However, the use of a vascularized free tissue transfer for the reconstruction will help to achieve a watertight dural seal, obliterate any communication between the cranial contents and the aerodigestive tract, and thus

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minimize the occurrence of postoperative complications in these patients. REFERENCES 1. Crile G. Excision of cancer or the head and neck with special reference to the plan of dissection based on one hundred and thirty two operations. JAMA. 1906;47:1780–1798. 2. Hobar PC, Barton FE. Head and neck II: Reconstruction. Selected Readings in Plastic Surgery. 1990: 6. 3. Ketcham AS, Hoye RC, Van Buren JM, et al. Complications of intracranial facial resections for tumors of the paranasal sinuses. Am J Surg. 1966;112:591–596. 4. Ward GE, Loch WE, Lawrence W. Radical operation for carcinoma of the external auditory canal and middle ear. Am J Surg. 1951;82:169–178. 5. Parson H, Lewis JS. Subtotal resection of the temporal bone for cancer of the ear. Cancer. 1954;7:995–1001. 6. Murray JE, Matson DD, Habal MB, et al. Regional cranio-orbital resection for recurrent tumors with delayed reconstruction. Surg Gynecol Obstet. 1972;134:437–447. 7. Golovine SS. Procede de cloture plastique de l’orbite apres l’exenteration. Arch d’Opthalmol. 1898;18:679–682. 8. Gillies HD. Plastic Surgery of the Face. London: Oxford University Press, 1920. 9. Ariyan S, Stahl RS. Reconstruction following cranio-orbital resection. In: Ariyan S, ed. Cancer of the Hand and Neck. St Louis, MO: C. V. Mosby Company, 1987:379–387. 10. Bakamjian VY, Souther SG. Use of the temporalis muscle flap for reconstruction after orbito-maxillary resections for cancer. Plast Reconstr Surg. 1975;56:171–177. 11. Holmes AD, Marshall KA. Uses of the temporalis muslce flap in blanking out orbits. Plast Reconstr Surg. 1979;63:336–343. 12. Sypert GW, Habal MB. Combined cranio-orbital surgery for extensive malignant neoplasms of the orbit. Neurosurgery. 1978;2:8–14. 13. Thomson HG. Reconstruction of the orbit after radial exenteration. Plast Reconstr Surg. 1970;45:119–123. 14. McGregor IA. The temporal flap in introral cancer: its use in repairing the post-excisional defect. Br J Plast Surg. 2004;16:318– 322. 15. Bakamjian VY. A two stage method for pharyngoesophageal reconstruction with a primary pectoral flap. Plast Reconstr Surg. 1965;36:173–184. 16. McGregor IA, Jackson IT. The extended role of the deltopectoral flap. Br J Plast Surg. 1970;23:173–185. 17. Jackson IT, Hide TAH. A systematic approach to tumors of the base of the skull. J Maxillofac Surg. 1982;10:92–98. 18. Lewis MB, Remensnyder JP. Forehead flap for reconstruction after ablative surgery for oral and oropharyngeal malignancy. Plast Reconstr Surg. 1978;62:59–65. 19. Park JS, Sako K, Marchetta FC. Reconstructive experience with the medially based deltopectoral flap. Am J Surg. 1974;128:548– 552. 20. Ariyan S. The pectoralis major myocutaneous flap. A versatile flap for reconstruction of the head and neck. Plast Reconstr Surg. 1979;63:73–81. 21. Ariyan S. Further experiences with the pectoralis major myocutaneous flap for the immediate repair of defects from excisions of head and neck cancers. Plast Reconstr Surg. 1979;64:605–612. 22. Quillen CG, Shearin JC Jr, Georgiade NG. Use of the latissimus dorsi myocutaneous island flap for reconstruction in the head and neck area. Case report. Plast Reconstr Surg. 1978;62:113–117. 23. Neligan PC, Boyd JB. Reconstruction of the cranial base defect. Clin Plast Surg. 1995;22:71–77. 24. Irish J, Gullane PJ, Gentili F, et al. Tumors of the skull base: Outcome and survival analysis of 77 cases. Head Neck. 1994;16:3– 10. 25. Jones NF, Schramm VL, Sekhar LN. Reconstruction of the cranial base following tumour resection. Br J Plast Surg. 1987;40:155– 162.

26. Sandor GK, Charles DA, Lawson VG, et al. Transoral approach to the nasopharynx and clivus using the Le Fort I osteotomy with midpalatal split. Int J Oral Maxillofac Surg. 1990;19:352– 355. 27. Ousterhout DK, Tessier P. Closure of large cribriform defects with a forehead flap. J Maxillofac Surg. 1981;9:7–9. 28. Westbury G, Wilson JSP, Richardson A. Combined craniofacial resection for malignant disease. Am J Surg. 1975;130:463–469. 29. Jackson IT, Marsh WR, Hide TAH. Treatment of tumors involving the anterior cranial fossa. Head Neck. 1984;6:901–913. 30. Scher RL, Cantrell RW. Anterior skull base reconstruction with the pericranial flap after craniofacial reconstruction. Ear Nose Throat J. 1992;71:210–212. 31. Noone MC, Osguthorpe JD, Patel S. Pericranial flap for closure of paramedian anterior skull base defects. Otolaryngol Head Neck Surg. 2002;127:494–500. 32. Jackson IT, Adham MN, Marsh WR. Use of the galeal frontalis myofascial flap in craniofacial surgery. Plast Reconstr Surg. 1986;77:905–910. 33. Schramm VL Jr, Myers EN, Maroon JC. Anterior skull base surgery for benign and malignant disease. Laryngoscope. 1979;89:1077–1091. 34. Neligan PC, Mulholland RS, Irish J, et al. Flap selection in cranial base reconstruction. Plast Reconstr Surg. 1996;98:1159–1166. 35. Rosen HM. The extended trapezius musculocutaneous flap for cranio-orbital facial reconstruction. Plast Reconstr Surg. 1985;75:318–327. 36. Califano J, Cordeiro PG, Disa JJ, et al. Anterior cranial base reconstruction using free tissue transfer: Changing trends. Head Neck. 2003;25:89–96. 37. Mulholland RS, Boyd JB, Irish J, et al. Flap selection in cranial base reconstruction—local, pedicled or free? Plast Surg Forum. 1993;62:265–266. 38. Teknos TN, Smith JC, Day TA, et al. Microvascular free tissue transfer in reconstructing skull base defects: Lessons learned. Laryngoscope. 2002; 112:1871–1876. 39. Urken ML, Turk JB, Weinberg H, et al. The rectus abdominus free flap in head and neck reconstruction. Arch Otolaryngol Head Neck Surg. 1991;117:857–866. 40. Sekhar LN, Schramm VL, Jones NF. Combined resection of large neoplasms involving the lateral and posterior cranial base. In: Sekhar LN, Schramm VL, eds. Tumors of the Cranial Base: Diagnosis and Treatment. New York: Futura Publishers, 1986. 41. Fisch U, Fagan P, Valavanis A. The infratemporal fossa approach for the lateral skull base. Otolaryng Clin North Am. 1984;17:513– 552. 42. Bakamjian VY, Long M, Rigg B. Experience with the medially based deltopectoral flap in reconstructive surgery of the head and neck. Br J Plast Surg 1971;24:174–183. 43. Patel SG, Singh B, Polluri A, et al. Craniofacial surgery for malignant skull base tumors. Cancer. 2003;98:1179–1187. 44. Nahabedian MY, Singh N, Deune EG, et al. Recipient vessel analysis for microvascular reconstruction of the head and neck. Ann Plast Surg. 2004;52:148–155. 45. Lipa JE, Butler CE. Enhancing the outcome of free latissimus dorsi muscle flap reconstruction of scalp defects. Head Neck. 2004;26:46–53. 46. Badie B, Preston JK, Hartig GK. Use of titanium mesh for reconstruction of large anterior cranial base defects. J Neurosurg. 2000;93:711–714. 47. Imola MJ, Sciarretta V, Schramm VL. Skull base reconstruction. Curr Opin Otolaryngol Head Neck Surg. 2003;11:282–290. 48. Seddon HJ. Three types of nerve injury. Brain. 1943;66:237–238. 49. Sunderland S. Nerve and Nerve Injuries. Edinburgh: Churchill Livingstone, 1978. 50. Mackinnon SE, Dellon AL. Surgery of the Peripheral Nerve. New York: Thieme Medical Publishers, 1988. 51. Myckatyn TM, Mackinnon SE. The surgical management of facial nerve injury. Clin Plast Surg. 2003;30:307–318. 52. Kalantarian B, Rice DC, Tiango DA, et al. Gains and losses of the XII-VII component of the “babysitter” procedure: a morphometric analysis. J Reconstr Microsurg. 1998;14:459–471.

Chapter 8: Reconstruction of Skull Base Defects 53. Mersa B, Tiango DA, Terzis JK. Efficacy of the “babysitter” procedure after prolonged denervation. J Reconstr Microsurg. 2000;16:27–35. 54. Conley J, Gullane PJ. Facial rehabilitation with termporal muscle. New concepts. Arch Otolaryngol. 1978;104:423– 426. 55. Gullane PJ. Extratemporal facial rehabilitation. J Otolaryngol. 1979;8:477–486. 56. Manktelow RT, Tomat LR, Zuker RM, et al. Smile reconstruction in adults with free muscle transfer innervated by the masseter motor nerve: Effectiveness and cerebral adaptation. Plast Reconstr Surg. 2006;118:885–899.

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57. Brandt K, Evans GRD, Ang KK, et al. Postoperative irradiation: Are there long-term effects on nerve regeneration ? J Reconstr Microsurg. 1999;15:421–425. 58. Evans GRD, Brandt K. Peripheral nerve regeneration: The effects of postoperative irradiation. Plast Reconstr Surg. 2003;112:2023– 2024. 59. Gullane PJ, Havas TJ. Facial nerve grafts: Effects of postoperative irradiation. J Otolaryngol. 1987;16:112–115. 60. Manktelow RT. Free muscle transplantation for facial paralysis. Clin Plast Surg. 1984;11:215–220. 61. Gullane PJ, Lipa JE, Novak CB, et al. Reconstruction of skull base defects. Clin Plast Surg. 2005;32(3):391–400.

9 Prosthetic Rehabilitation of Patients Undergoing Skull Base Surgery Theresa M. Hofstede, Rhonda F. Jacob, Pattii C. Montgomery, Peggy J. Wesley, Jack W. Martin, and Mark S. Chambers

alveolar ridge, and hard palate as supporting tissues for prostheses. The important supporting mandibular landmarks are the alveolar ridge, retromolar pad, and buccal shelf. Preserving, enhancing, or reconstructing these tissues is important for support and retention of a prosthesis. Periodontally healthy teeth and edentulous ridges are essential structures for prosthesis retention and support. Conservation of the supporting tissues, if possible, after eliminating disease, is important for optimal outcome; albeit, treatment of disease takes priority (9–11).

This chapter presents current concepts regarding oral and facial prosthetic rehabilitation and oral oncologic principles in patients with head and neck cancer. Multidisciplinary therapeutic techniques are commonly used in the care of patients with advanced disease of the head and neck. The surgical technique is used to eliminate local disease and aid in the preservation of function, mobility, and physical appearance. Hence, collaboration and team efforts between the head and neck surgeon, plastic reconstructive surgeon, maxillofacial prosthodontist, speech pathologists, and other vital members are important in improving a patient’s quality of life. Prior to the surgical procedure, the head and neck team specialists formulate plans and preparations for prosthetic rehabilitation. This can help prevent and minimize postsurgical complications and reconstructive dilemmas. Clear and open communication between the head and neck surgeon and the maxillofacial prosthodontist is of utmost importance for successful prosthetic rehabilitation (1–5). Early dental intervention can help reduce future challenges such as oral infection by decreasing risk factors for oral complications, such as periodontal disease, osteoradionecrosis, and caries. For this reason, patients are referred to the maxillofacial prosthodontist as early as possible for evaluation of their oral and dental condition and for discussion of treatment options in prosthetic rehabilitation (5,7). In some cases, for instance, ablated structures can be replaced immediately with prostheses that restore function and improve appearance. The primary head and neck surgeon integrates this information into the treatment plan. Essentially, rehabilitation of function and improved physical appearance as well as reduction of posttreatment sequelae are the primary aims after elimination of disease (1,3).

ORAL AND DENTAL EVALUATION A preoperative evaluation should include medical history, intercurrent illnesses, oral and dental status, previous chemotherapy or radiation treatment, and other factors, such as age, nutritional status, and history of tobacco and alcohol use (7,11,12). The oral and dental evaluation is part of the routine head and neck examination. The head and neck surgeon will identify acute or chronic pathologic conditions related to the dentition or supporting structures, such as advanced periodontal disease, gross dental caries, tissue irritation from poorly fitting prostheses, and poor oral hygiene (1). Gross caries, plaque, and calculus formation on teeth indicate poor oral hygiene, possibly periodontal disease, and a precipitating factor for sepsis. Oral and dental abnormalities are documented during the initial medical examination (7). The patient is then referred to a maxillofacial prosthodontist for further evaluation and treatment. The initial oral and dental examination by the prosthodontist confirms the existence of acute and chronic oral pathologic conditions, such as dental abscess, teeth with advanced periodontal disease, or dental calculus causing gingivitis (1,7). Diagnostic radiographs are required to evaluate any tumor involvement in the bone, periodontal bone loss, periapical or periodontal abcesses, and gross carious lesions. The more common diagnostic imaging used in an oral and dental examination are the panoramic, periapical, bitewing, and occlusal radiography. A panoramic radiograph shows the overall topographic features of the dentition, maxilla, mandible, sinuses, nasal cavity, and temporomandibular joints (1,13,14). These radiographs can be of great value to the head and neck surgeon in diagnosis of bony invasion by tumor of the maxilla or mandible and are easily obtained from most dental offices. Periapical, bitewing, and occlusal radiographs show a more detailed view of the teeth and bone. Stone casts obtained from impressions of the maxilla and mandible during the initial dental visit can be useful if a surgical prosthesis (intraoral, extraoral, or both) is needed, such as a surgical obturator for a patient who has to undergo

ORAL AND DENTAL ANATOMY Communicating the patient’s oral and dental status is of paramount importance during treatment planning between the surgeon and maxillofacial prosthodontist. It is important that the surgeon knows which teeth are to be extracted for the surgical procedure so that the maxillofacial prosthodontist can plan and fabricate an immediate or postoperative prosthesis. The universal numbering system of teeth is used for this purpose (Fig. 1). In this system, adult teeth are numbered sequentially from 1 to 32, starting with the right maxillary third molar (#1), going to the left maxillary third molar (#16), continuing with the opposing left mandibular third molar (#17), and finishing with the right mandibular third molar (#32) (8). Anatomic landmarks important in prosthetic rehabilitation in the edentulous maxillary arch are the tuberosity, 149

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Figure 1 The universal numbering system of teeth.

maxillectomy (15–17). Teeth having a poor or uncertain prognosis are identified and extracted before or during the primary ablative surgical procedure (17).

PREPROSTHETIC PRINCIPLES Radiation therapy to the head and neck often causes collateral damage to the salivary glands causing reduced salivary function in varying degrees and increased susceptibility to dental caries and oral infection (1–3). The extent of the morbidity is related to radiation dose, volume of tissue treated, and age of the patient when treated (1,7). These patients need to maintain meticulous oral hygiene and be placed on a caries preventive regimen (i.e., daily fluoride) and sialogogues for the rest of their lives. Numerous studies have shown that fluoride reduces radiation decay of teeth if used in a systematic and predictable manner (1,16,18). Caries are an important complication for patients with autoimmune- or radiation-induced xerostomia (1,18). Reducing the risk of dental infection while maintaining optimal oral health can decrease the risk of osteoradionecrosis or a septic condition in the care of a patient who undergoes radiation therapy or chemotherapy (3,6,19–24). Some patients who have ablative surgery due to head and neck cancer need removable (maxillofacial) prostheses to replace anatomic structures (1,2,16). There are usually three phases of prosthetic rehabilitation: surgical, interim, and definitive. Each phase includes fabrication or modification of a prosthesis. These phases span several months to a year. Surgical and interim prostheses may have to be adjusted frequently while tissues are healing (1,15). In the maxillectomy patient, the surgical obturation prostheses are used to restore oral contour and function immediately after maxillectomy. The obturator separates the oral and nasal cavities to allow normal speech and swallowing. A common problem associated with maxillary obturator prostheses is leakage of fluid around the prosthesis and through the nose. Speech and swallowing can be compromised but in most cases can be corrected immediately during the postoperative period.

Most patients are hesitant about starting oral and dental hygiene postoperatively for fear of disturbing the surgical site. However, meticulous oral, dental, and prosthetic hygiene is encouraged immediately after head and neck surgery to reduce oral microbes and associated infections (1,25). Routine oral and dental hygiene can be initiated 2 weeks after surgery; however, initial postoperative oral care should be limited to oral lavage and decontaminating rinses (1,6,25). Postoperative physiotherapy for trismus is a consideration in rehabilitation. Suitable techniques can be discussed and explained to the patient before surgery and reinforced postoperatively. Such therapy can maintain the oral opening and allow the patient better access to the surgical defect and to the rest of the oral cavity (1,25,26). Opening exercises with wooden tongue blades or sophisticated oral opening devices R (i.e., TheraBite
oral opening device, Atos Medical Co., R Milwaukee, WI; Dynasplint
, Dynasplint Systems, Inc., Severna Park, MD) can be effective in maintaining or restoring oral opening following surgery (1–3,17). Reduced mobility of the jaw is a serious and sometimes painful condition that prohibits patients from doing simple tasks such as chewing, swallowing, speaking, or maintaining oral hygiene. Pain can be persistent and coupled with limited functioning. The patient’s quality of life is significantly affected. Oral opening exercises can improve jaw opening by stretching connective tissues, mobilizing joints, strengthening muscles, and activating anti-inflammatory properties, leading to reduction of pain and inflammation. A physiotherapist may be consulted in more complex cases to implement electrotherapy, lymphedema therapy, ultrasound, and other advanced techniques as needed (1–3,17). Complications vary and depend on the patient’s oral and dental status, type of malignancy, and type of oncologic therapy. Thorough oral and dental assessment and treatment by a maxillofacial prosthodontist can greatly minimize oral complications, promote oral health, and optimize the reconstruction outcome.

SURGICAL TECHNIQUES TO ENHANCE PROSTHETIC REHABILITATION Maxilla Resected lesions of the maxillary sinus, hard palate, and alveolar ridge can cause postoperative speech and swallowing problems. These difficulties can be minimized or eliminated with careful surgical planning (1–3). The dental cast obtained at the initial dental visit is used in discussion with the surgeon for the surgical planning and fabrication of the surgical prosthesis. Several surgical techniques can be incorporated into maxillectomy procedure to improve prosthetic rehabilitation. 1. Alveolar osteotomies are made through the socket of an extracted tooth or an edentulous space to prevent iatrogenic bone loss and to ensure the longevity of the tooth next to this osteotomy (1,15,16). 2. When making the palatal osteotomy, as much of the premaxilla as possible is spared. The premaxilla is important for the support and retention of a prosthesis. If the tumor is in the anterior region of the sinus, it may be possible to spare the maxillary tuberosity on the side of the defect, which would also increase prosthetic support. 3. A split-thickness skin graft or allogenic material is placed in the maxillary defect (1,27). The skin graft provides an excellent scar tissue band for retention of the prosthesis, and decreases mucus secretion, nasal polyps, and crust

Chapter 9: Prosthetic Rehabilitation of Patients Undergoing Skull Base Surgery

4. 5.

6.

7.

8.

formation in the ablated sinus; the result is improved hygiene. The palatal mucosa, if not affected by disease, can be retained and wrapped around the midline portion of the palatal cut. Removal of the inferior and middle turbinates allows proper extension of the prosthesis into the defect area. If not removed, the turbinates can be irritated by the prosthesis, and be a constant source of irritation and bleeding (1–3,17). Consideration is given to removing the posterior mandibular molars on the side of maxillectomy. These teeth can cause a hygiene problem and are essentially nonfunctional after maxillectomy (25). The Weber–Fergusson incision is used in some cases for access in a maxillectomy; however, an intraoral approach is increasingly becoming utilized in eliminating the facial incision. This makes manipulation of the lip and cheek easier for the dentist and patient during postoperative prosthetic procedures (1,9,15,17,27). A surgical obturator prosthesis is placed to restore the oral contour for immediate function and good postoperative appearance. This prosthesis supports the surgical packing and can be fixed to the remaining teeth with surgical wire or retained with a bone screw in an edentulous patient. Use of an obturator can obviate use of a nasogastric tube and decrease the duration of postoperative rehabilitation. The obturator maintains proper lip and cheek support during healing and helps to reduce contracture of scar tissue. When the surgical packing is removed, usually within 5 to 7 days of the procedure, the surgical obturator can be converted into an interim prosthesis. Use of a surgical prosthesis can improve the patient’s psychologic status, as it allows them to speak and eat following surgery (1,9,15,27).

As previously discussed, there are three distinct phases of maxillary obturator rehabilitation: surgical, interim, and definitive (1). The size and location of the surgical defect, dentition status, and supporting surface area of remaining palate and overlying structures determine the stability and retention of an obturator (1,2,6,10,17,28). As the size of the defect increases and the residual palatal tissues decrease, stability and functionality of the prosthesis reduce significantly due to the lack of teeth for direct clasp retention or surface area to engage undercuts (1,2,6,10,28). Some clinicians suggest that maxillary defects should be closed completely using free-tissue grafts (1,6,17,28,29). Function and cosmesis can be effectively restored with surgical reconstruction. This method does occlude the surgical defect but may preclude prosthetic rehabilitation and may become a challenge if fistulation develops or flap bulkiness occurs, thus, disallowing oral function and prosthetic placement. Surgical reconstruction is an excellent alternative for patients if a microvascular osteocutaneous flap is harvested and implants can be placed to retain a prosthesis (1,6,29–31).

SURGICAL RECONSTRUCTION WITH MICROVASCULAR TECHNIQUES Maxillary reconstruction provides a separation between the oral cavity from the sinus and nasal cavities, thus eliminating problems associated with obturator prostheses. Current microvascular techniques have facilitated the use of osteocutaneous free flaps to reconstruct orofacial defects by providing adequate amounts of bone and soft tissue in a single

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surgical procedure (32). Since the use of the first fibula free flap, surgical reconstruction of orofacial defects has become a routine procedure (33,34). Numerous cases of mandibular reconstruction have been reported, whereas accounts of bilateral maxillary reconstruction are more rare (34–39). Successful reconstruction of the maxilla requires an osseous element that relays occlusal forces to the cranium, resists long-term resorption, and allows esthetic and functional rehabilitation with implants [Fig. 2(A)–2(D)] (31,40). The cutaneous element of the reconstruction should separate the oral cavity from the sinus/nasal cavities, thereby allowing proper speech and deglutition (31,40). The free fibula flap is well suited for reconstruction of the both the mandible and the maxilla. The fibula provides an adequate length of bone that can be segmented to replace the contour of the alveolar ridge. The length is sufficient for reconstruction of large defects. The bicortical configuration and vertical height of the fibula are ideal for endosseous implant placement. Studies have found the vertical height of the fibula to be between 13.1 and 16.7 mm, with an average of 15.2 mm (31,40,41). This can provide bicortical fixation of implants that can ultimately improve osseointegration. Long-term observation has found only 2% to 7% bone resorption in the vascularized fibula (42). The soft pliable skin paddle can be used for reconstruction of intraoral or cutaneous tissue (32).

Soft Palate When some soft palate is removed in the surgical procedure, the surgeon must consider whether the remaining soft palate will be functional. It is easier to rehabilitate a patient’s speech and swallowing if the soft palate is removed totally (1,6). If the remaining soft palate is nonfunctional, rehabilitation can be difficult or even impossible. Sometimes a thin strip of soft palate can be useful for prosthesis retention in a patient with limited supporting tissue (1, 2,9,17). Primary irradiation of the soft palate can cause palatal incompetency due to fibrosis and tumor necrosis. Patients with this dilemma may regurgitate liquid and food through the nose, and speech may be hypernasal (6,9,17). In this situation, prosthetic rehabilitation can be impossible because of poor access to the oral pharynx.

Extraoral Lesions Lesions involving facial structures can necessitate prosthetic rehabilitation. The reconstructive surgeon must understand both the limitations of facial prostheses and the surgical techniques that enhance the adaptation and appearance for successful prosthetic rehabilitation. The restoration of facial defects is a difficult challenge. As previosuly stated, the success of a maxillofacial or facial prosthesis can be greatly enhanced by careful presurgical evaluation and communication involving the patient, surgeon, and maxillofacial prosthodontist (43,44). Facial prostheses can be made from a variety of materials, such as polymethyl methacrylate or medical-grade platinum silicone elastomer with or without a polyurethane backing (45). These prostheses are retained with medical-grade prosthetic adhesives, medical-grade double-sided tape, anatomic undercuts, acrylic substructures with magnets, or in some cases, extraoral osseointegrated implants or a combination thereof (1,43,46). Facial and intraoral prostheses can be connected with magnets to aid in retention and functionality. The esthetic result depends on the amount of tissue removed, type of reconstruction, morbidity of adjunctive treatment (radiation and chemotherapy), and the physical characteristics of the tissue base available to support and retain the prostheses (1,17,47).

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Figure 2 (A) A 15-year-old patient with history of osteosarcoma of left maxilla underwent infrastructure maxillectomy and delayed reconstruction with a free fibula microvascular flap. (B) Implants were placed 3 months following fibula reconstruction. (C) Transmucosal implant attachments ready for prosthesis impression. Granulation tissue through the skin flap is common and may require limited surgical removal, repeated application of topical steroids, and aggressive hygiene practices. (D) Transitional obturator prosthesis supported by dentition and implants.

Orbit In total orbital exenteration, several surgical considerations can improve prosthetic rehabilitation [Fig. 3(A) and 3(B)]. The eyelid is resected while the position of the eyebrow is

maintained. Sharp or rough bony margins are smoothed and rounded. If possible, the infraorbital bony margin is reconstructed. A split-thickness skin graft is placed into the area of the defect to cover exposed bone creating a concavity to house the prosthesis. Sufficient depth of defect is essential in order to fabricate an esthetic orbital prosthesis. Hygiene becomes easier for the patient, and the prosthesis can be extended into the defect for greater orientation and stability (1–3,46).

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Figure 3 (A) A 64-year-old man with a history of neuroendocrine small cell carcinoma of the right orbital region; treated with orbital exenteration, reconstruction with a split-thickness skin graft, and postoperative external beam radiation treatment. (B) Final elastomeric orbital prosthesis is supported by a prosthetic substructure within the orbital defect.

Resection of lesions involving the nose can necessitate partial or total nasal restoration [Fig. 4(A) and 4(B)]. The nasal spine is left intact, if possible, for stability of the nasal prosthesis. Unsupported tissue tags are removed, because they can make impression techniques difficult and can compromise the final prosthesis by hindering the patient in placing and adhering a prosthesis. Rough tissue margins or distortion of adjacent facial contours compromises the concealment of the prosthetic margins and retention. A split-thickness skin graft is placed over the resected bone margins to increase the stability of the nasal prosthesis (1–3). Grafts or flaps are used to maintain the position of the upper lip.

Ear Operations on the ear can vary from subtotal resection to total auriculectomy [Fig. 5(A)–5(C)]. It is easier to replace a complete ear than a partial ear with a prosthesis. With a

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troublesome when the patient attempts to insert or place the prosthesis (43). The superior half of the auricle has better cartilaginous support yet tends to become distorted after the operation. This distortion is accentuated when the residual auricle is rotated and used to close the defect. A preserved portion of the root of the helix is a good landmark and support for eyeglasses (1). This area can help later in vertical support of the prosthesis. The anterosuperior helical rim is left in place if possible. Posterior regions can be grafted. Though surgical techniques can enhance the recipient tissue bed for the prostheses, it is understood that the main concern of the treating surgeon is elimination of disease.

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Figure 4 (A) A 82-year-old man with a history of invasive squamous cell carcinoma of the nose, status post complete rhinectomy with a partialthickness skin flap reconstruction. (B) Final nasal prosthesis, supported by medical grade adhesives, provides form and function.

total replacement, the maxillofacial prosthodontist has more freedom in shape, size, and location of the prosthesis. First, the recipient area must be flat or concave. Convexities from excessive tissue bulk can hamper esthetic results. Second, skin devoid of hair provides a good adhesive base, although a split-thickness skin graft is better. Tissue pockets assist in orientation and stabilization of the prosthesis and allow the margins to extend in a 0-degree emergence profile (1–3,43). If tissue can be spared, the tragus is the first choice. It is a good separate landmark that is not easily displaced (1–3,43). The tragus allows the anterior margin of the prosthesis to be hidden behind the posterior flexure. It also aids the patient in proper positioning of the prosthesis by providing a placement reference. Hair, the angle of the helical rim, or both provide posterior margin concealment. The inferior half of the soft-tissue pinna is of little or no use. Because it lacks cartilaginous support, the lobe of the auricle is normally drawn down and away from the head. It is difficult to capture this effect in an impression, and bilateral symmetry usually cannot be achieved. The lobe margin is difficult to maintain and can be

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OSSEOINTEGRATED DENTAL IMPLANTS Osseointegrated dental implants have become an excellent alternative to conventional prosthetic rehabilitation (1,17,31,48–50). The principle of osseointegration of commercially pure titanium through the intermediary of the layer of titanium oxide and integration with surrounding bone opened a completely new field of clinical application for biotechnology in prosthetic dentistry [Fig. 6(A)–6(D)] (51,52). Implant designs fall into three main categories: endosseous, subperiosteal, and transosteal. There are over 50 implant subtypes from which the prosthodontist can choose in rehabilitating the patient (49,51). Additionally, there are numerous abutments available that range from fixed (cemented) and fixed-removable (screw or clip retained) designs to removable affixed by o-rings, clips, or snap designs (1,49). The most common implants used today are endosseous implants that are surgically inserted into the maxillae or mandible and integrate with the surrounding bone (50). Endosseous implants have provided the support, retention, and stability that is greatly needed in compromised oral cavities following tumor ablative procedures (1,17,31,50). Several common terms are used today in oral implantology: dental implant, endosteal dental implant, abutment, and osseointegration (1,51). A dental implant is a device, specially designed to place surgically within or on the mandibular or maxillary bone in providing resistance to displacement of an overlying prosthesis. It can be placed transgingivally or fully embedded subgingivally (1,51). The

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Figure 5 (A) A 72-year-old man with a history of basal cell carcinoma of the right ear, status post subtotal auriculectomy, reconstructed with a full-thickness skin graft. (B) Final auricular prosthesis restores esthetic appearance. (C) The auricular prosthesis has an intimate fit with remaining superior tissue tag.

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Figure 6 (A) Patient with a previous iliac crest flap mandibular reconstruction and endosteal implants without benefit of medical models or 3-D imaging. (B) Twenty years later, the patient has a second primary in the floor of mouth and requires resection of the iliac crest flap and another microvascular reconstruction. A 3-D model is created, surgery is performed, and a mandibular template is created for preforming a reconstruction plate. (C) Panoramic radiograph reveals six osteotomies in the microvascular fibula flap to gain appropriate mandibular adaptation to the reconstruction plate. (D) Mandibular contour without benefit of 3-D modeling (left) and second mandibular reconstruction 20 years later with 3-D modeling and model surgery (right).

endosteal dental implant is an implant of which a part is anchored within the maxillary or mandibular bone (17,31,51). An abutment is a component connected to the endosteal part of the dental implant and allows retention or support of a dental implant (17,31,51). The abutment connects the fixture (implant) to a superstructure and overlying prosthesis (49–51). Osseointegration is a direct structural and functional connection between vital bone and the surface of a load-carrying implant (51, 52). Finally, the endosseous dental implants can be divided into different categories according to their shape, surface characteristics, chemical composition, or the way the implant is inserted into the bone (1,51). Meticulous, surgical, and prosthetic planning is required prior to the placement of implants (50). If adequate supporting tissues exist or can be established, patients may function satisfactorily with routine prostheses, or they may be considered for implants if the recipient sites are appropriate. There are several types of implants currently utilized for intraoral and extraoral maxillofacial uses (1,31,47). Most implants used in maxillofacial prosthetics are made of titanium and are cylindrically designed utilizing threads that anchor them in the bone. Such implants are produced in a variety of lengths and widths. In most of these implant systems, placement involves a two-stage procedure. The first

stage, performed under local or general anesthesia, is the placement of the implant into the bony recipient site (1,49,50). Placement is performed in a very precise fashion to ensure the least amount of damage to the adjacent bone and soft tissue, particularly in irradiated tissues. Following placement, the implant is covered primarily by the initial tissue flap and allowed to integrate with the bone for 12 or more weeks. The purpose is to promote peri-implant integration with the implant interface as described previously. Confirmed osseointegration, by radiographic and clinical interpretation, implies a direct and lasting connection between vital bone and the titanium implant of defined surface topography and geometry (1–3). In the second stage, only the superior portion of the implant is uncovered and an abutment, usually made of titanium alloy, is placed onto the implant (1). This connection will join the implant to the prosthesis. The number of implants and type of retention as well as prosthetic designing are at the discretion of the restoring prosthodontist. In general, the prosthesis is fabricated so that it can be easily removed by the patient and allow maintenance and proper oral hygiene. Most irradiated maxillofacial patients are restored using removable prostheses (1,47). For those patients, implant rehabilitation can be successfully restored with an overlying removable prosthesis using

Chapter 9: Prosthetic Rehabilitation of Patients Undergoing Skull Base Surgery

ball abutments and o-ring attachments embedded in the prosthesis. Implants can be placed during or after the primary reconstructive procedure if the host bone has acceptable cortical plates suitable for fixation of implants (53,54). The fibula tissue graft is an excellent recipient site for such implants (55). The fibula free flap provides a long segment of bone and can include a large fasciocutaneous component (55–60). As such, this versatile flap may be harvested as an osteomyocutaneous flap or a purely osseous flap. The pedicle runs the length of the fibula, with perforators extending to the skin paddle (1,55–60). It provides the longest segment of bone currently available for harvest; up to 26 cm can be taken without affecting leg function. Many bony defects of the head and neck region are well suited for reconstruction with a fibula free flap. Functional rehabilitation can be optimal. Patients who have osseointegrated implants placed in the fibula graft can have near-normal mastication and speech re-established (55,56). In most cases, the placement of implants is best accomplished during a secondary procedure when a premade surgical stent can guide the prosthodontist in aligning and positioning the implants (1). Patients who have received postoperative radiation in proximity to the proposed implant

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site may be poor candidates due to hypovascularity in the volume of tissue radiated and may benefit from hyperbaric oxygen therapy prior to implant placement (19,61–66). The goals of prosthetic rehabilitation with implants include predictability and simplicity. Fabrication of a fixed implant prosthesis often involves methods and materials that are complicated and increase costs to the restoring dentist and patient. Additional prosthetic components as well as additional appointments to complete the prosthesis can create unnecessary inconveniences; therefore, a removable prosthesis should be considered initially in treatment planning for a patient with maxillofacial deficits (1,50). Aside from patient factors, decision-making on the type of implant to use as well as restoring materials and prosthetic rehabilitation should be based on evidence from clinical protocols and facts and figures of corporate products. Improvements in dental implants, biomaterials, bioengineering, and preserving-surgical techniques increase the retention, stability, and longevity of prosthetic rehabilitation and ultimately a patient’s quality of life (1,17,67). The use of osseointegrated implants and guided tissue regeneration (i.e., synthetic membranes) procedures in irradiated patients have great promise (48,68). The cellular and metabolic changes in

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Figure 7 (A) Microvascular reconstruction with a fibula flap involving the entire hard palate in this irradiated patient who lost left maxilla due to adenoid cystic carcinoma and later lost right maxilla due to osteoradionecrosis. Fibula and skin paddle created the separation between the oral cavity and paranasal sinuses. (B) Reformatted 3-D images of microvascular fibula flap. (C) Panoramic radiograph reveals fibula flap and subsequent implant reconstruction. (D) Full face of patient who has undergone a reconstructed maxillae and dental rehabilitation.

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the irradiated bone may affect both the quality and quantity of osseointegration (1,47). Important factors in successful dental restoration are the influence of radiation dose, delivery system (e.g., intensity modulated radiation therapy, IMRT), implant biomaterials, time from radiation therapy to implant surgery, the experience of the prosthodontist, fixture and abutment lengths, appropriate implantation sites, and type of prosthetic retention on implant survival (1–3). In addition, the benefit of osteogenesis and angiogenesis of hyperbaric oxygen therapy in conjunction with reconstructive techniques in the irradiated patient is also being studied (61,66). New physiotherapy methods are being developed to improve the postoperative function of patients with head and neck cancer (1–3,26). Tissue engineering, stereolithography, and rapid prototyping technology have recently resulted in the successful formation of new tissue equivalents of bone and cartilage that will enhance prosthetic rehabilitation in the future (68–71). Stereolithography (SL) is a computerized technology that uses computed tomography (CT) scans to fabricate an accurate three-dimensional model of a structure. This technology has been used extensively to preplan craniofacial surgery (72). SL models are reported to have an accuracy of 97.9%, with an average difference of 0.12 mm on mandible specimens (73). A study of SL models made from cadaver skull specimens found that the mean overall difference ranged from 0.8 to 2.5 mm (74). The accuracy is improved with smaller cuts during CT acquisition. Such accuracy has allowed surgeons to create templates to harvest bone flaps and prefabricate plates for surgical reconstruction [Fig. 7(A)–7(D)] (75–77).

CONCLUSIONS Fostering communication and compliance among members of the multidisciplinary treatment team will ensure quality of preventive, therapeutic, and maintenance care to patients with head and neck cancer. Thoughtful collaboration among the surgical oncologist, radiation and medical oncologist, maxillofacial prosthodontist, and implant surgeon optimizes the delivery and timing of dental care; therefore, improving the quality of the prosthetic rehabilitation. A functional, esthetic dental prosthesis after cancer treatment is a critical component of patient management that focuses on improving quality of life. To achieve these goals, each member of the multidisciplinary team must have working knowledge of the principles of prosthetic rehabilitation and appreciate the potential adverse impact that a suboptimal prosthesis could have on the patient’s functional, esthetic, and emotional outcome. The dental status has a persistent impact on quality of life in patients who have been successfully treated for head and neck cancer. REFERENCES 1. Chambers MS, Lemon JC, Martin JW. Surgical techniques to enhance prosthetic rehabilitation. In: Bailey BJ, Johnson JT, Newlands S, eds. Head and Neck Surgery-Otolaryngology. Philadelphia, PA: Lippincott Williams and Wilkins, 4th edition, Chapter 127; 2006:1853–1865. 2. Lemon JC, Martin JW, Jacob RF. Prosthetic rehabilitation. In: Weber RS, Miller MJ, Goepfert H, eds. Basal and squamous cell skin cancers of the head and neck. Baltimore: Williams & Wilkins, 1996:305–312. 3. King GE, Jacob RF, Martin JW. Oral and dental rehabilitation. In: Johns ME, ed. Complications in otolaryngology head and neck surgery. Philadelphia, PA: BC Decker, 1986:131.

4. Van Blarcom CW. The glossary of prosthodontic terms, 8th ed. J Prosthet Dent. 2005;94:51. 5. Jacob RF. The traditional therapeutic paradigm: Complete denture therapy. J Prosthet Dent. 1998;79:6–13. 6. Jacob RF, King GE. Indirect retainers in soft palate obturator design. J Prosthet Dent. 1990;63:311–315. 7. Lingeman RE, Singer MJ. Evaluation of the patient with head and neck cancer. In: Sven JY, Myers EN, eds. Cancer of the head and neck. New York: Churchill Livingstone, 1981:15. 8. Fuller JL, Deneky GE. Concise dental anatomy and morphology, 2nd ed. Chicago, IL: Mosby Year Book, 1984:9. 9. Beumer JP, Curtis TA. Restoration of acquired hard palate defects. In: Maxillofacial rehabilitation: prosthodontic and surgical considerations. St. Louis: Mosby, 1979:188. 10. Okay DJ, Genden E, Buchbinder D, Urken M. Prosthodontic guidelines for surgical reconstruction of the maxilla: A classification system of defects. J Prosthet Dent. 2001;86:352– 363. 11. Genden EM, Okay D, Stepp MT, Rezaee RP, Mojica JS, Buchbinder D, Urken ML. Comparison of functional and qualityof-life outcomes in patients with and without palatomaxillary reconstruction. Arch Otolaryngol Head Neck Surg. 2003;129:775– 780. 12. Silverman S. Oral Cancer: Complications of therapy. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 1999;88:122–126. 13. Langland OE, Langlois RP, Morris CR. Principle and practice of panoramic radiology. Philadelphia, PA: WB Saunders, 1982:131–156. 14. Blaschbe DP, Osborn AG. The mandible and teeth. In: Bergeron RT, Osborn AG, San PM, eds. Head and neck imaging. St. Louis: Mosby, 1984:279. 15. Martin JW, Jacob RF, Larson DL, et al. Surgical stents for the head and neck cancer patient. Head Neck Surg. 1984;7:44. 16. Curtis TA, Beumer J. Restoration of acquired hard palate defects: Etiology, disability, and rehabilitation. In: Beumer J, Curtis TA, Firtell DN, eds. Maxillofacial Rehabilitation: Prosthodontic and Surgical Considerations. St. Louis: CV Mosby Co., 1979:188– 243. 17. McCord JF, Michelinakis G. Systematic review of the evidence supporting intra-oral maxillofacial prosthodontic care. Eur J Prosthodont Restor Dent. 2004;12(3):129–135. 18. Fleming TJ. Oral tissue changes of radiation oncology and their management. Dent Clin North Am. 1990;34:233–237. 19. Marx RE, Johnson RP. Studies in the radiobiology of osteoradionecrosis and their clinical significance. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 1987;64:379–390. 20. Marx RE. Radiation injury to tissue. In: Kindwall EP, ed. Hyperbaric medicine practice. Flagstaff, AR: Best Publishing, 1994;447–503. 21. Marx RE, Ehler WJ, Tayapongsak P, et al. Relationship of oxygen dose to angiogenesis induction in irradiated tissue. Am J Surg. 1990;160:519–524. 22. Marx RE, Johnson RP, Kline SN. Prevention of osteoradionecrosis: A randomized, prospective clinical trial of hyperbaric oxygen versus penicillin. J Am Dent Assoc. 1985;11:49–54. 23. Ang E, Black C, Irish J, et al. Reconstructive options in the treatment of osteoradionecrosis of the craniomaxillofacial skeleton. Br J Plas Surg. 2003;56:92–99. 24. Marx RE, Johnson RP. Problem wounds in oral and maxillofacial surgery: The role of hyperbaric oxygen. In: Davis JC, Hunt TK, eds. Problem Wounds: The Role of Oxygen. New York: Elsevier, 1988:65–123. 25. Martin JW, Austin JR, Chambers MS, et al. Postoperative care of the maxillectomy patient. ORL Head Neck Nurs. 1994;12:15–20. 26. Barrett NV, Martin JW, Jacob RF, et al. Physical therapy techniques in the treatment of the head and neck patient. J Prosthet Dent. 1988;59:343. 27. Teichgraeber J, Larson DL, Castaneda O, et al. Skin grafts in intraoral reconstruction: A new stenting method. Arch Otolaryngol Head Neck Surg. 1984;101:463. 28. Aramany MA. Basic principles of obturator design for partially edentulous patients. Part II: design principles. J Prosthet Dent. 1978;40:656–662.

Chapter 9: Prosthetic Rehabilitation of Patients Undergoing Skull Base Surgery 29. Olsen KD, Meland N, Ebersold MJ, et al. Extensive defects of the sino-orbital region: Results with microvascular reconstruction. Arch Otolaryngol Head Neck Surg. 1992;118:828–833. 30. Dexter WS, Jacob RF. Prosthetic rehabilitation after maxillectomy and temporalis flap reconstruction: A clinical report. J Prosthet Dent. 2000;83:283–286. 31. Fukuda M, Takahashi T, Nagai H. Implant-supported edentulous maxillary obturators with milled bar attachments after maxillectomy. J Oral Maxillofac Surg. 2004;62(7):799–805. 32. Triana RJ Jr, et al. Microvascular free flap reconstructive options in patients with partial and total maxillectomy defects. Arch Facial Plast Surg. 2000;2(2):91–101. 33. Taylor GI, Miller GD, Ham FJ. The free vascularized bone graft. A clinical extension of microvascular techniques. Plast Reconstr Surg. 1975;55(5):533–544. 34. Ferri J, et al. Use of the fibula free flap in maxillary reconstruction: A report of 3 cases. J Oral Maxillofac Surg. 2002;60(5):567–574. 35. Disa JJ, Cordeiro PG. Mandible reconstruction with microvascular surgery. Semin Surg Oncol. 2000;19(3):226–234. 36. Hannen EJ. Recreating the original contour in tumor deformed mandibles for plate adapting. Int J Oral Maxillofac Surg. 2006;35(2):183–185. 37. Peled M, et al. The use of free fibular flap for functional mandibular reconstruction. J Oral Maxillofac Surg. 2005;63(2):220–224. 38. Mukohyama H, et al. Rehabilitation of a bilateral maxillectomy patient with a free fibula osteocutaneous flap. J Oral Rehabil. 2005;32(7):541–544. 39. Barnouti L, Caminer D. Maxillary tumours and bilateral reconstruction of the maxilla. ANZ J Surg. 2006;76(4):267–269. 40. Funk GF, Arcuri MR, Frodel JL Jr. Functional dental rehabilitation of massive palatomaxillary defects: Cases requiring free tissue transfer and osseointegrated implants. Head Neck. 1998;20(1):38–51. 41. Peng X, et al. Maxillary reconstruction with the free fibula flap. Plast Reconstr Surg. 2005;115(6):1562–1569. 42. Disa JJ, Hidalgo DA, Cordeiro PG, et al. Evaluation of bone height in osseous free flap mandible reconstruction: An indirect measurement of bone mass. Plast Reconstr Surg. 1999;103:1371. 43. Eggbeer D, Bibb R, Evans P. Assessment of digital technologies in the design of a magnet retained auricular prosthesis. J Maxillofac Prosth Tech. 2006;9:1–4. 44. Beumer J, Roumanas E, Nishimura R. Facial defects: Alterations oat surgery to enhance the prosthetic prognosis. First Int Congress on Max Fac Prosth. 1995;18:104–107. 45. Udagama A. Urethane-lined silicone facial prosthesis. J Prosthet Dent. 1987;58:351–354. 46. Lemon JC, Chambers MS. Conventional methods of retention of facial prostheses. First Int Congress on Max Fac Prosth. 1994;1:116–119. ¨ G, Tjellstrom ¨ A, Brsnemark PI, et al. Bone anchored47. Granstom reconstruction of the irradiated head and neck cancer patient. Otolaryngol Head Neck Surg. 1993;108:334–343. 48. Hong WL, Chu SA, Dam JG, et al. Oral rehabilitation using dental implants and guided bone regeneration. Ann Acad Med Singapore. 1999;28:697–703. 49. Lee MB. Implants. [email protected]. Support Central. April 2003. 50. Eckert SE, Desjardins RP. The impact of endosseous implants on maxillofacial prosthetics. In: Taylor TD, ed. Clinical Maxillofacial Prosthetics. Chiacgo: Quintessence, 2000:145–153. 51. Scortecci GM. Introduction to oral implantology in restorative dentistry. In: Scortecci GM, Misch CE, Benner KU, eds. Implants and Restorative Dentistry. New York: Martin Dunitz Ltd, 2001:1–25. 52. Branemark PI, Zarb G, Albrektsson T. Tissue-integrated prostheses. In: Branemark PI, ed. Osseointegration in Clinical Dentistry. Chicago: Quintessence, 1985:1–50. 53. Lemon JC, Chambers MS, Wesley PJ, et al. Rehabilitation of a midface defect with reconstructive surgery and facial prosthetics: A case report. Int J Oral Maxillofac Implants. 1996;11:101–105.

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54. Benner KU. Morphological aspects of oral implantology. In: Scortecci GM, Misch CE, Benner KU, eds. Implants and Restorative Dentistry. New York: Martin Dunitz Ltd, 2001:26–46. 55. Schusterman MA, Reece GP, Miller MJ, et al. The osteocutaneous free fibula flap: Is the skin paddle reliable? Plast Reconstr Surg. 1992;90:787. 56. Winslow CD, Wax MK. Tissue transfer: Fibula. Available at: www.Emedicine.com. Accessed on August 28, 2003. 57. Anthony JP, Rawnsley JD, Benhaim P. Donor leg morbidity and function after fibula free flap mandible reconstruction. Plast Reconstr Surg. 1995;96(1):146–152. 58. Disa JJ, Cordeiro PG. The current role of preoperative arteriography in free fibula flaps. Plast Reconstr Surg. 1998;102(4):1083– 1088. 59. Hidalgo DA. Fibula free flap mandibular reconstruction. Clin Plast Surg. 1994;21(1):25–35. 60. Urken ML, Cheney ML, Sullivan MJ. Fibula free flaps. In: Atlas of Regional and Free Flaps for Head and Neck Reconstruction. New York, NY: Raven Press, 1995. 61. Ferguson BJ, Hudson WR, Farmer JC. Hyperbaric oxygen for laryngeal radiation necrosis. Ann Otol Rhinol Laryngol. 1987;96:1– 6. 62. Tibbles PM, Edelsberg JS. Hyperbaric-oxygen therapy. N Engl J Med. 1996;334(25):1642–1648. 63. Feldmeier JJ, Jelen I, Davolt DA, et al. Hyperbaric oxygen as a prophylaxis for radiation induced delayed enteropathy. Radiother Oncol. 1995;35:138–144. 64. Feldmeier JJ, Davolt DA, Court WS, et al. Histologic morphometry confirms a prophylactic effect for hyperbaric oxygen in the prevention of delayed radiation enteropathy. Undersea Hyper Med. 1998;25(2):93–97. 65. Feldmeier JJ, Newman R, Davolt DA, et al. Prophylactic hyperbaric oxygen for patients undergoing salvage for recurrent head and neck cancers following full course irradiation (abstract). Undersea Hyper Med. 1998;25(Suppl):10. 66. Ueda M, Kaneda T, Takahashi H. Effect of hyperbaric oxygen therapy on osseointegration of titanium implants in irradiated bone: A preliminary report. Int J Oral Maxillofac Implants. 1993;8:41–44. 67. Kornblith AB, Zlotolow IM, Gooen J, et al. Quality of life of maxillectomy patients using an obturator prosthesis. Head Neck. 1996;18:323–334. 68. Thompson RC, Mikos AG, Beahm EB, et al. Guided tissue fabrication from periosteum using preformed biodegradable polymer scaffolds. Biomaterials. 1999;20:2007–2018. 69. Miller MJ, Goldberg DP, Yasko AW, et al. Guided bone growth in sheep: A model for tissue-engineered bone flaps. Tissue Eng. 1996;2:51–59. 70. Reitemeier B, Notni G, Heinze M, et al. Optical modeling of extraoral defects. J Prosthet Dent. 2004;91(1):80–84. 71. Eppley BL. The accuracy of stereolithography in planning craniofacial bone replacement. J Craniofac Surg. 2003;14(6):934– 935. 72. Sinn DP, Cillo DE Jr, Miles BA. Stereolithography for craniofacial surgery. J Craniofac Surg. 2006;17(5):869–875. 73. Bouyssie JF, et al. Stereolithographic models derived from x-ray computed tomography. Reproduction accuracy. Surg Radiol Anat. 1997;19(3):193–199. 74. Chang PS, et al. The accuracy of stereolithography in planning craniofacial bone replacement. J Craniofac Surg. 2003;14(2):164– 170. 75. Cunningham LL Jr, Madsen MJ, Peterson G. Stereolithographic modeling technology applied to tumor resection. J Oral Maxillofac Surg. 2005;63(6):873–878. 76. Kernan BT, Wimsatt JA. Use of a stereolithography model for accurate, preoperative adaptation of a reconstruction plate. J Oral Maxillofac Surg. 2000;58(3):349–351. 77. Al-Sukhun J, et al. Stereolithography and the use of pre-adapted or fabricated plates for accurate repair of maxillofacial defects. Br J Oral Maxillofac Surg. 2006.

10 Radiobiology and Radiation Therapy of Skull Base Tumors Simon S. Lo, John H. Suh, and Eric L. Chang

break can either be achieved by a single particle track creating breaks in both strands or a combination of two individual particle tracks creating two individual single-strand breaks close to each other in space and time. A single-strand break is sublethal and repairable but double-strand breaks are not. The linear-quadratic equation below describes this model:

OVERVIEW Skull base tumors can be separated into three broad groups: (i) tumors arising from neural and vascular structures and meninges of the base of the brain (e.g., schwannoma, meningioma, pituitary adenoma, craniopharyngioma, paraganglioma); (ii) tumors arising from the skull base (e.g., chordoma, chondrosarcoma, osteosarcoma, plasmacytoma); and (iii) tumors arising from below the skull base (e.g., nasopharyngeal carcinoma, paranasal sinus tumor). This chapter covers the radiobiologic principles and radiotherapeutic aspects of skull base tumors. Other aspects of skull base tumors are being discussed in other chapters.

Surviving fraction (SF) = e −(α D+β D ) , 2

where D is the radiation dose absorbed in Gray (Gy). α is the coefficient associated with single-event cell kill and β represents the coefficient associated with cell kill as a result of interaction of sublethal events. When radiation is fractionated, the linear-quadratic equation then becomes
 2 SF = Number of fractions (n) × e −(α D+β D )

RADIOBIOLOGY OF SKULL BASE TUMORS Radiation can be divided into directly or indirectly ionizing radiation. Electromagnetic radiation such as photons and gamma rays are indirectly ionizing radiation (1). Charged particles such as electrons, protons, and heavily charged ions are classified as directly ionizing radiation (1). Photons and gamma rays as well as electrons are most commonly used for radiation therapy. The availability of particle beam therapy is limited to specialized facilities. In the United States, there are currently five proton beam facilities that are actively treating patients. The biologic effect of radiation is a result of damage to DNA (1). Any kind of radiation can have direct and indirect action on the critical targets in the cells. The direct action of radiation involves direct interaction of the radiation with the critical targets in the cells leading to ionization or excitation of the atoms of the critical targets and biologic changes. This is the main mechanism of cell kill in high linear energy transfer radiation such as alpha particles and other heavily charged ions (1). Indirect action of radiation involves production of free radicals from the interaction of the radiation with the atoms or molecules in the cells. The free radicals can affect DNA and this leads to cell kill. This is the predominant mechanism of cell kill in low linear energy transfer radiation such as photons and gamma rays (1). Cell survival after a single dose of radiation is a probability function of the radiation dose (in Gray) absorbed. A typical cell survival curve consists of a shoulder at the lowdose region followed by a steeply sloped portion at high-dose regions. The shoulder is thought to represent accumulation of sublethal damages in the low-dose region and the steep portion cell kill as a result of the combination of two or more sublethal damages (Fig. 1) (1). Most cell survival curves fit into the linear quadratic model. The target for cell kill by ionizing radiation is the double helix of DNA. Therefore, double-strand breaks are required for cell kill to occur. A double-strand

Alpha–beta ratio (α:β) represents the relative contribution of the α and the β components to cell kill by radiation. α:β is different for different normal tissues and different tumor types and therefore the shapes of cell survival curves are different for different tissues. In general, tissues can be divided into two broad groups according to the values of their α:β—early- and lateresponding tissues. Normal brain parenchyma and critical structures such as the inner ear, optic pathway, pituitary, brainstem, and spinal cord are generally regarded as lateresponding tissues. Typically, early-responding tissues have much higher α:β values than late-responding tissues, which means the contribution of interaction of potentially reparable sublethal events is much smaller in early- than in lateresponding tissues. Therefore, in the setting of fractionated radiation therapy, the sparing effect on late-responding tissue by fractionation is more pronounced than that on earlyresponding tissue. The advantage of fractionated radiation therapy can be exploited if the tumor treated by radiation therapy is composed of early-responding tissue and is surrounded by late-responding tissue such as brain parenchyma. Malignant tumors typically have high α:β values (1). Benign skull base tumors such as meningiomas, acoustic schwannoma, pituitary adenomas, and craniopharyngiomas are regarded as late-responding tissues and they have low α:β values. When fractionated radiation therapy is used to treat these tumors, the sparing effects on tumor and normal brain parenchyma and other critical neural structures are similar. In circumstances where the radiation dose required to permanently control these tumors exceeds the constraints of normal brain parenchyma and critical structures, the use of radiation techniques or modalities that can achieve a very conformal radiation dose distribution and a very steep dose gradient beyond the tumor volume is indicated. 159

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and critical structures. Some of the structures at risk include brain parenchyma, brainstem, spinal cord, optic pathway, and inner ear/cochlea. In the treatment planning of fractionated radiation therapy (including IMRT, FSRT, and proton beam therapy) and SRS, the radiation dose constraints of the critical structure have to be taken into account. The commonly quoted radiation dose constraints are as follows: Brainstem—50 to 54 Gy for conventionally fractionated radiation therapy. Spinal cord—45 to 50 Gy for conventionally fractionated radiation therapy. Optic pathway—50 to 54 Gy for conventionally fractionated radiation therapy, and 8 Gy for SRS. Cochlea/inner ear—50 to 54 Gy for conventionally fractionated radiation therapy.

Figure 1

Typical cell survival curve for early- and late-responding tissues.

When a single high dose of radiation, as in stereotactic radiosurgery (SRS), is used to treat skull base tumors, the sparing effect of fractionation does not apply. From the radiobiologic standpoint, radiosurgical targets can be divided into four classes (2): Class A—target tissue is late-responding tissue and there is normal brain parenchyma within the target (e.g., arteriovenous malformation). Class B—target tissue is late-responding tissue and there is no normal brain parenchyma within the target (e.g., meningioma, acoustic neuroma, pituitary adenoma, and craniopharyngioma). Class C—target tissue is early-responding tissue and there is normal brain parenchyma within the target (e.g., low-grade glioma). Class D—target tissue is early-responding tissue and there is normal brain parenchyma within the target (e.g., highgrade glioma and brain metastasis). Class B and D targets are deemed suitable for SRS. Most skull base tumors are either class B (e.g., meningioma, acoustic neuroma, pituitary adenoma, craniopharyngioma, glomus tumor) or class D targets (e.g., chordoma, chondrosarcoma) and therefore they could be amenable to treatment with SRS. With the delivery of a single high dose of radiation that is necessary to kill the tumor, the level of cell kill will fall on the steep portion of the cell survival curve. In order to avoid collateral damage to the surrounding brain parenchyma and critical structures, the radiation dose fall-off beyond the target volume treated should be very steep such that region immediately adjacent to the target volume receives only a fraction of the prescribed dose. A stereotactic radiation delivery system can achieve this goal.

NORMAL TISSUE TOLERANCE OF CRITICAL STRUCTURES Because of the critical location of most skull base tumors, patients are at risk of developing radiation-induced complications as a result of injury to the normal brain parenchyma

Significant effort should be made to keep the radiation doses to these critical structures below the constraints to minimize the risk of radiation-induced complications. Advanced radiation techniques that can achieve very conformal isodose distribution and steep radiation dose fall-off are well suited in cases in which the tumor treated is very closed to one or more of these critical structures.

ADVANCED RADIATION THERAPY TECHNIQUES AND MODALITIES FOR SKULL BASE TUMORS There has been significant development of radiation therapy technology in the past 20 years. The skull base is a challenging area to treat with radiation therapy because two critical structures including the optic pathway and brainstem are often in close proximity. In the past, radiation therapy was delivered using two-dimensional techniques. The determination of target volume was based on bony landmarks. Because of the simplistic beam arrangement, a significant amount of brain tissue received the prescribed dose. With the advent of the three-dimensional treatment planning utilizing computerized tomography (CT) and image registration or fusion with magnetic resonance imaging (MRI), target volume coverage can be improved and more normal tissue can be spared. With further advancement of technology, it is possible to place dose constraints for various critical structures. Intensity modulated radiation therapy (IMRT) utilizes inverse planning, which allows for the placement of dose constraints on critical structures resulting in better normal tissue sparing (3). SRS is a radiation technique in which multiple external radiation beams are aimed at an imaging defined target volume to deliver a single high dose of radiation (4). A gamma R Knife
unit, a linear accelerator or a cyclotron that produces protons, can be used as a platform in the delivery of SRS, which has been used to treat various skull base tumors. For skull base tumors that are larger in size and closer to critical structures, fractionated stereotactic radiotherapy (FSRT) is often used (5). The common feature of SRS and FSRT is the rapid dose fall-off beyond the target volume. Most skull base tumors are extra-axial in location and have a very sharp margin of demarcation with surrounding normal brain tissue. This makes SRS and FSRT well suited for the treatment of most skull base tumors. Because of the very favorable physical characteristics of proton beams, protons are well suited in the treatment of skull base tumors. The relatively low entrance dose and the absence of radiation dose beyond the end range known as the Bragg peak makes it possible to reduce the amount of

Chapter 10: Radiobiology and Radiation Therapy of Skull Base Tumors

radiation delivered to nontarget tissue (6). Proton beam therapy is particularly suitable for the treatment of skull base tumors that require a high radiation dose to achieve durable tumor control (6). Compared to other radiation techniques using photons, proton beam radiation therapy can result in better target volume coverage and sparing of normal structures, and a lower nontarget integral dose as a result of the Bragg peak (6).

CLINICAL APPLICATIONS OF RADIATION THERAPY (INCLUDING STEREOTACTIC RADIOSURGERY) IN SKULL BASE TUMORS Pituitary Adenomas Pituitary adenoma is a broad term that encompasses all benign primary tumors arising from pituitary glandular tissue. It can broadly be divided into nonsecretory and secretory types. Dependent upon the type of secretory cells from which they arise, secretory pituitary adenomas can be subdivided into growth hormone (GH)–secreting, prolactin-secreting, adrenocorticotrophic hormone (ACTH)– secreting, gonadotropin-secreting, and thyroid stimulating hormone–secreting tumors. The goals of treatment of pituitary adenomas are tumor control and normalization of the hypersecreted hormone (for secretory tumors). With the exception of prolactinomas, surgical resection is usually recommended because it can decompress the optic apparatus if it is compressed by the tumor and it can rapidly normalize the hypersecreted hormone in a secretory tumor (7). However, complete surgical resection is not always achievable because of involvement of critical structures (Fig. 2). Therefore, postoperative radiation therapy is often necessary to stop the growth of the residual tumor and normalize the hypersecreted hormone. Radiation therapy is also indicated for recurrent pituitary adenomas as well. There is abundant literature on the use of conventional radiation therapy for the treatment of pituitary adenoma. The typical dose used range from 45 to 54 Gy in conventional fractionation. For nonfunctioning pituitary adenoma, the

Figure 2 Coronal MRI showing extensively infiltrating pituitary adenoma centered on sella turcica and extending bilaterally into cavernous sinuses, and encasing both cavernous carotid arteries with suprasellar extension and upward bowing of optic chiasm.

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reported 10-year progression-free survival rate after radiation therapy ranged from 80% to 98% (8–13). For secretory tumors, apart from control of tumor growth, normalization of hypersecreted hormones is one of the main goals of treatment. For GH-secreting tumors, conventional fractionated radiation therapy is efficacious in the normalization of GH. However, the GH levels tend to fall slowly after treatment and it may take years for the level to normalize. By 10 years, approximately 70% to 90% will have their GH levels normalized (9,10,14,15). In patients with lower pretreatment GH levels, normalization tends to occur earlier. Because of the metabolic effects and the cosmetic deformities associated with acromegaly, medical therapy may be given to patients before their GH levels normalize. Colleagues from St. Bartholomew’s Hospital recently reported the world’s largest series of patients with acromegaly treated with pituitary radiotherapy (16). GH level decreased to <2.5 ng/mL in 22%, 60%, and 77% of the 884 patients treated with radiotherapy for acromegaly at 2, 10, and 20 years, respectively (16). Sixtythree percent of patients had a normal insulin-like growth factor (IGF-I) level by 10 years (16). Another recent study showed similar findings (17). Table 1 summarizes the treatment outcomes of selected series. Prolactin-secreting tumors are usually managed initially by the use of bromocriptine R or cabergoline (Dostinex
). When evaluating the treatment outcomes, it is important to distinguish between pituitary stalk effect and prolactin hypersecretion. The serum prolactin level is usually lower in the case of stalk effect, which is defined as the loss of hypothalamic inhibition due to compression of the pituitary stalk. Conventional fractionated radiation therapy is usually offered to patients who cannot tolerate bromocriptine or similar medical therapy or those who develop disease progression during medical therapy. Normalization of prolactin levels occurs in 50–70% of the patients after fractionated radiation therapy (Table 1) (18–25). Patients with ACTH-secreting tumors present with Cushing disease when the tumor is still small in size, and therefore, they usually have microadenomas. Because these tumors are typically very small, they may not be detected on a regular brain MRI. Sometimes, a dynamic MRI or bilateral venous simultaneous selective venous sampling of ACTH from the inferior petrosal sinuses is done to establish a diagnosis. The metabolic effects of Cushing disease are very crippling and if longstanding, can be fatal. Therefore, the goal of treatment is rapid normalization of the ACTH, and surgical resection is usually the recommended initial treatment. Fractionated radiation therapy is recommended in patients who have residual tumor after surgery and in patients who are medically inoperable. Remission occurs in approximately 50% to 80% of the patients after fractionated radiation therapy (Table 1) (24,26–29). Nelson syndrome is described as the hypersecretion of ACTH by a pituitary adenoma in patients who have undergone bilateral adrenalectomy for Cushing disease. Unlike the usual ACTH-secreting pituitary adenomas, pituitary tumors associated with Nelson syndrome are usually macroadenomas. Surgical resection is the recommended initial treatment although surgical cure could only be achieved in less than one-third of the patients. Radiation therapy is indicated if the ACTH level remains elevated after surgery. Data on the use of fractionated radiation therapy to treat Nelson syndrome are limited. In one series, approximately 50% of patients benefited from fractionated radiation therapy in terms of clinical, biochemical, and radiographic responses (27). SRS has also been used in the treatment of pituitary adenomas. Because the optic apparatus is in proximity to the

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Table 1

Summary of Treatment Results of Fractionated Radiation Therapy for Pituitary Adenomas

Series

Type

No. of pts

Tx

Endpoint

Grigsby (10) Grigsby (9) Ludecke (15) Eastman (14)

Acromegaly Acromegaly Acromegaly Acromegaly

12 22 30 87

S + RT RT alone RT alone RT ± S

DFS DFS GH <10 ng/mL GH <5 ng/mL

Jenkins (16) Biermasz (17)

Acromegaly Acromegaly

884 36

RT ± S S + RT

GH < 2.5 ng/mL Normal IGF-I without medication Normalization of GH suppression during GTT Both of the above

Grigsby (19) Grigsby (18) Tsagarakis (21) Littley (20) Johnston (22) Rush (25) Clarke (23) Hughes (24)

Prolactinoma Prolactinoma Prolactinoma Prolactinoma Prolactinoma Prolactinoma Prolactinoma Prolactinoma

Normal PRL biochemically and clinically Normal PRL biochemically and clinically Normal PRL Normal PRL Normal PRL Normal PRL Normal PRL Normal PRL

Howlette (28) Howlette (28) Vicente (27) Littley (29) Hughes (24) Estrada (26)

Cushing ds Cushing ds Cushing ds Cushing ds Cushing ds Cushing ds

RT alone S + RT RT alone RT ± S RT ± S RT alone RT ± S S + RT RT alone RT RT for recurrent disease RT for recurrent disease RT RT RT for recurrent disease

17 28 36 58 14 10 14 19 6 21 9 14 24 40 30

Remission Remission Remission Tumor control/ remission Disease free Regression of clinical features of Cushing ds + Normal urinary cortisol excretion + Low plasma cortisol concentration in the morning after 1 mg of dexamethasone at midnight

Control (yr) 76% (10) 69% (10) 88% (5) 30%/53%/77%/89% (5/10/15/20) 22%/60%/77% (2/10/20) 75% (?) 65%/69%/71% (2.5/10/15) 40%/61%/65%/63% (3–5, 6–10, 11–15,>15) 82% (10) 93% (10) 50% (2–13) 50% (10) 43% (9) 70% (3.8) 71% (7.5) 62% (5) 50% (5) 57% (9.5) 56% (3) 61%/70% (1/2) 33% (7.7) 59% (10) 83% (3.5)

Abbreviations: No. of pts, number of patients; Tx, treatment; yr, year; S, surgery; RT, radiation therapy; DFS, disease-free survival; GH, growth hormone; IGF-I, insulin-like growth factor; GTT, glucose tolerance test; PRL, prolactin; Cushing ds, Cushing disease.

pituitary gland, a 3 to 5 mm gap is required to respect the tolerance of the optic chiasm (Fig. 3). If one anticipates that the maximum dose to the optic apparatus cannot be limited to 8 to 10 Gy while delivering an adequate dose to the tumor or target volume, fractionated radiation therapy or FSRT should be recommended instead. There are abundant data in the literature demonstrating that it is a safe and efficacious procedure for the treatment of pituitary adenomas. Again, the aims of the treatment are control of tumor growth and normalization of hormone level. SRS is very effective in the control of tumor growth in that it yields a tumor control rate of 92% to 100% (30). The tumor control rate in patients with endocrine-inactive pituitary tumors treated to lower marginal doses of 14 to 25 Gy is similar to that of patients with secretory pituitary tumors treated to marginal doses of 14 to 34 Gy. In terms of normalization of hormone level, the inconsistencies of the endpoints used in various studies render interpretation of results difficult (30). A decrease in hormone hypersecretion can occur within a few months after SRS but complete normalization can take up to 8 years. Data in the literature suggest that there is a radiation dose response in terms of normalization of hormone levels. It is also suggested that the use of antisecretory medications at the time of SRS has a negative impact on the efficacy of the procedure (30). For endocrine-inactive tumors, a dose of 15 to 20 Gy is usually used; for secretory tumors, a higher dose should be considered. For patients with acromegaly, the reported rates of endocrine cure ranged from 0% to 90% (30). However, the criteria of endocrine cure in those studies were either not defined or inconsistent. From the endocrinologists’ standpoint, an endocrine cure is usually defined as a GH level of ≤1 ng/mL

Figure 3 This Gamma Knife plan shows a dose of 25 Gy prescribed to the 50% isodose line for a growth hormone-secreting pituitary adenoma; the optic apparatus is contoured and the dose is limited to 8 Gy.

Chapter 10: Radiobiology and Radiation Therapy of Skull Base Tumors

and a normal IGF-I. A comprehensive review was done examining the outcomes of SRS for the treatment of acromegaly (30). Among the studies using the criteria of endocrine cure closest to the criteria used by the endocrinologists, the rate of endocrine cure ranged from 20% to 82% (30). The author commented that this wide variation might be a result of the different percentage of patients receiving antisecretory medications during SRS. For prolactinomas, SRS results in an endocrine cure rate approximately 30% and a significant reduction of PRL levels in 29% to 100% of the patients (30). The variation in results may be related to different proportions of patients receiving antisecretory medications. The post-SRS stalk effect may cause the PRL to be slightly elevated even when the hypersecretion is well controlled (30). For ACTH-secreting tumors, the reported endocrine cure rates after SRS ranged from 10% to 100% (30). However, some of the studies did not specify the criteria of endocrine cure and other studies used various different criteria. Among the studies with defined criteria of endocrine cure, the rates of endocrine cure ranged from 28% to 100% (30). Data on SRS for the treatment of Nelson syndrome is scarce in the literature. The endocrine cure rates ranged from 0% to 36% (30). In the recent years, data on the use of FSRT for the treatment of pituitary adenomas have been emerging. The prescribed dose ranged from 45 to 52.2 Gy in conventional fractionation. The tumor control rates ranged from 85% to 98% (7). The reported complication rates were low. Longer follow-up is required to determine the long-term efficacy and toxicity of FSRT for the treatment of pituitary adenomas.

Acoustic Schwannoma Acoustic schwannomas are slow growing benign tumors and are usually managed with microsurgery, SRS, FSRT, or observation. Since acoustic schwannoma are slow growing tumors, some physicians favor close observation of smaller tumors. However, tumor progression can result in permanent loss of hearing function and can increase the risk of complications associated with surgery or SRS/FSRT. Comparisons have been made between microsurgery and SRS; it is demonstrated that SRS yields similar tumor control rates but a lower incidence of cranial nerve deficits although very long-term data are lacking for SRS (31–34). Acoustic schwannomas are regarded as Class B targets, which are ideal targets for SRS (Fig. 4). There are abundant data in the literature on the utilization of SRS for the treatment of acoustic neuroma. There has been an evolution of the treatment techniques, imaging, and radiation dosing for SRS in the management of acoustic schwannoma. In the past, more rudimentary planning was used and plans were typically less conformal given earlier computer algorithms and CT-based

Figure 4 Axial MRI showing acoustic schwannoma involving the right internal auditory canal and extending into the right cerebellopontine angle with central necrosis following stereotactic radiation therapy.

planning. Modern treatment planning entails the use of larger number of shots to improve the conformality around the tumor (35). The availability of inverse planning in linear accelerator-based SRS has also improved the conformality index. In regard to dosing, the prescribed dose for acoustic schwannoma has been lowered over the past one to two decades. In the earlier studies, marginal doses in the range of 16 to 20 Gy were used (35–37). Although the reported tumor control rates were excellent, the incidence of radiationinduced hearing loss and cranial nerve deficits (mainly trigeminal and facial nerves) was substantial prompting physicians to lower the prescribed dose for SRS (35–38). More recent series utilizing a lower prescribed dose of 12 to 13 Gy did not show inferior tumor control rates (37–48). In terms of hearing preservation, a much higher proportion of patients retained serviceable hearing. There is also a lower incidence of trigeminal and facial nerve injury from SRS. Table 2 summarizes the treatment results of selected SRS series. One of the largest series of 829 acoustic schwannoma patients treated with Gamma Knife-based SRS from University of Pittsburgh reported a 10-year tumor control rate of 97% (37). Other series reported similar high tumor control rates (38–42,44,47,48). Another study from the same institution examined the treatment outcomes of patients with acoustic schwannoma treated with a reduced dose of 12 to

Table 2 Summary of Results of Selected SRS Series for Acoustic Neuroma Series Flickinger (38) Inoue (39) Petit (40) Paek (41) Iwai (44) Weber (45) Combs (49)

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No. of pts

Modality/dose

Tumor control (Follow-up)

Hearing preservation

V/VII nerve toxicity

313 18 47 25 51 88 26

GK/12–13 Gy GK/10–12 Gy GK/12 Gy GK/12 Gy GK/12 Gy Protons/12 Gy LINAC/13 Gy

98.6% (6 yr) 93.3% (6–13 yr) 96% (3.6 yr) 92% (45 mo) 92% (60 mo) 93.6% at 5 yr (38.7 mo) 91% at 10 yr (110 mo)

78.6% 80% 88% 52% 59% 33% 55% at 9 yr

4.4%/0 0/0 0/4% 5%/0 0/0 10.6%/8.9% 8%/5%

Abbreviations: SRS, stereotactic radiosurgery; No. of pts, number of patients; V/VII nerve toxicity, trigeminal/facial nerve toxicity; GK, Gamma Knife; LINAC, linear accelerator.

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13 Gy and demonstrated that tumor control was not compromised (38). With a median follow-up of 24 months, the rates of preservation of facial nerve function, trigeminal nerve function, and serviceable hearing were 100%, 95.6%, and 78.6%, respectively (38). A series from University of Maryland utilizing a reduced dose of 12 Gy for SRS for acoustic schwannoma showed a tumor control rate of 96% with a median follow-up of 3.6 years (40). Eighty-eight percent of the patients retained hearing. No patient experienced facial numbness. Transient facial numbness was reported in 4% of the patients (40). Another series from Japan utilizing a reduced dose of 12 Gy showed a similarly high tumor control rate with none of the 51 patients developing any facial numbness or weakness (44). Colleagues from Harvard University demonstrated that proton beam SRS yielded a 5-year tumor control rate of 95.3% with a median follow-up of 38.7 months (45). The prescribed dose was 12 cobalt Gray equivalent (CGE). The trigeminal and facial nerve toxicity rates were 10.6% and 8.9%, respectively (45). The hearing preservation rate was 33.3% (45). The group from University of Heidelberg reported the long-term treatment outcomes of patients with acoustic schwannoma treated with linear accelerator-based SRS. A median dose of 13 Gy was prescribed to the 80% isodose line. With a median follow-up of 110 months, the 5- and 10-year tumor control rates were 91% (49). The rates of radiation-induced trigeminal neuralgia and facial weakness were 8% and 5%, respectively (49). The hearing preservation at 9 years was 55% (49). Other series showed similar results for tumor control and trigeminal and facial nerve toxicities and varying hearing preservation rates. The follow-up times of most of these studies are relatively short and additional follow-up is required to determine the long-term efficacy and toxicity of SRS using a reduced dose approach. FSRT using conventional or hypofractionation has also been used to treat acoustic neuromas (43,50–60). In particular, patients with large acoustic schwannoma not suitable for SRS may be offered FSRT. The largest body of experience with conventional FSRT came from University of Heidelberg, Germany. A total of 106 patients with acoustic schwannoma were treated with FSRT (50). The prescribed dose was 57.6 Gy in conventional fractionation. With a median follow-up of 48.5 months, the 5-year actuarial tumor control was 93% (50). The toxicities associated with the treatment were low with 3.4%, 2.3%, and 6% developing trigeminal nerve, facial nerve, and vestibulocochlear nerve complications, respectively (50). Investigators from University of California, Los Angeles demonstrated similar results with the use of FSRT for the treatment of acoustic schwannoma (57). Investigators from Loma Linda University also reported their treatment results of fractionated proton beam radiotherapy for the treatment of acoustic neuroma. The prescribed dose was 54 CGE or 60 CGE (for patients with no serviceable hearing) in 30 fractions (61). With a median follow-up of 34 months, the tumor control rate was 100% (61). No trigeminal or facial nerve toxicity was reported. The hearing preservation rate was 31% (61). The group from Thomas Jefferson University also showed similar tumor control rates and incidence of cranial nerve toxicity (trigeminal and facial nerves) for patients with acoustic schwannoma treated with FSRT in conventional fractionation (43). In patients with sporadic tumors, the probability of retaining serviceable hearing was 81%. Hypofractionated regimens have also been described for FSRT (51–54,62,63). The regimens used include 3 Gy × 10, 5 Gy × 4, 5 Gy × 5, 4 Gy × 5, 6 Gy × 3, and 7 Gy × 3. Regardless of the regimen used, the tumor control rate ranged from 94% to 100%. The rates of trigeminal and facial nerve toxicity were low. Approximately

one-fourth to one-third of the patients developed complications related to hearing. The median follow-up intervals for the FSRT studies ranged from 21 to 48.5 months. It is still too early, due to recent SRS dose reductions, to draw conclusions as to whether FSRT or SRS with lowered prescribed doses has the advantage in terms of the therapeutic ratio. However, in patients not eligible for SRS based on tumor size, FSRT represents a reasonable treatment alternative.

Meningioma Skull base meningiomas can be addressed with skull base surgical techniques. However, the critical structures that reside in the region of the skull base can prevent complete resection from being performed safely, leading to increased risk of tumor progression. To improve tumor control, postoperative radiation therapy is indicated for patients who have subtotally or minimally resected newly diagnosed or recurrent skull base meningiomas (64). There are abundant data in the literature supporting the use of conventional fractionated radiation therapy in the management of patients with subtotally or minimally resected newly diagnosed or recurrent skull base meningiomas (64). The majority of the series included meningiomas in skull base as well as non–skull base locations. The typical prescribed dose ranges from 50 to 54 Gy for benign meningiomas in most cases. For patients who receive radiation therapy after subtotal resection, it is reasonable to expect a 10-year local control rate of at least 70% to 80% based on the long-term results reported in the literature. For patients with unresectable disease, radiation therapy provides a degree of tumor control and symptomatic relief. In the series from Royal Marsden Hospital, United Kingdom, the reported 5-, 10-, and 15-year disease-free survival rates for patients with unresectable meningiomas were 53%, 47%, and 47%, respectively (65). For patients with recurrent meningiomas, there is some suggestion that the outcomes are not compromised if radiation therapy is given at the time of recurrence compared to the outcomes of patients who receive immediate radiation therapy after subtotal tumor resection (66). Because of the presence of critical structures—such as the optic apparatus, the cranial nerves in the cavernous sinus and the brainstem—progression of a skull base meningioma can result in significant neurological morbidity. This question is best answered in a clinical trial setting. The European Organisation for Research and Treatment of Cancer (EORTC) is conducting a trial randomizing patients with subtotally resected or biopsied World Health Organization grade 1 cerebral meningiomas to observation or postoperative external beam radiation therapy or SRS (EORTC 26,021-22,021). Because meningiomas have a sharp margin of demarcation with normal brain parenchyma, they are excellent targets for highly precise radiation techniques such as IMRT, SRS, FSRT, and proton beam therapy [Fig. 5(A)]. The main advantage of using these techniques is the capability of minimizing radiation dose delivery to the areas outside the target volume. IMRT can produce highly conformal isodose distribution around a target volume while minimizing radiation dose delivery to surrounding critical structures or organs [Fig. 5(B)]. It is well suited for treatment of targets with complex shapes such as meningiomas. Colleagues from Baylor College of Medicine treated 40 meningioma patients (32 with skull base tumors) with IMRT to a dose of 50.4 Gy. With a median follow-up of 30 months, the 5-year tumor control was 93% (67). Acute and late complications occurred in 2.5% and 5% of the patients, respectively (67). Another study from University of Heidelberg examined the

Chapter 10: Radiobiology and Radiation Therapy of Skull Base Tumors

(A)

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(B)

Figure 5 (A) Axial MRI T1 postcontrast image showing hyperostosing en plaque meningioma of the right greater sphenoid wing with extension into the lateral portion of the right orbital apex and right parasellar region. (B) Intensity modulated radiation therapy plan to deliver 50.4 Gy in 30 fractions to this meningioma.

treatment outcomes of 20 patients with skull base meningiomas treated with IMRT. The prescribed dose was 57.6 Gy. With a median follow-up of 36 months, the tumor control rate was 100% with 25% of the tumors treated showing tumor shrinkage (68). The incidence of late complications was 10% (68). A recent study of 35 patients with 37 meningiomas treated with IMRT at Cleveland Clinic Foundation showed similar findings. The prescribed dose was 50.4 Gy. With a median follow-up of 19.1 months, the 3-year local control was 97% and no late complications were observed (69). Overall, all these studies had relatively short follow-up intervals ranging from 19.1 to 36 months. Extended follow-up is required to determine whether IMRT can improve the therapeutic ratio compared to conventional fractionated radiation therapy. Data on SRS for the treatment of skull base meningioma have emerged in the literature over the last two decades (64). Meningiomas are category 2 targets with a sharp margin of demarcation from normal brain parenchyma, and therefore, they are ideal targets for SRS (2). The typical prescribed dose was 12 to 18 Gy. Numerous reports have demonstrated the high efficacy and the low toxicity associated with SRS for the treatment of skull base meningioma (70–74). Colleagues from Mayo Clinic reported the results of 49 patients with cavernous sinus meningioma treated with Gamma Knife-based SRS. The mean margin dose was 15.9 Gy. With a median follow-up of 58 months, the tumor control rate was 100% (70). Twenty-six percent of patients with preexisting diplopia or facial numbness/weakness had improvement of their symptoms. Ten percent of patients developed worsening of trigeminal nerve function after treatment (70). One hundred fifty-nine patients with cavernous sinus meningioma were treated at University of Pittsburgh with Gamma Knife-based SRS. The median margin dose was 13 Gy. Neurologic status remained stable or improved after treatment in 91% of patients (72). Tumor progression occurred in 6% of patients. Adverse effect occurred in 6.7% of patients. The 5- and 10-year tumor control rates were both 93.1%. At the same institution, 62 patients with petroclival meningiomas were treated with Gamma Knifebased SRS (75). The median margin dose ranged from 11 to 20 Gy. With a median follow-up of 37 months, tumor progression occurred in 8% of the patients (75). New cranial nerve

deficits occurred in 8% of patients. Other SRS series, either Gamma Knife- or linear accelerator-based, showed similar tumor control and toxicity rates for skull base meningioma (71,73,74). There does not appear to be any significant difference between Gamma Knife-based and linear acceleratorbased SRS in terms of treatment outcomes. FSRT can be offered to patients with skull base meningiomas not suitable for treatment with SRS either due to the size limit or the proximity to critical structures like the optic apparatus. It is also a reasonable treatment alternative to either fractionated radiation therapy or SRS. Data on FSRT for the treatment of skull base meningiomas have emerged over the last 10 years. Colleagues from Royal Marsden Hospital, United Kingdom reported their preliminary treatment outcomes of patients with mostly skull base meningiomas treated with FSRT in two separate publications (76,77). The prescribed dose was 50 to 55 Gy in conventional fractionation. None of these patients developed any tumor recurrence. The group from University of Heidelberg reported the results of one of the largest FSRT series for skull base meningiomas. The prescribed dose was 56.8 Gy in conventional fractionation. The tumor control rate was 98.3% and the complication rate was 1.6% with a median follow-up of 35 months (78). Other studies using the same approach showed similar tumor control and complication rates (79–81). However, the follow-up times of those studies were relatively short. Given the indolent nature of benign meningiomas, a prolonged follow-up of these patients is necessary to determine the long-term outcomes. Secondary to the lack of wide availability of proton beam facilities worldwide, protons have not been routinely used in patients with skull base meningiomas. Proton beam therapy has been used as the sole modality or combined with photon beam therapy for the treatment of skull base meningioma. Investigators from Institut Curie, France treated 51 patients with skull base meningioma with a combination of photon and proton beam therapy. With a median follow-up of 25.4 months, the 4-year local control was 98% (82). The prescribed dose was 60.6 CGE. Investigators from South Africa treated 23 patients with skull base meningiomas with either hypofractionated stereotactic proton beam radiation

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therapy (31.5 CGE in 3 fractions) or stereotactic proton beam radiation therapy (54 CGE in 27 fractions to 61.6 CGE in 16 fractions). With a median clinical and imaging follow-up of 40 and 31 months, respectively, 88% of the patients treated with hypofractionated and 100% of the patients treated with conventionally fractionated stereotactic proton beam radiation therapy achieved tumor control documented by imaging (83). Other proton beam radiotherapy series for meningiomas that included tumors of all locations showed similar outcomes (84–86).

Craniopharyngioma Craniopharyngiomas are benign tumors arising from the Rathke’s pouch. Although they are slow growing and well circumscribed, their frequent involvement of adjacent structures such as the optic apparatus, pituitary stalk, hypothalamus, and major blood vessels can contribute to significant morbidity and can render safe complete surgical resection difficult. Surgical intervention is the standard initial therapy for the purpose of tissue diagnosis and decompression. Attempts at achieving complete surgical resection can be associated with significant morbidity. Therefore, limited surgical resection and postoperative radiation therapy can be used to achieve satisfactory rates of tumor control. Conventional fractionated radiation therapy has been shown to be effective in the setting of postoperative treatment as well as for salvage treatment. Because craniopharyngiomas are very well circumscribed tumors, they are very suitable targets for advanced radiation therapy techniques such as IMRT, SRS, FSRT, and proton beam therapy. In patients with a cystic lesion, intralesional phosphorus-32 (P-32) may be used to treat the tumor. Conventional radiation therapy may be offered in two different settings—for initial treatment of a subtotally resected tumor and for salvage treatment of recurrence after surgical resection. Data in the literature showed that radiation therapy is effective in the reduction of the risk of recurrence in both settings (87). The most commonly prescribed dose is 50 to 54 Gy. For patients who receive immediate postoperative radiation therapy, the 10- and 20-year local control or progression-free survival ranged from 57% to 89.1% and from 54% to 79%, respectively (87). For patients who receive postoperative radiation therapy as salvage treatment, similar outcomes were observed (87). This raises the question as to whether delayed instead of immediate radiation therapy should be employed, especially in young children. The inverse planning nature of IMRT enables radiation oncologist to select dose constraints to critical structures and is well suited for the treatment of craniopharyngiomas that are well circumscribed. However, because it is a recently developed treatment technique, long-term data on its efficacy and toxicity for the treatment of craniopharyngioma are lacking. Recently, there is renewed interest in the use of proton beam therapy for the treatment of brain and skull base tumors, especially in children. The physical characteristics of protons can yield an improved isodose distribution over what can be achieved with photons (Fig. 6). This is especially important in young children who receive radiation therapy for brain or skull base tumors. Colleagues from Harvard University reported their experience of combining photons and protons for the treatment of craniopharyngioma. A total of 15 patients, 5 children (median age, 15.9 years) and 10 adults (median age, 36.2 years), were treated with 160 MeV proton beam therapy either for the entire course of treatment or combining with photon beam therapy. The median dose given was 56.9 CGE. With a me-

Figure 6 A proton beam radiotherapy plan showing a dose of 50.4 CGE in 28 fractions prescribed to this large craniopharyngioma.

dian follow-up of 11 years for the 11 surviving patients, the 5- and 10-year local control rates were 93% and 85%, respectively (88). The 10-year overall survival rate was 72%. None of the 10 adults treated had any change of functional status or working ability. One of the five children had learning difficulties comparable to pre-radiation therapy level; the remaining had professional achievements. SRS (Gamma Knife-based or linear accelerator-based) has been utilized to treat craniopharyngiomas. Because of the proximity of most craniopharyngiomas to the optic apparatus, there would be a risk of radiation-induced visual disturbance if the radiation dose exceeds the tolerance level. Typically, a 3 to 5 mm gap between the tumor and optic apparatus is needed to limit the radiation dose to the structure. Most SRS series showed a local control rate of 86% to 90% (87). In one Swedish series, the rates of tumor progression were 85% and 33% for tumors receiving <6 Gy and ≥6 Gy, respectively (89). The series showing good local control rates all had relatively short follow-up times of less 3.5 years (87). Longer follow-up is needed to determine the efficacy and toxicity of SRS for craniopharyngiomas. FSRT has also been used to treat children with craniopharyngiomas. Preliminary results from various studies showed that it was safe and efficacious (90–93). In one of the large studies from University of Heidelberg, 26 patients were treated with FSRT with a median dose of 52.2 Gy (range 50–57.6 Gy). With a median follow-up of 43 months, the 10year tumor control probability and survival rate were 100% and 83%, respectively (90). Out of the 18 patients at risk, three developed endocrine deficits (90). For patients with cystic tumors, intracavitary irradiation can be used as the primary treatment or adjuvant to surgery or external beam radiation therapy. In one of the large series from University of Pittsburgh, 49 patients were treated with colloidal chromic P-32 using a stereotactic approach. The prescribed dose to the cyst wall was a dose of

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200 to 250 Gy. The actuarial 5- and 10-year local control rates were 76% and 70%, respectively (94). Forty-eight percent of the patients treated had improvement or stabilization of their vision. Three of the 49 patients (6%) developed permanent radiation injury related to P-32 therapy (94). In another series of 62 patients with craniopharyngioma treated with yttrium-90 (Y-90) or P-32, the actuarial 5- and 10-year survival rates were 80% and 64%, respectively (95). After treatment, three patients developed amaurosis, one developed increased visual field cut, and another one developed oculomotor nerve deficit. Three patients developed hypothalamic-pituitary dysfunction after therapy (95).

Glomus Tumor Glomus tumors, also known as nonchromaffin paragangliomas, arise from neuroepithelial cells. The most common locations are carotid body and the temporal bone. Tumors arising along the superior bulb of the internal jugular vein and along the tympanic branch of glossopharyngeal nerve are called glomus jugulare and glomus tympanicum, respectively. They are low-grade malignant tumors where the main pattern of spread is local, and nodal and distant metastases are rare. Because these tumors are hypervascular, they are usually demonstrated very well on CT with contrast. They also have a characteristic appearance on MRI. Angiography is used to evaluate patients preoperatively. The standard treatment is surgical resection or radiation therapy. However, in cases where the risk is regarded as too high for surgical resection, radiation therapy is often offered (Fig. 7). Radiation therapy should also be considered after subtotal resection. The goals of the treatment include tumor and symptomatic control. Data in the literature showed that fractionated radiation therapy is an effective treatment for glomus tumors (96–103). In terms of target delineation, CT, MRI, and angiography can be used. Since the risk of nodal metastasis is low, the clinical target volume does not typically include the nodal regions. Usually, a prescribed dose of 45 to 50 Gy in conventional fractionation is used. Springate and colleagues did a comprehensive review of all the articles published on radiation therapy for glomus tumors from 1965 to 1988. The tumor control was 93% and the risk of complication was 2% to 3% (104). Table 3 summarizes the treatment outcomes of selected series for fractionated radiation therapy for glomus tumors. SRS has also been used to treat glomus tumors. SRS can yield a very conformal isodose distribution and a very rapid dose fall-off beyond the target volume. Multiple series in the literature showed tumor control rates of 63% to 100% and symptomatic control rates of 25% to 60% (105–111). Complications occurred in 4% to 40% of the patients. One note of caution is that these series only had follow-up intervals of 20.5

Figure 7 Coronal MRI T1 postcontrast MRI showing massive skull base/jugular foramen glomus tumor centered on the right occipital bone and clivus to include regions of the hypoglossal canal.

to 51 months. Because late recurrence can occur in glomus tumors, a much longer follow-up is required to determine the efficacy of SRS in the management of glomus tumors.

Chordoma Chordomas are rare tumors that originate from the rests of the embryonal notochord. Approximately one-third of these tumors occur in the skull base. They are locally aggressive tumors that are most often treated with maximal safe resection and postoperative radiation therapy. Although gross total resection is the goal of surgery, there are instances where this is not achievable (Fig. 8). Because of the aggressive nature of the tumor, there is a high risk of local recurrence after surgical resection. Postoperative radiation therapy is employed to reduce the risk of local recurrence. The most common cause of death is uncontrolled local tumor progression, so local tumor control is of utmost importance (6). Unfortunately, the location of these tumors renders the delivery of an adequately high dose of radiation to the area difficult even with highly conformal techniques with photon beam therapy, subsequently resulting in nondurable tumor control. The treatment outcomes with the use of conventional fractionated radiation therapy have been disappointing. The typical prescribed dose for conventional fractionated radiation therapy is 50 to 60 Gy (6). This strategy resulted in a recurrence rate of 50% to 100% (6). Other strategies to intensify the radiation

Table 3 Summary of Treatment Outcomes of Patients Treated with Conventional Fractionated Radiation Therapy for Glomus Tumors Series Pemberton (102) Krych (103) Wang (97) Konefal (99) Sharma (100) Hinerman (98) Cummings (101) Powell (96)

No. of pts

RT dose

Follow-up

Tumor control

49 23 15 22 40 43 45 46

37.5–50 Gy in 15–16 days 45 Gy 29–67.5 Gy 46–55 Gy 40–50 Gy 37.7–60 Gy 35 Gy in 3 wk 35–66 Gy

7.4 yr 13.4 yr 5–33 yr 10.5 yr 13 yr 11.1 yr 10 yr 9 yr

92% 100% 80% 91% 83% 93% 93% 85%

Abbreviations: No. of pts, number of patients; RT dose, radiotherapy dose.

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Figure 8 Axial MRI postcontrast showing chordoma centered at the sella region with extension into the left side of the midbrain and pons, and involvement of both cavernous sinuses, and encasement of the left internal carotid artery.

dose to skull base chordomas such as SRS and FSRT have also been used. In the SRS series from Mayo Clinic, with a median follow-up of 4.8 years, the 2- and 5-year tumor control rates were 89% and 32%, respectively (112). The median margin dose was 15 Gy. Patients who had prior fractionated radiotherapy had a higher risk of radiation-induced complications. Other studies also suggested that SRS may be an effective treatment for skull base chordomas (113,114). FSRT has also been used to treat skull base chordomas. The group from University of Heidelberg treated patients with skull base chordomas with FSRT. The prescribed dose was 66.6 Gy. The 2- and 5year local control rates were 82% and 50%, respectively (115). Secondary to the absence of exit dose from protons, a very conformal distribution around the target volume can be achieved in the three-dimensional space (6). This enables a higher dose of radiation to be delivered to the tumor (chordoma), thereby improving the chance of tumor control. A large body of experience has been accumulated over the years on the use of proton beam therapy for the treatment of skull base chordoma. In the United States, the proton beam experience for skull base chordomas came mainly from Lawrence Berkeley National Laboratory, Loma Linda University, and Harvard University. Investigators from Harvard University reported one of the largest experiences in using proton beam therapy (5 fractions per week, 4 with protons and 1 with photons) for the treatment of skull base chordoma and low-grade chondrosarcoma. The prescribed dose was 66 to 83 CGE in conventional fractionation. A relative biologic effectiveness of 1.1 was used. Out of the 519 patients, 290 had chordoma. With a median follow-up of 41 months, the 5- and 10-year local recurrence-free survival was 64% and 42%, respectively (6). Severe complications occurred in 8% of the patients. Colleagues from Loma Linda University treated 58 patients with skull base chordoma (n = 33) and low-grade chondrosarcoma (n = 25) with proton beam therapy. The median dose was 64.8 to 79.2 CGE (6). With a mean follow-up period of 33 months, eight (24%) of 33 patients with chordomas experienced recurrence. The 3-year local control rate was 67%. The 5-year overall survival rate was 79%. A group from Institut Curie treated 100

patients with base of skull or cervical spine chordomas with fractionated radiotherapy combining photons and protons. A prescribed dose of 67 CGE was given. With a median follow-up of 31 months, a total of 25 patients developed recurrence. The 2- and 4-year tumor control rates were 86.3% and 53.8%, respectively (116). Other proton beam radiotherapy series have shown similar results (117–122). Given the more favorable outcomes associated with the use of proton beam radiotherapy compared to those achieved with photon beam irradiation alone, proton beam radiotherapy should be considered in most patients with skull base chordomas. Carbon ion therapy combines the physical advantages of protons with the differential increase in relative biologic effectiveness (123). It is currently not available in the United States and is only available in even more limited facilities worldwide. The investigators from University of Heidelberg reported that a 3-year tumor control rate of 81% was achieved for patients with chordomas and no excessive toxicity was observed (123). At German Ion Research Center (GSI), a phase I/II trial of carbon ion therapy for the treatment of skull base chordomas and chondrosarcomas has been completed in 2001. With a median follow-up of 32 months, the 4-year actuarial local control for chordomas was 74% (124). The prescribed dose was 60 GyE at 3 GyE daily, 7 days a week. These preliminary results appeared to be as favorable as those achieved with proton beam therapy. However, a longer follow-up is required to determine the long-term efficacy and toxicity associated with the treatment.

Chondrosarcoma Chondrosarcomas constitute 10% to 20% of all malignant bone tumors. Those occurring in the head and neck region most commonly arise from the sphenopetrosal and the spheno-occcipital synchondroses, the nasal cavity, and the paranasal sinuses. Complete surgical resection is the mainstay of treatment. Unfortunately, the location of the tumor often precludes the possibility of safe maximal resection. Postoperative radiation therapy is required to reduce the risk of recurrence. A high dose of radiation is required to achieve permanent local control. Similar to skull base chordomas, skull base chondrosarcomas are subject to the radiation dose constraints of surrounding critical or normal structures and the delivery of a high dose of conventional photon beam radiotherapy is often not possible. Advanced radiation techniques such as SRS and FSRT have been used to treat patients with skull base chondrosarcoma. In the series from Mayo Clinic, all the four patients with skull base chondrosarcoma treated with Gamma Knife-based SRS achieved tumor control with a median follow-up of 4.8 years (112). Similarly, good results were shown in the study from University of Pittsburgh (113,114). At the University of Heidelberg, eight patients were treated with FSRT for skull base chondrosarcoma. The prescribed dose was 64.9 Gy. None of the patients treated developed recurrence after 5 years (115). There were several proton beam radiotherapy studies pertaining to management of skull base chondrosarcoma. The largest experience came from Harvard University where 200 patients were treated. The prescribed dose was 72.1 CGE. The 5-year local control was 99% (125). Other proton beam studies utilizing similar radiation dose levels showed similar tumor control rates (117–120). Carbon ion therapy has been used to treat patients with skull base chondrosarcomas. Fifty-four patients were treated for skull base low- or intermediategrade chondrosarcoma at GSI in Germany. A dose of 60 CGE (weekly dose 7 × 3 CGE) was prescribed to the tumor volume (126). With a median follow-up of 33 months, the tumor

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control rates at 3- and 4-years were 96.2% and 89.8%, respectively (126). The grade 3 late-toxicity rate was 1.9% (126). Carbon ion therapy appears to yield similar tumor control and low toxicity rate compared to proton beam radiotherapy on short-term follow-up.

Nasopharyngeal Carcinoma Nasopharyngeal carcinoma (NPC) is relatively rare in the western hemisphere. Because of its tendency to involve the fissures and the foramina in the skull base, all of these areas are included in the radiation field. NPC also carries a high risk of bilateral neck node metastases, the whole neck has to be included in the radiation therapy field even if there is no clinical evidence of cervical node involvement (127). Unlike other head and neck cancer, NPC is managed primarily with radiation therapy with or without chemotherapy and the role of surgery is limited to neck dissection if there is residual disease after radiation therapy and to salvage nasopharyngectomy for recurrent disease after primary radiation therapy. The typical radiation dose for gross disease is 70 Gy although a dose of 66 Gy have been used in patients with nonkeratinizing carcinoma and undifferentiated carcinoma with good results. Multiple phase III trials have established the role of concurrent chemoradiation therapy in the management of NPC (128,129). A recent meta-analysis showed that chemotherapy did lead to a small but significant benefit for overall survival and event-free survival in locally advanced NPC and the advantage was seen mainly when chemotherapy was given concurrently with radiotherapy (128). Because of the complex shape of the target volume to be treated and the close proximity of the portion of the target volume in the skull base to various critical structures, the use of advanced technology such as IMRT can help optimize the therapeutic outcome (130,131). Data on the use of IMRT for the treatment of NPC are emerging over the past 5 years. Preliminary results reported in various publications showed good tumor control rates and capability of normal tissue sparing. In the study from the University of California, San Francisco, sixty-seven patients with NPC were treated with IMRT. The 4-year local progression-free, local-regional progression-free, and distant metastasis-free rates were 97%, 98%, and 66%, respectively (132). The 4-year overall survival was 88% (132). The toxicity rate was low. Other studies also showed favorable results (133,134). The ongoing Radiation Therapy Oncology Group 0615 trial involves concurrent chemoradiotherapy using 3-D conformal radiotherapy or IMRT plus bevacizumab for locally or regionally advanced nasopharynx cancer.

Paranasal Sinus Tumors Paranasal sinus tumors are rare malignancies. Histologic subtypes include epithelial tumors such as squamous cell carcinoma, undifferentiated carcinoma, malignant salivary gland tumors (adenocarcinoma, adenoid cystic carcinoma, and mucoepidermoid carcinoma), and esthesioneuroblastoma, melanoma, rhabdomyosarcoma, plasmacytoma, and lymphoma. For lymphoma and plasmacytoma, low-tomoderate dose radiation therapy (30–50 Gy) with or without chemotherapy (for lymphoma, depending on histology) is the mainstay of treatment. For other histologies, surgical resection should be considered. Radiation therapy with or without chemotherapy is often combined with surgical resection for the management of paranasal sinus tumors to enhance tumor

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control. Typically, a higher dose of radiation is required. This presents a therapeutic challenge because the target volume to be treated is often in close proximity to critical structures such as the eyes and the optic apparatus. For patients with squamous cell carcinoma of the paranasal sinus, surgical resection is typically followed by postoperative radiation therapy (135,136). However, patients often present with very advanced disease that renders surgical resection not feasible. Primary radiation therapy is offered in that setting. Data in the literature showed that the treatment results were suboptimal. The reported 5-year tumor control rate ranged from 41% to 78% (136). The 5-year overall survival rate ranged from 27% to 55% (136). High nodal failure rates have been reported when elective neck irradiation is not given. Sinonasal undifferentiated carcinoma is a rare malignancy that runs a very aggressive course. If feasible, patients are frequently managed with surgical resection with or without adjuvant or neoadjuvant radiation therapy, chemotherapy, or both. If the disease is too advanced for surgical extirpation, primary radiation therapy with or without chemotherapy can be offered (137). The reported survival rates after treatment ranged from 20% to 63% (137). Given the high risk of cervical nodal metastasis, elective neck irradiation is usually recommended (137). Esthesioneuroblastoma is usually managed with surgical resection followed by postoperative radiation therapy. For patients who are not candidates for surgery, primary radiation therapy is given (138). Overall, the treatment outcomes associated with primary radiation therapy alone are poor and a complete resection followed by postoperative radiation therapy is associated with much better outcomes (139–141). Late recurrences have been observed in a significant proportion of patients after treatment, so the importance of long-term follow-up of these patients cannot be overemphasized (142,143). Because a high dose of radiation (60–70 Gy) is required for the treatment of paranasal sinus epithelial tumors, there is a substantial risk of retinopathy and optic neuropathy. To decrease the risk of collateral damage, different strategies have been used. The use of 1.2 Gy twice daily regimen have been used by the group at University of Florida (137). With the availability of advanced technology, a highly conformal radiation dose distribution around the target volume can be readily achieved. The use of intensity-modulated radiation therapy for the treatment of paranasal sinus tumors have been reported in the literature and the preliminary results appeared to be promising in terms of reduction of toxicity (144–146).

RADIATION TOXICITY The complications related to radiation therapy for skull base tumors are dependent upon the critical structures treated and the radiation dose delivered. The skull base is a challenging location for radiation delivery because various critical structures are located in the area. Structures at risk include normal brain parenchyma, optic apparatus, cranial nerves, major arteries, inner ear, brainstem, spinal cord, pituitary, and hypothalamus. For very young patients or children receiving fractionated radiation therapy for the treatment of skull base tumors, they are especially at risk of developing neurocognitive deficits and growth impairment. As most skull base tumors are benign tumors that run a long clinical course, there is a concern for radiation-induced tumors.

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SUMMARY Skull base tumors present a challenge to neurosurgeons, otolaryngologists, and radiation oncologists. The best management approach for patients with skull base tumor is interdisciplinary treatment planning. Before any treatment is initiated, it is important for the treatment team to plan ahead of time the anticipated extent of surgery and the need for postoperative radiation therapy. For instance, a subtotal skull base tumor resection followed by postoperative radiation therapy can yield similar outcomes as a complete resection and it can reduce the risk of operative morbidity and mortality. With modern radiation therapy technology, it is possible to achieve a very conformal radiation dose distribution with a steep radiation dose gradient beyond the target volume treated, thereby reducing the degree of collateral damage to the critical structures and normal brain parenchyma. Furthermore, most skull base tumors have sharp margins of demarcation from the surrounding normal structures and are well suited for conformal radiation techniques. Hopefully, with the sophistication of surgical and radiation techniques, patient outcomes can be further improved and toxicities can be reduced.

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11 Chemotherapy for Skull Base Tumors Bilal Ahmed, Ehab Y. Hanna, and Merrill S. Kies

control and organ preservation. We will review data largely generated in phase II studies, in an attempt to define active systemic regimens with acceptable toxicity and applicability to combined modality programs. In doing so, we should also consider directions for future clinical investigations.

CHEMOTHERAPY FOR SKULL BASE TUMORS Skull base tumors are rare, and the site of origin may be difficult to determine as often there is involvement of multiple skull base compartments with variable effects on important neurovascular structures (1). Infiltrating skull base cancers may arise from the nasopharynx, paranasal sinuses, major and minor salivary glands, and skin. Treatment of nasopharyngeal cancers has been the subject of excellent recent reviews (2,3), and will not be addressed in this chapter. We will focus our discussion on chemotherapy for sinonasal cancers since they are a common malignancy that involve or invade the cranial base. Sinonasal cancers are uncommon and constitute 3% of head and neck cancers (4). These cancers present a special set of problems for clinicians as diagnosis is often delayed and symptomatology tends to emerge with involvement of vital local structures. Infiltrating disease in the nasal cavity may precipitate epistaxis or obstruction; orbital involvement may produce proptosis or diplopia; and skull base and intracranial tumor leads to variable neurologic deficits. Squamous cell carcinoma, adenocarcinomas, adenoid cystic carcinoma, neuroendocrine cancers, melanomas, Merkel cell malignancies, sarcomas, and lymphomas are among a diverse group of malignancies encountered. Surgery has generally been the mainstay of therapy for these tumors but frequently resections are subtotal necessitating multidisciplinary management. Even radical surgical excisions such as craniofacial resection, total maxillectomy, or orbital exenteration produce in aggregate less than 50% 5-year survival with both local and distant tumor failure patterns common (3). So with time, the skull base team has evolved to include surgical, radiation, and medical oncologists; neuro-otologists; oncologic nursing; rehabilitation specialists; social service staff; and psychology consultants. Proximity to many vital structures renders surgical resection often complicated. However, for squamous cell and neuroendocrine malignancies, surgery has traditionally been the cornerstone of management with radiation therapy administered as a postoperative adjunct for patients with locally advanced disease. Chemotherapy has previously been reserved for palliation in patients with incurable, locally far advanced, or metastatic disease. Standard surgical approaches may require orbitectomy or rhinectomy in some patients, obviously major debilitating events. So, as we consider that tumor control and health-related quality of life (5) are important outcome measures in assessing the potential benefits of combined modality therapy for skull base cancers, the subject of this chapter will be on the emerging role of systemic drug therapy as a component of primary treatment plans for selected patients. Induction chemotherapy, described as neoadjuvant therapy in some centers, may be of particular value in therapeutic strategies designed with dual objectives of tumor

TREATMENT RESULTS FOR PARANASAL SINUS CANCER Squamous Cell Carcinoma For patients with locally advanced disease, surgical resection followed by postoperative radiotherapy is common practice. Nonetheless, frequent involvement of vital structures and high locoregional failure risks call for a revision of older treatment plans. Overall disease-free survival at 5 years is less than 50% and 25% to 30% with more advanced disease (3,6,7). That is why new approaches such as induction chemotherapy followed by concomitant chemoradiotherapy or surgical resection with postoperative radiotherapy have been an area of active interest in recent studies. A Swedish group (8) presented an analysis of a mix of patients with paranasal sinus cancers treated with induction cisplatin and fluorouracil before radiotherapy then surgery. Seventy percent achieved a clinical partial tumor response to the drug therapy. Lee et al. (9) reported a University of Chicago experience in 16 patients receiving induction chemotherapy with cisplatin and infusional fluorouracil, then surgical resection and postoperative chemoradiotherapy with concomitant fluorouracil, hydroxyurea, and radiotherapy. Ten-year local and distant disease control exceeded 90%. For early-stage disease without extensive locoregional involvement, excision of the tumor followed by radiation seems to be the reasonable approach. However, for advanced stage M0 disease we recommend that trimodal strategy (surgery, radiation, and chemotherapy) should be used. The optimal sequence for chemotherapy and surgery or radiotherapy is not very clear. Isobe et al. reported a large, retrospective analysis examining the effect of sequencing chemotherapy in the management of squamous cell cancer of the maxillary sinus. Patients were divided into two groups, those who received cisplatin and peplomycin in the neoadjuvant settings and those who received concurrent chemoradiation. The study failed to show a significant effect for treatment sequence on survival (10). Intra-arterial (IA) chemotherapy is an alternative approach. This strategy aims to induce tumor regression to limit surgery and the associated detrimental effects on quality of life. Paranasal sinus cancers supplied by the internal maxillary artery are the most suitable targets for this highly selective approach. IA chemotherapy is facilitated greatly by technologic improvements and has the potential for increasing drug concentration at tumor sites and lowering systemic exposure. Increased tumor drug concentration for cisplatin is achievable and may be important, because 175

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dose-response relations seem to exist in head and neck cancers. Lee et al. (11) reported that IA cisplatin could be administered through superselective indwelling catheters and combined with systemic chemotherapy to achieve an overall response rate of 80% (30% complete) in advanced paranasal sinus tumors. The MD Anderson Cancer Center has further explored this approach with induction chemotherapy consisting of IA cisplatin and systemic paclitaxel and ifosfamide (12). To be eligible, disease was locally advanced and would require orbital exenteration or craniofacial resection. If substantial tumor response obtained, patients proceeded directly to definitive local treatment with radiotherapy, and surgery was avoided. Initial results with this approach were promising in terms of tumor response and local control. Eleven of 19 evaluable patients achieved a tumor response, and eyesparing surgery followed by radiotherapy was feasible in seven patients and radiotherapy without surgery in seven patients. At completion of treatment, 14 patients (61%) were disease-free with organ-preservation in 21 of 24 (88%). Overall survival at 2 years was 60%. Toxicity was substantial with two patients experiencing cerebral vascular ischemia (one transient) and three cranial neuropathy (one not reversible). Madison and colleagues have also reported promising results, from the University of Tennessee, and a series of 11 patients treated with preoperative, IA cisplatin and concurrent radiation therapy followed by a conservative craniofacial resection (13). In our experience with a mix of tumor histologies, progression-free survival at 5 years is 67%. All agree that further study in a research setting is warranted. Efforts are now focused on improved assessment of the response to therapy, and integration of targeted systemic drug administration with radiotherapy and surgery. For locally extensive disease, where a complete excision is likely to result in significant morbidity, we presently consider use of induction chemotherapy with docetaxel, cisplatin, and fluorouracil to induce disease regression before definitive local therapy, surgery, or possibly concomitant chemoradiotherapy. This strategy can be expected to reduce risk of distant disease recurrence; if there is a marked tumor response, there may also be an enhancement of the efficacy of local therapy. Cisplatin and infusional fluorouracil is a highly active drug regimen first developed as an induction regimen (14,15). Since then, the value of chemotherapy for the primary treatment of locally advanced squamous cancers of the pharynx and larynx has been demonstrated in a series of controlled trials (14,16–19) and meta-analyses (20). Concomitant chemotherapy and radiotherapy is superior to radiotherapy administered as a single modality with improved local tumor control and overall survival. Cisplatin, administered 100 mg/m2 during weeks 1, 4, and 7 with fractionated radiotherapy once daily now represents an accepted standard of care for patients with stage III and IV M0 disease. Study of concomitant cisplatin and radiotherapy in the postoperative setting has also shown a survival advantage for high-risk patients with positive resection margins or demonstrated extracapsular tumor extension (21,22,23). Moreover, alternative drug and radiotherapy schedules are under study. The updated meta-analysis of Monnerat and colleagues (24) also describes a survival advantage for patients receiving cisplatin and fluorouracil as the induction schedule. However, induction chemotherapy has not yet been accepted as a standard of care and there are ongoing randomized trials (14) addressing the value of this approach. Renewed interest in the administration of induction chemotherapy for squamous cancers of multisite origin has followed the reports of increased chemotherapy efficacy with

the addition of a taxane, such as paclitaxel or docetaxel, to the basic cisplatin and fluorouracil combination. Hitt et al. (25) compared induction programs with cisplatin and fluorouracil with or without paclitaxel. They observed a significantly higher response rate with the experimental regimen with no overall increase in toxicity. Patients with disease considered unresectable at diagnosis then proceeded to concomitant chemoradiotherapy and there was a survival advantage for the three-drug arm (p = 0.04). More recent presentations by Vermorken (26) and Posner (27) have furthered research interest in this area. In an EORTC phase III study comparing induction cisplatin and fluorouracil with docetaxel, cisplatin, and fluorouracil, 358 patients were entered. Following induction chemotherapy, all patients received radiotherapy as a single local treatment modality. With median follow-up of 32 months, the three-drug arm achieved superior tumor responses with significant progression-free and overall survival hazard ratios, 0.72 and 0.73, respectively. Also, more toxic deaths 5.5% versus 2.3% were observed in the cisplatin and fluorouracil group. In TAX 324, patients were randomized to receive induction chemotherapy with docetaxel 75 mg/m2 , cisplatin 100 mg/m2 , and fluorouracil 1000 mg/m2 /d (TPF) in a continuous infusion over 96 hours versus the standard cisplatin and fluorouracil schedule. Three treatment cycles were administered before patients proceeded to concomitant chemoradiotherapy with carboplatin AUC 1.5 administered weekly. Surgery was performed as salvage for residual disease. There appears to be a significant overall survival advantage for the patients receiving TPF. With a hazard ratio 0.70, 62% of patients receiving TPF were alive at 36 months versus 48%. Moreover, the authors have reported that there is the potential for TPF to have had a favorable effect on local disease control. At the MD Anderson Cancer Center, we are commencing a phase II trial with induction TPF followed by definitive chemoradiation for responding patients and surgical salvage if there is evidence for residual disease after the conclusion of radiotherapy. Patients whose tumors failed to respond to the induction program will proceed to definitive surgical resection and postoperative radiotherapy.

Sinonasal Undifferentiated Carcinoma Sinonasal undifferentiated carcinoma is a rare, highly aggressive, and distinct entity believed to have originated from the Schneiderian epithelium or from the nasal ectoderm of the paranasal sinuses. These cancers often present as a rapidly enlarging mass, involving multiple sites, and extending beyond the anatomic confines of the sinonasal tract. Associated symptoms reflect an enlarging mass effect, nasal obstruction, epistaxis, proptosis, facial pain, and cranial nerve palsies (28,29). This tumor is highly virulent. Frierson and colleagues (28) reported a median survival of 12.4 months in patients treated with radiotherapy, with or without chemotherapy. Only a single patient in this group underwent craniofacial resection. At the University of Virginia, experimental induction chemoradiotherapy with cyclophosphamide, doxorubicin, and vincristine is followed by craniofacial resection with reports of 65% 2-year survival in patients completing the treatment sequence. Subsequently, Rischin et al. (30) reported a series of seven patients treated with induction chemotherapy with cisplatin or carboplatin and infusional fluorouracil followed by radiotherapy with concomitant platinum administered during the first and last weeks of radiation. Four patients were disease free at 8 to 51 months follow-up. Kim and

Chapter 11: Chemotherapy for Skull Base Tumors Table 1 Kadish Staging System Stage

Tumor extension

A B C

Tumor limited to the nasal cavity Tumor involves nasal cavity and paranasal sinuses Tumor extends beyond the nasal cavity and paranasal sinuses

Enepekides (31) have reviewed retrospective reports from the literature. Prospective studies are needed to better identify molecular correlates that may predict for more effective treatment sequence, and a genomic or biomarker signature that can be used to select patients for more targeted and individualized medical therapy.

Esthesioneuroblastoma Esthesioneuroblastoma is a rare malignancy that originates from the olfactory epithelium. It comprises approximately 6% of paranasal tumors and less than 1% of all malignancies (32). Most often, this cancer arises from the superior nasal vault and invades the paranasal sinuses, orbit, and skull base, extending to CNS. Distant metastases occur in 20% to 25% of patients, with brain, lung, and bone as common sites. The Kadish staging system is presented in Table 1. Traditionally, this tumor has been treated with craniofacial resection followed by radiation therapy, and this approach is effective in Kadish stage A and B lesions, with long-term control exceeding to 75%. Chemotherapy has generally been reserved for recurrent or metastatic disease not amenable to curative local therapy. However, some more recent evidence is that chemotherapy should be integrated into primary management of advanced tumors. Resto et al. (33) have reported a retrospective review of 20 patients treated at Johns Hopkins University Hospital. These patients underwent surgical resection; with median follow up of 3.9 years, 12 patients were recurrence free. Nine of the 12 had negative surgical margins. All but two patients also received postoperative radiotherapy. Three patients had received induction chemotherapy with doxorubicin-based regimens with no response observed. Two patients received chemotherapy in sequence with radiation. A tumor response was observed to an alternating regimen with cyclophosphamide, doxorubicin, and vincristine (CAV) and cisplatin and etoposide. Also, one patient received postoperative cisplatin and etoposide with radiation, and was free of tumor recurrence at the time of the report. Polin et al. (34) analyzed 34 consecutive patients treated at the University of Virginia. In a multivariate regression analysis of potential prognostic factors, 21 patients were identified who had preoperative radiation or chemotherapy (with alkylatorbased regimens). Responding patients (n = 14) had improved survival. Overall, 5- and 10-year survival rates were 81% and 55%, respectively. Further, this group favors inclusion of chemotherapy as a component of multimodal care for patients with advanced disease. McLean et al. (35), from Emory University, have recently described their institutional experience with a total of 21 patients. Median follow up was 47 months. Surgical resection was performed in 90% of patients and postoperative radiotherapy in 73%. Multimodality therapy with chemotherapy was administered to seven patients. Overall, eight patients (38%) have had local disease recurrence, and the 5-year overall survival was 58%. The authors concluded that there should be further investigation of multimodal therapy with craniofacial resection, intensity modulated radiation therapy, and chemotherapy for patients with Kadish C lesions.

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Adenoid Cystic Carcinoma Adenoid cystic carcinoma (ACC) originates from the salivary, lacrimal, and other exocrine glands. There are differences in gene and protein expression between adenoid cystic cancers and normal salivary glands, with over expression of c-kit (36,37). This is the most common malignancy of minor salivary glands. Skull base involvement is frequent (38), a presumed consequence of the tendency for neurotropic tumor progression, often with “skip” metastases. There may be tumor progression along the V2 and V3 branches of the trigeminal nerve to the skull base with resultant facial numbness. Tumor involvement of the skull base by direct extension also may obtain by direct invasion through the paranasal sinuses. Esmali et al. recently reported a case series demonstrating the aggressive nature of this tumor where all seven patients had perineural and skull invasion and had to be treated with orbital exenteration (39). ACCs are not highly sensitive to cytotoxic chemotherapy although regimens consisting of cyclophosphamide, doxorubicin, and cisplatin (CAP) or vinorelbine and cisplatin will induce disease regression in subsets of patients with metastatic disease (40). Surgery is clearly the mainstay for the treatment of localized disease, however, given the high incidence of perineural invasion, postoperative radiation therapy is generally recommended to encompass associated nervous pathways, up to and including the base of the skull. Notably, a significant fraction of patients may present with locally advanced and unresectable disease, e.g., in the nasopharynx. Definitive concomitant chemoradiotherapy with weekly paclitaxel and carboplatin (41) or cisplatin administered during weeks 1, 4, and 7 of a daily radiotherapy treatment schedule (42) may have substantial activity with sustained disease remission. Also to be considered is that ACC may often have a prolonged clinical course with local recurrences and distant metastases occurring years after presentation (43,44). For the asymptomatic patient, particularly if older, with very slowprogressing lung metastases a period of observation may be appropriate, especially if comorbidities are more immediately problematic. However, for disease that is more obviously advanced, not amenable to local therapy, and objectively progressive often with lung and bone involvement, systemic chemotherapy or investigational treatment should be considered. CAP has been reported to induce tumor responses in as high as 46% patients (45). Platins, fluorouracil, doxorubicin, and vinorelbine are recognized as having some efficacy as single agents (46). In an early report, Glisson et al. (47) observed stabilization of metastasis in 60% of patients treated with gefitinib, the oral epidermal growth factor receptor tyrosine kinase inhibitor, receiving 250 mg daily. Hotte et al. reported no objective responses in 15 patients with overexpression of wild-type C-kit (48). Molecular markers predictive of activity for specific drug strategies have not yet been found effective in ACC.

Neuroendocrine Carcinoma Neuroendocrine carcinomas are rare sinonasal malignancies. First described in 1982 (49), this may be an aggressive cancer with poorly differentiated histology, especially the small cell subtype, with high risk for locoregional and distant disease recurrence and overall poor survival (50). Chemotherapy is under investigation as a component of primary management. At the Massachussetts General Hospital, 19 patients with either neuroblastoma or neuroendocrine tumors received two induction cycles with cisplatin and etoposide followed by

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proton-photon therapy. Responders then received an additional two chemotherapy cycles, with achievement of a 5-year survival rate 74% (51). A similar approach followed by Bhattacharyya et al. with induction chemotherapy consisting of cisplatin and etoposide followed by proton therapy again showed considerable activity in patients with quite bulky disease (52). As has been demonstrated in the treatment of small cell lung cancers, chemotherapy should be considered as a component of primary management in patients with locallyadvanced, poorly-differentiated disease. The experience with chemotherapy has largely been with platin and etoposide combinations, but other agents with potential activity are doxorubicin, cyclophosphamide, and camptothecins. In patients with advanced disease, we support a strategy with induction cisplatin 80 mg/m2 day 1 and etoposide 100 mg/m2 IV dose equivalent days 1–3 to be followed by concomitant chemoradiotherapy for responding patients. Certainly, an alternative may be to initiate treatment with concomitant chemoradiotherapy. Surgical resection is reserved for patients with tumors not responsive to drug or for salvage (6). It is not clear if heavy particle radiation is superior to intensitymodulated therapy.

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CONCLUSION In our view, there is an accumulating experience with chemotherapy as a component of primary management for many patients with skull base and sinonasal cancers. Much work needs to be done, and we strongly endorse support of clinical trials. Given the relative rarity of this group of diseases, phase II trials will be more likely and often may need to be performed in cooperative group settings. Innovative studies, with correlative scientific inquiries, tumor banking, and long-term outcome measures of tumor control, patient performance status, and life quality are imperative. For patients presenting with locally advanced disease and as we integrate systemic with locoregional therapy for patients presenting with locally advanced disease, complex treatment planning is necessary for optimal results. REFERENCES 1. Raso JL, Gusmao S. Transbasal approach to skull base tumors: Evaluation and proposal of classification. Surg Neurol. 2006;65(Suppl 1):S1:33–S1:38. 2. Tao Q, Chan AT. Nasopharyngeal carcinoma: Molecular pathogenesis and therapeutic developments. Expert Rev Mol Med. 2007;9(12):1–24. 3. Day TA, Beas RA, Schlosser RJ, et al. Management of paranasal sinus malignancy. Curr Treat Options Oncol. 2005;6(1):3–18. 4. Morita A, Sekhar LN, Wright DC. Current concepts in the management of tumors of the skull base. Cancer Control. 1998;5(2):138–149. 5. Kelleher MO, Fernandes MF, Sim DW, et al. Health-related quality of life in patients with skull base tumours. Br J Neurosurg. 2002;16(1):16–20. 6. Diaz EM Jr, Kies MS. Chemotherapy for skull base cancers. Otolaryngol Clin North Am. 2001;34(6):1079–1085, viii. 7. Blanco AI, Chao KS, Ozyigit G, et al. Carcinoma of paranasal sinuses: Long-term outcomes with radiotherapy. Int J Radiat Oncol Biol Phys. 2004;59(1):51–58. 8. Bjork-Eriksson T, Mercke C, Petruson B, et al. Potential impact on tumor control and organ preservation with cisplatin and 5-fluorouracil for patients with advanced tumors of the

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12 Rehabilitation of Speech and Swallowing of Patients with Tumors of the Skull Base Gail L. Davie, Denise A. Barringer, and Jan S. Lewin

INTRODUCTION

NORMAL NEUROPHYSIOLOGY OF SWALLOWING AND COMMUNICATION

The inability to communicate or eat normally are two of the most disturbing outcomes of head and neck, brain, and skull base tumors (1). Both communication and swallowing are complex processes that require a highly specific interplay between the efferent signals from the cortex, subcortex, and brainstem and the afferent signals from the structures of the aerodigestive tract, including the pharynx, larynx, and oral cavity. Skull base tumors, regardless of the site of the lesion or its pathology, put patients at risk for the development of a variety of communication and/or swallowing deficits. Despite lower morbidity and mortality rates resulting from recent advances in the medical treatment of skull base tumors, the frequency and severity of residual deficits in both communication and alimentation have changed little (2). As a result, many of these patients, although cured of their disease, become social recluses because of their functional disabilities. Early preoperative consultation with speech-language pathologists who are expert in the management of patients with skull base tumors is critical. Data show that optimal recovery is facilitated when the patient and family receive important information regarding the disease and its effect on survival and posttreatment quality of life (3). Critical information provided by an experienced speech-language pathologist helps the medical team prepare the patient and family for the potential effects of treatment on later speech and swallowing function. In addition, experience has shown that patients who are knowledgeable are often better able to accept their treatment and the potential for functional consequences. Therefore, it is important that patients with skull base tumors and their families thoroughly understand the crucial need for posttreatment rehabilitation. This chapter highlights critical components in the evaluation and rehabilitation of patients with communication and swallowing disorders associated with tumors of the skull base. To enhance the reader’s understanding of this complex topic, we have divided the chapter into three areas of focus: (i) normal neurophysiology of swallowing and communication, (ii) common swallowing and communication disorders associated with tumors of the base of skull and their treatment, and (iii) assessment and treatment of communication and swallowing disorders in patients with tumors of the base of skull.

Swallowing Swallowing is a complex interaction of biomechanical, neurophysiologic, and behavioral events that occur in strict hierarchic sequence and depend upon intact sensory awareness and basic recognition of the act of eating. Historically, swallowing was considered solely a brainstem function of sensory and motor integration coordinated by the reticular nuclei within the pons and medulla (4–5). However, recent research using functional magnetic resonance imaging has shown broad cortical involvement during swallowing, with the most prominent centers of activity located within the lateral precentral and postcentral gyri and the right insula (6). Although the sequence of muscle activity in swallowing generally occurs once the pharyngeal swallow has been triggered; sensory feedback may alter the precise occurrences of muscle contractions. Sensory innervation to the mouth, pharynx, and larynx is generally provided by the trigeminal (cranial nerve V), glossopharyngeal (cranial nerve IX), and vagus (cranial nerve X) nerves. Each of these nerves provides important sensory information that helps initiate and control the act of swallowing. Motor innervation in swallowing is mediated primarily via cranial nerves V, IX, X, and XII (hypoglossal) (7). Many of the techniques used for swallowing rehabilitation rely on this sensorimotor interrelationship, utilizing sensory pathways to stimulate motor function (8). Swallowing is generally described in four phases or stages: oral preparatory, oral, pharyngeal, and esophageal. The sequence of these stages is generally predictable, although the relative timing varies depending on the size and texture of the item being swallowed. It is the responsibility of the speech pathologist to evaluate the first three phases, while the evaluation of esophageal anatomy and disorders is the responsibility of the gastrointestinal radiologist. Thus, esophageal functioning is not discussed within this chapter and the reader is referred elsewhere for information. Swallowing has been recognized as a largely reflexive activity, as only the oral preparatory and oral phases are purely voluntary. The oral preparatory phase initiates the process of swallowing. During this phase, smooth coordination and transition between mastication and manipulation prepare and form the food into a cohesive, manageable bolus. The oral stage of swallowing begins as the tongue starts to

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move in an anterior to posterior rolling or stripping motion, propelling the bolus posteriorly to the oropharynx. The oral stage of swallowing typically lasts less than 1.5 seconds, but may take slightly longer with increased bolus viscosity. The pharyngeal phase of swallowing occurs with the initiation or “trigger” of the swallowing reflex. Generally, the area between the anterior faucial arches and the point at which the tongue base crosses the rim of the mandible is considered to be the key location for initiation of the pharyngeal swallow. The swallow trigger primarily depends on cranial nerve IX. In synchrony with the trigger of the swallow reflex, the soft palate elevates and retracts to close the velopharyngeal port to prevent nasal regurgitation of swallowed material. The base of tongue makes contact with the bulging posterior pharyngeal wall to help propel the food through the pharynx, while the larynx and hyoid bone move superiorly and anteriorly to prevent food from entering the airway, thereby directing the bolus posteriorly into the cervical esophagus. The elevation and anterior movement of the hyolaryngeal complex are essential to the opening of the upper esophageal sphincter or cricopharyngeus muscle, which allows the bolus to enter the cervical esophagus without aspiration. The pharyngeal phase also typically lasts less than 1.5 seconds, but unlike the oral preparatory and oral stages, the pharyngeal phase retains both voluntary and involuntary mechanisms of control.

Communication Analogous to swallowing, the complexity of communication is often not appreciated until it is lost. Communication is more than simply the articulation of sounds and syllables into meaningful utterances, or speech. Communication begins within the cerebral cortex and subcortex as a thought, an internal representation of an experience. Within the perisylvian region, specifically Broca area and the insula, the thought is organized and converted into language, a rulegoverned system of symbols represented by words that are eventually converted into speech. The sounds of the language are applied and the motor program, or directions for speech production, is generated. The motor program or plan is trans-

ferred from the premotor cortex to the lower portion of the motor cortex through tracts to the cranial nerves for activation of the muscles of the respiratory tract, larynx, and oral cavity into speech (9). It is important to remember that the network of association tracts communicates between critical areas of the brain and is essential to maintaining the speed and accuracy of normal communication. Therefore, any disruption or injury, focally or indirectly, to these regions or tracts will result in communication problems. The type of communication problem depends on the particular process or processes affected.

COMMON DISORDERS OF SWALLOWING AND COMMUNICATION Disorders of Swallowing Swallowing disorders associated with tumors of the skull base are not generally the result of a single cause; rather, they are the culmination of multiple insults resulting from the tumor itself, the surgical resection, the surgical approach, and/or the adjuvant treatments used to cure the disease. In general, tumors that affect the posterior skull base will result in more profound swallowing dysfunction because the cranial nerves critical to swallowing originate in this region. Table 1 summarizes the swallowing deficits and salient features associated with each cranial nerve. The consequences of damage to these nerves are often devastating, and many patients require long-term use of a gastrostomy tube for nutrition and a permanent tracheotomy tube because of chronic aspiration, which can lead to aspiration pneumonia, a frequent and serious problem in patients with skull base tumors. In addition to the posterior skull base, the anterior and middle regions of the skull base each have specific tumor- and treatment-associated swallowing disorders.

Anterior Skull Base Swallowing disorders associated with anterior skull base tumors occur as a result of anatomic alterations rather than cranial nerve dysfunction. The surgical exposure of anterior skull base tumors may require resection of structures such as the

Table 1 Speech and Swallowing Impairments Associated with Each Cranial Nerve Cranial nerve CN V CN VII CN VIII

CN IX

CN X

CN XII

Disordered physiology

Swallowing symptoms

• ↓ jaw movement • ↓ face, mouth and jaw sensation • ↓ facial movement and sensation • ↑ salivation • ↓ hearing • ↓ balance

• ↓ mastication • ↓ oral containment • Residue in the lateral sulci • Drooling N/A

• Delayed pharyngeal trigger • ↓ velopharyngeal closure • ↓ laryngeal elevation • ↓ palatal, pharyngeal, laryngeal excursion

• Aspiration before and during the swallow • Stasis/residue in the valleculae, posterior pharyngeal wall and pyriform sinuses • Aspiration during or after the swallow

• ↓ true vocal cord abduction and/or adduction • ↓ pharyngeal sensation

• Inability to cough

• ↓ lingual range of motion and strength

• ↓ bolus consolidation • ↓ anterior to posterior movement of the bolus • Oral residue

Speech symptoms • Unilateral: insignificant • Bilateral: severely ↓ articulatory precision • Mild distortion of b, p, f, v, • Distortion of resonance • ↓ articulatory precision of all sounds over time • Hypernasality • Hypernasality • Breathiness and hoarseness • ↓ pitch range • ↓ vocal loudness • Imprecise articulation of l, t, d, s, z, sh, ch, k, g

Chapter 12: Rehabilitation of Speech and Swallowing of Patients with Tumors of the Skull Base

maxilla or mandible that provide important structural support during swallowing. Therefore, functional deficits most commonly occur in the oral preparatory and/or oral phases of swallowing. In general, anterior skull base tumors do not affect the pharyngeal stage of swallowing. Labial sensory loss resulting from splitting of the maxilla often renders patients unable to maintain a labial seal, which results in drooling and food loss from the mouth. More extensive surgical approaches such as total maxillectomy cause palatal defects that hinder oral transit, lingual movements and contacts, and often result in velopharyngeal incompetency and nasal regurgitation. These deficits can be extremely detrimental to patient’s quality of life, preventing them from eating in public, and in the extreme, from eating by mouth.

Middle Skull Base Like tumors of the anterior skull base, tumors of the middle skull base are more apt to affect the oral preparatory and oral phases of swallowing than the pharyngeal phase. Damage to the middle skull base can result in unilateral or bilateral impairment of cranial nerves V and/or VII, which control the ability to open the mouth, masticate, and to maintain facial tone and symmetry. Generally, patients are able to compensate for unilateral damage affecting one or both nerves. However, bilateral damage can lead to profound dysfunction in the oral preparatory phase owing to the inability to close the mouth, maintain buccal tension, or engage in rotary chewing.

Posterior Skull Base Although anterior and middle skull base tumors can cause significant swallowing difficulties and impede the speed, adequacy, and efficiency of oral intake, patients can usually compensate for these deficits. However, tumors that affect the posterior skull base generally result in significantly more severe deficits and present greater challenges for rehabilitation of swallowing function. In most cases, injuries to cranial nerves IX and X occur together because both nerves exit the base of skull through the jugular foramen. Injury to cranial nerve IX impairs the pharyngeal swallowing reflex, pharyngeal contraction, and velopharyngeal competency. The pharyngeal swallowing reflex may be delayed or even absent, resulting in aspiration before or during the swallow. Neural injury will impair normal pharyngeal contraction and velopharyngeal competency that will result in pharyngeal stasis of food after the swallow and nasal regurgitation. Injury to the vagus nerve is often even more debilitating, as this nerve is responsible for several physiologic activities that work in concert with the pharyngeal trigger of swallowing. The rate of postoperative vagal nerve injuries has been reported to be as high as 50% after specific approaches (10). High vagal injuries result in the most serious problems because they affect all three branches of the nerve: the pharyngeal, superior laryngeal, and recurrent laryngeal nerves (11). Therefore, patients with high vagal injuries will have difficulty moving food through the pharynx and aspirate as a result of injury to all three branches. Impairment at any level of the nerve may result in aspiration because of decreased laryngeal sensation, impaired pharyngeal contraction, or reduced airway closure. Clinically, the superior and recurrent laryngeal branches of the vagus nerve are most important for glottic airway protection, while the pharyngeal branch ensures adequate pharyngeal contraction via innervation to the pharyngeal constrictor musculature. Insults to the superior laryngeal nerve can leave patients insensate to aspirate, caus-

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ing them to silently, without coughing or any other indication of awareness, aspirate food into the trachea. Damage to the recurrent laryngeal nerve usually results in paresis or paralysis of one or both of the true vocal cords, depending upon the level of injury, impairing glottic valving in response to the aspirate. Clinicians should be advised that patients with vagal injuries are at high risk for aspiration pneumonia, and a lack of patient reaction should not be equated with safe swallowing in this population at high risk for silent aspiration. The tongue is one of the most critical structures in the oropharyngeal swallow. Any damage, unilateral or bilateral, to cranial nerve XII, the hypoglossal nerve, affects the lingual movements critical to the manipulation and transport of food from the anterior portion of the oral cavity to the pharynx. Patients with hypoglossal nerve injuries will have difficulty maintaining a cohesive food bolus during the oral stage of swallowing for efficient transport to the oropharynx. More importantly, base of tongue retraction to the posterior pharyngeal wall propels the food through the pharynx. If this movement is impaired, a significant amount of food collects within the valleculae, resulting in swallowing that is laborious, lengthy, and inefficient. Patients may thus expend an inordinate amount of energy for little nutritional gain. In addition, these patients remain at risk for aspiration because of the food that is left in the pharynx after the swallow. Cranial nerve injury is the most common cause of dysphagia associated with skull base lesions, with reports of aspiration in as many as 75% of patients (12). The cranial nerves affected and the level of injury determine the type and severity of the swallowing disorder. Furthermore, patients with gradual tumor progression generally will demonstrate the best potential for compensation of swallowing deficits, whereas patients who experience acute insults will have more severe problems because they have not had the benefit of time to adjust to their swallowing problems (2). It is therefore critical that patients with cranial nerve dysfunction be referred to a speech-language pathologist for early identification of dysphagia to maintain oral nutrition for as long as possible and to avoid further complications in this high-risk population.

Disorders of Communication The most common disorders of communication associated with skull base lesions and their treatment are those that affect the motor aspects of speech production rather than meaning or language. Dysarthria remains the primary communication impairment in this patient population. It refers to a group of speech disorders characterized by weakness, paralysis, incoordination, sensory deprivation, and alterations in muscle tone (13). Dysarthric speech is often described as slurred and imprecise. There are six subtypes of dysarthria, each of which is distinguished on the basis of its auditory perceptual characteristics, which in turn have diagnostic implications for lesion localization (14). The ability to differentiate between these subtypes requires specialized training and experience. Therefore, it is critical that patients be referred to speech pathologists who are expert in the differential diagnosis of dysarthria to ensure accuracy in both diagnosis and treatment.

Anterior Skull Base As in swallowing, communication impairments associated with the anterior skull base are generally a function of damage to the anatomic structures. For example, maxillectomy results in a palatal defect that impairs vocal resonance, or the quality of speech, as well as the overall intelligibility of

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speech. Palatal prostheses or obturators that fill the defect and reestablish anatomic continuity are generally the best way to manage these types of problems. When mandibular defects are involved, patients experience difficulty opening and closing their mouths and producing such sounds as /b/, /p/, and /m/. It is important to note that speech impairments that result from structural damage are not considered dysarthric, as they are not neurogenic in origin. Less commonly, larger lesions of the anterior skull base that require retraction of the frontal lobes may also result in language disorders. The most common of these are aphasia and right hemisphere disorder (RHD). Aphasia that affects verbal expression, writing, auditory comprehension, and reading is generally an outcome of insult to the perisylvian cortex of the dominant hemisphere or subcortical damage to the thalamus and basal ganglia (15). In contrast, RHD is a disorder of pragmatics or the social use of language. Unlike patients with aphasia or dysarthria, patients who have RHD exhibit appropriate use of grammar and words without misarticulations of speech, but their communication is nonspecific and inefficient. These patients frequently say things that are irrelevant, disconnected, incompatible with the situation, and produced without appropriate affect (16). The impact of such deficits may appear subtle but can be devastating to interpersonal relationships.

Middle/Posterior Skull Base Communication disorders that affect both the middle and the posterior base of skull result from cranial nerve dysfunction. Primary among such disorders is flaccid dysarthria, a subtype of dysarthria characterized by weakness of the muscles responsible for speech production, occurring as a result of cranial nerve dysfunction (14). Flaccid dysarthria occurs with similar frequency in patients with middle and posterior skull base tumors, with 14% of all reported cases, including those occurring from stroke, head injury, etc., attributed to surgical procedures involving the middle and posterior skull base regions (14). When lesions involve the cerebellum, the dysarthria will present as ataxic. In contrast to flaccid dysarthria, ataxic dysarthria is characterized primarily by irregularity of articulatory movements. Ataxic dysarthria resulting from brainstem tumors accounts for 3% of all reported cases (14). Damage to any of the lower cranial nerves will result in flaccid dysarthria. The resulting speech impairments will generally be consistent; however, the most prominent feature will depend upon the specific cranial nerve(s) involved and the extent of damage, unilateral or bilateral. Even skull base surgeries that do not result in nerve resection can damage nerves. Prolonged retraction or stretching of the nerve may result in deficits that cannot be restored completely (2). The critical nerves in the lower region for speech are cranial nerves V, VII, IX, X, and XII. Another lower cranial nerve, cranial nerve VIII, is not generally considered a nerve for speech but is imperative for hearing. Therefore, damage to this nerve, which is most often a result of acoustic neuromas and other types of tumors that affect the vestibular nerve, can be traumatic to both speech and communication. This topic, however, is beyond the scope of this chapter, and the reader is referred to the literature regarding vestibular tumors and hearing for a comprehensive review. The close proximity of cranial nerves IX and X makes it difficult to discern the impact of damage to cranial nerve IX on speech production, as it is rarely damaged in isolation

(11). Likely, the effect is on both resonance and phonation, but the importance of cranial nerve IX in the assessment of dysarthria is indeterminate for practical purposes (14). The effects of damage to cranial nerve X are more complicated because of its long course and its three major branches. Hypernasality, audible nasal emission, and imprecise production of consonants that require high oral pressure are usually the result of velopharyngeal incompetence owing to damage to the pharyngeal branch of the vagus nerve. Unilateral lesions that include the superior and recurrent laryngeal branches often result in breathiness or aphonia, reduced vocal intensity, and limited pitch range. Lesions of the superior laryngeal nerve that spare the pharyngeal and recurrent branches are most often associated with an inability to change the pitch of the voice. Sometimes mild breathiness or hoarseness may also be present. Unilateral recurrent laryngeal nerve lesions resulting in impaired true vocal fold motion cause weak vocal intensity, hoarse vocal quality, problems with pitch, and sometimes diplophonia, or double sound. Bilateral damage may cause inhalatory stridor or airway obstruction, depending on the type of vocal fold paralysis, abductor or adductor. Damage to cranial nerve XII can significantly affect speech production. The overriding speech characteristic in unilateral and bilateral XII nerve lesions is imprecise articulation, specifically of sounds involving the tongue. With unilateral lesions, compensation is generally adequate to allow for speech perception. Bilateral lingual weaknesses, however, result in greater articulatory distortion because of the inability to achieve the rapid movements and precise articulatory placements required for intelligible speech production. Direct or indirect damage to the cerebellum or surrounding regions, including the cerebellar pontine angle and the dentate nucleus, frequently result in ataxic dysarthria. In contrast to flaccid dysarthria, ataxic dysarthria’s hallmark feature is irregularity. Speech characteristics can include altered prosody, prolongation of sounds, and intermittent disintegration of articulation with irregular changes in pitch and loudness. This is most commonly described as “drunken” speech (14). One of the more unusual communication disorders associated with late presentation of severe ataxic dysarthria, cerebellar mutism syndrome (CMS), occurs mainly in children, without associated cranial nerve damage or long tract signs. CMS is characterized by a transient mutism that occurs within 48 hours after resection of the cerebellar mass lesion and may last up to 6 months, followed by severe dysarthria (17,18). Speech pathology services have been shown to facilitate recovery of function in patients whose symptoms persist beyond 8 weeks (19). CMS should also be considered in adults with large cerebellar lesions or with medulloblastomas greater than 5 cm in diameter (20,21).

ASSESSMENT AND INTERVENTION FOR SWALLOWING AND COMMUNICATION DISORDERS Evaluation of swallowing and communication should be performed as early as possible in patients with pretreatment tumor-related deficits and, preferably, before treatment begins in patients who are at high risk for treatment-related dysfunction. A comprehensive evaluation should include a thorough review of the patient’s history, a patient/family interview, a neurologic screening that includes an examination of the oral mechanism, and a speech profile. Formal measures

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provide additional information for differential diagnosis and lesion localization. The results from these examinations are carefully analyzed, and an individually tailored treatment plan specific to the presenting communication and swallowing symptoms is designed.

Assessment Swallowing Clinical Assessment The clinical or bedside swallowing examination allows observation of important events in the oral stage of swallowing, including labial and lingual control, palatal function, and oral sensitivity. It affords an opportunity to observe the patient’s reactions to swallowing and to assess the impact of behaviors such as attention, impulsivity, and judgment on the ability to eat safely. Clinical swallowing examinations provide important information regarding the need for further objective swallowing assessments such as the modified barium swallow study or the fiberoptic endoscopic evaluation of swallowing. Clinical assessments of swallowing are not reliable indicators of pharyngeal physiology, and therefore, should not be used as a replacement for objective swallowing measures. Instrumental Assessment There are two main instrumental studies of swallowing, the modified barium swallow (MBS) study and the fiberoptic endoscopic evaluation of swallowing (FEES). The indications for use of each test depend upon the presenting swallowing problem and the patient’s ability to undergo a radiographic examination. Modified Barium Swallow Study Perhaps the most widely used tool to evaluate oropharyngeal swallowing is the videofluoroscopic examination, or MBS study (22,23). The MBS study is different from the standard barium swallow in that it shows the entire oropharyngeal swallow, including all four stages of swallowing. It provides information regarding all events, allowing for the diagnosis of specific swallowing disorders and causes of aspiration. A further benefit is that it gives the clinician the opportunity to attempt specific therapeutic techniques during the study to determine their ability to alleviate the swallowing deficit.

Figure 1 Aspiration on an MBS study.

agnosing speech disorders such as dysarthria. Perceptual speech characteristics provide powerful information for accurately differentiating between speech disorders. When perceptual analyses are administered and interpreted properly, they may also provide critical information to help identify specific neurologic disease processes (14). It is important to remember, however, that accurate perceptual analysis is a difficult skill to master and requires significant training, experience, and practice that few clinicians achieve. In contrast, disorders of language such as aphasia and RHD are best evaluated using standardized test measures such as the Western Aphasia Battery and the Mini Inventory of Right Brain Injury-2 (25,26). These tests rely less on perceptual, subjective judgments and more on the objective analysis and documentation of the semantic and syntactic errors that commonly occur in patients with language disorders.

Treatment In general, treatment for speech and swallowing disorders either restores function or compensates for dysfunction. Therapeutic exercises that improve the strength and coordination of the oropharyngeal musculature are important

Fiberoptic Endoscopic Evaluation of Swallowing FEES is a videoendoscopic tool that can be used at the bedside or in the clinic by a single clinician (24). It is the key assessment tool for visualization of aspiration, airway protection, and laryngeal sensation. There are two distinct disadvantages associated with FEES, however. First, visualization of the oral stage of swallowing is obstructed during FEES. Second, much of the oropharyngeal physiology of swallowing must be inferred because of the limitations of endoscopy. Figures 1 and 2 compare aspiration as evaluated via MBS and FEES.

Communication The examination of communication includes a combination of formal standardized test batteries and informal perceptual measures that are selected on the basis of the patient’s presenting problems. Informal test measures that evaluate the rate, rhythm, and precision of speech production may include the repetition of sounds in isolation, the production of rapidly sequenced syllables, and maximum phonation duration. These measures, along with examination of the oral mechanism, are the most useful tools for differentially di-

Figure 2 Aspiration on an FEES examination.

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restorative techniques for both speech and swallowing disorders. Regardless of the potential for functional improvement, compensatory strategies are always important in the treatment of speech and swallowing impairments because they provide the patient with alternative ways to maintain their normal routine in the short term while working on long-term functional improvement. Compensatory strategies become the focus of treatment when full restoration of normal function is not a realistic goal. In cases of swallowing impairment, compensatory approaches control the flow of food and eliminate the patient’s symptoms such as aspiration, but do not necessarily change the physiology of the patient’s swallow (8). Examples of such approaches include postural changes, diet modifications, special feeding techniques, and the use of intraoral prosthetic devices. Patients with communication impairments, for example dysarthria, benefit from compensatory strategies such as a slow rate of speech or the use of an alternative communication device, a picture board or a voice-generated system, to improve listener understanding and reduce frustration. Aphasic patients may employ gestures or simplify their message to compensate for their language deficits.

CASE STUDIES Case Study 1 The patient was a 55-year-old right-handed woman with a diagnosis (in 1972) of anaplastic ependymoma of the fourth ventricle. She was status post three subtotal resections as well as radiation treatment to the posterior fossa for a total of 54 Gy (in 1991). The patient was eating a regular diet including both solids and liquids. She subsequently underwent percutaneous fluoroscopic gastrostomy in November of 1995 due to persistent dysphagia and recurrent episodes of pneumonia. She presented to the speech pathology service one year later (1996) with complaints of a progressive decline in speech and swallowing. An MBS study and speech assessment were performed. Clinical assessment revealed multiple cranial nerve palsies (III, V, VII, IX, X, and XII) characterized by articulatory imprecision due to lingual weakness, hypernasality, irregular prosody, and dysphonia. Conversational speech was approximately 50% intelligible. Results revealed a moderate to severe mixed flaccid-ataxic dysarthria. The patient was taught to use compensatory speech strategies to improve intelligibility to communicate needs with family members. The results from the MBS study showed impaired lingual strength and coordination, decreased bolus formation, delayed initiation of the swallow reflex, reduced base of tongue retraction, and reduced hyolaryngeal excursion. Silent aspiration occurred before, during, and after the swallows of thin liquids. Compensatory strategies and diet modifications were unsuccessful in alleviating aspiration. Objective swallowing examination facilitated diagnosis of a moderately severe oropharyngeal dysphagia. Recommendations included omission of oral intake of liquids. Swallowing was judged adequate for other food consistencies. No further episodes of aspiration pneumonia were documented.

Case Study 2 The patient was a 59-year-old right-handed woman diagnosed with a giant left petroclival meningioma. There was no documentation of any cranial nerve impairments, dysarthria, or dysphagia at baseline reported by the neurology service.

Resection of the tumor was performed via a two-staged, left suboccipital craniotomy with placement of a right frontal ventriculostomy. A speech pathology consultation was generated postoperatively. Results revealed multiple cranial nerve impairments (IX, X, and XII). A clinical swallow evaluation revealed continual throat clearing and the use of multiple swallows while eating suggesting probable pharyngeal dysphagia and aspiration. Objective examination of swallowing via an MBS study was recommended. Findings showed delayed initiation of the swallow and an inability to propel the bolus through the pharynx because of weak pharyngeal motility. A percutaneous endoscopic gastrostomy was performed due to inability to maintain oral nutrition and hydration. The results of speech and swallowing examination revealed moderate-severe flaccid dysarthria with severe pharyngeal dysphagia. A speech and swallowing treatment plan was designed based on the findings from clinical and objective examinations and was implemented during the patient’s hospitalization. Patient and family education was provided regarding treatment objectives to ensure realistic expectations for recovery and compliance with the treatment plan. The patient continued to receive speech and swallowing services following discharge. The patient presented for reevaluation three months postdischarge. Findings showed no significant swallowing deficits. The patient was able to eat by mouth and the percutaneous endoscopic gastrostomy tube was removed. Although dysarthria improved slightly, dysphonia persisted as a result of cranial nerve X dysfunction.

CONCLUSION Patients with skull base tumors present significant diagnostic, therapeutic, and rehabilitation challenges. Because the treatment is so complex and the potential for complications so high, a strong multidisciplinary team made up of specialists from many fields who work together is needed for the patient to benefit from the unique expertise of each team member. The diagnosis of a brain tumor creates turmoil and fear in both patients and their families. In addition, the acute effects of a skull base tumor can prevent normal communication, impede the ability to eat by mouth, and severely disrupt normal patient and family interactions, the effects of which are generally overwhelming. Whether the deficits are acute or long-term, the speech pathologist plays a critical role in providing information about normal function and rehabilitation, identifying and teaching compensatory strategies to the patient and family to preserve normal communication as much as possible, and providing appropriate intervention to help maintain oral nutrition while avoiding medical complications such as aspiration. It is, therefore, important that the speech pathologist be consulted early in the patient’s course of evaluation and treatment to give the patient and the family the opportunity to ask questions and to better understand information that at first seems overpowering and frightening, thus reducing the fears and misconceptions associated with skull base tumors. Appropriate and timely referral to a speech pathologist with expertise in the rehabilitation of skull base tumor patients helps patients and their families maintain realistic expectations about their functional recovery and provide a rehabilitative plan so that optimal communication and swallowing outcomes can be achieved and the best quality of life attained.

Chapter 12: Rehabilitation of Speech and Swallowing of Patients with Tumors of the Skull Base REFERENCES 1. Yorkston KM, Miler RM, Stand EA. Management of Speech and Swallowing in Degenerative Diseases. Austin, Texas: Pro-Ed, Inc, 1995. 2. Levine TM. Swallowing disorders following skull base surgery. Otolaryngol Clin North Am. 1988;21:751–759. 3. Portnoy RK. Head and Neck Cancer. New York, NY: Plenum Press, 1995:218–231. 4. Carptenter DO. Central nervous system mechanisms in deglutition and emesis. In: Schultz SG, ed. Handbook of Physiology. Gastrointestinal System Control of Food and Water Intake. Sect 6, Vol 1. Bethesda, MD: American Physiological Society, 1989:685– 714. 5. Jean A. Brainstem control of swallowing: Localization and organization of the central pattern generator for swallowing. In: Taylor A, ed. Neurophysiology of the Jaws and Teeth. New York, NY: MacMillan, 1990:294–321. 6. Martin RE, Goodyear BG, Gati JS, et al. Cerebral cortical representation of automatic and volitional swallowing in humans. J Neurophysiol. 2001;85:938–950. 7. Bhatnagar SC. Neuroscience for the Study of Communicative Disorders. Baltimore, Maryland: Lippincott Williams & Wilkins, 2002:333. 8. Logemann JA. Evaluation and Treatment of Swallowing Disorders. 2nd ed. Austin, TX: Pro-Ed, Inc, 1998. 9. Love RJ, Webb WG. Neurology for the Speech-Language Pathologist, 3rd ed. Boston, MA: Butterworth-Heinemann, 1996. 10. Cece JA, Lawson W, Biller HF, et al. Compilation in the management of large glomus jugulare tumors. Laryngoscope. 1987;97:152–157. 11. Eibling DE, Boyd EM. Rehabilitation of lower cranial nerve deficits. Otolaryngol Clin North Am. 1997;30:865–875. 12. Jennings KS, Siroky D, Jackson CG. Swallowing problems after excision of tumors of the skull base: Diagnosis and management in 12 patients. Dysphagia. 1992;7:40–44. 13. Dworkin JP. Motor Speech Disorders: A Treatment Guide. St. Louis, Missouri: Mosby, 1991.

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14. Duffy JR. Motor Speech Disorders: Substrates, Differential Diagnosis, and Management. St. Louis, Missouri: Mosby-Year Book, Inc, 1995. 15. Rosenbek JC, LaPointe LL, Wertz RT. Aphasia: A Clinical Approach. Boston, Massachusetts: College-Hill Press, 1989:215. 16. Myers P. Right Hemisphere Damage: Disorders of Communication and Cognition. San Diego, California: Singular Publishing Group, Inc, 1999:4–5. 17. Van Dongen HR, Catsman-Berrevoets CE, Van Mourik M. The syndrome of “cerebellar” mutism and subsequent dysarthria. Neurology. 1994;44:2040–2046. 18. Pollack IF, Polinko P, Albright AL, et al. Mutism and pseudobulbar symptoms after resection of posterior fossa tumors in children: Incidence and pathophysiology. Neurosurgery. 1995;37:885–893. 19. Sherman JH, Sheehan JP, Elias JW, et al. Cerebellar mutism in adults after posterior fossa surgery: A report of 2 cases. Surg Neurol. 2005;63:476–479. 20. Catsman-Berrevoets CE, Van Dongen HR, Mulder PG, et al. Tumor type and size are high risk factors for the syndrome of “cerebellar” mutism and subsequent dysarthria. J Neurol Neurosurg Psychiatry. 1999;67:755–757. 21. Idlan F, Tuna M, Erman T, et al. The evaluation and comparison of cerebellar mutism in children and adults after posterior fossa surgery: Report of two adult cases and review of the literature. Acta Neurochir (Wien). 2002;144:463–473. 22. Logemann JA. Imaging the oropharyngeal swallow. Adm Radiology. 1993;3:20–24, 43. 23. Logemann JA. Normal Radiographic Anatomy and Physiology of the Oropharynx. In: Hyams H, ed. Manual for the Videofluoroscopic Study of Swallowing, 2nd ed.: Austin, TX: Pro-Ed, Inc, 1993. 24. Langmore SE, Schatz K, Alson N. Endoscopic and videofluoroscopic evaluations of swallowing and aspiration. Ann Otol Rhinol Larygol. 1991;100:678–681. 25. Kertz A. The Western Aphasia Battery. San Antonio, TX: The Psychological Corporation Harcourt Brace Jovanovich, Inc, 1982. 26. Pimental PA, Knight JA. Mini Inventory of Right Brain Injury (MIRBI-2). Austin, Texas: Pro-Ed, Inc, 2006.

13 Quality of Life of Patients with Skull Base Tumors Ziv Gil and Dan M. Fliss

ics related to the QOL of patients with skull base neoplasms: (1) the available instruments for estimating their QOL, (2) the impact of surgery on different aspects of patients’ QOL following skull base procedures, and (3) the means to improve the QOL of this patient population.

INTRODUCTION Quality of life (QOL) is usually defined as a construct that reflects the individual perception of overall well-being (1). There is more and more recognition of the importance of topics addressing QOL issues of patients with neoplasms. QOL is assessed in an effort to improve treatment modalities, to promote restoration of patient’s daily functioning, and to accelerate his/her return to normal life. Estimation of the influence of surgical procedures on QOL can serve as a mean by which the most appropriate surgical approach can be selected for a given patient. Detailed understanding of the different aspects of QOL may help surgeons improve assessment and management of patients, identify specific impediments as early as possible during follow-up, and apply specific medical interventions to patients with increased risk and poor outcome (1). Furthermore, early access of patients to detailed information about their disease can lead to better adjustment to an imminent medical condition. A multidimensional evaluation of QOL involves retrieving information on the physical, emotional, social, and economical aspects of the patient’s lifestyle, as well as on specific symptoms associated with the patient’s disease. Valid interpretation of the data requires generic questionnaires or disease-specific instruments, which cover the morbidity associated with the site of neoplasia and its treatment (2). The technical development of skull base surgery has had a major positive impact on the long-term survival of patients with lesions involving the anterior or lateral cranial fossa, the paranasal sinuses, and the orbits (3). Various techniques have been developed for resection of these tumors, among them are the craniofacial and subcranial approaches (frequently used for anterior skull base tumors) and the middle fossa, translabyrinthine, and infratemporal fossa approaches (for lateral skull base tumors)(4,5). These procedures may, however, carry a considerable risk as well as serious morbidity (6). Although surgical procedures and radiation therapy are crucial for the treatment of skull base neoplasms, tumor control should not be the only goal of patient care. During the last decade, numerous studies have assessed QOL issues in patients with head and neck or brain tumors (7,8) These questionnaires were directed toward cancer of the upper aerodigestive tracts or brain parenchyma, and they included items that were unrelated to anterior or lateral skull base tumor morbidity. These instruments also lacked questions on issues which are frequently encountered among patients undergoing anterior or lateral skull base procedures. An instrument which focuses on a specific disease has the advantage of increasing the chances that the information provided by the patients is uniform, and it improves responsiveness by including questions which are relevant only to the specific population being studied. This chapter focuses on three top-

Methods for Estimating Quality of Life Generic Instruments Few psychometrically valid generic instruments have been developed during the last decade for estimating the QOL of patients in general and that of oncological patients in specific. Table 1 shows a few examples of commonly used instruments for assessing QOL in the general population or in patients with neoplasia. One of the most popular among them is a short form containing 36 items, also known as the short form 36 (SF-36) questionnaire. This generic instrument was first published in 1992 and further validated worldwide and in different languages. It can be completed with the aid of an interviewer or as a self-administered questionnaire (8). The items included in the SF-36 questionnaire are divided into eight domains with overall physical and mental health component scores. These domains are physical functioning, role limitations physical, bodily pain, social functioning, general mental health, role limitations emotional, vitality and general health. One advantage of the SF-36 questionnaire is the existence of normative data and the form’s documented reliability and validity in different countries. It was used extensively for estimating the QOL of patients with acoustic neuromas (9–13). A shorter generic form is the SF-12, developed as a condensed version of the SF-36 questionnaire (14). SF-12 contains 12 items and takes half the time to complete compared to the SF-36 questionnaire (i.e., 5 and 10 minutes, respectively). Another generic instrument commonly used for estimating QOL in cancer patients is the European Organization for Research and Treatment of Cancer (EORTC) QOLQ-C30 (15,16). Similar to the SF-36, different versions of this questionnaire are available in other languages. Table 1 summarizes the advantages and disadvantages of some of the generic QOL instruments in general use.

Disease-Specific Instruments Any instrument for estimating QOL needs to cover the morbidity associated with the specific site of the tumor and to allow an accurate and sensitive description of the patient’s condition. During the last decade, numerous studies have assessed QOL issues in patients with head and neck or brain tumors (17–19). These questionnaires were directed toward cancer of the upper aerodigestive tracts and included items that were unrelated to anterior skull base tumor morbidity. Site-specific modules incorporating questions addressing disease- and treatment-specific problems have since been 189

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Table 1 Generic Instruments Name

Description

SF-36

The most commonly used instruments for estimation of QOL. Contain 36 items divided into 8 domains. Can be completed with the aid of an interviewer or as a self-administered questionnaire. A short version of the SF-36 questionnaire A self-administered instrument with 30 items. Different versions of this questionnaire are available in other languages. A generic self-administered instrument, developed for cancer patients. Contains 27 items. Multilingual translations available. One of the most widely used measures to assess quality of life. Contains 136 items and 12 subscales. Can be completed with the aid of an interviewer or as a self-administered questionnaire.

SF-12 EORTC QOLQ-C30

FACT-G

SIP30

Advantage

Disadvantage

Tested for reliability and validity. Normative data available.

Not specific for tumor patients. Lack disease-specific items.

Valid, rapid application. Tested for validity and reliability. A head and neck module available. Tested for reliability and validity, fast application.

Same as SF-36. Not validated for SB patients. Takes 30 min to complete.

Tested for reliability and validity.

Not tumor specific. Takes >30 min to complete.

Limited experience in clinical trials

Abbreviations: SF-36, short form 36; EORTC, QOLQ-C30, European organization for research and treatment of cancer and quality-of-life questionnaire; FACT-G, functional assessment of cancer therapy, general module; SIP30, sickness impact profile to assess quality of life; SB, skull base.

developed based on the EORTC QOLQ-C30 questionnaire for the head and neck. The head and neck module of the EORTC, however, includes questions on swallowing, breathing, and mastication, which are not relevant to symptoms of patients with skull base neoplasms. The absence of questions related to the specific symptoms of patients with skull base tumors limits the application of these instruments to this subpopulation of oncological patients. These instruments also lack questions on issues which are frequently encountered in patients undergoing skull base surgery. Table 2 summarizes the advantages and disadvantages of few of the available disease-specific instruments for QOL evaluation of patients with head and neck cancer. It should be borne in mind that patients with skull base tumors suffer from symptoms which are directly related to their disease. Table 3 lists some of the common symptoms associated with tumors originated in the skull base and with the postoperative morbidity frequently encountered following their extirpation. The anterior skull base surgery (ASBS) questionnaire (Table 2) was established in 2003 as the main instrument for evaluating QOL in patients with anterior skull base neoTable 2

plasms (20). The ASBS questionnaire is a disease-specific instrument based on a pooling of questions related to general QOL (SF-36; Glasgow Benefit Inventory; The Center for Epidemiologic Studies Depression Scale) and to head and neck cancer (EORTC QLQ-C30 and UW-QOL). Questions were added to this instrument in order to cover symptoms specifically associated with anterior skull base tumors and postoperative morbidity (Table 3). These questions were generated from interviews with health professionals and surgeons as well as from interviews with patients and their caregivers. They covered problems with various aspects of taste, smell, appearance, epiphora, nasal secretions, and visual disturbances, which are frequently found in this patient population. During the development of this instrument, patients were asked to rate each item for its relative importance to their own QOL. They were also asked to contribute questions that they considered as being important but that had not been included in the questionnaire. Statistical analysis identified 35 items divided into six domains of QOL: role of performance (six items), physical function (seven items), vitality (seven items), pain (three

Disease-Specific Instruments

Name

Description

Advantage

ASBS

The only disease-specific instrument developed especially for patients with tumors of the anterior skull base. A self-administered instrument with 35 items divided into 6 domains. A self-administered instrument with 21 items developed for patients with HN cancer. Based on the QLQ-C30 generic instrument. A disease-specific, self-administered instrument developed for HN cancer patients. Based on the FACT-G generic instrument. A disease-specific, self-administered instrument developed for HN cancer patients. Version 4 also includes psychological domains. A disease-specific instrument with 21 items and 4 domains. Interviewer administered

Tested for validity, reliability, and internal consistency. Available in English, Hebrew, and Portuguese. Tested for validity and reliability in HN patients.

Validated only for patients with anterior skull base tumors.

Can be coadministered with FACT-G, fast application.

Not independently validated. Not validated for SB patients.

Reliability and validity in study.

Limited coverage, useful if combined with other measures.

Reliability and validity in study.

Further validation required.

EORTC HN Module

FACT-HN

UWQOL

University of Michigan HN QOL

Disadvantage

Not validated for SB patients.

Abbreviations: EORTC, QOLQ-C30, European organization for research and treatment of cancer and quality-of-life questionnaire; FACT-G, functional assessment of cancer therapy, general module; ASBS, anterior skull base surgery; HN, head and neck; SB, skull base; UWQOL, University of Washington Quality of Life Scale.

Chapter 13: Quality of Life of Patients with Skull Base Tumors

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Table 3 Functional Disabilities as a Result of Skull Base Tumors or its Extirpation and its Effect on Quality of Life Domains Organ involved

Functional disability

Vestibulocochlear nerve Olfactory nerve ablation Optic nerve and chiasma Orbital disfunction or exenteration Facial nerve Vagus nerve Glossopharyngeal and hypoglossal nerves Maxillofacial bones Trigeminal nerve Meninges Brain parenchyma

Hearing, communication Change in appetite, olfactory and gustatory function Visual Visual

Social function, role of performance Physical functioning Physical functioning Physical functioning

Cosmetic disfigurement and visual dysfunction Speech and swallowing, aspirations, and weight loss Swallowing, aspirations, and weight loss

Social function, psychological and physical functioning Social function, physical functioning Physical functioning

Cosmetic deformity, speech and swallowing Paraesthesia, neuralgia, use of painkillers CSF leak, recurrent meningitis Personality changes, mental impairment

Social function, psychological and physical functioning Pain, psychological functioning, role of performance Pain, psychological functioning, role of performance Social function, psychological and physical functioning, role of performance

items), influence upon emotions (five items), and specific symptoms (seven items). Table 4 summarizes the different QOL domains and items included in the ASBS questionnaire. An established approach for validating an instrument of this type is to examine its construct validity, which means testing whether specific clinical variables (i.e., clinical measures of disease severity) agree with the QOL domain score as hypothesized. Alternatively, construct validity estimates the ability of the instrument to differentiate between patient groups considered as having different health status. For example, it is expected that older patients will show significantly poorer scores relative to younger patients in physical function domains. Similarly, patients with malignant lesions undergoing adjuvant radiation therapy may have poorer scores than patients with benign lesions. Construct validity of the ASBS questionnaire was assessed by testing whether the clinical variable of the patient did influence the QOL domain score as hypothesized. The results showed that patients >60 years of age had signifi-

Table 4

Affected QOL domain

cantly poorer scores in the role of performance and physical function domains than younger patients. Also, patients with malignant tumors had significantly poorer scores in the domains of specific symptoms, influence upon emotions, physical function, and role of performance compared to patients with benign tumors (Fig. 1). Radiotherapy was associated with poorer scores in the domains of specific symptoms and influence upon emotions, and comorbidity was associated with poor physical function scores. The sensitivity of the instrument to changes over time was tested by comparing the scores of patients operated 3–6, 6–24, and >24 months before the study was activated. Using this approach, a gradual improvement in QOL measures was found during the first 6–24 months after surgery. A similar change in QOL measures after skull base surgery was found by De Jesus et al. (19) for meningiomas involving the cavernous sinus. A recent prospective study further established the ASBS questionnaire as the main instrument for evaluating QOL of patients with anterior skull base tumors

Studies Estimating Quality of Life (QOL) of Patients with Skull Base Tumors

Study

Tumor

Questionnaire

Gil et al. (20)

ASB

ASBS

Fukuda et al. (21)

ASB

NA

Mohsenipour et al. (22)

Meningioma

IHD and NHP

Lang et al. (23)

Meningioma

GOS, SF-36

Nikolopoulos et al. (18) Tufarelli et al. (24)

AS AS

GBI SF-36 and DHI

de Cruz et al. (25) Baumann et al. (26) Irving et al. (16) Myrseth et al. (11)

AS AS AS AS

SF-36 SF-36 EORTC, QOLQ-C30 GBI and SF-36

Sandooram et al. (27)

AS

GBI

Martin et al. (28)

AS

SF-36

Main finding 38% had a significant improvement and 36% reported no change in QOL after surgery 89% had some complaints and 63% reported worsened QOL after surgery 60% had mild-to-moderate impairment and 20% had moderate-to-severe impairment of their QOL 76% had good-to-moderate recovery 1 yr after surgery, but most of the patients were still functioning below accepted norms >53% of patients reported an overall decline in QOL QOL scores were lower than in the general population. Significant deterioration in elderly patients. Reduced QOL scores relative to a matched healthy population. Significant reductions in QOL compared to norms. Excellent QOL after resection of acoustic schwannomas 1.5 cm. QOL significantly better in the radiosurgery group than in the microsurgery group. Conservative management was associated with a better QOL compared with radiosurgery or microsurgery QOL was rated significantly below published norms. The physical functioning, vitality, and social functioning were reduced.

Abbreviations: ASBS, anterior skull base surgery; AS, acoustic schwannoma; NA, not applicable; IHD(NS), Innsbruck Health Dimensions Questionnaire for Neurosurgical Patients; GBI, Glasgow benefit inventory; DHI, Dizziness Handicap Inventory; NHP, Nottingham Health Profile; GOS, Glasgow Outcome Score; EORTC, QOLQ-C30, European organization for research and treatment of cancer quality of life questionnaire.

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Age

Radiotherapy

Role of performance

A

3.0

Role of performance

B

>60

Yes

3.0

<60

No

2.8

2.2

2. 4

2. 2

2. 2 2.4

2.4

2.8

2.6

2.6 2 .8 3 .0

3.0

Vitality

2.6

2 .8

3.0

2 .6

2. 8

2.4

2. 2

2.2

2 .4

2. 6

2.4

3.0

Specific symptoms

2.4

2. 8

2.6

2. 2

2. 6

2.8

2. 2

2 .4

3 .0

2. 4

2.4

2.2

2. 2

Vitality

2.6 2.8

2.8

3.0

3.0

Pain

Pain

Type of surgery

Comorbidity

Role of performance

C

Role of performance

D

Wide resection

3.0

Yes

3.0

Limited resection

No

2.8

2.8

Vitality

2. 8 2.6 2.4

2.2 2.4 2. 6

2.4

3 .0

2.8

2.6

2.2

2 .2

2.6

2 .8

3. 0

3 .0

2.8

2.4

2.2 2.4 2.6

2 .2

2.6

2. 4

2.4

3 .0

2.6

2. 2

2. 8

Specific symptoms

2.2

2. 8

2.4

2. 6

Vitality

Physical function

2.2

2.2

2.4

2. 8

2.4

2. 2

3 .0

2.6 2.6

3.0

2 .8

2.4

Specific symptoms

Role emotional

2 .2

2.2

2. 6

2.4

Physical function

3. 0

3 .0

2.6

2.8

Role emotional

Physical function

2 .6

2.4

2.2

3 .0

2.6

2 .2

Specific symptoms

Role emotional

2. 8

2. 8 2. 6

2.4 2.2

Physical function

3.0

2.6

3. 0

Role emotional

2.8

2.8 3.0

3.0

Pain

Pain

Figure 1 Polar graphs of QOL questionnaire scores distributed to demographic and clinical variants. Each graph (A–D) shows the average scores of six specific QOL domains represented by each axis. A higher score indicates a better QOL. The effect of (A) age (below or above 60 years), (B) radiotherapy, (C) type of surgery, and (D) patients’ comorbidity on different QOL measures are shown. Source: From Ref. 20.

and demonstrated its ability to distinguish between different patients at a given point of time from surgery (20). The complete questionnaire is found in the Appendix of this chapter. Health-related QOL questionnaires can be selfadministered or completed with the assistance of a trained interviewer. Although an interviewer-administered mode is resource intensive, it ensures compliance and decreases errors and the number of missing items due to misunderstanding.

QUALITY OF LIFE OF PATIENTS WITH SKULL BASE TUMORS Patients with Anterior Skull Base Tumors Surgical procedures for resection of neoplasms of the skull base can carry significant morbidity. Previous studies have shown that up to 44% of these patients may suffer from anosmia as a result of tumor resection (6). Other significant complications that may influence the functional outcome of patients are hearing loss, meningitis, cerebrospinal fluid leak,

Chapter 13: Quality of Life of Patients with Skull Base Tumors

Overall QOL

50

A

40 30

B

40 30 20

10

10

0

0 Worse

Same

Worse

Better

Financial status

60

C

Same

Better

Impact upon emotions

60

D

Patients (%)

Patients (%)

50

20

50

Social activity

60

Patients (%)

Patients (%)

60

193

40 30 20

50 40 30 20

10

10

0 Worse

Same

Better

Worse

Same

Better

Figure 2 The effect of surgery on different quality-of-life measures. (A) Overall quality of life. (B) Social activity. (C) Financial status. (D) Emotional state. Source: From Ref. 20.

osteoradionecrosis, fistula, mucocele, and visual disturbances (Table 3). In an early study, Janecka et al. used the Karnofsky performance score to evaluate the effect of cranial base surgery on patients’ QOL (20). They showed that 83% of these patients had improved or unchanged scores after surgery. Recently, the long-term QOL of patients undergoing anterior skull base tumor resection was assessed using a diseasespecific instrument (20,29–31). Figure 2 displays the mean change in QOL after anterior skull base tumor extirpation. The results found by Gil et al. showed that 38% of the patients reported a significant improvement in overall QOL and that 36% reported no change in QOL after surgical removal of their tumor (20). The minority of patients (26%) responded that the surgical procedure worsened their QOL. The scores of the social, financial, and emotional state domains were lower relative to the overall QOL score. The mean physical function score of patients younger than 60 years was significantly higher than that of older patients (Fig. 1). Patients with benign tumors reported higher scores in the domains of role of performance, physical function, specific symptoms, and impact upon emotions than patients with malignant tumors. Interestingly, both groups reported only a minor influence of the aspect of pain on their QOL. Perioperative radiotherapy was associated with significantly lower scores in the domains of specific symptoms and impact upon emotions. Extensive cranial resection was also associated with lower scores in the impact upon emotions domain. As expected, patients with an additional illness reported lower scores of QOL in the physical function domain.

Other aspects of QOL are the length of recovery after surgery and the stability of scores over time. The retrieved data showed improvement in QOL measures at 6 to 24 months following surgery compared to the 3 to 6 months following surgery and stability of the scores occurring >6 months postoperatively (Fig. 3). The overall results of this study showed that resections of tumors of the anterior skull base have a positive impact on the patients’ QOL. The relatively good scores recorded for the role of performance, pain, and specific symptoms domains further demonstrate this positive impact of surgery on different aspects of QOL. Another study on patients with anterior skull base tumors was performed by Fukuda et al. (21). In their study, the authors evaluated 13 patients who underwent classical craniofacial resection of malignant tumors: 12 patients had some complaints, and 8 of them reported that their QOL worsened after surgery. Mohsenipour et al. (22) recently showed that the majority of patients after meningioma resection had mild-tomoderate impairment of QOL, and that there was severe impairment in the physical handicap and energy level domains. Similar results were reported for meningiomas involving the cavernous sinus (19). In another study that looked at the outcome of 105 patients after excision of petroclival meningioma in which a standard lateral skull base approach was used (23), 76% of the patients reported good-to-moderate recovery at 1 year postoperatively, but 39–72% of these patients were still functioning below accepted norms.

Mean QOL score

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4.0 3.5 3.0 2.5 2.0

0.0

6.0

12.0

Time after surgery (months) Figure 3 Estimating the recovery period and stability of QOL measures before and after anterior skull base tumor resection. The average score of the overall health-related QOL before surgery and at 6 and 12 months afterward is shown. Bars indicate ±SEM.

Studies on patients with malignant intracranial tumors have demonstrated severely deteriorating QOL measures, with marked decline in cognitive, physical, emotional, and social functioning after surgery (32). The stability of QOL following surgery is an important issue of patients’ QOL and recovery. A dynamic evaluation of QOL after ASBS and excision of meningiomas involving the cavernous sinus showed a gradual improvement of QOL measures during the first year after surgery and stability of scores during the second year (33) Gradual deterioration of QOL, however, was observed during the postoperative period in patients with intracranial malignancy. Old age was associated with a negative impact on health-related QOL, following resection of anterior skull base tumors or cavernous sinus meningiomas (19,20). In contrast, young patients after excision of acoustic neuromas had a worse overall QOL and financial status compared to old ones (18). The discrepancy between these pathologies may stem from the fact that young patients with acoustic neuromas had a good preoperative QOL compared to young patients with anterior skull base tumors who invariably suffered from serious symptoms prior to surgery. It can be also presumed that younger patients cope better with anterior skull base neoplasms and surgery than do older patients with similar conditions. Perioperative radiotherapy was also found to predict poor QOL scores, especially in the specific symptoms and emotional functioning domains. Radiation therapy is used for patients with malignant tumors, and both factors in combination probably contributed to the deteriorating emotional states of these patients. Similar impacts on the patient’s overall QOL and emotional state were found in patients receiving radiation therapy for head and neck cancer (34) or other neoplasms (35).

Patients with Acoustic Schwannoma Estimation of health-related QOL is particularly important in patients with acoustic schwannoma. Nikolopoulos et al. (18) used the Glasgow Benefit Inventory for evaluating the patient’s QOL after resection of acoustic schwannoma and showed that more than 53% of their 53 patients reported an overall decline in QOL. They also showed that 29% of

their patients had declined financial status as a consequence of the operation. Tufarelli et al. (24) used both the SF-36 and the Dizziness Handicap Inventory and found significant deterioration of QOL among females and patients >45 years. Similar results were reported by de Cruz et al. (25) for the translabyrinthine and retrosigmoid approaches and by Baumann et al. (26) for the middle cranial fossa approach. In contrast, Irving et al. (16) used the EORTC generic instrument to show an excellent QOL after resection of acoustic schwannomas, especially for tumors smaller than 1.5 cm. An interesting study performed by Myrseth et al. (11) evaluated the QOL of patients treated for unilateral vestibular schwannoma either by microsurgery or by gamma knife radiosurgery. The QOL, posttreatment facial nerve function, and hearing were significantly better in the radiosurgery group. Improved QOL scores have been associated with better facial nerve and hearing function. In contrast, Sandooram et al. (27) suggested that a conservative management approach is associated with a better QOL outcome compared with both radiosurgery and microsurgery. In the largest study performed to date, Ryzenman et al. (36) used a disease-specific questionnaire and demonstrated that low QOL scores were specifically associated with postoperative headache symptoms after excision of schwannomas. Similar result was reported by Betchen et al. (37) using generic instruments. A negative impact of surgery on patients with acoustic schwannomas is expected since the preoperative healthrelated QOL is hardly affected by their clinical condition, especially when the tumors are small. In contrast, patients with anterior skull base tumors present with major debilitating symptoms, such as nasal obstruction and secretion, diplopia, epiphora, epistaxis, headache, visual disturbances, and facial deformities. Most of these symptoms are relieved following tumor extirpation, so it can be expected that the patients will experience some degree of improvement in their QOL following surgery. Table 5 summarizes the published data on the QOL of patients with skull base tumors of the anterior or lateral fossa.

Assessment of Quality of Life by Proxy Evaluation of QOL involves retrieving information on the physical, emotional, social, and economical aspects of patients’ activities of daily living, as well as on specific symptoms associated with their disease. Who should measure the QOL of patients? The primary source of information on a patient’s QOL is undoubtedly the patient himself. Proxy assessment of QOL may, however, be important as an adjunct to patients’ rating for several reasons: (1) it improves compliance and allows more accurate evaluation of patients’ conditions, especially for those whose medical conditions are poor; (2) it allows proper evaluation of patients with neuropsychologic dysfunction, who may be incapable of providing QOL information themselves; and (3) it serves as complementary data to increase score reliability and prevent potential bias. As mentioned earlier, previous works had focused on the subjective perception of QOL by the patient alone, but lay caregivers and health professionals can also play an important role in the rehabilitation and day-to-day care of patients both before and after surgery. The perception of a patient’s condition by the surgeon and caregiver is particularly important following complex surgeries that bear significant morbidity for which multidisciplinary medical treatment and rehabilitation efforts are required for long periods of time. The evaluation of QOL in patients with anterior skull base tumors is particularly challenging for several reasons.

Chapter 13: Quality of Life of Patients with Skull Base Tumors Table 5

Summary of Domain Questions in the ASBS QOL Questionnaire

Role of performance General performance Performance at work Performance at home Participation in social activities Communication with people Effect of health on performance Physical functioning Climbing stairs Leaning and standing Walking long distances Walking short distances Preferring to stay in bed Carrying out routine activities Reducing extent of physical activity because of disease Vitality Feeling weak Feeling tired Achieving goals Feeling enthusiastic Feeling motivated Feeling energetic Relationships with spouse Pain Experiencing pain Effect of pain on activity Use of painkillers Specific symptoms Change in appetite Altered sense of taste Altered sense of smell Altered appearance Nasal secretions Eye secretions Affect of surgery on vision Impact upon emotions Feeling tense Problems falling asleep Feeling worried or frustrated Feeling relaxed and calm Worrying about finances

195

showed a trend to overrate patients’ QOL, and only caregivers of patients over 60 years of age reported scores similar to that of the patient. Interestingly, patients’ with recurrent disease had the strongest agreement with their caregivers (r = 0.94). The general cross−correlation between caregivers and patients reporting is displayed in Figures 4 and 5. While the caregiver reported similar scores as the patient, the operating surgeon tended to overrate his patients’ QOL. Gil et al. showed that the surgeon’s perception of his patient’s QOL is not sufficiently accurate to correctly estimate the patients’ true QOL (30). The authors concluded that these judgments should come from the patient or his caregiver. Similar results were reported on outpatient oncological patients (40), patients with head and neck cancer (14), and patients with malignant brain tumors (41). Examination of the surgeon–patient agreement at both the group and the individual levels revealed overrating of patients’ QOL by the surgeon (30). This finding confirmed those of other studies that examined whether a physician or a health professional can make a valid assessment of his patients’ QOL (39,42). Similar studies on the perception of cancer-related fatigue also showed close agreement between patient and caregiver scoring, whereas there was a weaker correlation between patient and oncologist rating (43). In essence, the surgeon apparently believes that the patient has a better QOL than what the patient himself perceives. The surgeon’s perception of patients’ QOL is not sufficiently accurate for judging the physical, emotional, social, and economical status of his patients, and this suggests that health-care professionals need to work with patients and caregivers simultaneously to facilitate communication and discussion about expectations and choice of medical treatment. An original study by Lang et al. (29) estimated the influence of transpetrosal excision of petroclival meningiomas on the QOL of the patient’s caregiver. They found that more than one-half of the caregivers reported negative change in their lifestyle and more than one-third experienced a major decline in their work. They concluded that skull base procedures can not only affect the patient’s QOL but that they can also significantly increase the burden on the patient’s caregiver.

How Can We Improve Patients’ QOL? First, many of these patients have intracranial extension of their tumor (i.e., the patients are prone to brain injury during surgery and subsequently to cognitive dysfunction). Second, their medical treatment requires extensive surgical intervention, prolonged hospitalization, and long period of rehabilitation. Finally, many of these patients require multiple surgeries. All these factors taken together may eventually lead to problems with the accuracy of patients’ self-reporting. Little is known about the perceptions of QOL following a major head and neck surgery among cancer patients, their families, and the operating surgeon. The prevailing opinion of the limited ability of caregivers and oncologists to correctly assess patients’ QOL was challenged by recent studies, which found a good agreement between patient and proxy rating (30,38,39), that performed a triple survey in an effort to elucidate the lay caregivers’ and surgeons’ perception of patients’ QOL. An overall significant agreement was found between patients’ and caregivers’ scores, both at the group level (mean scores of each domain) and individual level (each patient’s pair). There was a minor correlation in the influence upon emotions domain and no correlation in the pain domain. Interestingly, they found no correlation between the surgeons’ and the patients’ ratings. In general, the caregivers

As physicians, we are trained to give our patients optimal treatment for achieving the highest survival rate with the least possible morbidity and mortality. Managing patients’ QOL is often forgotten in the shadow of providing the possibility for a cure. While increasing efforts have been made during the last 100 years to develop new surgical approaches and novel adjuvant modalities for the treatment of cancer, little progress has been made in developing new techniques for improving patients’ QOL. Extensive procedures involving extirpation of skull base tumors may be associated with high morbidity rates, thus having a negative impact on QOL. Earlier in this chapter, a review of the published data on QOL of patients with skull base tumors revealed that most patients with anterior skull base neoplasms show similar or better QOL scores following surgery with or without radiation. In contrast, most patients with acoustic schwannomas show deterioration of their QOL as a result of any clinical intervention (i.e., surgery or radiosurgery).

Control of Pain Few papers have assessed the level of chronic pain in head and neck cancer patients (44–49). In a recent study, the level of pain in 100 patients scheduled for oncological head and neck surgery was assessed prior to their operation, and only 10%

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Patient Caregiver 3.0

Mean score

2.8

2.6

2.4

2.2

2.0 >60 Malignant Benign No

Average <60

Age

Tumor

Yes

Radiation

No

Yes

Comorbidity

Figure 4 Demographic and clinical influence on patient-proxy scores. Mean scores of patients’ ratings (red bars) and caregivers’ ratings (green bars) of patients’ QOL. In general, caregivers reported higher scores than the patients themselves.

Specific symptoms 4.5 4.0 3.5

Health giver score

3.0 2.5 2.0 1.5 r = 0.71 1.0

p < 0.0001

0.5 0.0 0.0

0.5

1.0

1.5

2.0

2.5

3.0

3.5

4.0

4.5

Patient score

Figure 5 Relationship between patients’ ratings (x-axis) and caregivers’ ratings (y-axis) of patients’ health-related quality of life (QOL). Each point represents one patient–caregiver pair. Some of the points overlap. The graph shows the mean score of all QOL domains. The correlation coefficient r and statistical significance p are marked in the right bottom corner of each graph. The red line is the best-fit straight line to the measured points. The dashed green lines depict the 95% confidence intervals. Source: From Ref. 30.

of them reported that they were suffering from a significant level of pain as a result of their disease (50). One-half of the patients who were suffering from significant levels of pain had craniofacial tumors. Chaplin et al. (44) also reported that 8% of their patients suffered from severe pain prior to surgery and noted that the highest level of pain was among patients suffering from tumors originating in the nasopharynx. How can we improve patients’ QOL after resection of skull base tumors? One way to positively affect their postoperative QOL involves pain control. Skull base procedures are associated with a considerable level of pain during the early postoperative period (51). Numerous studies have assessed pain issues in oncological patients during the last decade (44), but the levels of pain following head and neck surgery in general and craniofacial or skull base procedures in particular have not been systematically evaluated. While many analgesic regimens are available [e.g., pro re nata (PRN), scheduled dosing, intravenous patient-controlled intravenous analgesia , little is known about the optimal therapeutic modality for the treatment of acute postoperative pain after head and neck procedures. In a multidepartmental survey of acute pain level measured following surgery, the neurosurgicaland craniofacial-related pain was rated 5 and 7 of 11, respectively, coming after orthopedic, abdominal, gynecologic, and urologic procedures and preceding plastic, ophthalmologic, vascular, and oral procedures (51). In a recent study, Gil et al. (50) estimated the level of pain following skull base surgery and used their data to tailor a specific pain-control protocol specific to each procedure. The overall results of that study showed that a PRN protocol is not adequate for the management of pain following skull base and maxillofacial procedures. Based on their findings, the authors suggest treating patients undergoing maxillofacial procedures with IV-PCA during days 1 to 3 and then with scheduled nonsteroidal anti-inflammatory drugs (NSAIDs), regardless of whether the patient complains of pain. The new regimen

Chapter 13: Quality of Life of Patients with Skull Base Tumors

showed a sharp reduction in the level of pain during the postoperative period among this subpopulation of patients. Patients scheduled for skull base procedures also suffered a moderate degree of pain shortly after surgery, unlike patients undergoing maxillofacial osteotomies; however, these patients reported a slow reduction in the level of pain (t0.5 = 6 days). Patients undergoing skull base procedures most frequently required continuous drainage of cerebrospinal fluid due to violation of the dura during surgery, and this mandates bed rest for 5 days until the drain is removed (52). These patients complained mainly of musculoskeletal and back pain as a result of lying in a supine position for a prolonged period of time. The authors recommended NSAIDs for these patients whether or not they requested painkillers. Patients after intracranial and skull base procedures are at risk for developing severe intracranial complications, such as meningitis, tension pneumocephalus, and hemorrhage. Treatment of pain with a non-opiate analgesic allows close monitoring of the patient’s neurological and mental conditions. It was therefore preferred to administer tramadol PRN as an adjuvant pain control, since this drug does not cause much sedation. NSAIDs have analgesic properties that are associated with opioid-sparing options and few side effects, and adequate postoperative analgesia may be provided by the routine administration of these drugs (53). Furthermore, because these drugs do not induce respiratory depression or sedation, their administration may facilitate less intensive postoperative monitoring and allow close neurological follow-up after intracranial procedures. In addition, NSAIDs do not require sophisticated delivery mechanisms. If administered at regular intervals, regardless of whether or not the patient requested pain relievers, NSAIDs can decrease patient dependence on opioids with satisfactory results.

A Multidisciplinary Team Approach In an effort to provide effective and efficient care to patients with chronic health conditions, the U.S. health-care system is in the process of redesigning its delivery system. One approach to meet the high demands of patients and to best utilize resources is the use of a multidisciplinary team approach to provide better care, compared to an individual patient–physician care protocol. When properly implemented, this team approach provides positive measurable outcomes. With a diverse group of health-care professionals, such as physicians, nurses, pharmacists, dietitians, and health educators with the patient at the center, the team can ensure that treatment goals are maintained for chronic diseases. The team approach can enhance patient satisfaction and self-management, development of a community support network, team coordination, team communication, patient follow-up, use of protocols and other tools, use of computerized information systems, and outcome evaluations. A multidisciplinary team can provide more comprehensive care than an individual patient–surgeon approach and so enhance the patient’s QOL. The management scheme should also include patient satisfaction and QOL questionnaires, self-management brochures, employment of a community support network, team coordination, team communication, scheduled follow-up, use of database information systems, and outcome measures. Paramedical support should involve practical, informational, and emotional support. Screening patients for psychosocial distress can be conducted quickly and is important to identify patients requiring additional interventions. Based on previous reports, the most influential factor on the QOL of patients with skull base tumors was malignancy, a factor that led to a signifi-

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cant decrease in the overall score (20). Radiotherapy, old age, comorbidity, and wide resection also significantly worsened QOL scores of specific domains (20). The main effort to improve QOL should focus on this subpopulation of patients who are prone to suffer significant impairment of their QOL. Psychosocial barriers and family issues are also key factors in determining QOL. The role of the health-care professionals who are part of the multidisciplinary team involves not only providing medical follow-up and treating short-term complications as a result of surgical or adjuvant therapy, but also supervising appropriate monitoring of long-term complications for early detection of depression or financial problems. Sources of assistance can be accessed by telephone, e-mail, and dedicated web pages, and they can include support groups, specialists who answer questions online and weblogs. (blogs).

Psychotherapy, Antidepressants and Group Support Up to two-thirds of patients with cancer may suffer from depression, with half of them having at least one episode of major depression (54). Pharmacological treatment was shown to induce significant improvement in depression symptoms compared to baseline within 6 weeks after administration antidepressant therapy (55,56). Psychotherapeutic cognitive and behavioral therapies were found to have an impact on the level of depression and symptoms in patients with cancer, and combined behavioral and pharmacological therapies were shown to even further reduce the level of depression in these patients (57,58). Psychological intervention by means of group support has been shown not only to increase QOL but also to provide survival benefit for patients with metastatic carcinoma of breast (59). Other studies have established the benefit of psychological group support in patients with other malignancies, including malignant melanoma, hematologic malignancies, and gastrointestinal cancers (60,61) In contrast, one recent randomized trial of group support failed to show any impact on health-related QOL (62). A module of psychological group support can include 5 to 10 patients with similar disease conditions and two leaders. The leaders should include one member of the surgical team and one member of the nursing team, along with a psychiatrist, a psychologist, or a social worker who are experienced in leading group support therapy (63). Group support may include discussions on relationships with family, friends, and the health caregivers; the effect of the disease on patient’s dayto-day life; and past/future treatment modalities. Another way of decreasing patients’ distress is by introduction to and discussion with cancer survivors who had been treated by the same multidisciplinary team. Patients may also be trained to practice relaxation exercises during each seminar and at home with or without the aid of a spouse or health caregiver. Finally, a web-based social support group can also be effective in reducing depressive symptoms in cancer patients (64).

CONCLUSIONS The overall QOL in the majority of patients after anterior skull base tumor extirpation can be classified as “good,” with significant improvement taking place within 6 months following surgery. Patients with acoustic schwannomas suffer from significant deterioration in their QOL after any intervention, including both surgery and radiosurgery. Data retrieved from specially designed questionnaires revealed that the financial and emotional QOL domains had the worse impact on

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the patients. Old age, malignancy, comorbidity, radiotherapy, and extensive surgery were found to be negative prognostic factors for QOL measures. Pain control regimens, antidepressants and other psychological modalities, including group support, can improve QOL measures in these patients. A multidisciplinary team approach emerged as being the best intervention modality for enhancing the health-related and overall QOL of patients with skull base tumors.

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21. Fukuda K, Saeki N, Mine S, et al. Evaluation of outcome and QOL in patients with craniofacial resection for malignant tumors involving the anterior skull base. Neurol Res. 2000;22:545–550. 22. Mohsenipour I, Deusch E, Gabl M, et al. Quality of life in patients after meningioma resection. Acta Neurochir (Wien). 2001;143:547–553. 23. Lang DA, Neil-Dwyer G, Garfield J. Outcome after complex neurosurgery: The caregiver’s burden is forgotten. J Neurosurg. 1999;91:359–363. 24. Tufarelli D, Meli A, Alesii A, et al. Quality of life after acoustic neuroma surgery. Otol Neurotol. 2006;27:403–409. 25. da Cruz MJ, Moffat DA, Hardy DG. Postoperative quality of life in vestibular schwannoma patients measured by the SF36 Health Questionnaire. Laryngoscope. 2000;110:151–155. 26. Baumann I, Polligkeit J, Blumenstock G, et al. Quality of life after unilateral acoustic neuroma surgery via middle cranial fossa approach. Acta Otolaryngol. 2005;125:585–591. 27. Sandooram D, Grunfeld EA, McKinney C, et al. Quality of life following microsurgery, radiosurgery and conservative management for unilateral vestibular schwannoma. Clin Otolaryngol Allied Sci. 2004;29:621–627. 28. Martin HC, Sethi J, Lang D, et al. Patient-assessed outcomes after excision of acoustic neuroma: Postoperative symptoms and quality of life. J Neurosurg. 2001;94:211–216. 29. Abergel A, Gil Z, Spektor S, et al. Quality of life following anterior skull base surgery. Harefuah. 2004;143:489–493. 30. Gil Z, Abergel A, Spektor S, et al. Patient, caregiver, and surgeon perceptions of quality of life following anterior skull base surgery. Arch Otolaryngol Head Neck Surg. 2004;130:1276–1281. 31. Gil Z, Abergel A, Spektor S, et al. Development of a cancerspecific anterior skull base quality-of-life questionnaire. J Neurosurg. 2004;100(5):813–819. 32. Osoba D, Aaronson NK, Muller M, et al. Effect of neurological dysfunction on health-related quality of life in patients with highgrade glioma. J Neurooncol. 1997;34:263–278. 33. Gil Z, Abergel A, Fliss DM. Quality of Life in Patients with Anterior Skull Base Tumors: A prospective study. Phoenix, AZ: North American Skull Base Society, 2006. 34. Shah S, Har-El G, Rosenfeld RM. Short-term and long-term quality of life after neck dissection. Head Neck. 2001;23:954–961. 35. Chandra PS, Chaturvedi SK, Channabasavanna SM, et al. Psychological well-being among cancer patients receiving radiotherapy–a prospective study. Qual Life Res. 1998;7:495–500. 36. Ryzenman JM, Pensak ML, Tew JM Jr. Headache: A quality of life analysis in a cohort of 1,657 patients undergoing acoustic neuroma surgery, results from the acoustic neuroma association. Laryngoscope. 2005;115:703–711. 37. Betchen SA, Walsh J, Post KD. Self-assessed quality of life after acoustic neuroma surgery. J Neurosurg. 2003;99:818–823. 38. Sneeuw KC, Aaronson NK, Osoba D, et al. The use of significant others as proxy raters of the quality of life of patients with brain cancer. Med Care. 1997;35:490–506. 39. Deschler DG, Walsh KA, Friedman S, et al. Quality of life assessment in patients undergoing head and neck surgery as evaluated by lay caregivers. Laryngoscope. 1999;109:42–46. 40. Kurtz ME, Kurtz JC, Given CC, et al. Concordance of cancer patient and caregiver symptom reports. Cancer Pract. 1996;4:185– 190. 41. Hahn CA, Dunn RH, Logue PE, et al. Prospective study of neuropsychologic testing and quality-of-life assessment of adults with primary malignant brain tumors. Int J Radiat Oncol Biol Phys. 2003;55:992–999. 42. Yeager KA, Miaskowski C, Dibble SL, et al. Differences in pain knowledge and perception of the pain experience between outpatients with cancer and their family caregivers. Oncol Nurs Forum. 1995;22:1235–1241. 43. Vogelzang NJ, Breitbart W, Cella D, et al. Patient, caregiver, and oncologist perceptions of cancer-related fatigue: Results of a tripart assessment survey. The Fatigue Coalition. Semin Hematol. 1997;34:4–12. 44. Chaplin JM, Morton RP. A prospective, longitudinal study of pain in head and neck cancer patients. Head Neck. 1999;21:531– 537.

Chapter 13: Quality of Life of Patients with Skull Base Tumors 45. Olsen KD, Creagan ET. Pain management in advanced carcinoma of the head and neck. Am J Otolaryngol. 1991;12:154–160. 46. Vecht CJ, Hoff AM, Kansen PJ, et al. Types and causes of pain in cancer of the head and neck. Cancer. 1992;70:178–184. 47. Grond S, Zech D, Lynch J, et al. Validation of World Health Organization guidelines for pain relief in head and neck cancer. A prospective study. Ann Otol Rhinol Laryngol. 1993;102:342– 348. 48. Carrol EN, Fine E, Ruff RL, et al. A four-drug pain regimen for head and neck cancers. Laryngoscope. 1994;104:694–700. 49. Keefe FJ, Manuel G, Brantley A, et al. Pain in the head and neck cancer patient changes over treatment. Head Neck Surg. 1986;8:169–176. 50. Gil Z, Smith DB, Marouani N, et al. Treatment of pain after head and neck surgeries: Control of acute pain after head and neck oncological surgeries. Otolaryngol Head Neck Surg. 2006;135:182– 188. 51. Bardiau FM, Taviaux NF, Albert A, et al. An intervention study to enhance postoperative pain management. Anesth Analg. 2003;96:179–185. 52. Gil Z, Cohen JT, Spektor S, et al. Anterior skull base surgery without prophylactic airway diversion procedures. Otolaryngol Head Neck Surg. 2003;128:681–685. 53. Shapiro A, Zohar E, Hoppenstein D, et al. A comparison of three techniques for acute postoperative pain control following major abdominal surgery. J Clin Anesth. 2003;15:345–350. 54. Massie MJ. Prevalence of depression in patients with cancer. J Natl Cancer Inst Monogr. 2004;2004(32):57–71. 55. Razavi D, Allilaire JF, Smith M, et al. The effect of fluoxetine on anxiety and depression symptoms in cancer patients. Acta Psychiatr Scand. 1996;94:205–210.

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14 Neurocognitive Assessment of Patients with Tumors of the Skull Base Mariana Witgert and Tracy Veramonti

INTRODUCTION

Pretreatment Studies Evidence of pretreatment cognitive impairment for at least some patients with skull base tumors has been documented. Meyers and colleagues (2000) (1) reported on a subset of nine patients with nasopharyngeal carcinoma who underwent neuropsychological evaluation prior to receiving paranasal sinus radiation. Although this small group, as a whole, performed better than patients who had previously undergone radiation, several patients did exhibit abnormal performance on objective measures of neurocognitive functioning prior to treatment. The authors noted that the presence of such pretreatment deficits may increase a patient’s vulnerability to adverse cognitive effects of radiation treatment. In a larger series of 28 patients with nasopharyngeal carcinoma who were evaluated prior to radiation therapy, neuropsychological test findings suggested impaired performance on measures of visuospatial reasoning (5). Additional evidence of pretreatment cognitive impairment was reported by Steinvorth et al. (2003) (6) in a study of 40 patients with skull base meningiomas. Pretreatment neuropsychological evaluation in these patients was notable for overall low average functioning, especially decreased information processing speed.

While neurocognitive symptoms are expected and often herald the diagnosis when patients present with intracerebral malignancies, patients with tumors of the skull base are also at inherent risk for development of neurocognitive symptoms, secondary to impingement and pressure effects on critical neuroanatomic structures as tumors in and around the cranial vault grow and crowd viable brain structures. Patients with anterior base of skull tumors (ABST) patients are further susceptible to cognitive symptoms as an unfortunate consequence of “incidental” neurologic involvement associated with common therapeutic treatments, for example, following radiotherapy to the paranasal sinuses (1). Furthermore, while surgical intervention has remained a “cornerstone” in the management of most patients with tumors of the skull base, more recently, improved patient outcomes have been associated with incorporation of other therapeutic strategies, such as chemotherapy in conjunction with radiotherapy (2). With the advent of more aggressive, multimodal treatment approaches, and improvements in radiation delivery techniques, the documentation of the cognitive sequelae of skull base cancer and its treatment remains essential.

Treatment Effects Even if the tumor itself does not result in cognitive impairments such as those described above, treatment may. Surgery may result in damage to normal tissue that surrounds the tumor, and yields more focal cognitive impairments that may resolve over time. In patients with skull base tumors, radiation is a more commonly utilized treatment than chemotherapy. Tolerance of radiation therapy varies among individuals. Important factors impacting individual tolerance include treatment factors such as dose, duration, and volume of brain irradiated, as well as patient variables such as age, genetic predisposition, preexisting neurologic diseases, systemic diseases that may predispose an individual to vascular injury, and concomitant chemotherapy (7). There is ample evidence that radiation therapy may be associated with the development of varying degrees of cognitive impairment both during and after treatment. Acute radiation encephalopathy develops within 2 weeks of initiation of treatment and is characterized by transient symptoms of headache, drowsiness, fever, and nausea (8). Early-delayed radiation encephalopathy develops 1–6 months after completion of radiotherapy and has been associated with transient declines in retrieval of verbal information in low-grade glioma patients (9,10). These impairments do not appear to be predictive of severe late-delayed, radiation-induced encephalopathy (9). The onset of late-delayed radiation encephalopathy can occur months to years afeter completion of radiation therapy and unlike acute and early-delayed effects,

WHY ARE ABST PATIENTS VULNERABLE TO NEUROCOGNITIVE DYSFUNCTION? Tumor Location The location of many skull base tumors places brain tissue, and consequently cognitive functioning, at risk of compromise secondary to compression of critical neuroanatomic structures in conjunction with tumor growth. Many skull base tumors are slow growing and become quite large before symptoms are noticed. For example, 62% of the 37 patients with olfactory groove meningiomas described by Turazzi et al. (1999) (3) and nearly 50% of patients with the same diagnosis in the Hentschel and DeMonte (2003) (4) study sample presented with tumors greater than 6 cm in diameter at the time of initial diagnosis. Symptom onset in these patients is commonly gradual until pressure effects lead to more significant problems. In the Hentschel and DeMonte (2003) (4) series of 13 patients, symptoms were often first noticed by family members and included a gradual onset of personality changes, such as apathy and akinesia, which is consistent with the subfrontal location of these tumors. Additionally, some patients experienced headaches, visual deficits (often inferior field cuts), and anosmia. Notably, anosmia is often reported only in hindsight, and is rarely a primary complaint of patients with olfactory groove meningiomas. 201

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tends to be irreversible (10). Impairments are associated with white matter changes secondary to demyelination and/or vascular damage, and occur on a continuum, ranging from mild to moderate cognitive impairments in attention and short-term memory to severe, progressive cognitive declines and dementia. In addition, endocrine dysfunction can be caused by damage to the hypothalamic–pituitary axis, leading to abnormalities in thyroid and human growth hormones (11), which have been associated with cognitive deficits (12– 14). While proton radiotherapy allows for relatively greater sparing of nontarget structures, and therefore may yield a reduction in radiation-induced morbidity, evidence suggests that radiation-induced endocrinopathy remains common even with advances in treatment modalities (15).

Posttreatment Studies A summary of studies investigating the effects of radiation treatment in skull base tumor patients is presented in Table 1. A review of Table 1 is notable for documented deficits in verbal and nonverbal memory, speed of mental processing, visual motor speed, executive functioning, fine motor coordination, attention and concentration, and visuospatial processing following radiation therapy to the skull base. In a study conducted by Steinvorth et al. (2003) (6), 40 patients with intracranial meningioma underwent neuropsychological evaluation prior to radiation treatment, following the first fraction of radiation, upon completion of treatment, and at 6 weeks, 6 months, and 12 months posttreatment. Examination of serial results from the follow-up evaluations revealed acute declines in verbal memory, regardless of the side of the brain that received radiation, with subsequent improvements over time. Follow-up in this study was limited Table 1

to 1 year and the authors stressed that the long-term effects of radiation treatment may not emerge until after this time period. The effects of radiation have also been investigated in other skull base tumor patients. Hua et al. (1998) (5) reported on the results of 27 patients with nasopharyngeal carcinoma who had undergone radiation to the brain. As compared to 35 healthy controls, patients who were evaluated postradiation performed worse on measures of auditory attention and concentration, verbal and nonverbal learning and memory, visuospatial reasoning, and manual dexterity. As compared to 27 patients with the same diagnosis who were awaiting radiation, the postradiation patients performed significantly worse on the measures of manual dexterity only. Additional information comes from Glosser et al. (1997) (16), who evaluated 17 patients with diagnoses of chordoma or low-grade chondrosarcoma before and after receiving radiation treatment. Following radiation, there was evidence of overall slowed performance, with a trend toward those patients who had received higher doses to be the slowest. There were no other noted declines. However, patients who were diagnosed with tumor recurrence or radiation necrosis were not included in the follow-up. The importance of long-term follow-up investigation of cognitive functioning was underscored by Meyers et al. (2000) (1), who performed neuropsychological assessment of 19 patients who had received therapeutic irradiation for skull base tumors at least 20 months prior. As a whole, patients performed below expectation on verbal memory, with 58% demonstrating difficulty learning new information and 69% demonstrating memory retrieval problems. Eighty percent of patients demonstrated accelerated forgetting of information

Summary of Studies Investigating Effects of Radiation on Cognitive Functioning in Patients with Skull Base Tumors

Study

Type of skull base tumor

n

Cognitive evaluation

Steinvorth et al., 2003

Intracranial meningioma

40

Glosser et al., 1997

Chordoma/low-grade chondrosarcoma

17

Pre-XRT; after 1st fraction; end of XRT, 6 weeks, 6 months, and 12 months post-XRT Postoperative/pre-XRT; post-XRT

Meyers et al., 2000

Paranasal sinus

28

n = 9, Pre- and post-XRT; n = 19, post-XRT only

Hua et al., 1998

NPC

90

n = 28, pre-XRT; n = 27, post-XRT; n = 35, healthy controls

Cheung et al., 2000

NPC

84

n = 53 NPC (31 w/TLN), post-XRT; n = 31 healthy controls

Cheung et al., 2003

NPC

50

≥1 year post-XRT

Lam et al., 2003

NPC

79

n = 60 NPC (40 w/TLN), ≥2 years post-XRT

a

Did not include patients with tumor recurrence or XRT necrosis at F/U. Abbreviations: NPC, nasopharyngeal carcinoma; XRT, radiation; TLN, temporal lobe necrosis.

Findings Acute decline in verbal memory, with subsequent improvements Post-XRT: slowed performance (trend = higher dose, slower performance); no other declinesa Impairments in learning and memory, visual–motor speed, and executive functioning Post-XRT vs. controls: worse auditory attention and concentration, verbal and visual learning and memory, visuospatial reasoning, and manual dexterity. Post-XRT vs. pre-XRT: worse manual dexterity only (trend for others). TLN associated with worse verbal and nonverbal memory, language, motor, and executive functioning, with relatively preserved intellectual, attention, and visual functioning. Trend for non-TLN patients to perform worse than healthy controls. Larger XRT-induced lesion volume associated with worse cognitive performance overall. Larger left-sided lesions associated with worse verbal memory and language. Larger right-sided lesions associated with worse visual memory. Both patient groups worse than controls on verbal memory.

Chapter 14: Neurocognitive Assessment of Patients with Tumors of the Skull Base

over time, a finding that was significantly associated with dose of radiation received; patients who received radiation doses greater than 60 Gy tended to have greater likelihood of impaired memory recall. Other areas of cognitive impairment included visual motor speed (35%), executive functioning (27–35%), and fine motor coordination (27–33%), with the overall pattern of findings consistent with frontal subcortical white matter dysfunction. The patients who had the worst outcome were those who received treatment prior to 1985 and who received higher doses of radiation. Studies investigating the late-delayed effects of radiation treatment have further confirmed the presence of cognitive deficits described by Meyers et al. (2000) (1), with those patients who develop radiation-induced necrosis demonstrating the weakest performance on measures of cognitive functioning. Cheung et al. (2000) (17) compared 53 patients with a diagnosis of nasopharyngeal carcinoma who had undergone radiation treatment with 31 healthy controls. Imaging evidence of temporal lobe necrosis (TLN) was observed in 31 of the 53 (58%) patients. TLN was associated with poorer verbal and nonverbal memory, as well as worse performance on measures of language, motor, and executive functioning. In addition, a nonstatistically significant trend was noted such that non-TLN patients generally performed worse than healthy controls but better than TLN patients. No significant differences between patients with and without TLN and controls were observed on measures of intellectual, attention, or visual functioning. In a subsequent study by Cheung and colleagues (2003) (18), 50 patients with nasopharyngeal carcinoma were evaluated at least one year after undergoing radiation therapy. Those with larger radiation-induced lesions were more likely to exhibit cognitive dysfunction. Left-sided lesions were associated with impairments in verbal memory and language, while right-sided lesions were associated with impairments in visual memory. Lam and colleagues (2003) (19) also reported impairments in verbal memory in a series of 60 patients with nasopharyngeal carcinoma (40 of whom had evidence of TLN) who were evaluated at least 2 years following completion of radiation. It is encouraging to observe that total dose of radiation treatment was the only major determinant of cognitive impairment in the Meyers et al. (2000) (1) study, whereas irradiated brain volume, laterality of radiation boost, and pretreatment chemotherapy were not significant factors. Current practice utilizes lower doses to the tumor as well as attempts to reduce exposure of the surrounding brain tissue. It is anticipated that new treatments will further improve dose density and limit incidental brain irradiation, and that cognitive complications will thus be minimized. However, as the effects of radiation treatment may not be evident for several years posttreatment, careful monitoring of cognitive function in patients over time remains necessary.

Frontal–Subcortical Circuits The pattern of neuropsychological findings associated with skull base tumors—which often includes impairments in processing speed, memory, visual motor speed, visuospatial reasoning, executive functioning, and fine motor coordination— is not surprising given the potential for disruption of frontal–subcortical circuits. In fact, ABST patients may be at particular risk for disruption of frontal–subcortical circuitry as tumors within the base of the cranial vault grow and disrupt these critical neuroanatomic networks (Fig. 1). In addition, previous research has documented that in patients with both cerebral and extracerebral malignancies, antineoplastic

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treatments, including chemotherapies and/or radiotherapies are associated with a pattern of cognitive deficits consistent with frontal–subcortical white matter dysfunction, including neuropsychological deficits in executive functions, verbal retrieval, cognitive processing speed, and speeded motor coordination, as well as inefficiencies in learning and retrieval of stored information in the context of relatively well preserved memory consolidation processes (20,21). A thorough discussion of frontal–subcortical circuits is beyond the scope of this chapter; readers are referred to Mega and Cummings (1994) (22) for a review. Briefly, frontal–subcortical circuits mediate motor functioning, executive functioning, personality, and motivation. Executive functioning, regulated in part by the dorsolateral prefrontal circuit, is defined as “the ability to organize a behavioral response to solve a complex problem” and may involve tasks such as learning new information, organization and planning, shifting set, and inhibiting inappropriate responses. Changes in mood, in the form of depression and anxiety, have also been observed in association with damage to this circuit. Personality functioning is mediated by the lateral orbitofrontal and anterior cingulate circuits. The lateral orbitofrontal circuit is responsible for mediating socially appropriate behavior. Dysfunction in this circuit is most often manifested in the form of behavioral disinhibition or lack of empathy. In contrast, the hallmark of damage to the anterior cingulate circuit is apathy; patients may exhibit limited initiation of speech and movement and fail to display emotion.

NEUROPSYCHOLOGICAL ASSESSMENT To determine the pattern of a patient’s cognitive strengths and weaknesses prior to and following treatment, objective assessment of cognitive functioning via comprehensive neuropsychological assessment is necessary. Knowledge regarding the presence and pattern of neurocognitive impairments prior to treatment is essential in determining whether a specific anticancer therapy is associated with risks or benefits to cognitive functioning. Armed with baseline information, one can determine whether or not an individual has experienced significant change following treatment. In the absence of that information, patients can easily be misclassified as cognitively intact, when in fact they have declined significantly from premorbid levels of functioning. The reverse is also true; patients with a lower level of premorbid functioning may be incorrectly classified as having declined. The identification of changes in cognitive functioning helps inform differential diagnoses and serves as a starting point for development of pharmacologic and behavioral interventions to improve functional well-being. Wefel et al. (2004) (21) describe the complexities involved in neuropsychological assessment of patients with cancer, noting that while the administration of objective measures is relatively simple, the selection and interpretation of appropriate measures requires greater knowledge and skill. Test selection varies as a function of the question being asked; in the case of cancer patients in general and skull base tumor patients in particular, it is important to select measures that are sensitive to subtle changes in functioning. Measures should be reliable and valid, as well as robust to practice effects, as patients are often tested multiple times within a relatively short time span. Alternative test forms, when available, should be used. In addition to the above considerations, a thorough neurocognitive assessment includes an assessment of the indirect effects of cancer on physical and emotional well-being, and the consequent impact of such symptoms on cognitive

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Figure 1 Origins of three frontal–subcortical circuits. (Top left) Dorsolateral prefrontal circuit (blue). (Bottom left) Anterior cingulate circuit (red). (Right) Lateral orbitofrontal circuit (green). Source: Reprinted with permission from Mega & Cummings (2004).

functioning. Mental and physical fatigue can negatively impact cognitive functioning, as can numerous medications and associated medical complications. The reverse can also occur, with cognitive impairment leading to affective distress and fatigue (see Valentine & Meyers, 2001, for a more thorough review) (23). Cognitive effects of affective distress may vary from very mild impairments on effortful tests to significant deficits in visuospatial skills, executive functions, and psychomotor speed (24). It is important to note that in cancer populations, self report of cognitive impairment has been shown to correlate more intensely with fatigue and mood disturbance than with objective evidence of cognitive dysfunction, as assessed by standardized neuropsychological tests (25–28). Thus, a thorough neuropsychological assessment is needed to elucidate whether perceived difficulties are secondary to cancer-related cognitive dysfunction and/or affective distress. Of note, too often the assessment of cognitive functioning in clinical and research settings has been limited to brief screening measures, such as the Mini Mental State Examination (29). The poor sensitivity of this tool for patients with cancer has been documented (30). In fact, the inclusion of even brief neuropsychological assessment in research trials has been shown to be effective in identifying the risk and benefits associated with various anticancer therapies (20). The utility of neuropsychological assessment in patients with cancer is underscored by evidence demonstrating that cognitive impairment, when documented via

formal neuropsychological testing, predicts survival better than clinical prognostic factors alone in patients with primary brain tumors, leptomeningeal disease, and parenchymal brain metastases (20,31–33). Further, Meyers and Hess (2003) (34) demonstrated that cognitive performance was a more sensitive predictor of time to tumor progression than MRI, as cognitive decline occurred an average of 6 weeks prior to radiographic failure in 80 patients with glioblastoma multiforme and anaplastic astrocytoma. Neuropsychological evaluations tend to be well tolerated by cancer patients, with good compliance rates documented (33). As mentioned above, patients with skull base tumors are particularly vulnerable to disruption of frontal– subcortical networks. Patients and their caregivers may describe problems with organization, multitasking, and distractibility, as well as perceived forgetfulness, behavioral disinhibition, or apathy. Such complaints warrant a referral for neuropsychological evaluation, which should include a thorough clinical interview to elucidate perceived cognitive difficulties and associated functional impairments, as well as to define any compensatory strategies that are being used. The evaluation should utilize measures that are specifically selected to tap the cognitive domains most intimately associated with frontal–subcortical systems. For example, test selection might include measures of executive functioning, including set shifting, planning and organization, and response inhibition. In addition, within the domain of memory, frontal–subcortical dysfunction might result in impaired

Chapter 14: Neurocognitive Assessment of Patients with Tumors of the Skull Base

learning efficiency and retrieval. Speed of processing and fine motor control may also be impacted by frontal–subcortical dysfunction, and therefore are also appropriate for inclusion in a neuropsychological battery. Assessment of these cognitive skills should not occur in isolation, but rather in the context of tests of a comprehensive neuropsychological evaluation. A thorough assessment, with all included measures meeting the criteria described above, allows for evaluation of patterns of performance that can aid in differential diagnosis and treatment planning. Interested readers are referred to Lezak et al. (2004) (35) for a more in-depth discussion of specific neuropsychological measures and assessment procedures.

MANAGEMENT OF COGNITIVE SYMPTOMS: PHARMACOLOGIC AND BEHAVIORAL INTERVENTIONS Chan et al. (2003) (36) investigated the effects of vitamin E in 29 patients with nasopharyngeal carcinoma who had imaging evidence of unilateral or bilateral temporal lobe necrosis. Neuropsychological evaluations were performed before the initiation of treatment with vitamin E and 1 year later. The 19 patients who were treated with vitamin E performed better than 10 nontreated controls on measures of verbal learning and memory, visual memory, and cognitive flexibility. The authors acknowledged several limitations to this study, including that the patients were not randomized or blinded to their treatment. Further research is necessary to investigate the long-term safety and side effects of treatment with vitamin E, as well as the impact on cognition when treatment is discontinued and the mechanism by which vitamin E may improve cognitive functioning. Treatment with methylphenidate has been found to be beneficial in combating cognitive symptoms associated with treatment-related frontal–subcortical dysfunction in patients with primary brain tumors (37), such that patients demonstrated significant improvements in memory, psychomotor speed, visual–motor function, executive function, and fine motor speed. Other pharmacologic interventions that have been utilized in the neuro-oncology populations include donepezil to combat difficulties with attention and memory (38) and modafinil to alleviate fatigue and improve quality of life (39). Further research is needed to determine the effectiveness of these pharmacologic interventions for patients with ABST. Finally, although there is a dearth of evidence from prospective, randomized, controlled trials supporting their effectiveness, there are numerous anecdotal reports of goalfocused compensatory interventions and behavioral strategies being useful in minimizing the impact of cognitive deficits on daily life in patients with cancer. In fact, traditional rehabilitation disciplines (treating survivors of traumatic brain injury, stroke, or patients with dementia) have contributed a wealth of knowledge regarding evidence-based compensatory strategies that may be applicable to patients with cancer-related cognitive dysfunction (see Cicerone et al. 2000, 2005) (40,41). For example, external memory aids such as memory notebooks, user-programmable paging systems, and medication reminder systems have all been used to assist neurologically impaired patients compensate for difficulties with forgetfulness.

SUMMARY Patients with skull base tumors may be vulnerable to cognitive impairments secondary to disruption of frontal–

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subcortical networks as a consequence of tumor growth and as an unfortunate side effect of antineoplastic treatments. Thorough neuropsychological evaluation is useful for assessing baseline (i.e., pretreatment) cognitive functioning, for monitoring the effects of cancer and cancer treatment on cognition, and for facilitating development and planning of behavioral and pharmacologic interventions to minimize the impact of symptoms on functional well-being and quality of life.

ACKNOWLEDGMENT We gratefully acknowledge Christina Meyers, Ph.D., ABPP, for her editorial suggestions. REFERENCES 1. Meyers CA, Geara F, Wong P-F, et al. Neurocognitive effects of therapeutic irradiation for base of skull tumors. Int J Radiation Oncology Biol Phys. 2000;46(1):51–55. 2. Prabhu SS, Demonte F. Treatment of skull base tumors. Curr Opin Oncol. 2003;15:209–212. 3. Turazzi S, Cristofori L, Gambin R, et al. The pterional approach for the microsurgical removal of olfactory groove meningiomas. Neurosurgery. 1999;45(4):821–825: discussion 825–826. 4. Hentschel SJ, Demonte F. Olfactory groove meningiomas. Neurosurg Focus. 2003;14(6):e4. 5. Hua M-S, Chen S-T, Tang L-M, et al. Neuropsychological function in patients with nasopharyngeal carcinoma after radiotherapy. J Clin Exp Neuropsychol. 1998;20(5):684–693. 6. Steinvorth S, Welzel G, Fuss M, et al. Neuropsychological outcome after fractionated stereotactic radiotherapy (FSRT) for base of skull meningiomas: A prospective 1-year follow-up. Radiother Oncol. 2003;69:177–182. 7. Taphoorn JB, Klein M. Cognitive deficits in adult patients with brain tumors. Lancet. 2004;3:159–168. 8. Keime-Guibert F, Napolitano M, Delattre J. Neurological complications of radiotherapy and chemotherapy. J Neurol. 1998;245:695–708. 9. Armstrong CL, Corn BW, Ruffer JE, et al. Radiotherapeutic effects on brain function: Double dissociation of memory systems. Neuropsychiatry Neuropsychol Behav Neurol. 2000;13:101–111. 10. Armstrong CL, Gyato K, Awadalla AW, et al. A critical review of the clinical effects of therapeutic irradiation damage to the brain: The roots of controversy. Neuropsychol Rev. 2004;14(1):65–86. 11. Darzy KH, Shalet SM. Hypopituitarism as a consequence of brain tumors and radiotherapy. Pituitary. 2005;8:203–211. 12. Dugbartey AT. Neurocognitive aspects of hypothyroidism. Arch Int Med. 1998;13:1413–1418. 13. Yudiarto FL, Muliadi L, Moeljanto D, et al. Neuropsychological findings in hyperthyroid patients. Acta Med Indones. 2006;38(1):6–10. 14. Deijen JB, Boer H, van der Veen EA. Cognitive changes during growth hormone replacement in adult men. Psychoneuroendocrinology. 1998;23:45–55. 15. Pai HH, Thornton A, Katznelson L, et al. Hypothalamic/pituitary function following high-dose conformal radiotherapy to the base of skull: Demonstration of a dose-effect relationship using dosevolume histogram analysis. Int J Radiation Oncology Biol Phys. 2001;49(4):1079–1092. 16. Glosser G, McManus P, Munzenrider J, et al. Neuropsychological functioning in adults after high dose fractionated radiation therapy of skull base tumors. Int J Radiation Oncology Biol Phys. 1997;38(2):231–239. 17. Cheung M, Chan AS, Law SC, et al. Cognitive function of patients with nasopharyngeal carcinoma with and without temporal lobe radionecrosis. Arch Neurol. 2000;57(9):1347–1352. 18. Cheung M, Chan AS, Law SC, et al. Impact of radionecrosis on cognitive dysfunction in patients after radiotherapy for nasopharyngeal carcinoma. Cancer. 2003;97(8):2019–2026.

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19. Lam LC, Leung SF, Chan YL. Progress of memory function after radiation therapy in patients with nasopharyngeal carcinoma. J Neuropsychiatry Clin Neurosci. 2003;15(1):90–97. 20. Meyers CA, Brown PD. Role and relevance of neurocognitive assessment in clinical trials of patients with CNS tumors. J Clin Oncol. 2006;8:1305–1309. 21. Wefel JS, Kayl AE, Meyers CA. Neuropsychological dysfunction associated with cancer and cancer therapies: A conceptual review of an emerging target. Br J Cancer. 2004;90:1691–1696. 22. Mega MS, Cummings JL. Frontal-subcortical circuits and neuropsychiatric disorders. J Neuropsychiatry Clin Neurosci. 1994;6:358–370. 23. Valentine AD, Meyers CA. Cognitive and mood disturbance as causes and symptoms of fatigue in cancer patients. Cancer. 2001;92(6):1694–1698. 24. Cull A, Hay C, Love SB, et al. What do cancer patients mean when they complain of memory problems? Br J Cancer. 1996;74:1674– 1679. 25. Castellon SA, Ganz PA, Bower JE, et al. Neurocognitive performance in breast cancer survivors exposed to adjuvant chemotherapy and tamoxifen. J Clin Exp Neuropsychol. 2004;26:955–969. 26. Jenkins V, Shilling V, Deutsch G, et al. A 3-year prospective study of the effects of adjuvant treatments on cognition in women with early stage breast cancer. Br J Cancer. 2006;94:828–834. 27. Schagen SB, Muller MJ, Boogerd W, et al. Cognitive dysfunction and chemotherapy: Neuropsychological findings in perspective. Clin Breast Cancer Suppl. 2002;3:S100–S108. 28. Houston WS, Bondi MW. Potentially reversible cognitive symptoms in older adults. In: Attix KD, Welsh-Bomer K, eds. Geriatric Neuropsychology Assessment and Intervention. New York, NY: Guilford Press, 2006:103–131. 29. Folstein MF, Folstein SE, McHugh PR. Mini-mental state. A practical method for grading the cognitive state of patients for the clinican. J Psych Res. 1975;12(3):189–198. 30. Meyers CA, Wefel JS. The use of the Mini-Mental State Examination to assess cognitive functioning in cancer trials: No ifs, ands, buts, or sensitivity. J Clin Oncol. 2003;19(1):3557–3558.

31. Sherman AM, Jaeckle K, Meyers CA. Pretreatment cognitive performance predicts survival in patients with leptomeningeal disease. Cancer. 2002;95(6):1311–1316. 32. Mehta MP, Shapiro WR, Glantz MJ, et al. Lead-in phase to randomized trial of motexafin gadolinium and whole-brain radiation for patients with brain metastases: Centralized assessment of magnetic resonance imaging, neurocognitive, and neurologic end points. J Clin Oncol. 2002;16:3445–3453. 33. Meyers CA, Smith JA, Bezjak A, et al. Neurocognitive function and progression in patients with brain metastases treated with whole-brain radiation and motexafin gadolinium: Results of a randomized phase III trial. J Clin Oncol. 2004;22(1):157– 165. 34. Meyers CA, Hess KR. Multifaceted end points in brain tumor clinical trials: Cognitive deterioration precedes MRI progression. Neuro-Oncology. 2003;5:89–95. 35. Lezak MD, Howieson DB, Loring DW. Neuropsychological Assessment. 4th ed. New York, NY: Oxford University Press,2004. 36. Chan AS, Cheung M, Law SC, et al. Phase II study of alphatocopherol in improving the cognitive function of patients with temporal lobe radionecrosis. Cancer. 2003;100(2):398–404. 37. Meyers CA, Weitzner MA, Valentine AD, et al. Methylphenidate therapy improves cognition, mood, and function of brain tumor patients. J Clin Oncol. 1998;16(7):2522–2527. 38. Shaw EG, Rosdhal R, D’Agostino RB, et al. Phase II study of donepezil in irradiated brain tumor patients: Effect on cognitive function, mood, and quality of life. J Clin Oncol. 2006;24(9):1415– 1420. 39. Nasir S. Modafinil improves fatigue in primary brain tumor patients (Abstract). Soc Neuro Oncol. 2003;5:335. 40. Cicerone KD, Dahlberg C, Kalmar K, et al. Evidence-based cognitive rehabilitation: Recommendations for clinical practice. Arch Phys Med Rehabil. 2000;81(12):1596–1615. 41. Cicerone KD, Dahlberg C, Malec JF, et al. Evidence-based cognitive rehabilitation: updated review of the literature from 1998 through 2002. Arch Phys Med Rehabil. 2005;87(3):1681– 1692.

15 Cerebrovascular Management in Skull Base Tumors Sabareesh Kumar Natarajan, Basavaraj Ghodke, and Laligam N. Sekhar

venous infarction. The vein of Labb´e often consists of multiple veins. One may drain into a tentorial sinus, and another may drain far anteriorly into the transverse sigmoid junction. This will have an influence on the approach being planned.

INTRODUCTION Cranial base tumors often involve the basal arteries and veins. Successful management of these lesions requires a multidisciplinary approach to patient care. An important component to this approach is the management of the cerebral vasculature, which includes preoperative assessment of the cerebral vasculature, preoperative embolization, arterial and venous preservation, and reconstruction during resection and the management of vasospasm after resection.

Preoperative Embolization We attempt to embolize all cranial base meningiomas, whenever feasible, to reduce the blood loss and operative time. When embolization is adequately performed, tumor necrosis or softening may also occur making the operation easier. Limited blood loss makes surgical resection safer and improves visualization. Necrosis often leads to softening of the tumor, which not only facilitates resection but also reduces the forces transmitted to adjacent sensitive neural structures. The arteries commonly embolized include meningohypophyseal branch of the ICA; branches of the external carotid artery—the sphenopalatine artery, middle meningeal artery, accessory meningeal artery, internal maxillary artery, ascending pharyngeal artery, and other; and rarely meningeal branches of the vertebral artery (VA). Tumor embolization is performed under local (ECA branches) or general (ICA branches) anesthesia. To facilitate the selective catheterization of the small branches, a R Renegade
(Boston Scientific, Natick, MA) (for larger pediR cles such as ascending pharyngeal artery) or Marathon
(ev3, Irvine, CA) (for smaller pedicles such as meningohypophyseal trunk) microcatheter is used. A manual injection of undiluted, nonionic contrast agent is performed with a 1.0 mL syringe, starting very slowly until the contrast agent becomes visible and then the rate of injection is increased slowly. If tumor vascularity is apparent, the injection is repeated, increasing the rate of injection to possibly identify reflux into the carotid siphon. Filming is biplane to evaluate potential cross filling of contralateral branches. An idea of the force required to cause reflux into cerebral arteries is thus obtained prior to the embolization procedure. Embolization is ideally performed 3 to 7 days before the planned procedure. The goal of embolization is to permeate the interstices of the tumor with particles, and occluding the feeding arteries at the very end, if they are large. Embolization material consists of particles of polyvinyl acetyl foam (PVA, Cook, Inc, Bloomington, IN) suspended in undiluted, nonionic contrast agent injected slowly. The size of the particle used depends on the potential for reflux and supply to cranial nerves from the pedicle being embolized. The average size of the particles used for embolization is 150 to 250 µ, with larger particles 250 to 400 µ being used for the embolization of the ascending pharyngeal artery to avoid occlusion of branches feeding cranial nerves X and XI. Additionally, small gelfoam pledgets are used to block arteries at the end of the procedure. In hypervascular tumors, liquid embolic

Preoperative Imaging The MRI scan is an important study. In short T2-weighted images, the presence of arterial encasement can be seen clearly. The extent of encasement and any narrowing of the artery is noted. Cerebral angiography is a must in all patients with arterial encasement. All major vessels must be studied in order to evaluate potential collateral sources, along with the evaluation of venous system. In case of internal carotid artery (ICA) encasement, we perform angiography with ipsilateral CCA compression. In a patient in whom surgical occlusion is planned, a carotid compression arteriogram with contralateral carotid and vertebral injection is performed in order to evaluate collateral flow through the anterior communicating artery (ACOM) or the posterior communicating artery. This information is used to decide whether the ECA (no cross flow) or ICA (cross flow present) should be used as the donor artery, which gives the surgeon some idea of collateral sources, to assess tolerance to temporary occlusion during a bypass procedure. Before operating on basal tumors or tumors located near the torcula, transverse and sigmoid sinuses, vein of Labb´e, or the straight sinus, angiography with filming of the venous phase is important to provide information about the adjacent veins and collaterals. The size and dominance of the transverse or sigmoid sinus and collateralization through the torcula can alter the surgical approach by revealing a very large sigmoid sinus or high riding jugular bulb, either of which can significantly affect the amount of exposure. Similarly, a small sigmoid sinus with excellent collaterals provides a wider presigmoid exposure with less consequences should sigmoid sinus occlusion occur. This also helps in decision making regarding possible venous occlusion. Configuration, relative sizes, and anastomotic relationships of the veins draining the temporal lobe are extremely important. In most patients, the veins of Labb´e and the superficial middle cerebral veins have a seesaw relationship, commonly being relatively equal in size. In some patients, one or more of these veins will be larger in size. The consequences of occluding a large or dominant vein must be factored into the surgical planning to protect them and avoid 207

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The use of bypasses for skull base tumors has declined in frequency due to the increasing use of radiosurgery for tumor remnants left around the carotid artery during surgery for basal meningiomas. However, this technique remains a valuable tool in the management of skull base tumors such as recurrent meningiomas, recurrent chordomas, chondrosarcomas, and other malignant tumors (1–7).

Operative Technique in a Tumor with Subarachnoid Encasement

Figure 1 Illustration showing cervical ECA to MCA-M2 bypass.

R agents such as Onyx
, n-BCA, or coils are used for flow reduction. The risks of embolization such as skin necrosis, cranial nerve dysfunction, stroke, blindness should be weighed against the perioperative and postoperative advantages. Embolization of some large or giant tumors may result in tumor swelling, which may precipitate emergent surgery.

MANAGEMENT OF ARTERIAL ENCASEMENT Intracranial skull base tumors frequently encase the basal arteries, ICA, VA, basilar artery (BA), and their branches. When the encasement is in the subarachnoid segment of the artery, the tumor can be dissected away from the artery due to existence of an arachnoid plane around the tumor. Such a plane is absent in cases of prior surgery or radiotherapy and such dissection is not feasible. When the tumor involves the extradural segment, dissectability depends upon the pathology of the tumor and the oncologic goals of the surgery. Schwannomas or cavernous hemangiomas are always dissectible. Meningiomas can often be dissected when the vessel is only encased, but usually not when the vessel is encased and narrowed. In patients with malignant tumors such as adenoid cystic carcinoma, the ICA has to be resected because of tumor invasion.

Figure 2

Illustration showing cervical ECA to supraclinoid ICA bypass.

Proximal control of the exposed artery is obtained, followed by adequate exposure of the tumor without brain retraction, and then distal exposure of the artery beyond the encasement. The artery is then traced through the tumor from both sides, with frequent debulking. Suction, bipolar cautery, fine dissectors, and microscissors are used for dissection of the artery. In case of an artery that has multiple perforators, the surface without perforators is dissected first, followed by the portion containing perforating branches (see Case Studies).

When to Bypass After Vascular Sacrifice? When the intracranial ICA or VA is occluded, whether or not a bypass is needed in all patients is controversial. A selective approach bases this decision on a balloon occlusion test, with monitoring of cerebral blood flow by SPECT, TCD, or angiography. A universal approach recommends a bypass in all patients. Based on a review of patients of senior author who were not revascularized and suffered strokes and the reports of other surgeons with a similar experience (8–11), a universal approach is presently followed if the ICA has to be occluded for tumor cases. In regards to the VA, if a vessel is markedly non dominant, it needs not be reconstructed. However, an equidominant or dominant VA must be reconstructed. If the BA is damaged, it must always be reconstructed, although when the patient has two large posterior communicating arteries, the patient may not suffer a stroke because of good collaterals. In the event of unexpected intraoperative injury to major arteries, it is best to reconstruct the vessel using either a local, regional, or extra-intracranial bypass technique, since the adequacy of collateral circulation cannot be determined.

Figure 3 (A, B) Terminal stitches are placed at the heel and the diametrically opposite ends. Also note the fish-mouthing of the STA. (C) One side is anastomosed with continuous sutures and (D) the opposite side with interrupted sutures.

Chapter 15: Cerebrovascular Management in Skull Base Tumors

130 79 7 7 5 32

raises the patients’ BP by about 20% during temporary occlusion, and places the patient in burst suppression with propofol, to protect the brain. Approximately 4000 to 5000 units of heparin are also administered during the vascular occlusion. Epidural hemostasis must be excellent, to prevent excessive oozing after heparinization. The heparin is not reversed at the end of the procedure.

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Table 1 Revascularization for Tumors 1988–2006 Number of patients Meningiomas Chondrosarcoma Chordoma Adenoid cystic carcinoma Miscellaneous Type of graft Radial artery graft Saphenous vein graft Extent of resection Gross total resection Incomplete resection Graft patency Immediate patency rate Delayed graft occlusion Mortality Due to Surgery Major stroke despite patent graft Preoperative deficits and morbidity after surgery Due to disease progression/recurrence

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82 (63%) 48 (37%) 124/130 (95.4%) 2 (managed by revision, patent at follow-up)

RAG or SVG is used for bypass, based on preoperative Duplex imaging. For a tumor involving the ICA, ECA or cervical ICA to MCA-M2 segment bypass is preferred (Fig. 1). When the MCA vessels are small, then the supraclinoid ICA may be used as a recipient vessel (Fig. 2). The cervical ICA is

2/130 (1.5%) 1 1 17/130 (13.1%)

Choice of Bypass Grafts Bypasses may be divided into two groups as: replacement bypasses (e.g., radial artery graft/saphenous vein to replace the ICA/VA) and augmentation bypasses (e.g., STA-MCA bypass performed in a patient with brain ischemia secondary to ICA occlusion). Most of the bypasses performed for skull base tumors are replacement bypasses with radial artery, saphenous vein, or rarely, the superficial temporal artery. A local repair of an injured artery may also be performed in some cases. The radial artery provides flow rates between 50 and 150 mL/min acutely and the flow can increase significantly over the ensuing days as measured by Duplex ultrasound (3). The radial artery is easier to harvest than the saphenous vein. However, a major problem with its use is the occurrence of postoperative spasm, which can be prevented by the use of the pressure distension technique (1,3,12). The saphenous vein graft is used when the radial artery is not available as a suitable vessel. It may also be used in cases where the radial artery graft, for one reason or the other, has failed. In children below the age of 12, where the radial artery graft is small in diameter, the saphenous vein graft is the only alternative. Graft flow in the saphenous vein has been measured from 100 to 250 mL/min. Because of the high flow through the saphenous vein graft, there may be a flow mismatch when it is anastomosed into the middle cerebral artery or the posterior cerebral artery, which could lead to turbulence and graft flow problems. It is more prone to kinking the distal anastomotic site and is technically more difficult to perform because of its thicker wall.

(A)

Anesthesia, Monitoring, and Preparation If a bypass procedure is a strong possibility, preoperative Duplex imaging of the radial arteries and saphenous veins, and an Allen test of the hands are performed to choose the vessel that may be used for bypass. The patient receives aspirin 82 mg preoperatively. Intraoperative monitoring of electroencephalogram, somatosensory evoked potentials, and motor evoked potentials is employed. Total intravenous anesthesia is used to allow monitoring of motor evoked potentials. If a bypass is performed, the anesthesiologist

(B)

Figure 4 (A) Normal type of vein of Labb´e. (B) Very anteriorly draining vein of Labb´e into a tentorial sinus. (continued on page 208).

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(C)

(D)

Figure 4

(C) Variation of anatomy of vein of Labb´e seen in angiogram. (D) Postoperative venous infarction of the temporal lobe.

exposed in the neck. The tumor is exposed after a craniotomy and an orbital or orbitozygomatic osteotomy. After tumor inspection, and in some cases, after attempted removal of the tumor, a decision is made to proceed with the bypass. Accordingly, the radial artery (the entire artery from the brachial artery bifurcation to the anterior wrist) or the saphenous vein (in the upper leg and lower thigh) is removed, flushed with heparinized saline, and distended under pressure to relieve

vasospasm. The distal anastomosis is performed first, to the MCA (M1 bifurcation or M2 segment) or to the supraclinoid ICA. This is followed by the proximal anastomosis to the ECA (if collateral circulation is poor) or to the ICA (if some collaterals are present). If the flow through the grafts is satisfactory by Doppler/intraoperative angiography, then the ICA is trapped between clips. The operation is stopped at this stage. A postoperative angiogram is performed the next day.

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(A)

Figure 5 Technique of inserting a butterfly needle into the sinus following placement of temporary clip to occlude the sinus.

For VA replacement, a RAG or saphenous vein interposition graft is employed. An extreme lateral retrocondylar or partial transcondylar approach is used. Proximal anastomosis to the VA is done at the level of C1–C2. If the distal anastomosis is distal to the PICA, then the PICA may be reimplanted or a PICA to PICA anastomosis performed. Alternatively, the PICA may be occluded if there is good collateral flow from the distal vessel. For BA injury, VA or ECA to PCA-P2 segment bypass is performed with RAG or saphenous vein

(B)

(C)

Figure 7 Repair of a superior sagittal sinus by graft. (A) Tumor invading the sinus. (B) Part of the patch graft is sutured to the sinus wall with tumor in situ. (C) Patch graft sutured after tumor excision.

graft. A temporal craniotomy with a zygomatic osteotomy or a petrosal approach is used for the exposure of the PCA.

STA to MCA Bypass

(A)

(B)

Figure 6 (A, B) Direct repair of the sigmoid sinus after resection of a meningioma, which had encased the sinus.

The STA is exposed by a direct cut-down technique. The course of the vessel is traced by Doppler ultrasound or frameless neuronavigation and marked on the scalp. Working under the operating microscope, dissection is started distally, and the vessel is traced proximally. A small cuff of connective tissue is left around the artery. The vessel is left in situ until the bypass procedure. A T-incision is created from the skin incision made to expose the artery to facilitate the muscle dissection and the performance of a small pterional craniotomy. A middle cerebral branch in the distal Sylvian fissure (M3 branch), the largest temporal or parietal cortical branch relatively free of perforators, is used for anastomosis. Ideally, the recipient vessel has to be at least 1.5 mm in diameter but can be as narrow as 1.0 mm. The recipient vessel is dissected free of its arachnoidal covering, and a small rubber dam is placed under the artery. The STA is divided and an

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Indications for Reconstruction of Cerebral Venous Sinuses

Status

Decision

Collaterals Excellent collaterals Marginal collaterals Poor or no collaterals Sinus occlusion One wall involved, sinus occlusion <50% Two walls involved, sinus occlusion >50% Three walls involved, sinus occlusion >90%

Reconstruction unnecessary; provides practice for surgeons Reconstruction recommended Occlusion dangerous; reconstruction if there is accidental injury Resection, resuture or a small patch Resection possible, vein patch for repair, preserve collaterals Test occlusion with pressure monitoring, sinus repair if pressure > 5 mmHg

oblique arteriotomy with slight fish-mouthing of the STA is done. Anastomosis to the MCA is done using diametrically opposing sutures at the ends, and interrupted 9/0 or 10/0 nylon sutures (Fig. 3). Prior to tying the last suture, the lumen is flushed with heparinized saline and the suture tightened. Flow through the STA is checked with a Doppler probe.

Staged Operations When a bypass is performed, staged operations are usually preferred. Craniotomy, exposure osteotomies, and bypass are done during the first surgery, and is followed by tumor resection in the second operation 3 to 7 days later. This is because both aspirin and intravenous heparin are administered during the first operation, and tumor resection and repair of skull base may need extensive work on the same day. Exceptions to this are removal of tumors around the VA, which may require a short segmental bypass following removal of a small tumor, with critical vascular encasement.

to follow the volume flow through the graft. The systolic BP should be maintained below 140 mmHg for 2 to 3 days. Graft occlusion may occur, either during the operation or within the first 24 hours after surgery. If occlusion occurs during surgery, the problem is corrected. If the occlusion occurs postoperatively, the patient needs to be reoperated. Rarely, endovascular thrombolysis can be done. Vasospasm occurs occasionally with radial artery grafts (despite the intraoperative pressure distention technique) and can be successfully treated by endovascular angioplasty. Following discharge (7–10 days), the patients are kept on statins for life as well as on aspirin (81 mg PO once daily) for life in case of vein graft and at least for 1 year in case of radial artery grafts. The graft is followed by 3D CTA or MRA at 3 months postoperatively and also by using graft flow measurements with Duplex imaging. Subsequently we recommend a 3D CTA at one year, and thereafter every 1 to 2 years.

Results Postoperative Management Postoperative monitoring of graft patency is usually done by Doppler evaluation. A CT angiogram is done immediately after the operation if an intra-arterial DSA was not performed to evaluate the graft. Otherwise, a postoperative DSA is performed at 12 hours after surgery. Patients are started on aspirin, 81 mg once daily and statins. Patients with saphenous vein grafts are maintained on subcutaneous heparin, 5000 U every eight hours for 3 days in addition to aspirin and statins. Duplex ultrasound studies are performed

One hundred and thirty patients underwent bypasses for tumors from 1988 to 2006 (79 for skull base meningiomas, 7 chondrosarcomas, 7 chordomas, 5 adenoid cystic carcinomas and other tumors like osteogenic sarcoma, schwannoma, hemangiomas, and hemangiopericytomas) (Table 1). The

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Figure 8 (A) Tumor encased and invaded the sigmoid sinus to narrow the sinus. (B) Part of the sinus was resected along with the tumor, and an interposition graft (saphenous vein) was placed (end-to-end anastomoses).

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Figure 9 (A) Tumor invading sinus. (B) Tumor resected with sinus and interposition graft (radial artery) placed (end-to-side anastomoses).

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Results of Venous Reconstruction from 1993 to 1999

Type of vein/venous sinus reconstructed Cortical vein Resuture graft SVG RAG Transverse sinus (pineal region) Division only Division + SVG Sigmoid sinus–jugular vein Division + resuture Repair after tumor excision SVG

No. of patients

No. of patients in which they are patent finally

1 1 1

1 1 1

5 1

NA 1

4 2 2

4 1 2

immediate patency rate for bypasses was 95.4%. Gross total resection was achieved in 82 (63%) of patients. There were 29 radial artery grafts and 101 saphenous vein grafts used. Two patients had delayed graft occlusions (after 2 years),

which were revised. Sixteen patients had disease progression or recurrence and died. One patient who was wheel chair bound with multiple lower cranial nerve palsies died 8 months after surgery. One patient had a major stroke despite functioning of the graft and died after 7 days.

PRESERVATION AND RECONSTRUCTION OF VEINS AND SINUSES Major cerebral veins are usually at risk during surgery for skull base tumors, because of displacement of veins from fixed drainage sites in the brain and/or their division to approach a lesion. When the venous outflow is compromised

Figure 10 Preoperative MRI images showing a giant petroclival Meckel’s cave and cavernous sinus meningiomas with severe brainstem compression displacing and adherent to the basilar artery.

Figure 11 Postoperative MRI images showing subtotal removal of the tumor with preservation of the basilar artery.

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Figure 13 Preoperative angiogram showing an isolated left anterior circulation. Figure 12 Preoperative MRI showing a recurrent meningioma involving orbit, cavernous sinus, and supracavernous regions with encasement and narrowing of the internal carotid artery.

due to a lack of adequate collateral circulation, venous infarction follows, with swelling, hemorrhage, and neuronal death. The clinical consequences, which can often be disastrous, will depend upon the region of involvement of the brain and size of the venous structure occluded. The consequences of cerebral venous sinus occlusion also depend upon the availability of collateral circulation. When such collaterals are not available, papilledema and visual loss and a pseudotumor cerebri syndrome are observed in milder cases, whereas severe diffuse brain swelling, coma, and death may be observed in severe cases. Acute venous or venous sinus occlusion is potentially very dangerous, whereas slow and chronic venous or venous sinus occlusion is better tolerated. Even in such patients, some neurologic manifestations may follow when the collaterals are poor. Veins have thinner walls and are not as tortuous as arteries, giving them less room for manipulation before rupture. Basal operations stretch the veins and put them at risk for rupture. To avoid rupture of a cerebral vein it should be stretched minimally either by minimizing the extent of brain retraction or by releasing it from adhesions to allow its lengthening. With basal lesions, veins at greatest risk for rupture are the temporal tip draining veins, and the vein(s) of Labb´e. In these instances, the surgeon must be aware of any aberrant venous anatomy before surgery to avoid major problems. In the majority of patients, the temporal tip draining veins can be divided without adverse consequences. However, when the Sylvian vein is very large or if the vein of Labb´e is absent due to prior surgery or is very small because of an anatomic variation, then the superficial middle cerebral (Sylvian) may not be safely occluded. In such a situation, a temporary clip can be placed on the concerned vein, and the brain is

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Figure 14 Illustration showing radial artery graft bypass from the ECA to the MCA-M2 and a saphenous vein graft from the cervical ICA to a different branch of MCA-M2 segment.

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Figure 15 Postoperative angiogram showing radial artery graft bypass from the ECA to the MCA-M2 and a saphenous vein graft from the cervical ICA to a different and slightly larger branch of MCA-M2 segment.

observed for swelling for 5 to 10 minutes. If the vein cannot be occluded safely, in many patients a change in the surgical approach or a small corticectomy will allow the operation to be performed. The vein(s) of Labb´e [Fig. 4(A)–4(D)] are at risk for injury during subtemporal and transpetrosal approaches (13–18). The partial labyrinthectomy petrous apicectomy transpetrosal approach, the translabyrinthine approach, and the total petrosectomy approach all move the surgeon anteriorly from the drainage point of the vein of Labb´e. However, in some patients, these strategies may not be enough to prevent excessive stretching of the vein. In some patients, the tentorium may be divided with minimal brain retraction, and then the retractor can be placed on the tentorium rather than the temporal lobe to prevent venous stretching. When the vein is very large and dominant with a very anterior drainage site [Fig. 4(B)], then the surgical approach may have to be changed to the retrosigmoid (or retrosigmoid + orbitozygomatic with frontotemporal craniotomy) to prevent venous injury, especially on the dominant side.

Figure 16 Postoperative MRI showing complete removal of the tumor.

brain. The only venous sinuses that may safely be occluded in most patients are the cavernous sinuses, the superior petrosal sinuses, and the nondominant, well-collateralized transverse and sigmoid sinuses. Occlusion of the cavernous sinus can usually be performed without adverse effects on vision and the orbit due to the presence of many collateral drainage channels from the orbit.

Venous Reconstruction The indications for venous reconstruction are accidental injury to large veins, if brain swelling is noted after the occlusion of a vein, or after the injury to any deep vein. In such patients, the easiest reconstruction may be by direct suture, using 8–0 nylon sutures. If the anastomosis is under tension, some of the tension can be released by dural mobilization. Direct repair is usually successful, even if the repaired vein is slightly stenotic. When a segment of the vein is missing and direct repair is difficult, a segment of saphenous vein from the leg, or a vein from the forearm or the neck, or the radial artery may be used as an interposition graft (17). Postoperative thrombosis is the main problem with venous reconstruction and may occur because of injury to the endothelium of the transplanted vein and the slow blood flow through the vein in general. To prevent this, we give the patients 4000 U of intravenous heparin during the reconstruction procedure, subcutaneous heparin during the first 7 postoperative days (5000 U q8h), and aspirin 325 mg daily thereafter for 2 to 3 months.

Cerebral Venous Sinuses Cerebral venous sinuses transmit a large volume of venous blood from the brain. The patency of the venous sinuses is very important to preserve the functional integrity of the

Intraoperative Sinus Occlusion Test During surgery, before occluding a sinus, a test occlusion must be performed (Fig. 5). To do this, the intrasinus pressure is measured by inserting a 20 gauge butterfly needle connected to a pressure transducer. The normal venous sinus pressure should be less than 15 mm Hg, depending upon the position of the head. After a stable reading is obtained, a temporary clip is applied on the venous sinus at the appropriate point of expected occlusion. Observation of the brain or cerebellum for swelling and the evoked potentials and intrasinus pressure is performed for at least 5 minutes. Intrasinus pressure is the most sensitive indicator of the three, but cerebellar swelling may occur very quickly. If brain swelling occurs, evoked potentials change, or intrasinus pressure increases by more than 5 mm Hg, then the temporary clip is removed and the sinus cannot be occluded. If the initial intrasinus pressure is above 15 mm Hg but there is no significant increase in the pressure, the sinus may be occluded, but continuous monitoring of the pressure must be done during the rest of the operation because a delayed increase in intrasinus pressure may occur and necessitate reconstruction. Preoperative occlusion tests of the venous sinuses are not safe because the clinical response is delayed, and the effects are not fully reversible.

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Figure 17 Preoperative MRI (A, B) showing chondrosarcoma involving the cavernous sinus and infiltrating the brain stem. (C) Illustration showing infiltration of cavernous ICA by the tumor.

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Figure 18 Illustration showing radial artery bypass to the MCA and removal of the tumor after trapping the ICA.

Reconstruction of Venous Sinuses Direct Repair When a small portion of the circumference of a venous sinus is involved by a tumor, direct repair is recommended. In such patients, the tumor is excised, and the sinus is repaired with 5– 0 prolene [Fig. 6(A) and 6(B)] sutures either by direct suturing or with a patch of dura mater or saphenous vein. The graft is sutured onto some of the sinus wall before removal of the tumor [Fig. 7(A) and 7(B)]. After removal of the tumor, the sinus may be allowed to bleed if it is a small rent, occluded with finger pressure or temporary clips if some collaterals exist, or occluded with a balloon shunt if high flow exists through the sinus [Fig. 7(C)]. If the repair is likely to take more than 10 minutes, then the patient will need to be heparinized. When the sigmoid sinus is divided to improve the exposure of the tumor, direct repair may be performed with 6–0 prolene sutures.

Graft Reconstruction Graft reconstruction of the sinus is performed in cases of total segmental defect (17), which cannot be repaired directly. The indications for such sinus repair are shown in Table 2. When the sinus to be repaired is large (≥1 cm diameter), the saphenous vein extracted from the thigh is used [Fig. 8(A) and 8(B)]. When the sinus has been previously partially occluded by the tumor, the radial artery is used because it tends to stay open even while the flow rate is low. Because of the discrepancy in size, an end-to-side technique is used for radial artery grafts [Fig. 9(A) and 9(B)], whereas an end-to-end technique is used for saphenous vein grafts.

Our Approach for Tumors Involving Cerebral Veins and Venous Sinuses Results of cerebral venous and venous sinus reconstruction in the 6 years from 1993 to 1999 for meningiomas are shown in Table 3. The principles that we follow in managing patients

with tumors involving the cerebral veins and venous sinuses are as follows: 1. Meningiomas are treated only if they are symptomatic, when they are found to involve the venous sinuses. 2. There are two options—radical resection with the involved sinus or conservative resection and radiosurgery. The decision to go ahead with radical resection involves the basic principles of any tumor resection such as age, comorbidities, and regions involved, major vascular and cranial nerve involvement. Once a decision is made to do a radical resection with the sinus, the principles of whether reconstruction is required or not is followed as described above. 3. Peeling of the tumor from the sinus can be done if only one of the walls is involved and the wall is reconstructed as described above. 4. If two walls are involved, the tumor may be still removed and repaired with a dural or venous patch. 5. If three walls or more than 50% of the sinus is involved, then sinus reconstruction may be required. 6. If the sinus is completely occluded preoperatively, no repair is needed. However, the surgeon must be prepared for sinus repair, if some flow exists intraoperatively. 7. Radiosurgery may cause delayed sinus thrombosis with brain edema and seizures. All veins should be preserved.

Vasospasm After Cranial Base Tumor Resection Cerebral vasospasm is well known to occur after various cerebral neurosurgical events that cause subarachnoid hemorrhage. Cerebral vasospasm can also occur after cranial base tumor resection (19). Vasospasm manifests clinically 7 to 30 days postoperatively. Pituitary tumors and craniopharyngiomas have a higher incidence of vasospasm, but the reason for this is not clear. Delayed neurologic deterioration in a patient who has undergone cranial base tumor surgery not explained by an intracranial mass lesion should be promptly investigated with angiography. If vasospasm is diagnosed,

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Figure 19 Postoperative MRI showing complete removal of the tumor. A (Axial), B (sagital).

it should be treated aggressively with hypertensive, hypervolemic therapy and if necessary, endovascular angioplasty.

CASE STUDIES Case Study 1 Meningioma with Subarachnoid Vascular Encasement A 43-year-old woman (Fig. 10) with a giant petroclival Meckel’s cave and cavernous sinus meningioma with severe brainstem compression, underwent a subtotal resection (Simpson grade III) of the tumor. This patient had a history of transient diplopia and facial numbness as well as some numbness involving the right side of the body. Frontotemporal craniotomy and a retrolabyrinthine transpetrosal approach were used to approach the tumor. The superior cerebellar artery had two branches encased by the tumor, which were dissected free. There were two brainstem perforators densely

adherent and partially encased just inferior to the superior cerebellar artery. These required very tedious and difficult dissection. The tumor was completely removed from the clival dura. The posterior communicating artery was preserved. The BA was completely dissected, and the tumor was gradually removed piecemeal in a complete fashion in this area. Tumor was left behind in the region of the Meckel’s cave, around the sixth nerve and in the posterior part of the cavernous sinus (Fig. 11). This was treated with radiosurgery. She has no postoperative neurologic deficits and required a ventriculoperitoneal shunt for hydrocephalus.

Case Study 2 Cavernous Sinus Meningioma: Postradiation Bypass A 47-year-old woman had headaches and ptosis was diagnosed to have a left-sided cavernous sinus meningioma (Fig. 12). She had fractionated, stereotactic, conformal

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Figure 20 (A) Axial and (B) sagittal contrast-enhanced T1 image of a magnetic resonance imaging scan showing the petroclival meningioma in Case 1.

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Figure 21 (A, B) Venous phase of angiogram showing prominent vein of Labb´e and dominance of the right lateral sinus.

Figure 22 Diagrammatic representation of the vein graft technique. Fish-mouth opening is made in the vein as well as in the graft to reduce the amount of stenosis later on. Also, a part of the sinus wall was removed.

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Figure 23 Diagrammatic representation of the vein graft technique (continued). The anastomosis is completed, and a pad of fat supports the graft.

radiotherapy 5 years ago; since that time, the tumor had been growing steadily and she has had spasm of the jaw. On examination, the patient had no vision in her left eye, partial ptosis, near complete ophthalmoplegia and restricted opening of the mouth without any sensitivity of the TM joint. MRI and angiography revealed an intracavernous and supracavernous tumor encasing and narrowing left ICA. The left ICA had a small ACA, but the circulation was nearly isolated in the left hemisphere (Fig. 13). She underwent RAG bypass from the cervical ECA to the M2 segment of the MCA followed by

SVG bypass grafting from the ICA to a different and slightly larger branch of the M2 segment of the MCA (Fig. 14). She had a temporal lobe clot on the immediate postoperative CT, which was evacuated. After 3 days, she had a gross total resection of the tumor. She had a CSF leak postoperatively, which was repaired by endonasal approach. She had no new neurologic deficits. She had no tumor remnant by MRI (Fig. 15) and patent grafts on CT angiogram after 10 months (Fig. 16).

Case Study 3 Recurrent Chondrosarcoma: Emergent Bypass Figures 17–19 show a patient with a recurrent chondrosarcoma involving the cavernous sinus and the brain stem. During the operation to remove the tumor, the intracavernous ICA was found to be severely invaded, and it ruptured. An emergent radial artery bypass graft was performed and the tumor was removed totally in two operations. She lost her vision (already impaired severely) but made an otherwise uneventful recovery. She remains tumor free after 3 years.

Case Study 4 Reconstruction of Vein of Labb´e

Transverse and sigmoid sinuses Figure 24 Operative picture of the completed anastomosis. The arrow points to the saphenous vein graft (SVG).

A 58-year-old woman presented with facial pain and numbness caused by a right petroclival meningioma extending into the Meckel’s cave and the cavernous sinus with mild brain stem compression (Fig. 20). The venous phase of the angiogram showed a prominent vein of Labb´e (Fig. 21). The tumor was removed by a transpetrosal retrolabyrinthine approach. However, early in the operation, an aberrant vein of Labb´e, draining the entire temporal lobe and draining into a dural sinus anterior to the transverse sinus, was damaged.

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Figure 25 (A, B) Three-dimensional computed tomographic angiogram of Case 4 showing a patent graft and sinus.

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Figure 26 Preoperative axial (A) and sagittal (B) enhanced MRI scan showing the lesion filling the right jugular foramen, petrous bone, and upper cervical area, with encasement and slight narrowing of the petrous ICA.

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Figure 27 (A) Preoperative right carotid angiogram reveals poor connection between the two transverse sinuses and the dominant right sinus. (Part B located on page 220).

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Figure 27 (B) Preoperative left carotid angiogram shows partial filling of the right carotid circulation and a stenotic but patent right jugular bulb.

Because significant temporal lobe swelling was noted, the vein of Labb´e was reconstructed with a short saphenous vein graft from the vein to the sigmoid sinus (Fig. 22). A special technique of venous attachment to the sigmoid sinus was used without significantly interrupting flow by placing the attaching sutures first and then cutting the hole into the sinus before tying the sutures (Figs. 23 and 24). The tumor was seen to involve the trigeminal fascicles severely. The temporal lobe swelling resolved postoperatively, and the patient recovered well. Postoperatively, the patient had partial sixth cranial nerve palsy and diminished sensation in the V1 and V2 region and absent corneal reflex. Postoperative MRV and threedimensional computed tomographic angiogram showed patency of the graft (Fig. 25). After a follow-up of 2 years, there was no tumor recurrence. The sixth cranial nerve palsy disappeared totally, but trigeminal loss persisted. The venous reconstruction was felt to be important in this patient in avoiding major problems.

Case Study 5 Vein Graft from IJV to Sigmoid Sinus

Figure 28 Illustration showing the saphenous vein graft, CN VII, the tumor bed, and the petrous ICA.

Figure 29 Postoperative angiography shows excellent patency of the vein graft (between arrows).

A 62-year-old man presented with worsening seizure, right sided tinnitus, and swallowing disturbances. On examination, he had 20% hearing loss in his right ear, was unable to perform tandem walk, and had nystagmus. MRI scan showed a highly vascular glomus jugulare tumor in the jugular foramen filling the region of right jugular bulb (Fig. 26) without occluding the sigmoid sinus and internal jugular vein (Fig. 27). The tumor encased the petrosal segment of the ICA bowing it forward. The sigmoid and transverse sinuses were larger on the right side but were subtotally occluded by the tumor. There was a good communication between the two

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sinuses at the torcular Herophili (Fig. 27). Therefore, it was felt to be safe to occlude the sinus during tumor resection. At operation, the intrasinus pressure was measured prior to sinus occlusion and excision of the tumor. Although the intrasinus pressure was initially unchanged after occlusion, the pressure increased steadily during the operation in the range of 35 to 40 torr. Because of this, reconstruction of the sinus was elected and performed with a saphenous vein graft (Fig. 28). A 5 cm long vein graft was sutured from the sigmoid sinus to the internal jugular vein. Patency of the graft was verified by intra-arterial and magnetic resonance angiography (Fig. 29). Postoperatively the patient had communicating hydrocephalus for which lumboperitoneal shunt was done. The patient had transient, postoperative facial nerve palsy, which recovered completely. After a follow up of 21 months, the patient was seen to have very mild impairment of tandem gait. There was no recurrence of the tumor and there was no other neurologic deficit.

REFERENCES 1. Mohit AA, Sekhar LN, Natarajan SK, et al. High-flow bypass grafts in the management of complex intracranial aneurysms. Neurosurgery. 2007;60:ONS105–122; discussion ONS122–103. 2. Natarajan SK, Sekhar LN, Schessel D, et al. Petroclival meningiomas: Multimodality treatment and outcomes at long-term follow-up. Neurosurgery. 2007;60:965–979; discussion 979–981. 3. Sekhar LN, Bucur SD, Bank WO, et al. Venous and arterial bypass grafts for difficult tumors, aneurysms, and occlusive vascular lesions: Evolution of surgical treatment and improved graft results. Neurosurgery. 1999;44:1207–1223; discussion 1223–1204. 4. Sekhar LN, Kalavakonda C. Cerebral revascularization for aneurysms and tumors. Neurosurgery. 2002;50:321–331. 5. Sekhar LN, Tzortzidis FN, Bejjani GK, et al. Saphenous vein graft bypass of the sigmoid sinus and jugular bulb during the removal of glomus jugulare tumors. Report of two cases. J Neurosurg. 1997;86:1036–1041. 6. Tzortzidis F, Elahi F, Wright D, et al. Patient outcome at long-term follow-up after aggressive microsurgical resection of cranial base chordomas. Neurosurgery. 2006;59:230–237; discussion 230–237.

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7. Tzortzidis F, Elahi F, Wright DC, et al. Patient outcome at longterm follow-up after aggressive microsurgical resection of cranial base chondrosarcomas. Neurosurgery. 2006;58:1090–1098; discussion 1090–1098. 8. Larson JJ, Tew JM Jr, Tomsick TA, et al. Treatment of aneurysms of the internal carotid artery by intravascular balloon occlusion: Long-term follow-up of 58 patients. Neurosurgery. 1995;36:26– 30; discussion 30. 9. McIvor NP, Willinsky RA, TerBrugge KG, et al. Validity of test occlusion studies prior to internal carotid artery sacrifice. Head Neck. 1994;16:11–16. 10. Origitano TC, Al-Mefty O, Leonetti JP, et al. Vascular considerations and complications in cranial base surgery. Neurosurgery. 1994;35:351–362; discussion 362–353. 11. Sekhar LN, Patel SJ. Permanent occlusion of the internal carotid artery during skull-base and vascular surgery: Is it really safe? Am J Otol. 1993;14:421–422. 12. Evans JJ, Sekhar LN, Rak R, et al. Bypass grafting and revascularization in the management of posterior circulation aneurysms. Neurosurgery. 2004;55:1036–1049. 13. Guppy KH, Origitano TC, Reichman OH, et al. Venous drainage of the inferolateral temporal lobe in relationship to transtemporal/transtentorial approaches to the cranial base. Neurosurgery. 1997;41:615–619; discussion 619–620. 14. Koperna T, Tschabitscher M, Knosp E. The termination of the vein of “Labbe” and its microsurgical significance. Acta Neurochir (Wien). 1992;118:172–175. 15. Kyoshima K, Oikawa S, Kobayashi S. Preservation of large bridging veins of the cranial base: Technical note. Neurosurgery. 2001;48:447–449. 16. Lustig LR, Jackler RK. The vulnerability of the vein of labbe during combined craniotomies of the middle and posterior fossae. Skull Base Surg. 1998;8:1–9. 17. Morita A, Sekhar LN. Reconstruction of the vein of Labbe by using a short saphenous vein bypass graft. Technical note. J Neurosurg. 1998;89:671–675. 18. Sakata K, Al-Mefty O, Yamamoto I. Venous consideration in petrosal approach: Microsurgical anatomy of the temporal bridging vein. Neurosurgery. 2000;47:153–160; discussion 160– 151. 19. Bejjani GK, Sekhar LN, Yost AM, et al. Vasospasm after cranial base tumor resection: Pathogenesis, diagnosis, and therapy. Surg Neurol. 1999;52:577–583; discussion 583–574.

Section 2 Site-Specific Considerations

16 Surgical Management of Tumors of the Nasal Cavity, Paranasal Sinuses, Orbit, and Anterior Skull Base Ehab Y. Hanna, Michael Kupferman, and Franco DeMonte

The roof of the nasal cavity is narrow from side to side, and slopes downward (at about a 30-degree angle) from front to back. The cribriform plate, which transmits the filaments of the olfactory nerve, forms the roof of the nasal cavity medial to the superior attachment of the middle turbinate. Lateral to the middle turbinate the fovea ethmoidalis forms the roof of the ethmoid sinuses. Careful assessment of the anatomy of the nasal roof, especially the relationship of the cribriform plate to the fovea ethmoidalis is critical in avoiding a cerebrospinal fluid (CSF) leak during transnasal surgery in this region. The cribriform plate is usually at a slightly lower horizontal plane than the fovea ethmoidalis forming a shallow olfactory groove. This configuration is described as Keros type I (Fig. 4). However, the cribriform plate may be moderately or significantly lower than the fovea ethmoidalis, resulting in a medium (Keros type II) or deep (Keros type III) olfactory groove. The topography of the roof may also be asymmetrical (1). The floor of the nasal cavity is concave from side to side and almost horizontal anteroposteriorly. The palatine process of the maxilla forms the anterior three-fourths, and the horizontal process of the palatine bone forms the posterior fourth of the nasal floor [Fig. 2(B)]. The majority of the nasal cavity is lined by pseudostratified ciliated columnar epithelium, which contains mucous and serous glands (respiratory epithelium). Specialized olfactory epithelium lines the most superior portion of the nasal cavity, and has direct connections with the olfactory tracts through openings in the cribriform plate. The arteries of the nasal cavities are the anterior and posterior ethmoidal branches of the ophthalmic artery, which supply the ethmoid and frontal sinuses and roof of the nose. The sphenopalatine artery supplies the mucous membrane covering the lateral nasal wall. The septal branch of the superior labial artery supplies the anteroinferior septum. The veins form a close cavernous plexus beneath the mucous membrane. This plexus is especially well marked over the lower part of the septum and over the middle and inferior turbinates. Venous drainage follows a pattern similar to arterial supply. The lymphatic drainage from the anterior part of the nasal cavity, similar to that of the external nose, is to the submandibular group of lymph nodes (Level I). Lymphatics from the posterior two-thirds of the nasal cavities and from the paranasal sinuses drain to the upper jugular (Level II) and retropharyngeal lymph nodes. The sensory nerves of the nasal cavity transmit either somato-autonomic or olfactory sensation. Somato-autonomic nerves include the nasociliary branch of the ophthalmic, which supplies the anterior septum and lateral wall. The anterior alveolar nerve, a branch of the maxillary (V2),

SURGICAL ANATOMY Nasal Cavity The nasal cavity is bounded by the bony pyriform aperture and the external framework of the nose (Fig. 1). The nasal cavity opens anteriorly through the skin-lined nasal vestibule into the nares, and communicates posteriorly through the choanae with the nasopharynx [Fig. 2(A)]. The nasal cavity is divided in the midline by the nasal septum, which includes both cartilaginous and bony components [Fig. 2(B)]. The cartilage of the septum is quadrilateral in shape, and is thicker at its margins than at its center. Its anterior margin is connected with the nasal bones, and is continuous with the anterior margins of the lateral cartilages; below, it is connected to the medial crura of the greater alar cartilages by fibrous tissue (Fig. 1). Its posterior margin is connected with the perpendicular plate of the ethmoid; its inferior margin is connected with the vomer and the palatine process of the maxilla. On the lateral nasal wall are the superior, middle, and inferior nasal turbinates, and below and lateral to each turbinate (concha) is the corresponding nasal passage or meatus [Fig. 3(A) and 3(B)]. Above the superior turbinate is a narrow recess, the sphenoethmoidal recess, into which the sphenoid sinus opens. The superior meatus is a short oblique passage extending about halfway along the upper border of the middle turbinate; the posterior ethmoid cells open into the front part of this meatus. The middle meatus is below and lateral to the middle turbinate. The anatomy of the middle meatus is fully displayed by removing the middle turbinate [Fig. 3(A) and 3(B)]. The bulla ethmoidalis is the most prominent anterior ethmoid air cell. The hiatus semilunaris is a curved cleft lying below and in front of the bulla ethmoidalis. It is bounded inferiorly by the sharp concave margin of the uncinate process of the ethmoid bone, and leads into a curved channel, the infundibulum, bounded above by the bulla ethmoidalis and below by the lateral surface of the uncinate process of the ethmoid. The anterior ethmoid air cells open into the front part of the infundibulum. The frontal sinus drains through the nasofrontal duct, which, in approximately 50% of subjects, will also drain into the infundibulum, but when the anterior end of the uncinate process fuses with the front part of the bulla, this continuity is interrupted and the nasofrontal duct then opens directly into the anterior end of the middle meatus. Below the bulla ethmoidalis, and partly hidden by the inferior end of the uncinate process, is the ostium of the maxillary sinus. An accessory ostium from the maxillary sinus is frequently present below the posterior end of the middle nasal concha. The inferior meatus is below and lateral to the inferior nasal turbinate. The nasolacrimal duct opens into the inferior meatus under cover of the anterior part of the inferior turbinate. 227

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Anterolateral view Frontal bone Nasal bones Frontal process of maxilla

Inferior view Major alar cartilage Lateral crus

Medial crus

Lateral process of septal nasal cartilages Septal cartilage Minor alar cartilage Accessory nasal cartilage

Major alar cartilage

Lateral crus Medial crus

Septal nasal cartilage Anterior nasal spine of maxilla Alar fibrofatty tissue

Alar fibrofatty tissue Septal nasal cartilage

Infraorbital foramen

provides sensory innervation to the inferior meatus and inferior turbinate. The nasopalatine nerve supplies the middle of the septum. The anterior palatine nerve supplies the lower nasal branches to the middle and inferior turbinates. The nerve of the pterygoid canal (vidian) and the nasal branches from the sphenopalatine ganglion supply the upper and posterior septum and superior turbinate. The olfactory nerve fibers arise from the bipolar olfactory cells and unite in fasciculi, which form a plexus beneath the mucous membrane and then ascend passing into the skull through the foramina in the cribriform plate. Intracranially, olfactory nerve fibers enter the undersurface of the olfactory bulb, in which they ramify and form synapses with the dendrites of the mitral cells of the olfactory tract.

Anterior nasal spine of maxilla Intermaxillary suture

Figure 1 Anatomy of the external nose. Source: From: Netter’s Atlas of Human Anatomy, Elsevier Inc.

the zygomatic process. Its roof or orbital wall is frequently ridged by the infraorbital canal, while its floor is formed by the alveolar process of the maxilla and is usually 1 to 10 mm below the level of the floor of the nose (Fig. 6). Projecting into the floor are several conical elevations corresponding with the roots of the first and second molar teeth, and in some cases the floor is perforated by one or more of these roots. The natural ostium of the maxillary sinus is partially covered by the uncinate process and communicates with the lower part of the hiatus semilunaris of the lateral nasal wall (Figs. 3 and 5). An accessory ostium is frequently seen in, or immediately behind, the hiatus. The maxillary sinus appears as a shallow groove on the medial surface of the bone about the fourth month of fetal life, but does not reach its full size until after the second dentition.

Maxillary Sinus The maxillary sinus (antrum of Highmore), the largest of the accessory sinuses of the nose, is a pyramidal cavity in the body of the maxilla (Figs. 5 and 6). Its base is formed by the lateral wall of the nasal cavity, and its apex extends into

Ethmoid Sinus The ethmoidal air cells consist of numerous thin-walled cavities situated in the ethmoidal labyrinth and bounded by the frontal, maxillary, lacrimal, sphenoid, and palatine bones.

Medial Wall of Nasal Cavity (Nasal Septum)

Frontal sinus Sphenoidal sinus Nasal septum

Falx cerebri Cribriform plate of ethmoid bon. Dura mater Sella turrica

Frontal bone

Choanae Lateral process of septal nasal cartilage

Nasal bone Vomer

Major alar cartilage Nasal vestibute Anterior nasal spine Incisive canal

Squamous part Sinus Nasal spine

Vomerine grove (for nasopalatine nerve and vessels Septal cartilage Major alar cartilage (medial crus)

Oral cavity Tongue Soft palate

Anterior nasal spine Maxilla

Nasal crest Incisive canal Palatine process

Crista galli Cribriform plate Perpendicular plate

Ethmoid bone Crest Body Sphenoidal sinus Medial, Lateral Plates of pterygoid process

Spenoid bone

Basilar part of occipital bone Pharyngeal tubercle Perpendicular plate Nasal crest Posterior nasal spine Horizontal plate Lesser palatine foramen

Palatine bone

Greater palatine foramen

Figure 2 (A) Anatomy of the nasal septum. (B) Skeletal framework of the nasal septum. Source: From Netter’s Atlas of Human Anatomy, Elsevier Inc.

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puberty. The frontal sinus is lined with respiratory epithelium and drains into the anterior part of the corresponding middle meatus of the nose through the nasofrontal duct, which traverses the anterior part of the labyrinth of the ethmoid. The soft tissues of the forehead are located anteriorly, the orbits are located inferiorly, and the anterior cranial fossa is located posteriorly (Fig. 3). Blood and neural supply is from the supraorbital and supratrochlear neurovascular bundles.

They lie in the upper part of the nasal cavity between the orbits (Fig. 6). The ethmoid sinuses are separated from the orbital cavity by a thin bony plate, the lamina papyracea. On either side they are arranged in three groups: anterior, middle, and posterior. The anterior and middle groups open into the middle meatus of the nose, the former by way of the infundibulum and the latter on or above the bulla ethmoidalis (Fig. 3). The posterior cells open into the superior meatus under cover of the superior nasal concha. Sometimes one or more ethmoid air cells extend over the orbital cavity (supraorbital ethmoid cells) or the optic nerve (Onodi cell). The ethmoidal cells begin to develop during fetal life.

Sphenoid Sinus The sphenoid sinus begins at the most posterior and superior portion of the nasal cavity (Fig. 3). This midline structure, which is contained within the body of the sphenoid bone, is irregular and often has an eccentrically located intersinus septum. When exceptionally large, the sphenoid sinus may extend into the roots of the pterygoid processes or great wings, and may pneumatize the basilar part of the occipital bone. The sphenoid sinus ostium is located on the anterior wall of the sinus and communicates directly with the sphenoethmoidal recess above and medial to the superior

Frontal Sinus The paired frontal sinuses appear to be outgrowths from the most anterior ethmoidal air cells. They are situated behind the superciliary arches, are rarely symmetrical, and the septum between them frequently deviates to one or the other side of the midline. Absent at birth, the frontal sinuses are generally fairly well developed between the seventh and eighth years, but only reach their full size after

Lateral Wall of Nasal Cavity Sphenoethmoidal recess Opening of sphenoidal sinus Hypophysis (pituitary gland) in sella turcica Sphenoidal sinus Phyaryngeal tonsil (adenoid if enlarged) Basilar part of occipital bone Pharyngeal raphe Choana Torus tubarius Opening of pharyngotympanic (auditory) tube Pharyngeal recess Horizontal plate of palatine bone Soft palate

Frontal sinus Superior nasal concha Superior nasal meatus Middle nasal concha Agger nasi Atrium of middle nasal meatus Middle nasal meatus Inferior nasal concha (turbinate) Limen nasi Nasal vestibute Inferior nasal mealus Palatine process of maxilla Incisive canal Tongue

Middle nasal concha Middle nasal meatus Bulging septum Airway to nasopoharynx Inferior nasal concha Inferior nasal meatus Floor of nasal cavity Speculum view Frontal sinus Probe passing from semilunar hiatus into frontal sinus via frontonasal duct

Cribriform plate of ethmoid bone Probe in opening of sphenoidal sinus Sphenoidal sinus Superior nasal meatus with opening of posterior ethmoidal cells Basilar part of occipital bone Torus tubarius Opening of phyaryngotympanic (auditory) tube Anterior arch of atlas (C.I vertebra)

Middle nasal concha (cut surface) Ethmoidal bulla Openings of middle ethmoidal cells Semilunar hiatus with opening of anterior ethmoidal cells Uncinate process Inferior nasal concha (cut surface) Opening of nasolacrimal duct Inferior nasal meatus

Figure 3

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Opening of maxillary sinus

Dens of axis (C2 vertebra)

(A) Anatomy of the lateral nasal wall. Removal of the middle turbinate demonstrates the anatomy of the middle meatus (lower image).

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Lacrimal bone Middle nasal concha Uncinate process Ethmoid bone Cribriform plate Superior nasal concha Highest nasal concha

Squamous part Sinus Nasal spine

Frontal bone

Sphenoethmoidal recess

Nasal bone

Sphenopalatine foramen

Agger nasi

Basilar part of occipital bone

Lateral process of nasal septal cartilage Major alar cartilage Alar fibrofatty tissue

Frontal process Anterior nasal spine Maxilla

Incisive canal Palatine process Alveolar process

Inferior nasal concha

Sphenoidal sinus Medical and Lateral Sphenoid bone plates of pterygoid process Pterygoid hamulus Sphenoidal process Orbital process Posterior nasal spine Palatine bone Perpendicular plate Horizontal plate

Ethmoidal bulla Frontal sinus Opening of frontonasal canal

Opening of middle ethmoidal cells Superior nasal concha (cut away) Openings of posterior ethmoidal cells

Middle nasal concha (cut away) Openings of sphenoidal sinus Infundibulum leading to frontonasal canal Semilunar hiatus (osteomeatal unit) with opening of anterior ethmoidal air cells

Openings into maxillary sinus Sphenopalatine foramen

Uncinate process Inferior nasal concha (cut away) Opening of nasolacrimal canal

Ethmoidal process of inferior nasal concha Lesser palatine foramen Greater palatine foramen

Figure 3 (B) Skeletal framework of the lateral nasal wall. Removal of the middle turbinate demonstrates the anatomy of the middle meatus (lower image). Source: From Netter’s Atlas of Human Anatomy, Elsevier Inc.

turbinate (Fig. 3). The sphenoid sinuses are present as minute cavities at birth, but their main development takes place after puberty. The posterosuperior wall of the sphenoid sinus displays the forward convexity caused by the floor of the sella turcica, which contains the pituitary gland. The optic nerve and the internal carotid artery are closely related to the superolateral wall of the sphenoid sinus, and their bony canals may be dehiscent within the sinus cavity (Fig. 7). Vascular and neural supplies come from the sphenopalatine and posterior ethmoidal arteries and the branches of the sphenopalatine ganglion, respectively.

Infratemporal Fossa The infratemporal fossa is an irregularly shaped space, situated below and medial to the zygomatic arch. It is bounded, anteriorly by the posterior surface of the maxilla, superiorly by the greater wing of the sphenoid and by the undersurface of the squamous portion of the temporal bone medially by the lateral pterygoid plate; and laterally by the

ramus of the mandible. It contains the inferior aspect of the temporalis muscle, and the medial and lateral pterygoid muscles (Fig. 8). It also contains branches of the internal maxillary vessels including the middle meningeal artery, and the mandibular (V3) nerves including the lingual, inferior alveolar, and auriculotemporal nerves. The foramen ovale and foramen spinosum open on its roof, and the alveolar canals on its anterior wall. The inferior orbital and pterygomaxillary fissures communicate with and may act as routes of spread of cancer to the infratemporal fossa. The infratemporal fossa also contains the upper carotid sheath, including the internal carotid artery, internal jugular vein and the last four cranial nerves (Fig. 8).

Pterygopalatine Fossa The pterygopalatine fossa is a small, triangular space situated behind the maxillary sinus, in front of the pterygoid plates, and beneath the apex of the orbit. This fossa communicates with the orbit by the inferior orbital fissure, with the nasal

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foramina: the anterior, situated about the middle of the lateral margin of the olfactory groove, transmits the anterior ethmoidal vessels and the nasociliary nerve; the nerve runs in a groove along the lateral edge of the cribriform plate; and the posterior ethmoidal foramen opens at the back part of this margin under cover of the projecting lamina of the sphenoid, and transmits the posterior ethmoidal vessels and nerve. More laterally, the cranial floor forms the orbital roof and supports the frontal lobes of the cerebrum. Further back in the middle is the planum sphenoidale forming the roof of the sphenoid sinus, and the anterior margin of the chiasmatic groove, running laterally on either side to the upper margin of the optic foramen (Fig. 9).

Orbit

Figure 4 Anatomy of the ethmoid roof and lateral lamella of the cribriform plate: (A) Keros type I, (B) Keros type II, (C) Keros type III, and (D) asymmetrical ethmoid roof. Note that the right lateral lamella of the cribriform plate is very thin and long and is obliquely oriented including much of the right ethmoid roof. Abbreviations: OP, Orbital plate of frontal bone; LCPL, Lateral cribriform plate lamella; EB, Ethmoid bulla.

cavity by the sphenopalatine foramen, and with the infratemporal fossa by the pterygomaxillary fissure (Fig. 5). Five foramina open into it. Of these, three are on the posterior walls, which are the foramen rotundum, the pterygoid canal, and the pharyngeal canal, in this order downward and medial. On the medial wall is the sphenopalatine foramen, and below is the superior orifice of the pterygopalatine canal (Fig. 5). The fossa contains the maxillary nerve, the sphenopalatine ganglion, and the terminal part of the internal maxillary artery. The fissures and foramina of the pterygopalatine fossa serve as “highways” for spread of cancer from the sinonasal region to the orbit, infratemporal fossa, and cranial base.

Anterior Cranial Fossa The floor of the anterior fossa is formed by the orbital plates of the frontal bone, the cribriform plate of the ethmoid, and the lesser wings and front part of the body of the sphenoid. In the midline, it presents, from anterior to posterior, the frontal crest for the attachment of the falx cerebri; the foramen cecum, which usually transmits a small vein from the nasal cavity to the superior sagittal sinus; the crista galli, the free margin of which affords attachment to the falx cerebri (Fig. 9). On either side of the crista galli is the olfactory groove formed by the cribriform plate, which supports the olfactory bulb and presents foramina for the transmission of the olfactory nerves. Lateral to either olfactory groove are the internal openings of the anterior and posterior ethmoidal

The orbits are two quadrilateral pyramidal cavities, their bases being directed forward and lateral, and their apices backward and medial, so that their long axes diverge at a 45degree angle and, if continued backward, would meet over the body of the sphenoid. The orbit is anatomically defined by seven bones (Fig. 10): frontal, zygomatic, maxillary, lacrimal, ethmoid, sphenoid and palatine; and by the orbital septum which originates at the arcus marginalis, fusing with the levator aponeurosis above and the capsulopalpebral fascia below. It is bounded by the ethmoid and sphenoid sinuses at its medial aspect, the frontal sinus superomedially, the cranial vault superiorly and posteriorly, the temporal fossa laterally, and the maxillary sinus inferiorly. Each orbital cavity has a roof, a floor, a medial and a lateral wall, a base, and an apex. The roof is formed anteriorly by the orbital plate of the frontal bone, and posteriorly by the lesser wing of the sphenoid. It presents medially the trochlear fovea for the attachment of the cartilaginous pulley of the superior oblique muscle and laterally the lacrimal fossa for the lacrimal gland. The floor is formed mainly by the orbital surface of the maxilla; anteriorly and laterally, by the orbital process of the zygomatic bone; and posteriorly and medially, to a small extent, by the orbital process of the palatine bone. At its medial angle is the superior opening of the nasolacrimal canal, immediately to the lateral side of which is a depression for the origin of the inferior oblique muscle. Running anteriorly near the middle of the floor is the infraorbital canal, ending anterior to the maxilla in the infraorbital foramen and transmitting the infraorbital nerve and vessels. The medial wall is formed from anteriorly to posteriorly by the frontal process of the maxilla, the lacrimal bone, the lamina papyracea of the ethmoid, and a small part of the body of the sphenoid anterior to the optic foramen. Anteroinferiorly, the lacrimal sac is situated between the anterior and posterior lacrimal crests, at the junction between the medial wall and the floor. The lacrimal part of the orbicularis oculi arises from the posterior lacrimal crest. At the junction of the medial wall and the roof, the frontoethmoidal suture presents the anterior and posterior ethmoidal foramina, the former transmitting the nasociliary nerve and anterior ethmoidal vessels and the latter the posterior ethmoidal nerve and vessels. These foramina indicate the level of the cranial base within the orbit. The lateral wall is formed by the orbital process of the zygomatic and the orbital surface of the greater wing of the sphenoid. On the orbital process of the zygomatic bone are the orbital tubercle (Whitnall) and the orifices of one or two canals, which transmit the branches of the zygomatic nerve. Between the roof and the lateral wall, near the apex of the orbit, is the superior orbital fissure (SOF). Through this fissure the oculomotor, the trochlear, the ophthalmic division

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Frontal sinus

Posterior ethmoidal foramen Orbital process of palatine Optic foramen

Anterior ethmoidal foramen

Sphenopalatine foramen Sella turcica Probe in foramen rotundum

Fossa for lacrimal sac Uncinate process of ethmoid Openings of maxillary sinus Inferior nasal concha

Probe in pterygoid canal Probe in pterygopalatine canal Palatine bone Lateral pterygoid plate

Pyramidal process of palatine

Figure 5

Anatomy of the maxillary sinus (lateral wall removed). Source: From Ref. 22.

of the trigeminal (V1), and the abducent nerves enter the orbital cavity, also some filaments from the cavernous plexus of the sympathetic and the orbital branches of the middle meningeal artery. Passing posteriorly through the fissure are the ophthalmic vein and the recurrent branch from the lacrimal artery to the dura mater. The lateral wall and the floor are separated posteriorly by the inferior orbital fissure, which transmits the maxillary nerve (V2) and its zygomatic branch, the infraorbital vessels, and the ascending branches from the sphenopalatine ganglion. The base of the orbit (orbital rim), quadrilateral in shape, is formed superiorly by the supraorbital arch of the frontal bone, in which is the supraorbital notch or foramen for the passage of the supraorbital vessels and nerve; inferiorly by the zygomatic bone and maxilla, united by the zygomatico-maxillary suture; laterally by the zygomatic bone and the zygomatic process of the frontal joined by the zygomatico-frontal suture; medially by the frontal bone and the frontal process of the maxilla united by the frontomaxillary suture. The apex is situated in the posterior aspect of the orbit. The optic foramen is a short, cylindrical canal, through which passes the optic nerve and ophthalmic artery. The extraocular muscles—four rectus muscles and two obliques—effect movement of the eye. The third cranial nerve innervates all but the lateral rectus and the superior oblique

muscles, which are innervated by the sixth and fourth cranial nerves, respectively. The rectus muscles originate at the annulus of Zinn and insert on the globe forming a muscle cone, which is the central anatomic space in the orbit. The lacrimal system is composed of secretory and drainage systems. Secretory glands—the glands of Moll, Kraus, and Wolfring—may be found along the margin of the eyelid. The lacrimal gland with its palpebral and orbital lobes is located in the superotemporal orbit (Fig. 11). The lacrimal drainage system, located in the inferonasal orbit, is represented by the puncta, canaliculi, lacrimal sac, and nasolacrimal duct. Tumor involvement of the lacrimal system may present with epiphora. The skin of the eyelid is continuous with the palpebral and bulbar conjunctivae, which are, in turn, contiguous with the globe. Each of these epithelial surfaces represents a potential site of origin for cancer.

REGIONAL PATHOLOGY AND DIFFERENTIAL DIAGNOSIS Tumors of the Nasal Cavity and Paranasal Sinuses The mucosal lining of the nose—the Schneiderian membrane— is derived from ectoderm. This is uniquely different from the mucosa of the rest of the upper respiratory tract, which is derived from endoderm. Olfactory neuroepithelium lines

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Coronal section Olfactory bulbs

Celebral falx Brain

Frontal sinus

Nasal cavities

Orbital fat

Nasal septum Ethmoidal cells Middle nasal concha

Opening of maxillary sinus

Middle nasal meatus

Infraorbital Zygomatic

Maxillary sinus

Alveolar

Inferior nasal meatus

Recesses of maxillary sinus

Buccinator muscle Alveolar process of maxilla

Inferior nasal concha

Body of tongue Hard palate Sublingual gland Oral cavity Mandible (body)

Sagittal section Ethmoidal cells Frontal sinus

Opening of sphenoidal sinus

Opening of frontonasal duct Sphenoidal sinus

Semilunar hiatus

Middle nasal concha (cut away)

Uncinate process Opening of maxillary sinus Inferior nasal concha

Figure 6 Anatomy of the ethmoid and maxillary sinuses. (Coronal section). Source: From Netter’s Atlas of Human Anatomy, Elsevier Inc.

the superior portion of the nasal cavity and the roof of the nose, and gives rise to neuroectodermal tumors such as olfactory neuroblastoma and neuroendocrine carcinoma (2–4). The sinonasal epithelium also has minor salivary glands, and gives rise to salivary gland tumors such as adenoidcystic carcinoma and mucoepidermoid carcinoma (5–8). However, the most common epithelial neoplasms of the sinonasal tract are those arising from “metaplastic” squamous epithelium, namely, squamous cell carcinoma, and those originating from the seromucinous glands of the mucosal lining, collectively known as adenocarcinomas (9). The unique histology of this region is reflected in the histogenesis of a complex variety of epithelial and nonepithelial tumors (Table 1). These tumors have a wide range of biologic behavior, and a few arise exclusively in the sinonasal tract (e.g., inverted papilloma, olfactory neuroblastoma). Nonepithelial tumors are similar to those in other regions in the head and neck. The details of some of these tumors, such as squamous and nonsquamous carcinoma, melanoma, esthesioneuroblastoma, sarcomas, and angiofibromas and fibro-osseous lesion, are discussed in more detail in other chapters in section three of the book. Overall, sinonasal cancer accounts for about 1% of all malignancies and approximately 3% of cancer of the head

and neck. There is a male predominance [Fig. 12(A)], with a strong predilection for Caucasians [Fig. 12(B)]. The majority of patients are over 50 years of age at the time of diagnosis [Fig. 12(C)]. The most common malignant tumor of the nasal cavity and paranasal sinuses is squamous cell carcinoma [Fig. 12(D)]. Although the maxillary antrum is the most commonly involved sinus [Fig. 12(E)], anterior skull base invasion is most frequently encountered with malignant neoplasms of the nasal cavity and ethmoid sinus. Upward extension of these neoplasms toward the cribriform plate or fovea ethmoidalis is not uncommon, and heralds intracranial extension (10). Primary carcinoma of the frontal sinus is uncommon, and those arising in the sphenoid sinus are rare (11). Unfortunately, despite significant improvement in diagnostic techniques such as nasal endoscopy and high-resolution imaging, most patients present with advanced stage disease [Fig. 12(F)].

Tumors of the Orbit The majority of malignant tumors involving the orbit represent direct extension of tumors of the sinonasal tract. Cancers arising primarily within the orbit are less common, and may be classified broadly into pediatric and adult groups. Further

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(A)

(B)

Figure 7 (A) Cadaver dissection of the sphenoid sinus (SS). The sinus is located in the midline superior to the nasopharynx (NP). The sella turcica (ST) forms a convexity in the posterosuperior wall. The internal carotid artery (arrow) courses through the lateral wall of the sinus and is related superiorly to the optic nerve (ON). (B) Endoscopic view of the left sphenoid sinus. Note the internal carotid artery (ICA) and optic nerve (ON) impressions on the lateral and superior walls. A bony septum within the sinus inserts into the optico-carotid recess (OCR). Source: This illustration in the property of The Department of Head and Neck Surgery, M.D. Anderson Cancer Center is used with permission.

(A)

(B)

(C)

Figure 8 Anatomy of the infratemporal fossa. (A) Inferior view. (B) Lateral view. (C) Anterior view. Abbreviations: TM, temporalis muscle; MM, masseter muscle; MPM, medial pterygoid muscle; LPM, lateral pterygoid muscle; IMA, internal maxillary artery; MMA, middle meningeal artery; ICA, internal carotid artery; IJV, internal jugular vein; LN, lingual nerve; IAN, inferior alveolar nerve; ATN, auriculotemporal nerve; V3, third division of the trigeminal nerve; ET, Eustachian tube; CN, cranial nerve (VII, IX, X, XI, and XII).

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Figure 9 The floor of the anterior cranial fossa. The cribriform plate (CP) is characterized by the presence of foramina for the olfactory nerves on each side of the crista galli (CG), which is seen in the midline. Lateral to the cribriform plate (CP) is the ethmoidal roof, and even more lateral the roof of the orbit. Posterior to the cribriform plate is the planum sphenoidale (PS). The optic nerves (ON) form the optic chiasm behind the planum sphenoidale. Source: This illustration in the property of The Department of Head and Neck Surgery, M.D. Anderson Cancer Center is used with permission.

subclassification may be according to site of origin, histologic type, or both. The most common intraocular tumor seen in children is Retinoblastoma, which usually presents by the third year of age. Other common tumors in the orbit in children include rhabdomyosarcoma, neuroblastoma, lymphoma, and leukemia. Rhabdomyosarcoma is the most common primary cancer and Neuroblastoma is the most common metastatic cancer to the orbit in children. Granulocytic sarcoma as a primary orbital neoplasm may precede or follow systemic leukemia. Primarily found in children with myelogenous leukemia, this tumor rarely occurs in adults (1). In adults, approximately 65% of orbital tumors are malignant. The most common benign tumors are vascular malformations and pleomorphic adenoma of the lacrimal gland. Malignant tumors of the lacrimal gland are most commonly lymphomas or tumors of salivary gland origin. Overall, lymphoma is the most common tumor of the orbit in adults. The main differential diagnosis is lymphoid hyperplasia and orbital pseudotumor. Malignant salivary gland tumors of the lacrimal gland include adenoid cystic carcinoma, ma-

lignant mixed cell tumor, and mucoepidermoid carcinoma. Neoplasms of the lacrimal sac include squamous cell carcinoma, adenocarcinoma, transitional cell carcinoma, salivary gland carcinoma, and poorly differentiated carcinoma. Cancer of the skin of the lid includes basal cell carcinoma, squamous cell carcinoma, sebaceous cell carcinoma and malignant melanoma, any of which may invade the orbit. Tumors arising from the conjunctiva may also invade the orbit, including malignant melanoma, squamous carcinoma, and lymphoma. Choroidal melanoma is the most common of all intraocular malignancies, and is biologically distinct from conjunctival or cutaneous melanoma (1). Primary intraorbital malignancies in adults are rare. Malignant neurogenic tumors of the orbit are uncommon, but those of peripheral nerve sheath origin predominate. They most commonly represent malignant degeneration in patients with multiple benign neurofibromatosis. Other sarcomas that infrequently arise within the orbit include osteosarcoma, chondrosarcoma, malignant fibrous histiocytoma, hemangiopericytoma, and liposarcoma. Multiple myeloma may present in the orbit as a solitary plasmacytoma

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Orbital surface of frontal bone Optic canal (foramen)

Posterior ethmoidal foramen Anterior ethmoidal foramen

Orbital surface of lesser wing of sphenoid bone Superior orbital fissure

Orbital plate of ethmoid bone

Orbital surface of greater wing of sphenoid bone Lacrimal bone Orbital surface of zygomatic bone

Fossa for lacrimal sac Inferior orbital fissure

Orbital surface of maxilla Infraorbital groove Orbital process of palatine bone

Figure 10 Anatomy of the right orbit. Source: From Ref. 22.

or the orbit may be involved as part of disseminated disease. Hematogenous metastasis to the orbit most commonly originates from a primary in the lung or prostate in males. In females, carcinoma of the breast is the most common source of metastasis to the orbit (1).

Frontal bone (cut away) Orbital part of lacrimal gland Palpebral part of lacrimal gland Excretory ducts of lacrimal gland Plica semilunaris and lacrimal lake Lacrimal caruncle Inferior lacrimal papilla and punctum Opening of nasolacrimal duct

Superior lacrimal papilla and punctum Lacrimal canaliculi Lacrimal sac Nasolacrimal duct Middle nasal concha Nasal cavity Inferior nasal concha (cut) Inferior nasal meatus

Figure 11 Anatomy of the lacrimal system. Source: From: Netter’s Atlas of Human Anatomy, Elsevier Inc.

CLINICAL ASSESSMENT Clinical evaluation of patients with cancer of the nasal cavity, paranasal sinuses, and orbit should help to achieve three objectives: (1) establishment of the diagnosis, (2) determination of the extent of and stage disease, and (3) development of a plan for treatment. These objectives are usually achieved through a detailed history, comprehensive clinical examination of the head and neck, imaging, and biopsy.

History and Clinical Examination The signs and symptoms of early sinonasal tumors are very subtle and nonspecific. Early lesions are often completely asymptomatic or mimic more common benign conditions such as chronic sinusitis, allergy, or nasal polyposis. Since early detection of sinonasal tumors is probably the most important factor in improving prognosis, a high degree of suspicion is necessary to diagnose smaller lesions. Common symptoms include nasal obstruction, “sinus pressure” or pain, nasal discharge that may be bloody, anosmia, or epistaxis. Failure of these symptoms to respond to adequate medical therapy or the presence of unilateral signs and symptoms should alert the physician to the possibility of malignancy, and warrants further investigation by high-resolution

Chapter 16: Surgical Management of Tumors of the Nasal Cavity, Paranasal Sinuses, Orbit, and Anterior Skull Base Table 1 Tumors of the Sinonasal Tract Benign Epithelial Papilloma Adenoma Dermoid Nonepithelial Fibroma Chondroma Osteoma Neurofibroma Hemangioma Lymphangioma Nasal glioma Intermediate Schneiderian papilloma Inverted Papillary Cylindrical Angiofibroma Ameloblastoma Fibrous dysplasia Ossifying fibroma Giant cell tumor Malignant Epithelial Squamous cell carcinoma Differentiated (well, moderately, poorly) Basaloid squamous Adenosquamous Nonsquamous cell carcinoma Adenoid cystic carcinoma Mucoepidermoid carcinoma Adenocarcinoma Neuroendocrine carcinoma Hyalinizing clear cell carcinoma Melanoma Olfactory neuroblastoma Sinonasal undifferentiated carcinoma Nonepithelial Chordoma Chondrosarcoma Osteogenic sarcoma Soft tissue sarcoma Fibrosarcoma Malignant fibrous histiocytoma Hemangiopericytoma Angiosarcoma Kaposi sarcoma Rhabdomyosarcoma Lymphoproliferative Lymphoma Polymorphic reticulosis Plasmacytoma Metastatic Source: From Ref. 1

imaging. Comprehensive examination of the nasal cavity should be done after topical decongestion and anesthesia using rigid or flexible endoscopy (Fig. 13). The presence of intranasal masses, ulcers, or areas of contact bleeding may indicate a malignant tumor. Although unilateral “polyps” may be inflammatory, they are more commonly neoplastic. Tumors may also present as submucosal masses without

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changes in the mucosa, other than displacement. Any suspicious lesions should be biopsied; preferably after highresolution imaging has been obtained to avoid severe bleeding and/or CSF leak as discussed below. Extension of sinonasal tumors to adjacent structures renders the diagnosis obvious, but is a late manifestation of the disease. Soft tissue swelling of the face may indicate tumor extension through the anterior bony confines of the nose and sinuses (Fig. 14). Inferior extension toward the oral cavity may present with an ulcer or a submucosal mass in the palate or the alveolar ridge (Fig. 15). Middle ear effusion may indicate tumor involvement of the nasopharynx, Eustachian tube, pterygoid plates, or tensor veli palatini muscle. Extension to the skull base may lead to involvement of the cranial nerves leading anosmia, blurred vision, diplopia, or in hyposthesia along the branches of the trigeminal nerves. The presence of associated neck masses usually represents metastatic disease in the cervical lymph nodes. Orbital involvement is common in patients with cancer arising from the ethmoid, maxillary, frontal, and sphenoid sinuses in descending order of frequency. Less commonly, the orbit is involved by a primary tumor of the eye or its adnexa. Signs and symptoms of tumors in the orbit are usually due to mass effect or neuromuscular dysfunction. The patient may complain of proptosis, irregular shape of the eyelid, or blepharoptosis. Epiphora usually indicates involvement of the nasolacrimal duct (Fig. 11). Double vision may result from compression or infiltration of ocular nerves or muscles. Visual loss secondary to optic nerve involvement is usually a late sign, although more subtle signs of optic nerve dysfunction, including afferent pupillary defect, loss of color vision, and visual field defect are more frequently encountered. Finally, orbital involvement may be asymptomatic, and is only discovered on CT or MRI evaluation of patients with sinonasal complaints. Evaluation of patients with suspected primary or secondary malignancy in the orbit should include a detailed neuro-ophthalmologic examination. This usually includes detailed assessment of visual acuity, visual fields, and ocular motility. Other ophthalmologic evaluation includes careful pupillary examination for afferent pupillary defect or anisocoria, external examination to include Hertel exophthalmometry, and marginal reflex distance as an indicator of eyelid position. Slit lamp examination of the conjunctivae, cornea, anterior chamber, and lens is appropriate. Finally, detailed examination of the fundus may reveal compressive effect, intraocular malignancy, or an unrelated reason for visual loss. Formal testing of color vision and automated visual fields is commonly appropriate.

IMAGING Indications Imaging of the nasal cavity, paranasal sinuses, and orbit is indicated whenever there is clinical suspicion of a neoplastic process. Imaging is also indicated for obtaining pretreatment information regarding the location, size, extent, and invasiveness of the primary tumor, as well as the presence of regional and distant metastasis. Such information is crucial in deciding on therapeutic options and for proper preoperative planning of the optimal surgical approach. Imaging also plays an important role in the posttreatment follow-up, indicating areas of residual or recurrent disease, and defining suspicious areas for biopsy.

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Figure 12 Patients with sinonasal cancer seen at MD Anderson Cancer Center between 1944 and April 2007. (N = 2698 patients). Source: This illustration in the property of The Department of Head and Neck Surgery, M.D. Anderson Cancer Center is used with permission.

Imaging Modalities Both computed tomography (CT) and magnetic resonance imaging (MRI) may be needed for optimum radiologic assessment of sinonasal malignancy, particularly in assessing the cranial base, orbit and pterygo-palatine, and infratemporal fossae. Coronal images best delineate involvement of the orbital walls and invasion of the skull base, particularly the cribriform plate. Axial images are particularly helpful in demonstrating tumor extension through the posterior wall of the maxillary sinus into the pterygopalatine fossa and infratemporal fossae. Sagittal images are particularly helpful in evaluating extension along the cribriform plate, planum sphenoidale, and clivus (Fig. 16). The main advantage of CT scans is in delineating the architecture of the bones, especially in “bone windows” [Fig. 16(A) and 16(B)]. The addition of contrast enhancement

increases tumor definition from adjacent soft tissue, especially intracranially. Bone destruction and soft tissue invasion suggest an aggressive lesion, usually a malignant neoplasm. Widening or sclerosis of the foramina of the infraorbital, vidian, mandibular, or maxillary nerves may indicate perineural spread (Fig. 17). MRI is unsurpassed in delineating soft tissue detail, both intra- and extracranially (Fig. 16). Obliteration of fat planes in the pterygopalatine fossa, infratemporal fossa, and nasopharynx usually indicates tumor transgression along these boundaries. Dural thickening or enhancement is usually an indication of tumor involvement, and evaluation of critical structures such as the brain and carotid artery is best delineated by MRI. Similarly, enhancement or thickening of cranial nerves indicates perineural spread, which is better detected on MRI than CT (12) (Fig. 17). Perhaps one of the most

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significant advantages of MRI is the ability to distinguish tumor from retained secretions secondary to obstruction of sinus drainage (Fig. 18). MRI is also particularly helpful in monitoring patients in the postoperative follow-up period, although this role may be supplanted in the near future by positron emission tomography (PET) scans because of its ability to distinguish between tumor recurrence and posttreatment fibrosis. PET–CT is also helpful in delineating regional and distant metastasis (Fig. 19). Angiography is not indicated in the routine assessment of patients with neoplasms of the nose, paranasal sinuses, and orbit. In certain selected cases, however, angiography may be necessary. These cases include vascular neoplasms of the sinonasal region, where angiography will not only delineate the tumor extent and the blood supply but also permit the use of selective embolization of the vascular supply to the tumor (Fig. 20). This reduces intraoperative blood loss, facilitating surgical resection. Figure 13 Carcinoma of the nasal cavity. Endoscopic view showing a tumor arising from the floor of the right nasal cavity. Biopsy revealed squamous cell carcinoma. Source: This illustration in the property of The Department of Head and Neck Surgery, M.D. Anderson Cancer Center is used with permission.

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Figure 14 Advanced ethmoid carcinoma. Clinical photographs showing the mass centered on the nasion, and causing widening of the interpalpebral distance (telecanthus). The mass shows involvement of the overlying skin and destruction of the underlying nasal bone. Source: This illustration in the property of The Department of Head and Neck Surgery, M.D. Anderson Cancer Center is used with permission.

BIOPSY Nasal Cavity and Paranasal Sinuses The definitive diagnosis of a neoplasm of the nasal cavity and paranasal sinuses relies on expert histopathologic review of any biopsy specimens by a head and neck pathologist to confirm the exact diagnosis prior to treatment. This is critical since the treatment and prognosis of sinonasal cancer is greatly influenced by histology (13). The vast majority of sinonasal neoplasms are accessible for biopsy through a strictly endonasal approach. A wide variety of rigid nasal endoscopes offers superb visualization of intranasal lesions with a high degree of optical resolution and bright illumination (Fig. 13). The application of topical anesthetics and decongestants improves visualization and allows thorough examination of the nasal cavity. The site of origin of the lesion and its relation to the nasal walls (septum, floor, roof, and lateral nasal wall) should be noted. An adequate specimen should be obtained, avoiding crushing of tissue, and submitted for histopathologic examination. If the diagnosis of lymphoma is suspected, fresh tissue should be sent in saline, rather than fixed in formalin. Most endonasal biopsies can be performed in the outpatient setting with minimal discomfort to the patient. In certain cases, the diagnosis of a highly vascular neoplasm, such as angiofibroma, may be suspected on clinical grounds. Under these circumstances, it is prudent not to perform the biopsy until imaging and angiography (possibly with embolization) are performed (Fig. 20). Preoperative biopsy can then be performed in the operating room under controlled conditions to confirm the diagnosis before surgical resection. If a nasal mass is suspected to have an intracranial communication such as an encephalocele, meningocele, or nasal glioma, this should be confirmed with imaging to avoid inadvertent CSF leak and subsequent meningitis (Fig. 21).

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Figure 15 Carcinoma of the maxillary sinus may extend inferiorly and destroys the palate presenting as an ulcer (A) or submucosal mass (B). Source: This illustration in the property of The Department of Head and Neck Surgery, M.D. Anderson Cancer Center is used with permission.

In most cases of primary intraorbital tumors, the approach used to obtain a biopsy is dictated by the location of the tumor. Lesions in the superior orbit may be addressed by a coronal flap or through a brow incision (modified Kronlein or Stallard-Wright incision). Lateral orbital lesions may require removal of the orbital rim. The transconjunctival approach, with detachment of the lateral canthal tendon, provides access to the orbital floor. The medial orbit may be entered

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Figure 16 Ethmoid carcinoma. Coronal and sagittal images showing bony destruction on CT scan (A and B) and intracranial invasion on T1-MRI with contrast (C and D). Source: This illustration in the property of The Department of Head and Neck Surgery, M.D. Anderson Cancer Center is used with permission.

through a modified Lynch or transcaruncular incision. Lesions within the muscle cone may be addressed by elevating conjunctiva and Tenon’s capsule from the globe and detaching the necessary rectus muscle. Lacrimal gland lesions are best approached through the upper lid crease (1).

PREOPERATIVE PREPARATION A thorough preoperative assessment should determine the candidacy of a patient for surgical management of his or her neoplasm. This involves a careful “mapping” of the tumor extent, as well as the general medical condition and functional status of the patient. This is usually accomplished by a detailed history and physical examination, and comprehensive examination of the head and neck region including endoscopy of the sinonasal region. Cranial nerve examination as well as ophthalmologic evaluation should

be done to evaluate cranial base and orbital extension, respectively. High-resolution imaging should be obtained using CT or MRI, or both, to accurately assess the tumor extent. In certain cases, angiography will be needed to determine the extent of carotid arterial involvement. The balloon occlusion test should be performed if carotid artery resection or reconstruction is contemplated. Preoperative embolization may be indicated in certain vascular tumors. Neurosurgical consultation is needed if a combined craniofacial approach is anticipated. If free vascularized flaps will be used for reconstruction, expertise with microvascular surgery is needed, and appropriate consultation should be obtained. Evaluation by a maxillofacial prosthodontist is required in most patients to obtain preoperative dental impressions and design surgical obturators or splints for maintenance of proper dental occlusion and oral rehabilitation. Similar expertise is essential in cases where prosthetic

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Figure 17 Perineural spread of adenoid cystic carcinoma along the third division of the trigeminal nerve: (A) A coronal CT with IV contrast showing widening of the left foramen ovale (black arrow), compared to the one on the right. There is also an enhancement and thickening along the left Meckel cave (white arrows). (B) A coronal T1-weighted MRI with gadolinium showing marked thickening and enhancement of V3, trigeminal ganglion, and the lateral cavernous sinus (CS). The tumor abuts the cavernous carotid artery (white arrow). There is enhancement of the dura along the floor of the middle cranial fossa (black arrow). This “dural tail” is usually a sign of involvement of the dura with tumor. Source: This illustration in the property of The Department of Head and Neck Surgery, M.D. Anderson Cancer Center is used with permission.

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Figure 18 Sinonasal Melanoma. (A) Coronal CT scan demonstrating opacification of the right nasal cavity as well as the maxillary and ethmoid sinuses. There appears to be destruction of the lateral nasal wall and the nasal septum. The lesion is abutting the orbital floor and the cribriform plate, but it is unclear whether or not these structures are involved. (B) Coronal T1-weighted MRI with gadolinium of the same patient revealing that the lesion is limited to the nasal cavity and ethmoid sinuses and that the changes in the maxillary sinuses are due to retained secretions secondary to obstruction of the ostium, rather than soft tissue involvement. It also demonstrates that the lesion does not invade the orbit or the cranial base. The presence of low signal areas within the lesion gives it a heterogeneous appearance, which is characteristic of sinonasal melanoma. Source: This illustration in the property of The Department of Head and Neck Surgery, M.D. Anderson Cancer Center is used with permission.

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Figure 19 PET–CT of head and neck. These images are from the same patient whose CT and MRI are depicted in Figure 16. The fused PET–CT images show ethmoid carcinoma (A) with metastasis to the retropharyngeal lymph nodes (B, C), which were not detected on CT or MRI. Source: This illustration in the property of The Department of Head and Neck Surgery, M.D. Anderson Cancer Center is used with permission.

orbital, nasal, or facial rehabilitation is required. Consultations with ophthalmology should be considered for detailed neuro-ophthalmologic examination of all patients with known or suspected orbital involvement. If orbital exenteration is contemplated, visual function of the contralateral eye should be carefully assessed. Consultations with medical and radiation oncology colleagues should be done to consider incorporation of chemotherapy or radiation in the treatment plan. Radiation and/or chemotherapy may be used preoperatively as induction (neoadjuvant), or postoperatively as adjuvant therapy. This is particularly important in patients with advanced stage disease (e.g., dural or orbital involvement) or high-grade lesions (e.g., sinonasal undifferentiated carcinoma. In selected cases, chemotherapy and/or radiation may be reasonable alternatives to surgery. Such decisions are best discussed in the format of a multidisciplinary tumor board. If surgery is chosen as a treatment modality, the plan for the surgical approach, the extent of resection, and reconstructive options should then be formulated. This plan should be communicated clearly among the various members of the surgical team, particularly the otolaryngologists, head and neck surgeons, neurosurgeons, and plastic and reconstructive surgeons. Careful assessment of the patient’s general medical condition should be carried out prior to surgery. Preoperative chest radiograph, blood counts, liver and renal function tests, blood sugar, electrolytes, coagulation studies, and an electrocardiogram should be performed routinely. Appropriate consultations from medical colleagues should be obtained in order to optimize the patient’s medical status before surgery, and help in management postoperatively. The patient’s nutritional status should be evaluated, and if indicated, enteral or parenteral feeding may be considered. High-resolution imaging for metastatic workup is not routinely performed, unless indicated by history, clinical examination, chest radiograph results, or blood test abnormalities. Finally, the surgical team should discuss with the patient and family the nature of the disease, the evaluation, the indications, risks, possible complications, sequelae, and

alternatives of therapy. The expected postoperative course including length of stay in the hospital, feeding, rehabilitation, and need for adjunctive therapy should be described. This ongoing communication should be maintained in a clear, honest, and sympathetic fashion throughout the course of patient care.

SURGERY Indications and Contraindications Surgery is indicated when there is adequate evidence that the tumor can be completely resected with acceptable morbidity. For early stage disease (T1–T2), surgery alone may be adequate treatment, but for more advanced stage resectable disease, postoperative adjuvant radiation or chemoradiation is commonly used to improve tumor control (14). In the presence of tumor extension to the cavernous sinus, internal carotid artery, optic chiasm, extensive brain parenchymal involvement, or distant metastasis, surgery is usually contraindicated. However, in selected cases, surgery with proper adjuvant therapy may still offer the most effective local disease palliation even in the presence of extensive disease.

Surgical Principles When dealing with the subject of surgical treatment of sinonasal cancer, a distinction has to be made between the terminology used to describe the surgical approach on the one hand, and the extent of resection on the other hand. A surgical approach describes the various incisions, soft tissue dissection, and skeletal osteotomies required to expose the tumor and adjacent structures to perform a complete and safe resection. On the other hand, the extent of tumor resection describes the various structures that need to be surgically extirpated to achieve total tumor removal with tumor-free margins. Obviously, both the surgical approach and the extent of resection are closely related and depend on the extent of tumor, its aggressiveness, and related critical structures. The various surgical approaches and extent of resection are listed in Table 2 (1). The choice of surgical approach and

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Figure 20 Juvenile Nasopharyngeal Angiofibroma.Coronal (A, B) and axial (C) CT with contrast and axial T1-axial MRI with contrast (D) showing the mass in the nasal cavity, maxillary sinus, nasopharynx, sphenoid sinus, pterygoid plates, and pterygo-palatine and infratemporal fossa. The mass involves the floor of the middle cranial fossa and extends intracranially to the cavernous sinus. Continued

extent of resection will generally depend on the location and the extent of the tumor. In some cases, different approaches may be equally effective for resection of a particular tumor. For example, a tumor of the nasal cavity, lateral nasal wall, ethmoid, sphenoid and medial maxillary sinus requiring a medial maxillectomy and a total sphenoethmoidectomy may be adequately resected using a transfacial, endoscopic, or sublabial approach (Figs. 18 and 22). However, the following principles should always guide the surgeon in

choosing the optimal approach and extent of resection for all patients undergoing surgical treatment of sinonasal cancer:

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Adequate oncologic resection Minimal brain retraction Protection of critical neurovascular structures Meticulous reconstruction of the skull base Optimal esthetic outcome

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Figure 20 T1-sagittal MRI (E, F) shows flow voids of increased extensive vascular supply coming from the internal maxillary artery (E) and internal carotid artery (F). Early phase angiogram showing the blood supply from the internal maxillary artery (G) and late phase showing significant tumor vascular blush and contribution from the internal carotid artery (H). Source: This illustration in the property of The Department of Head and Neck Surgery, M.D. Anderson Cancer Center is used with permission. Continued

Surgical Approach Endonasal Approaches Endoscopic endonasal approaches (EEA) are being increasingly used for surgical excision of selected tumors of the sinonasal tract, either alone or in combination with open approaches. The long-term oncologic results of EEA in treating malignant sinonasal tumors are still being defined. The keys to adequate oncologic results using EEA are good selection of patients and the surgeon’s experience with this approach. EEA are most suited for central tumors involving the nasal septum, nasal cavity and lateral nasal wall, ethmoid and sphenoid sinuses, and clivus (Fig. 22). The advantages of EEA include direct bilateral access to the tumor, superior illumination, magnification and visualization of the surgical field (Fig. 7), wider angles of vision using angled endoscopes, and relatively less morbidity compared to the open surgical approaches. The limitations of EEA include lack of binocular vi-

sion and depth perception, which is important when dealing with critical neurovascular structures. Ergonomic limitations include the inability of the primary surgeon to control the endoscope and two instruments simultaneously and hence the reliance on a surgical assistant for camera control during twohanded surgery. The major limitation of EEA is the inability to repair or patch dural defects with suture techniques, which limits the reconstructive options after endoscopic resection of intradural tumors. We are currently exploring new applications in robotic surgery to overcome some of these limitations (15) (Fig. 23).

Transfacial Approaches: Lateral Rhinotomy and Weber-Fergusson Transfacial approaches are the most commonly used surgical approaches for resection of locally advanced sinonasal

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Figure 21 Meningo-encephalocele. Sagittal (A) and coronal (B) T1-MRI with gadolinium showing a defect and in the anterior cranial base at the right fovea ethmoidalis and cribriform plate. There is herniation of a meningo-encephalocele, which presented as a nasal mass. Inadvertent biopsy of such lesions may lead to CSF leaks and should be avoided. Source: This illustration in the property of The Department of Head and Neck Surgery, M.D. Anderson Cancer Center is used with permission.

tumors. They allow adequate exposure of the nasal cavity, maxillary sinus, pterygo-palatine fossa, pterygoid plates, ethmoid sinuses, medial and inferior orbital walls, sphenoid sinus, nasopharynx, clivus, and the medial aspect of the infratemporal fossa. The lateral rhinotomy is the standard incision for exposure of sinonasal tumors through a transfacial approach (Fig. 24). It can be used alone, or various extensions of the basic incision may be added for further exposure depending Table 2 Surgical Treatment of Sinonasal Cancers Surgical approach Endoscopic Lateral rhinotomy and Weber-Fergusson Transoral–Transpalatal Facial “Degloving” Craniofacial Extent of resection Ethmoidectomy Inferior maxillectomy Medial axillecotmy Total maxillectomy Anterior cranial base resection Infratemporal fossa dissection Orbital exenteration

on the extent of tumor (1). The Weber-Fergusson incision adds a lip-splitting and subciliary incision for added exposure of the maxillary bone. We prefer to extend the lateral rhinotomy toward the medial brow, a Lynch-type extension, and avoid the subciliary incision of the classic Weber-Fergusson to minimize eyelid complications, as will be discussed further under the section on “Total maxillectomy”. The basic lateral rhinotomy incision provides adequate exposure when performing a medial maxillectomy. Elevation of the soft tissues of the cheek is done in a subperiosteal plane over the maxilla and around the inferior orbital nerve [Fig. 25(A)]. The attachment of the medial canthal tendon to the nasal bone is released. The periorbita is elevated over the medial orbital wall exposing the lacrimal crest, the lamina papyracea, and the frontoethmoidal suture. This suture serves as a landmark for the position of the floor of the anterior cranial fossa, and when followed posteriorly, leads to the anterior and posterior ethmoidal foramina. The anterior and posterior ethmoidal arteries are cauterized with the bipolar electrocautery, clipped or ligated, and transected [Fig. 25(B)]. The optic nerve is located 4- to 5-mm posterior to the posterior ethmoidal artery. The orbital floor should be dissected as far lateral as the inferior orbital fissure. The lacrimal sac is identified in its fossa between the anterior and posterior lacrimal crests. If a medial maxillectomy is performed, the lacrimal sac is elevated from the fossa, and the lacrimal duct

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Figure 22 Hemangiopericytoma of the sinonasal region. Preoperative (A) and 3 years postoperative (B) MRI of a patient who underwent endoscopic resection of hemangiopericytoma of the sinonasal tract. Source: This illustration in the property of The Department of Head and Neck Surgery, M.D. Anderson Cancer Center is used with permission.

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Figure 23 Robotic assisted endoscopic surgery of the anterior skull base (Cadaveric Dissection). (A) Soft tissue approach: Bilateral sublabial incisions and soft tissue flap elevation. (B) Bilateral anterior maxillary antrostomies. (C) Robotic ports placement. The camera port is placed into the right nostril, and the right and left surgical arm ports through the respective anterior then middle antrostomies. (D) Bimanual sharp dissection of the mucosa covering the fovea ethmoidalis and cribriform plate.

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Figure 23 (E) Wide sphenoidotomy with excellent access to the sella turcica (ST) and para-sellar region (PS). (F) The cribriform plate (CP) is removed bilaterally, and the cut edges of the olfactory nerves (ON) are shown. The dura is incised or resected to expose the inferior surface of the frontal lobes (FL) intracranially. (G) Dural repair. Suturing the dural edges, making a loop, and tightening the knot. Source: From Ref. 15.

transected, and the sac marsupialized into the nasal cavity to provide adequate drainage of the lacrimal system and to prevent stenosis [Fig. 25(C)].

Midfacial Degloving and Sublabial Approaches The midfacial degloving approach is most commonly used in the management of large benign lesions of the sinonasal region and the skull base, such as juvenile nasopharyngeal angiofibroma, for selected malignancy in this area and to afford access to the nasopharynx and infratemporal fossa. The main advantage of the “degloving” approach is that an external facial incision is avoided. Another advantage is providing simultaneous exposure to the inferior and medial maxilla, bilaterally (Fig. 26). This is particularly helpful when approaching tumors with bilateral involvement of the nasal cavity and maxillary sinus. A major disadvantage, however, is the limited superior and posterior exposure, and the need for constant retraction of the soft tissue envelope for continued adequate exposure. The midfacial degloving approach requires a basic level of proficiency and understanding of closed rhinoplasty incisions. It involves a complete transfixion incision of the membranous septum. This is joined endonasally with a bilateral

intercartilaginous incision, with soft tissue elevation over the nasal dorsum as far superior as the nasal root. The nasal skeleton is therefore “degloved” from overlying soft tissues as far lateral as the pyriform aperture. A gingivobuccal incision extends bilaterally across the midline to both maxillary tuberosities laterally. Subperiosteal dissection is continued cephalad over the face of both maxillae. The dissection joins the nasal degloving using sharp dissection over the pyriform aperture attachments (Fig. 26). The sublabial approach may also be used to access tumors of the sphenoclival region such as chordoma, particularly if the lesion extends lower than the horizontal plane of the palate, for example the lower third of the clivus and craniovertebral junction (Fig. 27). A Le Fort I osteotomy is done and the maxilla is displaced inferiorly after posterior osteotomies separate the maxilla from the pterygoid plates. We prefer a combination of unilateral or half a Le Fort I osteotomy with a median or paramedian palatal osteotomy for better displacement of the maxilla inferiorly and laterally. This offers a wider exposure because it avoids the cantilever effect of the posterior maxilla upward restricting exposure when the anterior maxillary segment is displaced inferiorly when the bilateral (complete) Le Fort osteotomy is used.

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below the level of the frontoethmoidal suture to avoid injury to the floor of the anterior cranial fossa. The superior attachment of the middle turbinate is then transected along the roof of the nose. Posteriorly, the lateral nasal wall cuts are connected with right-angled scissors behind the turbinates. The specimen is thus delivered and examined for margins with frozen section control. If the tumor involves the nasal septum, it should be included in the resection specimen by adding appropriate septal cuts to allow for tumor-free margins. Closure begins by reattachment of the medial canthal tendon to the nasal bone in its anatomic position. Meticulous multilayered closure of the lateral rhinotomy is performed and usually results in excellent healing and acceptable postoperative appearance [Fig. 25(E)]. If a sublabial approach is done, the mucosal incisions are closed with absorbable suture. Nonadherent nasal packing may be left for 1 to 2 days.

Inferior Maxillectomy Figure 24 Lateral rhinotomy incision (1, 2, and 3) and its extensions (4 and 5). A temporary tarsorrhaphy protects the ipsilateral globe. The basic lateral rhinotomy incision is outlined by connecting three surface points. The first point (1) is marked half way between the nasion (A) and the medial canthus (B). The second point (2) is where the alar crease begins and the third point (3) is at the base of the columella. The basic incision provides adequate exposure for a medial maxillectomy. The basic incision may be extended to include a lip-splitting extension (4) or a “Lynch” type extension (5) if further exposure is necessary. The extended incision provides adequate exposure for a total maxillectomy. Source: This illustration in the property of The Department of Head and Neck Surgery, M.D. Anderson Cancer Center is used with permission.

This procedure involves resection of the inferior maxillary sinus below the plane of the infraorbital nerve. It is most commonly used for neoplasms of the alveolar process of the maxilla with minimal extension to the maxillary antrum. Similarly, lesions of the hard palate sparing the antrum can be treated by an inferior maxillectomy. A combination of sublabial and palatal incisions is usually used for exposure and osteotomies are done around the lesion, ensuring an adequate margin of resection (Fig. 28). Alternatively, a midfacial degloving can be used for lesions crossing the midline and involving the inferior maxilla bilaterally.

Total Maxillectomy

Extent of Resection Medial Maxillectomy The most common indication for medial maxillectomy is in the treatment of tumors of the nasal cavity, lateral nasal wall, and medial maxillary sinus (Fig. 18). Medial maxillectomy includes removal of the lateral nasal wall, and the medial maxillary segment bounded laterally by the infraorbital nerve. In addition, a complete sphenoethmoidectomy is usually performed. The incision most commonly used for exposure is the lateral rhinotomy (Fig. 24). Alternatively, a midfacial degloving, as will be described later, may be used, and is preferable if bilateral medial maxillectomy is needed (Fig. 26). Endonasal endoscopic medial maxillectomy and sphenoethmoidectomy may also be performed for appropriately selected tumors (Fig. 22). If the lateral rhinotomy is performed and soft tissue exposure is completed as discussed in the previous section, osteotomies are done as shown in Figure 25(D), and the anterior wall of the maxillary sinus above the level of dental roots and medial to the infraorbital nerve is removed. Lateral to the infraorbital foramen, the anterior wall antrostomy may be enlarged to expose the zygomatic recess of the antrum. Resection of the lateral nasal wall begins with an inferior osteotomy along the nasal floor below the attachment of the inferior turbinate, starting at the pyriform aperture, and carried posteriorly to the posterior maxillary wall. With the orbit retracted laterally and protected with a malleable brain retractor, the lamina papyracea is identified and, if necessary, resected. A complete sphenoethmoidectomy is done, staying

If the extent of resection requires a total maxillectomy, the lateral rhinotomy incision may be extended by adding lipsplitting, gingivo-buccal, and palatal incisions inferiorly. The lip-splitting incision, which may be done along the philtrum or in the midline, connects the lateral rhinotomy with the sublabial incision, thus allowing more lateral elevation of the facial flap. The gingivo-buccal incision starts from the lip-splitting incision and extends as far laterally as the region of the first molar and over the lateral surface of the maxillary tuberosity. In patients undergoing total maxillectomy, a median or paramedian palatal incision is performed over the hard palate extending from an inter-incisor space anteriorly, to the junction of the soft and hard palate posteriorly. The incision then continues laterally between the hard and the soft palate to curve posterolaterally around the maxillary tuberosity meeting the gingivo-buccal incision [Fig. 29(A)]. In patients undergoing total maxillectomy with orbital preservation, we prefer to extend the lateral rhinotomy superiorly beneath the medial brow rather than laterally through a subciliary incision used in the classic Weber-Fergusson approach [Fig. 29(B)]. We described several advantages to this modification (16). First, avoiding a subciliary incision eliminates any disruption to the lower lid skin–muscle– tarsus complexthat minimizes lower eyelid complications, particularly ectropion and prolonged eyelid edema. Another advantage is avoiding trifurcation of the incision reducing the risk of skin breakdown at the medial canthal area. This is especially important for previously irradiated patients, who are more prone to develop medial canthal skin dehiscence. Similarly, since the vascularity of the thin lower eyelid skin is not affected with the extended lateral rhinotomy incision, patients who undergo orbital floor reconstruction with implants such as titanium mesh have less chance to

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Figure 25 Lateral rhinotomy and Medial Maxillectomy. (A) Elevation of the soft tissues of the cheek is done in a subperiosteal plane over the maxilla and around the inferior orbital nerve (ION). The periorbita is elevated over the anterior lacrimal crest (ALC) to expose the lacrimal sac (LS). (B) Dissection of the medial periorbita over the lamina papyracea reveals the anterior ethmoid artery (arrow) at the level of the frontoethmoidal suture line, which marks the level of the anterior cranial floor. The artery is coagulated by bipolar electrocautery, clipped or ligated and then transected. (C) After the lacrimal sac is transected, it is marsupialized into the surgical cavity as a dacryocystorhinostomy. Silicone stents are placed through the upper and lower canaliculi and brought into the nasal cavity to prevent postoperative epiphora. These stents are removed in about 3 to 6 months. (D) Medial Maxillectomy. Osteotomies: (A) vertically medial to the infraorbital foramen (arrowhead), (B) horizontally above the level of dental roots and into the pyriform aperture, and (C) obliquely along the nasomaxillary suture line. If the lateral nasal wall is to be resected, the lacrimal sac (arrow) is transected and marsupialized into the nasal cavity. (E) Postoperative appearance of a lateral rhinotomy incision. Source: This illustration in the property of The Department of Head and Neck Surgery, M.D. Anderson Cancer Center is used with permission.

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Figure 26 Sublabial “facial degloving” approach. In addition to avoiding facial incisions, the sublabial approach has the advantage of providing bilateral access to the medial and inferior maxillary segments. Source: This illustration in the property of The Department of Neurosurgery, M.D. Anderson Cancer Center is used with permission.

develop wound breakdown and implant exposure. While the extended lateral rhinotomy incision has several functional and cosmetic advantages, it does not compromise exposure and provides an adequate approach for a safe oncologic resection. The extension of the lateral rhinotomy incision beneath the medial eyebrow shifts the fulcrum of rotation of the soft tissue flap superiorly and laterally enhancing lateral exposure, which is not less from that obtained with a classic Weber-Fergusson incision [Fig. 29(B)]. Transection of the infraorbital nerve allows even more lateral and posterior elevation of the soft tissues, to expose the entire maxillary bone as far lateral as its zygomatic extension, and posteriorly to the pterygomaxillary fissure and over the pterygoid plates. Additionally, its postoperative cosmetic appearance is superior to the Weber-Fergusson incision [Fig. 25(E)]. Whichever incision is used, elevation of the facial flap is usually done in the subperiosteal plane. However, if the tumor has invaded the anterior wall of the maxillary antrum, a supraperiosteal plane is used. Occasionally, the cheek skin overlying the maxilla is included with the specimen, if it is involved with tumor. With the globe protected with a temporary tarsorrhaphy stitch, the periorbita is dissected along the medial, inferior, and lateral orbital walls.

Lateral osteotomies are performed along the frontal and temporal processes of the zygoma [Fig. 29(B)]. Medial osteotomies are done along the frontal process of the maxilla and along the medial orbital wall just below the frontoethmoidal suture, extending posteriorly to the level of the posterior ethmoidal foramen. The medial and lateral osteotomies are then connected superiorly across the orbital floor along the inferior orbital fissure. Inferiorly, a midline sagittal osteotomy is made across the hard palate. The ipsilateral central incisor should be preserved, if possible, to enhance prosthesis retention. Finally, after the internal maxillary artery is identified at its entrance through the pterygomaxillary fissure, ligated, and transected, a posterior osteotomy is done to disarticulate the maxilla from the pterygoid plates. The maxilla is delivered by anteroinferior traction, while remaining soft tissue attachments are cut using a curved heavy scissors. Bleeding is usually encountered at this point, and is controlled by temporary packing of the cavity, followed by electro coagulation of bleeding mucosal surfaces or ligature of bleeding points. The pterygoid plexus of veins may be a source of persistent bleeding, and can be managed by hemostatic figure-of-8 sutures and surgical packing. Bleeding is usually minimized if the internal maxillary artery is ligated before the posterior osteotomy is done along the pterygomaxillary fissure. Total maxillectomy usually involves removal of the entire maxillary bone including the palate and the orbital floor [Fig. 29(C)]. Preservation of the orbital floor (subtotal maxillectomy) or the palate (suprastructure maxillectomy) may be done if these structures are not involved by tumor. Depending on the extent of the lesion, resection may extend beyond the posterior wall to the pterygo-palatine fossa and pterygoid plates. Perineural spread of tumor along V2 may be resected by following the nerve through foramen rotundum and into Meckel cave (17) (Fig. 30).

Craniofacial Resection Surgical resection of the anterior cranial base is commonly indicated for patients with sinonasal tumors involving the cribriform plate or fovea ethmoidalis. This is done, by definition, for most cases of esthesioneuroblastoma, as well as carcinoma of the ethmoid or maxillary sinuses approaching or involving the anterior cranial base (Fig. 16). Tumors transgress the cribriform plate either by direct bony invasion or by perineural spread along the filaments of the olfactory nerves. The dura of the anterior cranial fossa forms a barrier that delays, to a certain extent, brain invasion. Dural resection in patients with intracranial but extradural disease or patients with limited dural involvement often provides an adequate oncologic margin. However, malignant tumors that transgress the dural barrier and involve the underlying brain parenchyma are usually associated with poor prognosis (18). However, even in some cases with limited frontal lobe involvement, anterior craniofacial resection may still be indicated for local control of the disease. Resection of the floor of the middle cranial fossa is sometimes performed in patients with sinonasal tumors to achieve tumor-free surgical margins for lesions extending to the roof of the infratemporal fossa or for those tumors that exhibit perineural spread along the branches of the trigeminal nerve to the Gasserian ganglion, most commonly adenoid cystic carcinoma. Craniofacial approaches combine extra- and intracranial access to the anterior and lateral skull base. Extracranial

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Figure 27 Sublabial approach and inferior maxillotomy for access to sphenoclival region. (A) Preoperative (upper) and postoperative (lower) coronal and sagittal MRI of a patient with clival chordoma. (B) Le Forte I Osteotomy (black arrow) is done on one side only and connects the pyriform aperture. A second paramedian palatal osteotomy is performed (white arrow). (C) Inferior displacement of the maxilla (maxillotomy) to expose the sphenoid sinus, nasopharynx, and clivus. (D) Rigid fixation of the maxillary segments using “preregistered” titanium microplates to avoid any malocclusion. Source: This illustration in the property of The Department of Head and Neck Surgery, M.D. Anderson Cancer Center is used with permission.

approaches may include transfacial, sublabial, or endonasal approaches as previously described (Fig. 31). The bicoronal incision starts in a preauricular crease anterior to the tragus. The superficial temporal artery should be dissected and preserved. The scalp incision is extended in

the coronal plane, staying behind the hairline along its entire course, to the contralateral preauricular region. We prefer to gently curve the incision anteriorly at the midline [Fig. 32(A) and 32(B)]. The scalp flap is elevated in a subgaleal plane superficial to the pericranium between the superotemporal

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Figure 28 Inferior maxillectomy. Gingivo-buccal and palatal incisions and osteotomies are done around the lesion as shown in (A). If there is adequate space between the central incisors, the osteotomy may be performed using a micro–reciprocating saw in the interincisor space. Otherwise, the ipsilateral central incisor should be extracted and the osteotomy placed in the tooth socket in order to avoid loss of bony support to the remaining contralateral incisor. Inferior maxillectomy specimen (B) showing adequate surgical margins around an upper alveolar ridge carcinoma (arrow). Source: This illustration in the property of The Department of Head and Neck Surgery, M.D. Anderson Cancer Center is used with permission.

lines bilaterally. Lateral and inferior to the superotemporal lines, an incision is made through both the superficial and deep layers of the temporalis fascia 1 to 1.5 cm posterior to the superior orbital rim and extends posteriorly parallel to the course of the zygomatic arch [Fig. 32(C)]. Dissection proceeds below the plane of the deep layer of the temporalis fascia to preserve the frontal branch of the facial nerve, which is superficial to the fascia. The scalp flap is elevated anteriorly toward the superior orbital rims and posteriorly toward the vertex. Pericranial incisions are made as far posteriorly as necessary to provide adequate length for the pericranial flap and along the superotemporal lines bilaterally. The pericranial flap is dissected free from the underlying bone and reflected anteriorly [Fig. 32(D)]. Careful dissection and preservation of the supraorbital neurovascular pedicles is necessary to provide a well-vascularized pericranial flap for reconstruction of the cranial base defect. The supraorbital nerves and vessels are located along the medial one-third of the superior orbital rim. Elevation of the supraorbital rim periosteum begins laterally and proceeds medially, until the margin of the supraorbital groove is carefully exposed with a fine elevator. The nerve and vessels may exit the skull either through a notch or a true foramen. If a notch is present then the nerve can be dissected free without difficulty. If a foramen rather than a notch is found, the floor of the foramen is removed with a fine osteotome. This liberates the pedicle and further elevation of the superior periorbita is then achieved. Frontal, temporal, or frontotemporal craniotomy is then performed to allow access to the floor of the anterior or middle cranial fossa or both, respectively. For a frontal craniotomy, bilateral burr holes are then placed in the depression posterior to the frontal-zygomatic sutures (MacCarty keyhole), after reflection of the temporalis muscle leaving a cuff of fascia at the superotemporal line for reattaching the muscle during closure [Fig. 32(E)]. These anatomic keyholes provide access to the anterior fossa dura and by inferior enlargement

the periorbita, if needed. A burr hole is then placed on the superior sagittal sinus, well anterior to the coronal suture, exposing the dura on both sides of the sinus. The bifrontal craniotomy is performed between the burr holes. The craniotomy may be extended inferiorly to the level of the frontonasal suture. Compared to frontal craniotomy, subfrontal approaches have the advantage of minimizing brain retraction by providing wider and more direct exposure of the floor of the anterior cranial fossa (Fig. 33). This is especially helpful in more posteriorly located lesions such as those involving the planum sphenoidale, clivus, orbital apex, and optic chiasm (Fig. 34). The subfrontal approach is done by adding osteotomies that allow incorporation of the superior orbit and/or nasal bone to the craniotomy. These skeletal elements may be removed in several subunits or as a single bone flap (10) (Fig. 35). Bilateral nasal osteotomies are done along the lower border of the nasal bones and then along the suture line between the nasal and lacrimal bones [Fig. 35(C)]. The osteotomies are connected across the midline below the frontoethmoidal suture line and in front of the anterior ethmoidal vessels. This avoids injury to the cribriform plate and olfactory nerves. After the dura and periorbita have been carefully dissected from the bone, the lateral wall and roof of each orbit are removed in separate orbital osteotomies [Fig. 35(C)]. Under direct visualization, taking care to protect the periorbita and dura, an anteroposterior cut is made at the medial aspect of the orbital roof staying lateral to the ethmoid sinus. A second anteroposterior cut is made at the inferior aspect of the lateral orbital wall. These cuts are connected posteriorly with protection of the tissues of the SOF. The bone flap consisting of the frontal bone, orbital roof, superolateral orbital rims, and nasal bones can be removed for wide exposure [Fig. 35(D) and 35(E)]. After completing the craniotomy, brain “relaxation” is achieved by opening the dura and allowing release of CSF or by withdrawing CSF from a lumbar subarachnoid drain,

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Figure 29 Total maxillectomy. (A) Intraoral incisions. (B) The exposure offered through an extended lateral rhinotomy shown in this figure is not less than that offered by the Weber-Fergusson incision. The advantage of the former is avoiding a subciliary incision and its potential for lower eyelid ectropion and edema. Osteotomies have been performed as indicated by the arrows.(C) En bloc resection specimen. Note tumor involvement of the orbital floor, which had to be resected. The tumor did not transgress the periorbita, therefore the eye was preserved. (D) Total maxillectomy defect with removal of the orbital floor and periorbita. Source: This illustration in the property of The Department of Head and Neck Surgery, M.D. Anderson Cancer Center is used with permission.

hypocapnia through controlled hyperventilation, mannitol diuresis, or steroids. This also lessens the need for brain retraction, which minimizes postoperative brain edema. Next, the dura is carefully dissected along the floor of the anterior cranial fossa to expose the crista galli and olfactory grooves. The olfactory nerves are transected to expose the cribriform plate. Dural elevation is continued to expose the fovea ethmoidalis and orbital roofs. Posteriorly, the planum sphenoidale and the base of the anterior clinoid process may be exposed as dictated by the extent of the tumor. If the dura is

involved by the tumor, intradural exposure is achieved and dura incisions are made around the tumor and then the dissection proceeds in a subdural plane and the dura and even brain tissue, if involved, is resected along with the tumor. With simultaneous exposure provided superiorly through the intracranial approach and inferiorly through the extracranial approach, osteotomies of the cranial floor around the tumor can be safely completed. Malleable retractors are used to protect the brain and the orbit as osteotomies are made. The placement of osteotomies and the extent of

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Foramen rotundum Periorbita

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Figure 30 Dissection of the foramen rotundum through the transmaxillary route (A) and close-up schematic (B). Intraoperative view (C) of thickened V2 within the foramen rotundum (arrow). Source: This illustration in the property of The Department of Neurosurgery, M.D. Anderson Cancer Center is used with permission.

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Figure 31 Anterior craniofacial resection: Extracranial approaches. In addition to the frontal craniotomy, the extracranial approach may be transfacial (A), sublabial (B), or endonasal (C). Source: This illustration in the property of The Department of Neurosurgery, M.D. Anderson Cancer Center is used with permission.

resection are dictated by the extent of tumor involvement, and tailored in each case. Typically, however, osteotomies are made from the planum sphenoidale, along the roof of the ethmoid, and forward to the front of the cribriform plate (Fig. 36). Frozen section control of the margins should be done to ensure the adequacy of resection.

Figure 33 Subfrontal approach. Note the increased basal exposure provided by the subfrontal approach by incorporating the supraorbital rim and glabella and nasal bones with the frontal craniotomy. Source: This illustration in the property of The Department of Neurosurgery, M.D. Anderson Cancer Center is used with permission.

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Figure 32 Frontal Craniotomy. (A, B) Bicoronal incision. (C) Incision of the superficial layer of the deep temporalis fascia. Further dissection is done deep to this plane to preserve the frontal branch of the facial nerve. (D) The pericranial flap. Adequate length and good vascular supply of the flap are prerequisites for effective reconstruction of the skull base defect. (E) Frontal craniotomy (schematic). (F) Frontal craniotomy (intraoperative photograph). Source: This illustration in the property of The Departments of Head and Neck Surgery (A–D, F) Neurosurgery (E), M.D. Anderson Cancer Center is used with permission.

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resection (12). Even with the best imaging techniques, the definitive and most accurate assessment of the extent of orbital invasion, and whether the eye could be preserved, has to be made intraoperatively. This needs to be clearly discussed with the patient and family, and an informed consent for possible exenteration needs to be obtained in high-risk cases. There is an evolving role for induction chemotherapy and concurrent chemoradiation in the management of patients with orbital invasion by advanced sinonasal cancers (Fig. 37). The role of such neoadjuvant treatment in enhancing the chances of orbital preservation continues to be investigated (19). If a decision is made to exenterate the orbit, supraand subciliary incisions are made around the upper and lower eyelids, respectively. This allows for preservation of the

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Figure 34 Pre- (A) and postoperative (B) MRI of tumor involving the planum sphenoidale and upper two-thirds of the clivus removed via a subfrontal approach. Source: This illustration in the property of The Department of Neurosurgery, M.D. Anderson Cancer Center is used with permission.

Management of the Orbit Sinonasal Tumors Every effort should be made to preserve the eye as long as preservation does not compromise the adequacy of oncologic resection. Attempts at orbital preservation in the face of gross residual disease, however, usually result in poor disease control and ultimate loss of orbital function. Most studies have shown that if orbital invasion is limited to the bony orbit or the periorbita, orbital preservation is possible without compromising oncologic outcome (1). Orbital exenteration is usually indicated when there is gross invasion of the periorbital fat, extraocular muscles, or optic nerve. The presence of proptosis or diplopia may be due to displacement rather than invasion of the intraorbital contents. Decreased visual acuity or visual fields, or the presence of an afferent pupillary defect, usually indicate gross invasion of the orbit. Orbital invasion by perineural spread rather than direct extension may be missed unless careful examination of the cranial nerves, especially V1 and V2, is done. Detailed neuro-ophthalmologic examination should be conducted on all patients with suspected or confirmed orbital involvement by sinonasal or other skull base tumors. If orbital exenteration is contemplated, always make sure that the patient has useful vision in the contralateral eye. In the absence of any ocular signs or symptoms, however, evaluation of the extent of orbital involvement relies mainly on imaging. High-resolution CT and MRI are complimentary and provide critical information regarding the extent of orbital bony and soft tissue involvement, respectively. CT scans obtained at 1- to 3-mm slices with detailed bone windows are best for evaluating bony involvement of the orbital walls. MRI is best used to evaluate the extent of soft tissue invasion beyond the periorbita (Fig. 37). MRI is also useful in detecting perineural spread proximally beyond the orbital apex and into the cavernous sinus or optic chiasm, which compromises surgical margins, local disease control, and survival, and as such is a contraindication for surgical

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Figure 35 Subfrontal approach. (A) Bicoronal incision and soft tissue dissection. The scalp flap is reflected anteriorly down to the level of the nasal bones. The supraorbital nerves were surrounded by complete foramina rather than a notch. Osteotomies around the foramina allow downward reflection of the nerves with the soft tissue flap. Burr holes are placed on either side of the SSS, anterior to the coronal suture. (B) Bilateral burr holes are placed posterior to the frontal-zygomatic sutures. These anatomic keyholes provide access to the anterior fossa dura and periorbita, separated by the bony orbital roof. (C) Orbital and nasal osteotomies. (D, E) The cranio-orbital– nasal bone flap is removed as a single unit as illustrated by the diagram (D) and intraoperative photograph (E). Source: This illustration in the property of The Department of Head and Neck Surgery, M.D. Anderson Cancer Center is used with permission.

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Figure 36 Resection of the floor of the anterior cranial fossa. (A, B) Osteotomies along the floor of the anterior cranial fossa. (C) Intraoperative photograph showing resection of the floor of the anterior cranial fossa and the medial orbital walls. Source: This illustration in the property of The Department of Neurosurgery (A andB) and Head and Neck Surgery (C), M.D. Anderson Cancer Center is used with permission.

eyelids, which can be used to line the orbit. If the eyelids are involved with cancer, they must be included in the resection (Fig. 38). The periorbita is incised over the superior and lateral orbital rims. Dissection continues along the roof of the orbit and lateral walls, until the SOF and the optic foramen are exposed. Lidocaine is injected around these structures to block any autonomic-induced cardiac arrhythmias. To prevent troublesome bleeding, the neurovascular structures in the SOF are slowly and carefully isolated, ligated or clipped, and transected. The optic nerve and the ophthalmic artery are then managed in a similar fashion. The extraocular muscles are transected at their origin in the orbital apex. The medial

and inferior orbit may be left attached to the specimen if en bloc resection of the eye in patients with sinonasal cancer is indicated. Osteotomies are done, as previously described, for total maxillectomy, except that the orbital bony cuts are connected at the orbital apex, rather than the inferior orbital fissure. Primary Orbital Tumors Surgery for primary orbital tumors will depend on whether the tumor is benign or malignant. Examples of benign tumors include vascular malformation, neurofibroma, osteoma, and pleomorphic adenoma of the lacrimal gland

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(Figs. 39–42). Examples of malignant tumors include lymphoma, which is the most common, and salivary gland tumors of the lacrimal gland such as adenoid cystic carcinoma (Fig. 43). In most cases of primary intraorbital tumors, the surgical approach is largely dictated by the location of the tumor. Tumors of the medial orbit may be removed through a transethmoidal modified Lynch approach (Fig. 41). The transconjunctival approach, with detachment of the lateral canthal tendon, provides access to the orbital floor. Tumors of the lateral orbit are best approached through a lateral orbitotomy, which can be done using either a brow incision (modified Kronlein or Stallard-Wright incision) or a hemi- or bicoronal approach. The advantages of the hemi- or bicoronal approaches include wider exposure for tumor resection, avoiding periocular incisions and excellent cosmetic result (Fig. 42). Tumors of the superior orbit or tumors invading intracranially are best resected through a cranio-orbito– zygomatic approach (Fig. 43).

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Figure 37 Sinonasal undifferentiated carcinoma with orbital invasion. (A) MRI showing tumor of the right sinonasal region with gross invasion of the medial and inferior orbital contents. The tumor also invades the anterior skull base with limited intracranial extension. (B) MRI of same patient 3 years after completing treatment with induction chemotherapy followed by concurrent chemoradiation. Imaging shows no evidence of residual disease. Surgery was avoided and the orbit was preserved. Source: This illustration in the property of The Department of Head and Neck Surgery, M.D. Anderson Cancer Center is used with permission.

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Meticulous reconstruction of surgical defects resulting from resection of sinonasal and orbital tumors is essential to preventing complications and optimizing surgical and functional outcome. The goals and strategies of reconstruction will depend on the extent and location of the surgical defect. Table 3 summarizes the major areas of reconstruction and their respective goals. Palatal Reconstruction: Oronasal Separation Effective separation between the oral and nasal cavities is essential for effective speech and deglutition. Palatal defects resulting from a maxillectomy are simply and effectively sealed using a prosthetic obturator. Preoperatively, the oromaxillofacial prosthodontist takes dental impressions,

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Figure 38 Orbital exenteration. (A) Circumorbital incisions. (B) Tumor specimen, including en bloc resection of the maxilla and orbit. (C) Immediate postoperative appearance. Source: This illustration in the property of The Department of Head and Neck Surgery, M.D. Anderson Cancer Center is used with permission.

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Figure 39 Orbital neurofibroma of the abducent nerve. (A) Axial CT scan and T1-MRI with gadolinium (B) showing the tumor following the course of the abducent nerve in the lateral orbit and extending to the cavernous sinus. Source: This illustration in the property of The Department of Head and Neck Surgery, M.D. Anderson Cancer Center is used with permission.

and designs a surgical obturator, which is used at the end of surgery to seal the palatal defect (Fig. 44) (20). The surgical obturator can be slightly modified intraoperatively to custom-fit the defect. The advantages of this immediate reconstruction are early postoperative restoration of normal speech and oral feeding. This minimizes the early postoperative morbidity of surgery, and obviates the need for enteral feeding. Preoperatively, a clear communication between the head and neck surgeon and the maxillofacial prosthodontist concerning the anticipated maxillary defect is required for optimal results. An additional advantage of the surgical obturator is its ability to support the surgical packing used to immobilize the skin graft lining the cheek flap. This epithelial lining, when completely healed, minimizes granulation tissue formation, provides a smooth mucosal lining, reduces scar contracture of the cheek, provides a scar band to support the obturator, and facilitates

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cavity hygiene [Fig. 44(A)]. At the end of the first postoperative week, and after removal of the surgical packing, the surgical obturator is replaced with an interim obturator [Fig. 44(B)]. This is used for several weeks after discharging the patient from the hospital and after completion of adjuvant therapy, allowing the surgical cavity to heal completely. Patients are instructed to remove the obturator periodically and clean the cavity with saline irrigation. At follow-up visits, the obturator is removed, and cleaned of any crusts or debris. Finally, a permanent obturator is designed to custom-fit the cavity after it matures to its final shape and dimensions. The acrylic dome incorporated into its design provides some cheek support [Fig. 44(C) and 44(D)]. In addition to being a simple and effective method of reconstruction of palatal defects, permanent obturators can also provide full dental restoration. At follow-up visits, removal of the obturator allows for

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Figure 40 Pleomorphic adenoma of the lacrimal gland. This young woman presented with proptosis and a palpable mass in the upper lateral right orbit (A). A coronal MRI (B) shows the mass in the region of the right lacrimal gland. Surgical resection via a lateral orbitotomy revealed a pleomorphic adenoma. Source: This illustration in the property of The Department of Head and Neck Surgery, M.D. Anderson Cancer Center is used with permission.

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Figure 41 Osteoma of the ethmoid and medial orbital wall. (A) Coronal CT showing an osteoma of the left ethmoid and medial orbital wall. (B) “Lynch” incision for an anterior ethmoidectomy. (C) Exposure of the tumor in the medial orbit. (D) Bony dissection around the tumor. (E) Surgical specimen. (F) Surgical field showing complete resection. (G) Closure. (H) Postoperative appearance. Source: This illustration in the property of The Department of Head and Neck Surgery, M.D. Anderson Cancer Center is used with permission.

easy inspection of the cavity for any evidence of recurrent disease. Surgical reconstruction of palatal defects with tissue flaps has the advantage of eliminating the need for regular hygiene of the surgical cavity. Flap reconstruction, however, requires more extensive surgery, adds donor site morbidity, does not allow rapid dental restoration, and conceals the surgical cavity from inspection for recurrent tumor. These disadvantages make prosthetic obturators the method of choice for reconstruction of surgical defects of the palate. The use of tissue flaps is usually reserved to patients who need additional reconstruction to the maxillary skeleton, orbital floor, or cranial base. In these cases, osseointegrated implants are used to facilitate dental restoration (see Fig. 2 in chap. 9, “Prosthetic Rehabilitation of Patients undergoing Skull Base Surgery”). Cranial Base Reconstruction: Cranionasal Separation Whenever the cranial and nasal cavities are joined by a surgical defect, as is the case with anterior craniofacial resection, watertight cranionasal separation is essential to reduce the risk of CSF leak, meningitis, and pneumocephalus. Meticulous closure of all dural incisions is necessary. Larger defects of the dura should be repaired using temporalis fascia, pericranium, or fascia lata grafts. Although bony reconstruction of the anterior skull base has been described using vascularized and nonvascularized bone grafts as well as bone cement,

reconstruction of the bone defect is not routinely necessary in most patients. The vascularized pericranial flap is currently the most frequently used flap for reconstructing defects of the floor of the anterior cranial fossa [Fig. 32(D)]. Flap handling and suturing should be meticulous in order to achieve a watertight seal (Fig. 45). Fibrin glue and tissue adhesives do not compensate for an imperfect closure. Lumbar subarachnoid drainage may be used for several days postoperatively to reduce CSF pressure and the possibility of a leak. Excessive lumbar drainage, however, may encourage the development of pneumocephalus. Occasionally, more bulk is needed to reconstruct the surgical cavity and reduce dead space, such as with extensive defects of the cranial base. Regional flaps, such as the temporalis muscle, are usually adequate for this purpose. If the muscle bulk is inadequate, or if its blood supply has been sacrificed, then a microvascular free flap is used (21). Table 3

Reconstruction of Surgical Defects

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Palate Cranial base Orbital-maxillary Dental Facial

Oronasal separation Cranionasal separation Eye and cheek support Restoration of dentition and occlusion Restoration of facial defects and cosmesis

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Figure 42 Bicoronal approach for lateral orbitotomy. (A) Preoperative axial T2-MRI showing a vascular malformation of the left orbit. (B) Postoperative axial T2-MRI showing complete resection of the tumor. (C–G) Intraoperative photographs showing bicoronal approach (C), orbito-zygomatic exposure and osteotomies (arrows) (D), orbito-zygmoatic bone segment including the lateral orbital rim and zygomatic arch (E), lateral orbitotomy provides wide exposure for tumor resection (F), and tumor specimen (G). (H, I) Postoperative photographs showing good eye position and cosmetic result. Source: This illustration in the property of The Department of Head and Neck Surgery, M.D. Anderson Cancer Center is used with permission.

Vascularized tissue may also be needed to protect the carotid artery if it is exposed to the surgical defect. This is done to prevent desiccation of the arterial wall and carotid artery blowout. This is particularly important if the patient received prior radiation therapy or will receive postoperative adjuvant radiation (see chap. 8, “Surgical Reconstruction of Skull

Base Defects,” for more detail on microvascular reconstruction lease). Orbito-Maxillary Reconstruction: Eye and Cheek Support The maxilla has three bony buttresses: the nasomaxillary, zygomatico-maxillary, and pterygo-maxillary. In addition to

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Figure 43 Adenoid cystic carcinoma of the lacrimal gland. Coronal CT (A) and MRI (B) showing bone destruction of the superior orbital wall and intracranial soft invasion, respectively. The tumor was completely resected through a cranio-orbito–zygomatic approach (C), and the superolateral orbital walls were reconstructed using porous polyethylene “Medpore” implant (D). Source: This illustration in the property of The Department of Head and Neck Surgery, M.D. Anderson Cancer Center is used with permission.

a palatal defect, total maxillectomy results in resection of all three buttresses and loss of adequate skeletal support to the soft tissues of the cheek [Fig. 29(D)]. Loss of the zygomaticomaxillary buttress results in inferior displacement of the orbit and flattening of the malar eminence. Loss of the nasomaxillary buttress results in superior and posterior deviation of the alar base of the nose. Loss of the pterygomaxillary buttress results in superior and posterior deviation of the upper lip. Resection of the inferior orbital rim and floor leads to loss of skeletal support to the eyelid and globe. The lack of adequate orbital support leads to enophthalmos, ectropion, hypoglobus, and diplopia resulting in unacceptable esthetic and functional outcome. The combined effects of loss of support of the eye and cheek result in the “typical” postmaxillary deformity [Fig. 46(A)]. Although a split thickness

skin graft and a palatal obturator are commonly used in reconstruction after maxillectomy, these methods of reconstruction do not provide adequate support for the cheek and eye. Skeletal reconstruction of the maxillary and orbital defects may be done using bone grafts, most commonly autogenous calvarial grafts. Demineralized and banked bone grafts, which are available in a variety of shapes and sizes, may also be used. Alternatively, alloplastic implants may be used for reconstruction of the maxillary buttresses, orbital rim, or orbital floor. Titanium mesh, bone cement, and porous polyethylene have all been successfully used in orbital and maxillary bony reconstruction. Whatever method is used for bone reconstruction, adequate coverage with well-vascularized soft tissue is essential

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Figure 44 Prosthetic rehabilitation of the palate. (A) Palatal defect resulting from maxillectomy with split thickness skin graft lining the surgical cavity. (B) Interim obturator effectively seals the palatal defect and allows patients to resume a soft diet. (C, D) Permanent obturator provides excellent palatal reconstruction and dental restoration, allowing the patient to resume a normal diet. Source: This illustration in the property of The Department of Head and Neck Surgery, M.D. Anderson Cancer Center is used with permission.

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Figure 45 Sagittal (A) and (B) axial views of pericranial flap reconstruction of anterior cranial base defect. Source: This illustration in the property of The Department of Neurosurgery, M.D. Anderson Cancer Center is used with permission.

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(A)

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Figure 46 Orbito-maxillary reconstruction. (A) Left total maxillectomy with no reconstruction. “Typical” postmaxillectomy deformity due to lack of support of the orbit and cheek. There is downward displacement of the orbit and medial canthus. Note the presence of enophthalmos as evidenced by a prominent upper eyelid sulcus. There is flattening of the cheek and deviation of the nasal tip. The patient had significant diplopia. These deformities can be avoided with adequate bony reconstruction. (B) Left total maxillectomy with orbito-maxillary reconstruction. Postoperative appearance showing good position of the eye, cheek, and nose. Source: This illustration in the property of The Department of Head and Neck Surgery, M.D. Anderson Cancer Center is used with permission.

to prevent resorption of bone grafts and infection or extrusion of alloplastic implants. The pedicled temporalis muscle flap, temporoparietal fascial flap, or septal mucosal flap are most commonly used for this purpose. Microvascular free flaps may be used to either provide soft tissue coverage of bone grafts or implants, or composite vascularized bone flaps may be used for full reconstruction of both soft tissue and bone defects (21). Primary reconstruction of defects of the maxilla and orbit at the time of maxillectomy is easier and results in better esthetic and functional outcome than delayed reconstruction [Fig. 46(B)]. Although secondary reconstruction after globesparing maxillectomy is feasible, it is often difficult and the results are limited by excessive scarring and soft tissue contracture, especially in patients who underwent adjuvant radiation therapy. These patients may benefit more from freetissue transfer reconstruction (21).

Dental Restoration Prosthetic rehabilitation using partial or full upper dentures is the easiest method of dental restoration in patients who have undergone maxillectomy (Fig. 44). Remaining contralateral teeth facilitate retention of partial dentures. In edentulous patients, dental fixatives can be used, but denture retention is more difficult. A soft palate “band” at the posterior edge of the defect may provide enough of a ledge for retaining the prosthesis. Retention of the prosthesis in edentulous patients who underwent an extended resection to include the soft palate may be extremely difficult. In such cases, the use of osteointegrated implants facilitates prosthetic dental restoration (see Fig. 2 in chap. 9, “Prosthetic Rehabilitation of Patients undergoing Skull Base Surgery”).

Another important aspect in the rehabilitation of patients after maxillectomy is the prevention of trismus. Patients who have undergone resection of the pterygoid plates or muscles of mastication are particularly prone to develop trismus. This may be severe enough to interfere with inserting and wearing a denture-bearing obturator. Early postoperative jaw-opening exercises using “stacked” wooden tongue blades or commercially available devices (e.g., Therabite) are extremely important in preventing or minimizing postoperative trismus. Restoration of Facial Defects Smaller defects of the face are optimally reconstructed using local flaps. Local skin flaps provide the best thickness and color match for facial defects. Reconstruction of more extensive facial defects may require regional or microvascular free flaps, but suffer from less optimal esthetic outcome due to color or thickness mismatch between the donor and defect sites. Facial defects resulting from orbital exenteration or total rhinectomy are best managed with prosthetic restoration (see Figs. 3 and 4 in chap. 9, “Prosthetic Rehabilitation of Patients undergoing Skull Base Surgery”).

SUMMARY Surgical management of tumors of the nasal cavity, paranasal sinuses, and orbit require in depth understanding of the biologic behavior of the various tumor types originating in this region. Careful assessment of the location and extent of the tumor is crucial in planning and executing the proper surgical approach for adequate oncologic resection. Meticulous reconstruction of the surgical defect(s) is critical in avoiding

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complications and maximizing functional and esthetic outcome. As with other types of cranial base tumors, multidisciplinary collaboration is essential for successful treatment of patients with tumors of this region.

REFERENCES 1. Hanna EY, Westfall CT, Myers EN, et al. Cancer of the nasal cavity, paranasal sinuses, and orbit. In: Myers EN, Suen JY, Myers JN, Hanna EY, eds. Cancer of the Head and Neck. Philadelphia, PA: Saunders, 2003:155–206. 2. Diaz EM Jr, Johnigan RH III, Pero C, et al. Olfactory neuroblastoma: The 22-year experience at one comprehensive cancer center. Head Neck. 2005;27(2):138–149. 3. Rosenthal DI, Barker JL Jr, El-Naggar AK, et al. Sinonasal malignancies with neuroendocrine differentiation: Patterns of failure according to histologic phenotype. Cancer. 2004;101(11):2567– 2573. 4. Girod D, Hanna E, Marentette L. Esthesioneuroblastoma. Head Neck. 2001;23(6):500–505. 5. Lupinetti AD, Roberts DB, Williams MD, et al. Sinonasal adenoid cystic carcinoma: The M. D. Anderson Cancer Center experience. Cancer. 2007;110(12):2726–2731. 6. Prokopakis EP, Snyderman CH, Hanna EY, et al. Risk factors for local recurrence of adenoid cystic carcinoma: The role of postoperative radiation therapy. Am J Otolaryngol. 1999;20(5):281–286. 7. Pitman KT, Prokopakis EP, Aydogan B, et al. The role of skull base surgery for the treatment of adenoid cystic carcinoma of the sinonasal tract. Head Neck. 1999;21(5):402–407. 8. Tirado Y, Williams MD, Hanna EY, et al. CRTC1/MAML2 fusion transcript in high grade mucoepidermoid carcinomas of salivary and thyroid glands and Warthin’s tumors: Implications for histogenesis and biologic behavior. Genes Chromosomes Cancer. 2007;46(7):708–715. 9. Hanna E, Vural E, Teo C, et al. Sinonasal tumors: The Arkansas experience. Skull Base Surg. 1998;8(Suppl):15.

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10. Hanna E, Linskey ME, Pieper D. Malignant tumors of the anterior cranial base. In: Sekhar LN, Fessler RG, eds. Atlas of Neurosurgical Techniques. New York: Thieme, 2006:588–598. 11. DeMonte F, Ginsberg LE, Clayman GL. Primary malignant tumors of the sphenoidal sinus. Neurosurgery. 2000;46(5):1084– 1091; discussion 1091–1092. 12. Hanna E, Vural E, Prokopakis E, et al. The sensitivity and specificity of high-resolution imaging in evaluating perineural spread of adenoid cystic carcinoma to the skull base. Arch Otolaryngol Head Neck Surg. 2007;133(6):541–545. 13. Cohen ZR, Marmor E, Fuller GN, et al. Misdiagnosis of olfactory neuroblastoma. Neurosurg Focus. 2002;12(5):e3. 14. Bristol IJ, Ahamad A, Garden AS, et al. Postoperative radiotherapy for maxillary sinus cancer: Long-term outcomes and toxicities of treatment. Int J Radiat Oncol Biol Phys. 2007;68(3):719–730. 15. Hanna EY, Holsinger C, Demonte F, et al. Robotic endoscopic surgery of the skull base: A novel surgical approach. Arch Otolaryngol Head Neck Surg. 2007;133(12):1209–1214. 16. Vural E, Hanna E. Extended lateral rhinotomy incision for total maxillectomy. Otolaryngol Head Neck Surg. 2000;123(4):512–513. 17. DeMonte F, Hanna E. Transmaxillary exploration of the intracranial portion of the maxillary nerve in malignant perineural disease. Technical note. J Neurosurg. 2007;107(3):672–677. 18. Feiz-Erfan I, Suki D, Hanna E, et al. Prognostic significance of transdural invasion of cranial base malignancies in patients undergoing craniofacial resection. Neurosurgery. 2007;61(6):1178– 1185; discussion 1185. 19. Essig GF, Newman SA, Levine PA. Sparing the eye in craniofacial surgery for superior nasal vault malignant neoplasms: Analysis of benefit. Arch Facial Plast Surg. 2007;9(6):406–411. 20. Dexter WS, Jacob RF. Prosthetic rehabilitation after maxillectomy and temporalis flap reconstruction: A clinical report. J Prosthet Dent. 2000;83(3):283–286. 21. Chang DW, Langstein HN, Gupta A, et al. Reconstructive management of cranial base defects after tumor ablation. Plast Reconstr Surg. 2001;107(6):1346–1355; discussion 1356–1357. 22. Gray H. Anatomy of the Human Body, 20th ed., edited by Lewis WH, New York: Bartleby, 2000.

17 Tumors of the Nasopharynx William Ignace Wei and Paul K. Y. Lam

The lymphatic supply of the nasopharynx is found mainly in the submucosal region, which drains into the retropharyngeal lymph nodes. Efferents lymphatics from these nodes and some of the lymphatics that come directly from the nasopharynx drain to the deep cervical lymph nodes. The lymphatic drainage through the neck nodes goes in an orderly fashion, from upper to lower cervical lymph nodes.

SURGICAL ANATOMY The pharynx is divided into three parts, the nasopharynx, oropharynx, and hypopharynx. The nasopharynx is the upper portion of the pharynx and is separated from the oropharynx by the soft palate. Anatomically, it is the space located behind the nasal cavities and its mucosal lining starts at the posterior choana. The undersurface of the body of the sphenoid bone forms the slanting roof of the nasopharynx that continues inferiorly into the posterior wall, which is formed by the arch of the atlas vertebra and upper part of the body of the axis vertebra. The floor of the nasopharynx is formed by the upper surface of the soft palate, which also separates the nasopharynx from the oropharynx below. The lateral wall of the nasopharynx is formed by the opening of the Eustachian tube superiorly and the upper part of the superior constrictor muscle inferiorly. The orifice of the Eustachian tube is guided by an incomplete cartilaginous ring, which is deficient in the inferolateral aspect. The medial portion of the incomplete cartilaginous ring elevates the overlying mucosa to form the medial crura. The slit-like space situated medial to this crura ¨ is the fossa of Rosenmuller; its size and depth varies between individuals. The superior constrictor forms the muscular layer of the nasopharynx starting from beneath the auditory tympanic tube, and investing this muscle externally is the pharyngobasilar fascia. This fascia joins its counterpart from the opposite side to form the median raphe, which extends from the skull base caudally throughout the posterior pharyngeal wall. The pharyngobasilar fascia together with the prevertebral fascia encloses the retropharyngeal space, which harbors the lymph node of Rouviere. Lateral to the superior constrictor is the parapharyngeal space, which contains the last four cranial nerves, the carotid sheath, and the sympathetic trunk. The superior wall of the nasopharynx is lined by pseudostratified ciliated epithelium near the choana. The posterior wall is lined with stratified squamous cells and the epithelium lies on a well-defined basement membrane. On the lamina propria, abundant lymphoid tissue can be found. This in the midline forms the pharyngeal tonsil or the adenoid tonsil, which is prominent in children. This lymphoid aggregate is a part of the Waldeyer ring of lymphatic tissue guarding the pharynx. The arterial blood supply of the nasopharynx comes from branches of the internal maxillary artery, while the venous drainage of the region goes to the pterygoid plexus and then onto the facial and the internal jugular veins. The nerve supply of the nasopharynx comes from the pharyngeal plexus, although the nasopharynx is immobile. The sensory nerve supply of the region comes from the branches of the maxillary nerve.

REGIONAL PATHOLOGY AND DIFFERENTIAL DIAGNOSIS Tumors in the nasopharynx include congenital, benign, and malignant neoplasms. Congenital tumors and tumor-like conditions are in general uncommon and include dermoids, teratomas, and encephalocele. These pathologies are usually seen in neonates or young children and they present with nasal obstruction or breathing problems. Subsequent investigations such as imaging studies or endoscopic examinations will give clues to the diagnosis.

Benign Tumors Benign tumors arising from the epithelial linings of the nasopharynx are rare. Other benign tumors include benign salivary gland tumors arising from the minor salivary glands and juvenile angiofibroma. Juvenile angiofibroma is a benign but locally aggressive tumor affecting most commonly adolescent boys. Symptoms include nasal obstruction and epistaxis, which may be severe. This tumor arises from the posterolateral aspect of the roof of the nasal cavity in the region of the sphenopalatine foramen (1). The tumor grows into the pterygopalatine fossa and then posteromedially into the nasopharynx or laterally to the infratemporal fossa. It may also extend superiorly eroding into the sphenoid sinus or anteriorly to affect the maxillary sinus. It may extend into the orbit through the inferior orbital fissure leading to proptosis and further invasion superiorly will go to the middle cranial fossa as well. Macroscopically, the tumor is lobulated with the consistency ranging from spongy to firm depends on the proportion of vascular tissue and fibrous component. Histologically, the tumor is noncapsulated and consists of numerous blood vessels of varying caliber coursing through a fibrous tissue stroma. The thickness of the muscular coat of these vessels varies and there is a lack of elastic fibers contributing to the frequent episodes of epistaxis. These clinical features frequently lead to the correct diagnosis of this condition, while imaging studies help to confirm it. Plain radiographs demonstrate the bowing of the anterior wall of the maxillary sinus anteriorly and the erosion of the base of the medial pterygoid plate. Angiography reveals a typical vascular tumor blush with the internal maxillary artery as the principal feeder. 267

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Malignant Tumors Adenoid cystic carcinoma and adenocarcinoma arising from the minor salivary glands situated in the nasopharynx are uncommon. Grossly, they may present as a polypoid mass (Fig. 1) or as a submucosal bulge in the nasopharynx. Symptoms associated with these tumors are usually trivial until they infiltrate and affect the surrounding structures such as the fifth cranial nerve. Then the patient may present with facial pain and trismus. Biopsy of the tumor confirms the diagnosis. Sarcoma of the nasopharynx is rarely seen and includes rhabdomyosarcoma in children and malignant fibrous histiocytoma in adults. The frequently encountered symptoms are nasal obstruction, epistaxis, and serous otitis media. The gross appearance is the presence of a firm smooth mass filling the nasopharynx and the exact diagnosis is confirmed by biopsy. Chordomas are malignant neoplasms arising from the remnant of notochord tissue located at the spheno-occipital region. The characteristic location of a cranial chordoma is at the clivus as it forms the posterior wall of the nasopharynx; many patients with chordoma present with a mass in the nasopharynx (Fig. 2). The symptoms are related to the cranial nerves involved and the effect of the tumor bulk. Extramedullary plasmacytoma are neoplasms that arise from the plasma cells located in the extraosseous soft tissue. This is more frequently seen in middle-aged or elderly men. The symptoms are related to the presence of the soft tissue tumor in the nasopharynx which might fill the entire nasopharynx and there is a tendency of metastasis to regional lymph nodes. As the lymphoid tissue in the nasopharynx is part of the Waldeyer ring, one of the differential diagnoses of malignant lesion in the region is malignant lymphoma. The majority of these are diffuse B cell lymphomas and the symptoms are again related to the presence of the mass in the nasopharynx causing nasal obstruction or impairing function of the Eustachian tube. Other malignant pathologies found in the nasopharynx are lesions in the nasal cavity that extend to the nasopharynx. These include the sinonasal carcinomas and malignant mucosal melanomas arising from the nasal lining. The common symptoms are nasal obstruction and epistaxis related to the tumor bulk and the superficial ulceration.

Figure 2 Plain lateral X-ray showing a chordoma producing a bulge at the posterior wall of the nasopharynx (arrow).

For inhabitants of southern China, northern Africa, and Alaska, the commonest malignancy in the nasopharynx is nasopharyngeal carcinoma (NPC). This carcinoma arises from epithelial lining of the nasopharynx, most frequently from ¨ the fossa of Rosenmuller, the recess located medial to the medial crura of the Eustachian tube. NPC is a squamous cell carcinoma with varying degree of differentiation and among the majority of the Chinese patients—these are undifferentiated squamous cell carcinoma (2). These malignant squamous cells are frequently intermingled with lymphoid cells in the nasopharynx, thus it was previously termed as lymphoepithelioma. Electron microscopy studies have, however, confirmed the squamous origin of these malignant cells. Patients suffering from NPC may present with one or more of the four groups of symptoms. Epistaxis, nasal obstruction, and discharge are related to the presence of tumor mass in the nasopharynx. When the tumor affects the Eustachian tube, the patient presents with hearing loss and tinnitus. Serous otitis media was noted in 40% of the newly diagnosed NPC patients. Thus when a Chinese adult patient presents with serous otitis media, then the possibility of NPC should be excluded (3). With the superior extension of the tumor to erode the skull base, the patient may present with headache and the tumor may involve the third, fourth, fifth, and sixth cranial nerves. Commonly, patients may present with enlarged cervical lymph nodes, which usually appear at the upper neck (Fig. 3). As the nasopharynx is located in the midline, it may metastasize to the opposite side, thus it is not uncommon to see patients presenting with bilateral enlarged cervical lymph nodes.

CLINICAL ASSESSMENT

Figure 1 Flexible endoscopic view of an adenocarcinoma in the nasopharynx (arrow). Left Eustachian tube cartilage is also shown (C).

For patient suspected of harboring pathology in the nasopharynx, a full clinical examination should be carried out to evaluate the general condition of the patient and to identify any evidence of distant metastasis. The age and medical history of the patient might give clues to the diagnosis. Comprehensive clinical evaluation of the head and neck region is also essential. The test of nasal obstruction either one side or bilaterally should be carried out and an

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Figure 4 A 0-degree rigid endoscopic view of an NPC (T) in the nasopharynx, located medial to the medial crura (C) of right Eustachian tube opening.

Figure 3 Clinical photograph of a patient suffering from NPC, presenting with cervical lymph node.

indirect examination of the nasopharynx with a mirror may reveal important information toward the diagnosis. The anterior nasal cavity should be examined for macroscopic tumor and lesions arising from the mucosa. The ears should be examined for hearing impairment and the presence of serous otitis media. The neck should always be palpated for the presence of metastatic cervical lymph node.

can be inserted through this channel to take a biopsy of the tumor under direct vision. It allows thorough examination of the entire nasopharynx when it is inserted through the nasal cavity. It may also be manipulated upward behind the soft palate to examine the nasopharynx from the inferior aspect. In view of the size of the endoscope and its flexibility, it is well tolerated by most patients. Despite all these advantages, the visual image gathered with the flexible endoscope is inferior to that of the rigid telescope. The cup size of the biopsy forceps is limited by the size of the channel on the endoscope, thus the amount of tissue obtained for histological examination might not be adequate. When biopsy is taken with the flexible endoscope, then multiple biopsies might have to be taken to increase the yield. Sometimes, NPC may be submucosally located in the submucosa, thus the mucosal surface has to be broken with the forceps to enable deeper tissue to be obtained (4).

Endoscopic Examination The nasal cavity and the nasopharynx can be examined with either the fiber-optic endoscope or the rigid telescopes under topical anesthesia. The rigid Hopkins telescopes are 2.7 or 4 mm in diameter with different angles of viewing. Both the 0-degree and the 30-degree telescopes give an excellent view of the nasopharynx (Fig. 4) and the location of the tumor in the nasopharynx. A 70-degree endoscope inserted behind the uvula allows visualization of the roof of nasopharynx and both Eustachian tube openings (Fig. 5). It gives an idea of the extension of the tumor across the midline and also the vascular nature of the tumor. These rigid telescopes, however, do not have a channel for suction or for the introduction of biopsy forceps. When a biopsy is needed, the biopsy forceps has to be inserted along the side of the endoscope. A relatively large biopsy forceps can be inserted to obtain an adequate amount of tumor for histological examination. The fiber-optic flexible endoscope for ordinary use has a diameter of 6 mm, it has a suction channel for the removal of nasal secretions during examination, and a biopsy forceps

Figure 5 A 70-degree endoscope inserted behind the uvula and the NPC (T) can be seen together with posterior edge of nasal septum (N) and the opposite Eustachian tube opening (arrow).

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and its vicinity. The neck should also be included in the imaging studies for the detection of occult cervical metastasis. These cross-sectional imaging studies provide information on the deep extension of the tumor including skull base erosion and extension of the lesion intracranially.

Computed Tomography Besides demonstrating the soft tissue extent of the tumor in the nasopharynx and its extension laterally into the paranasopharyngeal space (8), CT is also sensitive in detecting bone erosion at the skull base (Fig. 6). Tumor extension intracranially through the foramen ovale via perineural spread along the third division of the trigeminal nerve (V3) and even to the cavernous sinus should be evaluated (9). CT in the posttherapy phase may show bone regeneration and this indicates complete eradication of tumor (10).

Magnetic Resonance Imaging Figure 6 Direct coronal CT showing tumor in the paranasopharyngeal space eroding the skull base (arrow).

Serological Tests Serological tests are not applicable for most malignant lesions situated in the nasopharynx. It is applicable when the symptoms suggest that the patient may be harboring NPC, then their antibody titer, the immunoglobulin A, in response to the early antigen and the viral capsid antigen of Epstein Barr virus may further indicate the presence of the disease (5). Recently, cell-free DNA of the Epstein Barr virus (EBV) has been evaluated as a tumor marker for detection of NPC (6), yet its application in the detection of small recurrent tumor after radiotherapy is limited (7).

MRI provides multiplanar imaging abilities (Fig. 7) and has better delineation of tumor and soft tissue interface than CT (Fig. 8). MRI is able to detect bone marrow infiltration by tumors, while CT cannot detect this kind of infiltration unless there is associated bony erosion. MRI is also more sensitive at evaluating retropharyngeal and deep cervical nodal metastases (11). Despite all these advantages, MRI is not suited to evaluate details of bone erosion, and CT should be performed when the status of the base of the skull needs to be evaluated.

PET/CT Scan There is an increasing use of PET/CT scan in the diagnosis of malignancies in the head and neck region. It is useful in the nasopharynx region to differentiate inflammation from malignant tumors and in the detection of local recurrence after therapy. It is also helpful in the search for the primary at the skull base when the patient presents with a metastatic lymph node (12).

Diagnostic Imaging Cross-sectional imaging either by computed tomography (CT) or by magnetic resonance imaging (MRI) is invaluable in the investigation of pathologies in the nasopharynx. These imaging studies show the tumor in the nasopharynx, as well as any abnormal structural alterations in the nasopharynx

Figure 7 extension.

SURGICAL RESECTION OF TUMORS IN THE NASOPHARYNX For NPC, which is chemoradiosensitive, concomitant chemoradiation is the primary treatment modality (13). For

(Left) Direct coronal MR showing a schwannoma extending through the skull base. (Right) Axial MR of the same patient showing intracranial

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Figure 9 Schematic CT, (Left) The dotted lines mark the osteotomies. (Right) The right maxilla attached to the anterior cheek flap is swung laterally to expose tumor in the nasopharynx (arrow).

Figure 8 Axial MR showing a chordoma (Ch).

those patients who have residual disease or develop recurrence in the nasopharynx after chemoradiation, surgical salvage has been shown to be effective (14). As the nasopharynx and its nearby regions are located in the central portion of the head, it is difficult to approach and to expose the region adequately to carry out an oncological resection. A few approaches have been reported over the years to expose the nasopharynx to allow an oncological resection to be carried out for tumors situated in the region. To approach the region from the superior or the posterior aspects is not practical, as the brain and the spinal column are in the way which limits surgical exposure. The anterior approach to the nasopharynx through the transantral route or the midfacial degloving procedures exposes the anterior part of the nasopharynx. This approach does not provide adequate exposure of the whole nasopharynx, including the superior and lateral walls. These anterior approaches, even combined with the controlled fracture of the hard palate followed by its downward displacement, only increase the exposure of the superior and posterior walls of the nasopharynx and not its lateral walls which are frequently involved by most tumors. The nasopharynx and the central skull base can be approached from the inferior aspect employing the transpalatal, transmaxillary, and transcervical approaches (15,16). This approach is useful for tumors located in the central and lower posterior wall of the nasopharynx. For more extensive tumors, especially those situated on the roof and on the lateral wall, the exposure of the lateral aspect of the tumor is not adequate. The dissection of the paranasopharyngeal space is difficult with this inferior approach. The internal carotid artery lying in this area has to be protected during the removal of tumor and with this approach the control of the vessel is suboptimal. The surgical approach to the nasopharynx and its vicinity from the lateral aspect through the infratemporal fossa has been described (17). With this approach, a radical mastoidectomy has to be performed and some important structures have to be mobilized, which include the internal carotid artery, the fifth cranial nerve, and the floor of the middle cranial fossa. The resultant morbidities following this approach are significant; in addition, considerable surgical expertise is required to employ this approach to the central skull base. This approach exposes directly the lateral wall of the na-

sopharynx, including the ipsilateral internal carotid artery. It, however, does not provide adequate access to the lateral wall of the nasopharynx on the opposite side and thus have limitations when the tumor in the nasopharynx crosses the midline. The nasopharynx can also be approached from the anterolateral aspect through the lateral swing of the hard palate and the maxillary antrum. The maxilla remains attached to the anterior cheek flap, where it derives its blood supply. This maxillary swing approach exposes the nasopharynx and its vicinity widely for an oncological resection (Fig. 9). The approach offers unobstructed view of the region from the anterior, inferior, and lateral aspects. With the extensive exposure of the region, the internal carotid artery lying outside the pharyngobasilar fascia can be palpated and closely observed during the resection of the tumor. Following extirpation of tumor, the whole osteocutaneous complex can be returned to its original position and fixed to the rest of the facial skeleton. We have employed this approach for resection of tumors in the nasopharynx and those extending to nearby regions. The outcome has been satisfactory with no mortality and minimal morbidity (18–20).

Preoperative Preparation The general condition of the patient should be evaluated to ensure that the patient is fit for the surgery. This includes the cardiopulmonary status and hematologic status. The patient’s blood should be typed and screened in case there is excessive blood loss, blood transfusion can be given, although this is seldom required. Any trismus should be eliminated as much as possible through mechanical stretching before the operation. The interalveolar distance should be more than 3 cm to allow the intraoral procedures, such as lifting the palatal flaps and the insertion of the curved osteotome to separate the pterygoid plates from maxillary tuberosity. Preoperatively, the orthodontist should take an impression of the upper alveolus of the patient in order to make a dental plate. This dental plate conforming to the contour of the whole upper alveolus facilitates the accurate placement of the swung maxilla after its return to the original position following the extirpation of tumor in the nasopharynx. While attaching to the opposite upper alveolus, the dental plate also contributes to immobilize the swung maxilla to facilitate healing. As the surgical field involves the oral cavity, intravenous broad spectrum antibiotics are started preoperatively.

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SURGICAL TECHNIQUE Patient Position The operation is carried out under general anesthesia with a temporary tracheostomy performed for ventilation. This will leave the oral and nasal cavities free for the various operative maneuvers. The patient lies in supine position with the head slightly elevated. A temporary tarsorrhaphy suture is placed on the eyelid of the operative side while the other eye is covered with protective tape. The operative site is cleaned with antiseptic solution from the forehead down to the root of the neck and draped accordingly. The neck on the side of the operation is also prepared in case of the need for internal carotid artery control during the operation. The oral cavity is cleaned with antiseptic solution and a pharyngeal pack is inserted.

Incision The Weber-Ferguson incision is used. This starts at about 2 cm lateral to the outer canthus of the eye and should be close to the lower border of the zygomatic arch. The incision then extends medially at 3 mm below and parallel to the lower eyelashes. If the incision is placed too close to the eyelashes, edema may develop in the region above the incision, and if placed too far away, the patient may develop ectropion. When the incision reaches the medial canthus, it is curved inferiorly along the lateral border of the nose to reach the alar groove. The curve of the incision around the medial canthus is fashioned to be as obtuse as possible to ensure the tip of the skin has adequate blood supply to avoid necrosis. This is particularly important if the patient had previous radiotherapy. The incision continues inferiorly along the side of the nose to reach the midline, where it then turns downward at right angle, extends along the philtrum to divide the upper lip up to the vermilion. The incision over the vermilion part of the upper lip should be in a zigzag line to avoid subsequent contracture and upward retraction of the lip. This incision continues over the gum to reach the groove between the two central incisors (Fig. 10). The palatal incision is placed on the lingual aspect of the upper alveolus. It starts from the mucosa 0.5 cm from the canine on the opposite side and curves along the inner border of the upper alveolus toward the operative side, keeping a mucosal ridge of 0.5 cm. On reaching the third molar, it turns laterally toward the buccal mucosa behind the maxillary tuberosity (Fig. 11).

Figure 10 Facial incision for the maxillary swing approach to central skull base is marked.

The greater palatine vessel on the side of the swing should be divided between clamps. Following this, the elevated palatal flap can be lifted to expose the midline of the hard palate and posteriorly the attachment of the soft palate to the hard palate. This attachment should be divided to enter the posterior nasal cavity, thus detaching the soft palate from the hard palate.

Bony Dissection and Osteotomies A total of four osteotomies are required to detach the maxilla from the rest of the facial skeleton. The first horizontal osteotomy is placed on the anterior wall of the maxilla below the inferior rim of the orbit, thus the orbital floor is not disturbed. This osteotomy is extended laterally onto the zygomatic arch and then turns inferior, thus dividing only

Soft Tissue Dissection The transverse facial incision goes down onto the anterior wall of the maxilla. The soft tissue is elevated to expose only a strip of the anterior bony wall of the maxilla and the zygomatic arch in order to apply the oscillating saw and to place the miniplates. The infraorbital nerve and vessel should be divided and the anterior wall osteotomy usually goes through this infraorbital foramen (Fig. 12). The transverse incision continues to the lateral rhinotomy incision, which goes directly into the nasal cavity so that the entire upper and lower lateral cartilages on the side of the swing are lifted and turned medially up to the midline. The soft tissue over the incisor fossa is elevated to the anterior nasal spine in the midline. The amount of soft tissue lifted should again be limited to allow the placement of the miniplates and the insertion of the oscillating saw. The incision over the mucosa on the hard palate should be down to bone and the mucoperiosteum covering of the hard palate should be lifted from the canine tooth on the opposite side to the last molar tooth on the side of the swing.

Figure 11 The palatal incision is marked.

Chapter 17: Tumors of the Nasopharynx

Figure 12 The osteotomy line on the anterior wall of the maxilla is marked (arrow). Limited amount of soft tissue over the anterior wall of the maxilla is elevated, only adequate to expose a narrow strip of bone for the oscillating saw.

the lower half of the zygomatic arch. The oscillating saw then goes through the maxillary antrum to separate the posterior wall of the maxilla from its superior bony attachments. The second osteotomy divides the entire hard palate in the midline. Care should be taken to protect the elevated palatal flap and the soft palate from injury by the oscillating saw, both should remain intact after the osteotomy. Before making these two osteotomies, the miniplates intended for fixation of the maxilla, with holes for the screws drilled, should be placed across the proposed osteotomy paths. This will facilitate the repositioning of the maxilla after resection of the tumor at the skull base. In general, two 4-hole miniplates are employed: one across the osteotomy on the zygoma and the other across the midline below the nasal spine. The third osteotomy divides the lateral wall of the nose. It is placed above the upper border of the inferior turbinate and goes from anterior to posterior dividing the bony lateral wall of the nose together with the lacrimal duct. The fourth osteotomy separates the maxillary tuberosity from the pterygoid plates through the use of a curved osteotome (Fig. 13).

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Figure 13 Palatal flap (P) retracted medially and a curved osteotome (arrow) is inserted to separate the pterygoid plates from the maxillary tuberosity.

prevertebral muscle can be removed together with the tumor to increase the resection margin and for similar reason; the anterior wall of the sphenoid sinus is removed with a drill. The sphenoid sinus is thus opened while it is not necessary to remove its mucosa. The wide exposure achieved after the maxilla is swung laterally allows the dissection of the paranasopharyngeal space under direct vision. Thus lymph node or the tumor which has extended to this space such as schwannoma, angiofibroma, etc. can be removed under direct vision. The position of the internal carotid artery lying outside the pharyngobasilar fascia can be identified by palpation during the dissection and thus protected from injury.

Reconstruction While the maxilla is swung laterally, the inferior turbinate is removed (Fig. 16) and an inferior antrostomy is performed to improve the drainage from the maxillary sinus. The mucosa over the removed inferior turbinate is spread out as a sheet and placed on the raw area in the nasopharynx as a free mucosal graft (Fig. 16). After resection of tumor localized in

Following the osteotomies, the maxilla with half of the hard palate drops inferiorly but is still attached to the anterior cheek flap. This whole osteocutaneous flap can be swung laterally as one unit to expose the nasopharynx and the central skull base (Fig. 14).

Tumor Resection After the maxilla is swung laterally, pterygoid plates are separated from the muscular attachments and removed. The pterygoid muscles are retracted after plication to stop bleeding from the venous plexus. The posterior part of the nasal septum, the vomer and septal cartilage, is removed to improve exposure of the opposite nasopharynx. Then the entire nasopharynx and the paranasopharyngeal space on the side of the swing are exposed to allow an oncological resection. Tumor located in the nasopharynx and its vicinity can be removed under direct vision. For recurrent NPC, it is frequently attached to the auditory tympanic tube. As such, the cartilaginous portion of this tube together with the lateral wall of the nasopharynx including the fossa of Rosenmuller on the side of the swing is removed with the tumor en bloc (Fig. 15). The

Figure 14 The maxilla attached to the anterior cheek flap is swung laterally as an osteocutaneous flap to expose the nasopharynx and central skull base (N).

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Figure 16 (Left) Inferior turbinectomy carried out on the laterally swung maxilla. (Right) The mucosa from the inferior turbinate as a free graft (G) is laid onto the raw area in the nasopharynx following tumor resection.

drilled on the skull base bone to facilitate the insertion of sutures. The vascular pedicle is transposed inferiorly lateral to the wall of the oropharynx and the ascending ramus of the mandible. The microvascular vascular anastomosis is carried out with the facial vessels at the lower border of the mandible or in the neck.

Closure

Figure 15 Nasopharyngectomy specimen showing the tumor (T) and the Eustachian tube crura; the Eustachian tube opening is marked by a plastic tube (arrow).

the nasopharynx, the swung maxilla is returned to its original position and it is fixed to the rest of the facial skeleton with the two miniplates. One additional wire loop is used to approximate the upper medial angle of the swung maxilla and the nasal bone. This three-point fixation together with the prefabricated dental plate gives a stable reconstruction of the upper alveolus (Fig. 17). If a significant resection of the soft tissue such as the soft palate or lateral pharyngeal wall is done for oncological clearance, additional reconstruction with free tissue transfer is required. This also applies when a significant size of skull base bone is removed with or without resection of the dura, particularly in patients with previous radiotherapy. In addition to filling the soft tissue defect, the free tissue also contributes increased vascularity to prevent the development of osteoradionecrosis. The free flap of choice is the rectus abdominis muscle with or without the overlying skin island. When there is a pharyngeal defect, the skin island is useful for the reconstruction of this defect. Otherwise, the muscle alone is adequate to fill the soft tissue defect. The muscle component is insetted to fill the defect in the nasopharynx through stitching to the pterygoid muscle and tissue at the skull base. Occasionally, holes have to be

After returning and fixing of the swung maxilla to the facial skeleton with the two miniplates and one wire loop, the hard palate mucoperiosteum is repositioned (Fig. 18). Only a few stitches are required near the maxillary tuberosity. Stitching the palatal flap along the entire alveolar margin might produce tenting and deprive of its contact with the hard palate (21). The insertion of the prefabricated dental plate will ensure a close contact of this flap with the underlying bone. A nasogastric tube is inserted via the opposite nostril for postoperative feeding. The posterior part of the nose on the side of the swing might be packed with a Foley catheter.

Figure 17 The maxilla is fixed to the rest of the facial skeleton with miniplates (arrow heads) and one wire loop at the upper medial angle (arrow) of the maxilla.

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on the third postoperative day. At about 1 week after the operation, oral feeding can be started and nasal pack with the Foley catheter can also be removed. For those patients who had previous radiotherapy, oral feeding is usually started about 2 weeks after the operation.

Complications and Avoidance

Figure 18 (Left) The hard palate mucoperiosteum is repositioned (M) and only two stitches (arrow) are placed near the maxillary tuberosity, (Right) The prefabricated dental plate is placed to maintain the position of the palatal flap.

The blown-up balloon of the catheter will keep the mucosal graft in position and reduce the amount of blood or serum dripping into the oropharynx. The anterior nasal cavity is packed with Merocel and the facial wound is closed with interrupted suture in layers (Fig. 19).

Postoperative Care The patient is advised to have his head elevated at 30 degrees to reduce facial edema and nasal gastric tube feeding can be started after the patient recovers from general anesthesia. The tracheostomy tube can be removed when the patient has regained the ability to cough and this can usually be done

For patients who had previous radiotherapy, the possibility of development of osteoradionecrosis of the skull base bone is high. Yet with limited bone exposure, conservative management is usually adequate to limit such complications. For extensive area of osteoradionecrosis, the infection might extend intracranially. Early recognition of the problem and extensive adequate debridement followed by reconstruction with a microvascular free flap is essential for salvage. To avoid the development of osteoradionecrosis, all the exposed bone should be covered with soft tissue and when necessary, a microvascular free flap should be done initially. When the maxillary swing procedure was initially reported, the split of the mucoperiosteum and the hard plate was in the same plane. Thus the development of palatal fistula used to be one of the main complications. With the modification of the incision over the palate and the elevation of the palatal flap, the osteotomy of the hard palate and the incision of the mucoperiosteum are no longer in the same plane. Thus palatal fistula can be avoided in most patients nowadays. Another complication is the development of trismus. This is frequently encountered in patients who had previous radiotherapy. The trismus responds to passive mechanical stretching. Once interalveolar distance reaches 2 cm, normal oral feeding is usually smooth. Occasionally, patients may develop ectropion and this is related to the contracture of the lower eyelid. Revision of the scar together with the insertion of a small piece of full thickness skin graft will solve the problem.

Follow-up and Rehabilitation During follow-up sessions, endoscopic examination of the nasal cavity and the nasopharynx together with irrigation and cleansing should be carried out to reduce the incidence of infection. This is particularly important for patients with previous radiotherapy. The dental plate is removed at 1 week after operation and the patient is advised to have soft diet for 1 month to allow bony reunion of the osteotomies. All patients are advised to have active and passive stretching exercises to reduce trismus. Any recurrence of pathology in the nasopharyngeal region can be detected with endoscopic examination and other imaging studies, which are carried out as indicated.

REFERENCES

Figure 19 At the completion of operation, the facial wound is closed and the nasogastric tube inserted.

1. Harrison DFN. The natural history, pathogenesis, and treatment of juvenile angiofibroma. Personal experience with 44 patients. Arch Otolaryngol Head Neck Surg. 1987;13:936–942. 2. Nicholls JM. Nasopharyngeal carcinoma:Classification and histological appearances. Adv Anat Path. 1997;4:71–84. 3. Sham JS, Wei WI, Lau SK, et al. Serous otitis media. An opportunity for early recognition of nasopharyngeal carcinoma. Arch Otolaryngol Head Neck Surg. 1992;118;794–797. 4. Wei WI, Sham JS, Zong YS, et al. The efficacy of fiberoptic endoscopic examination and biopsy in the detection of early nasopharyngeal carcinoma. Cancer. 1991;67:3127–3130. 5. Chien YC, Chen JY, Liu MY, et al. Serologic markers of EpsteinBarr virus infection and nasopharyngeal carcinoma in Taiwanese men. N Engl J Med. 2001;345:1877–1882.

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6. Lo YM, Chan LY, Lo KW, et al. Quantitative analysis of cell-free Epstein-Barr virus DNA in plasma of patients with nasopharyngeal carcinoma. Cancer Res. 1999;59:1188–1191. 7. Wei WI, Yuen AP, Ng RW, et al. Quantitative analysis of plasma cell-free Epstein-Barr virus DNA in nasopharyngeal carcinoma after salvage nasopharyngectomy: A prospective study. Head Neck. 2004;26:878–883. 8. Sham JS, Cheung YK, Choy D, et al. Nasopharyngeal carcinoma: CT evaluation of patterns of tumor spread. AJNR Am J Neuroradiol. 1991;12:265–270. 9. Chong VF, Fan YF, Khoo JB. Nasopharyngeal carcinoma with intracranial spread: CT and MR characteristics. J Comput Assist Tomogr. 1996;20:563–569. 10. Fang FM, Leung SW, Wang CJ, et al. Computed tomography findings of bony regeneration after radiotherapy for nasopharyngeal carcinoma with skull base destruction: Implications for local control. Int J Radiat Oncol Biol Phys. 1999;44:305–309. 11. Dillon WP, Mills CM, Kjos B, et al. Magnetic resonance imaging of the nasopharynx. Radiology 1984;152:731–738. 12. Fukui MB, Blodgett TM, Snyderman CH, et al. Combined PETCT in the head and neck: Part 2. Diagnostic uses and pitfalls of oncologic imaging. Radiographics. 2005;25:913–930.

13. Wei WI, Sham JS. Nasopharyngeal carcinoma. Lancet. 2005;365:2041–2054. 14. Wei WI. Cancer of the nasopharynx: Functional surgical salvage. World J Surg. 2003;27:844–848. 15. Fee WE Jr, Roberson JB Jr, Goffinet DR. Long-term survival after surgical resection for recurrent nasopharyngeal cancer after radiotherapy failure. Arch Otolaryngol Head Neck Surg. 1991;117:1233–1236. 16. Morton RP, Liavaag PG, McLean M, et al. Transcervicomandibulo-palatal approach for surgical salvage of recurrent nasopharyngeal cancer. Head Neck. 1996;18:352–358. 17. Fisch U. The infratemporal fossa approach for nasopharyngeal tumors. Laryngoscope. 1983;93:36–44. 18. Wei WI, Lam KH, Sham JS. New approach to the nasopharynx: The maxillary swing approach. Head Neck. 1991;13:200–207. 19. Wei WI, Ho CM, Yuen PW, et al. Maxillary swing approach for resection of tumors in and around the nasopharynx. Arch Otolaryngol Head Neck Surg. 1995;121:638–642. 20. Wei WI. Nasopharyngeal cancer: Current status of management. Arch Otolaryngol Head Neck Surg. 2001;127:766–769. 21. Ng RW, Wei WI. Elimination of palatal fistula after the maxillary swing procedure. Head Neck. 2005;27:608–612.

18 Clival Tumors Franco DeMonte, Mark J. Dannenbaum, and Ehab Y. Hanna

INTRODUCTION

Multiplanar MRI with and without contrast enhancement best demonstrates the extent of the tumor and best identifies important adjacent neurovascular structures such as the brainstem, optic nerves and chiasm, and internal carotid and basilar arteries. Fat suppression techniques highlight tumoral contrast enhancement within or adjacent to fatty areas such as the orbits and bone marrow (5,6). Cerebral angiography is not typically necessary for the diagnosis of clival tumors. It is used when a detailed view of the head and neck and intracranial vasculature is desired. Important anatomic variations are noted, such as the pattern of venous drainage or the integrity of the circle of Willis. Vascular distortion or narrowing is well identified. Preoperative temporary balloon occlusion testing of the ICA may be performed if ICA occlusion or sacrifice is planned or if risk of arterial injury is deemed high. One or more complimentary investigations of cerebrovascular reserve such as transcranial Doppler (TCD), cerebral blood flow (CBF), or single photon emission computed tomography (SPECT) may be used in conjunction with the temporary balloon occlusion test. The differential diagnosis of an invasive clival mass includes chordoma, chondrosarcoma (although these tumors are usually found in a paramedian location), pituitary adenoma, metastasis, meningioma, nasopharyngeal carcinoma, and primary sphenoid sinus malignancy (Table 1). On conventional spin echo T1-weighted MRI, chordoma produces an intermediate to low signal intensity and is easily recognized among the high signal intensity of the fat within the clivus. Occasionally, small foci of hyperintensity may be seen within the tumor on T1-weighted sequences. This finding may represent either intratumoral hemorrhage or mucin production by the tumor. T2-weighted MRI usually demonstrates high signal as a result of the high-fluid content of the vacuolated cellular components. Areas within the tumor containing calcium, hemorrhage or densely proteinaceous mucus will most often produce T2 hypointensity. Interlaced low-intensity septations separating high signal intensity lobules are commonly visualized and correspond with the multilobular gross morphology of the tumor. Contrast enhancement is seen in the majority of chordomas and ranges from moderate to marked. The enhancement pattern of the tumor is often described as a “honeycomb” appearance that is created by intratumoral areas of low signal intensity [Fig. 2(A)–2(C)]. Fat suppressed images are useful for differentiating enhanced tumor margins from adjacent bright fatty bone marrow (5,6). As opposed to intracranial chordomas, which have a predilection for the midline of the skull base, the majority of chondrosarcomas are located more laterally along the petroclival fissure. Chondrosarcomas may, however, have a midline origin that makes preoperative differentiation from chordoma more challenging as both have similar signal intensity

This chapter focuses on the surgical treatment of clival tumors. Since clival chordoma is the archetypal tumor in this location, specific comments regarding this tumor type will be made. Irrespective of the pathology, the bone of the clivus may be infiltrated by tumor and require resection beyond the grossly visible tumor margin. The majority of tumors in this location are large at diagnosis and extend to the anterior cranial fossa or parasellar region or ventrally into the nasal cavity, paranasal sinuses or nasopharynx or to the middle fossa.

SURGICAL ANATOMY The clivus is formed from the part of the basilar occipital bone that extends anteriorly and superiorly from the foramen magnum and from the body of the sphenoid bone. These two bones articulate at the spheno–occipital synchondrosis. The clivus thus extends from the dorsum sella and the posterior clinoid processes to the foramen magnum. At its superior aspect, the clivus is bordered laterally by the petroclival fissure (synchondrosis) and the petrous temporal bone. The petroclival fissure terminates in the jugular foramen posterolaterally. The pharyngeal tubercle located on the anterior and inferior surface of the clivus is the site of attachment of the midline pharyngeal raphe. A rich venous plexus exists between the periosteal and meningeal layers of the clival dura. The inferior petrosal sinus runs along the petroclival fissure and connects the clival venous plexus and the posterior cavernous sinus to the jugular bulb. The medulla, pons, and midbrain and the vertebrobasilar arterial tree lay directly behind the clivus. The abducens nerve penetrates the meningeal layer of the clival dura at Dorello’s canal and courses superiorly, medial to the petrous apex, to enter the posterior cavernous sinus. The posterolateral aspects of the basiocciput form the occipital condyles and transmit the hypoglossal nerves (1–4).

DIAGNOSTIC IMAGING, REGIONAL PATHOLOGY, AND DIFFERENTIAL DIAGNOSIS High-resolution computed tomographic (CT) scanning allows the accurate assessment of bony destruction by the tumor, which is universally present in chordomas (5) (Fig. 1). Integrity of the optic and carotid canals can be best assessed in this way. Tumoral calcification is well seen if present. If there is a question of occipitocervical instability, plain x-ray films of the cervical spine, both in flexion and extension, are performed. 277

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Differential Diagnosis of Clival Tumors

Chordoma Chondrosarcoma Nasopharyngeal carcinoma Pituitary macroadenoma Fibrous dysplasia Metastasis Meningioma Rhabdomyosarcoma Craniopharyngioma Dermoid Epidermoid

Figure 1 Axial CT scan with bone windowing in patient with clival chordoma. Note the destruction of the central portion of the clivus with a loss of the cortical bone and islands of calcification within the tumor. Source: From The Department of Neurosurgery, M.D. Anderson Cancer Center. Used with permission.

on T1- and T2-weighted MR images [Fig. 3(A)–3(C)]. Chondrosarcoma can sometimes be distinguished by the presence of linear, globular or arc-like matrix calcifications. Clival meningiomas represent another, yet, small subset of the pathologies encountered in this area. On MR imaging they appear as a well circumscribed, avidly and homogenously contrast enhancing mass with a dural attachment. They do not have the bony destruction associated with chordomas, but may be associated with hyperostosis. Nasopharyngeal cancers including nasopharyngeal carcinoma, lymphoma, and plasmacytomas must always be considered in the differential diagnosis of clival chordoma. They usually extend more anteriorly and may be associated with head and neck lymphadenopathy. These masses may produce lytic destruction of the skull base as well, which when centrally located may produce imaging that exactly mimics clival chordoma.

Pituitary macroadenomas may at times appear to involve and/or originate from the clivus. The inability to identify the pituitary gland in the presence of a large clival mass should raise the possibility of pituitary macroadenoma [Fig. 4(A) and 4(B)]. A markedly elevated serum prolactin level may obviate the need for biopsy or resection. Rhabdomyosarcoma represents another pathology that in children may develop in the clival region. This lesion takes origin in the nasopharynx and manifests as a large, bulky, intra- and extracranial tumor with associated lytic osseous destruction of the skull base.

CLINICAL ASSESSMENT All patients have a complete history and physical examination including a neuro–ophthalmologic evaluation, which assesses visual acuity and fields, pupillary function, and ocular motility. Less than one-third of these patients have a normal neuro–ophthalmologic examination. Patients with upper clival tumors undergo a complete endocrinologic assessment to identify evidence of pituitary or hypothalamic dysfunction. Patients with mid to lower clival tumors are assessed by an otolaryngologist with specific attention to hearing and lower cranial nerve function. An audiogram and direct laryngoscopy are usually performed.

Figure 2 (A) Axial T1-weighted MRI, (B) axial T2-weighted MRI, (C) axial T1-weighted postcontrast MRI of the skull base in a patient with a left lower clival chordoma with extension to the cervicomedullary junction. On precontrast T1-weighted imaging, note the loss of the marrow fat signal in the lower left clivus. The tumor is isointense to brain on T1-weighted imaging. On T2-weighted imaging, the tumor is bright but there are areas of heterogeneity within the tumor of lesser signal intensity. Following contrast administration, only mild contrast enhancement is identified. Source: From The Department of Neurosurgery, M.D. Anderson Cancer Center. Used with permission.

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Figure 3 (A) Axial T1-weighted MRI, (B) axial T2-weighted MRI, (C) postcontrast T1-weighted MRI of a patient with a right skull base chondrosarcoma. On T1-weighted imaging, the tumor is of decreased signal intensity. Note the loss of marrow fat in the right petrous apex. On T2-weighted imaging, the lesion is homogenously of high signal, which is slightly unusual for chondrosarcoma that tends to have more of a heterogenous T2-signal, similar to chordoma. There is moderate to marked homogenous enhancement following contrast administration. Source: From The Department of Neurosurgery, M.D. Anderson Cancer Center. Used with permission.

The symptoms resulting from clival tumors depend on the specific sites of their extension Table 2. The most common manifestation is a headache located in the occipital or occipitocervical area and may be aggravated by changes in neck position. Diplopia is the initial symptom experienced by most patients and is almost always the result of abducens neuropathy. Larger tumors may produce additional cranial nerve palsies manifesting as decreased visual acuity, facial weakness or numbness, hearing loss, dysphagia, and dysphonia. When tumors enlarge and produce brainstem or cerebellar compression, patients may develop ataxia, dysmetria, and motor weakness. When tumor extends into the retropharyngeal space or the nasal cavity, symptoms such as nasal obstruction, epistaxis, or throat fullness may develop.

SURGICAL MANAGEMENT There have been numerous surgical approaches used to access the clivus. The choice of one approach over another needs to factor in the parameters of tumor location, size, extension, unique patient anatomy and functional requirements, and experience, expertise, and preference of the surgical team. Small, midline upper clival tumors without lateral extension are, for example, probably best removed through a transsphenoidal approach (open or endoscopic), while large tumors with lateral and intradural extensions may require both a transfacial and intracranial approach for adequate tumor removal. Table 3 lists the various surgical approaches, which are useful for clival tumor resection. Although each will be discussed briefly, the transmaxillary, transmandibular, transbasal, and transcondylar approaches will be dealt with in greater detail.

Transsphenoidal Approach The transsphenoidal approach works well for smaller tumors located in the upper and middle clivus. Excellent exposure of the sphenoid sinus, sella turcica, and upper and middle clivus is possible (7). It has the disadvantages of limited inferior and lateral exposure although the lateral exposure can be improved by entry into the medial maxillary sinus and removal of the pterygoid plate. The surgical field is typically deep and narrow and thus there is little room to allow aggressive bone resection (8). These disadvantages are much less of an issue with current endoscopic instrumentation, although Figure 4 (A) Sagittal postcontrast MRI imaging, (B) coronal postcontrast MRI imaging of a patient with a large clival mass scheduled for open surgical resection. It was noted that the pituitary gland could not be visualized clearly on any of the sequences. A serum prolactin level was performed and was noted to be massively elevated at 345,000 ng/mL. The tumor responded very well to medical treatment with cabergoline without biopsy or resection. Source: From The Department of Neurosurgery, M.D. Anderson Cancer Center. Used with permission.

Table 2

Symptoms of Clival Tumors Based on Site of Origin

Upper clivus Mid clivus

Lower clivus

Pituitary endocrinopathy, visual loss, chiasmal syndrome, cavernous sinus syndrome Nasopharyngeal mass, abducens nerve palsy, multiple cranial neuropathies, brainstem syndrome, hydrocephalus, cerebellopontine angle syndrome Hypoglossal nerve palsy, foramen magnum syndrome

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Table 3 Surgical Approaches to the Clivus Transsphenoidal-–open, endoscopic Transsphenoethmoidal Transoral-transpalatal Transmaxillary Transmandibular circumglossal retropharyngeal Extended transbasal Anterior transtemporal Posterior transtemporal Transcondylar

further refinement is necessary (1, 2). Entirely endoscopic transsphenoidal resection of clival tumors is increasingly being reported [Fig. 5(A) and 5(B)]. (See chapters 7 and 23)

Transsphenoethmoidal Approach In order to expand the exposure offered by the transsphenoidal approach, an external ethmoidectomy with or without a medial maxillectomy can be employed. Lalwani et al. found this approach to be “adequate for the majority of tumors and disease processes present in the sphenoid sinus and clivus” (9). The addition of the medial maxillectomy in instances of a narrow ethmoid sinus or inferiorly extending tumor allows improved access. Disadvantages include the necessity of a facial incision, and the relatively limited exposure. The inferior limits can be extended by a medial maxillectomy as described above, but lateral reach is limited to approximately 2 cm from the midline.

Transoral–Transpalatal Approach Following the placement of an appropriate oral retractor system, the posterior pharyngeal wall and soft palate are divided to expose the clivus and upper cervical spine. Most commonly employed for odontoidectomy, the exposure obtained with this approach is relatively quite limited (10). It is adequate for tumor biopsy or in the case of small lower clival tumors

[Fig. 6(A)–6(C)]. Repair of intraoperative cerebrospinal fluid leakage is problematic. Although fat and/or fascial tissue can be placed posterior to the pharyngeal wall, the pharyngeal wall rarely approximates well and gaps are common, thus increasing the risk of CSF leakage. The transoral–transpalatal approach should not be the primary approach to intradural lesions at the foramen magnum unless other approaches prove ineffective (11). (See chapter 28)

Transmaxillary Approaches The transmaxillary approaches may prove useful for clival tumors that extend into the nasopharynx or craniocervical junction with minimal lateral extension [Fig. 7(A) and 7(B)]. Numerous variations of this approach have been described. Most are based on a Le Fort I osteotomy with or without midline splitting of the hard and soft palates or a unilateral maxillotomy with median or paramedian splitting of the hard and soft palates (12–15). We prefer approaches that avoid displacing or sectioning the palate and alveolar arch (3,16– 18). Access to the maxilla is obtained via a facial degloving approach or through a lateral rhinotomy with lip split (3,19). Lateral exposure is limited by the pterygoid plates, the ICA at the level of the foramen lacerum and cavernous sinus, the hypoglossal canal and the jugular foramen. Removal of the pterygoid plates allows for access to the ITF (20,21). Disadvantages of the transmaxillary approaches include the risk of ischemic osteonecrosis with multisegment osteotomies. This risk can be minimized by subtotally splitting the soft palate if palatal osteotomies are necessary and by leaving wide soft tissue attachments to freed maxillary compartments during swing procedures, or avoided entirely by transantral approaches. The principal disadvantage of the transmaxillary approach, however, is the inability to reliably stop CSF leakage. Direct repair of the dura is rarely possible and must rely on packing with fat, fascia, and fibrin glue without the availability of firm tissue support to hold the repair in place. Elevation and use of vascularized mucosal flaps (septal, nasal, or turbinate) helps with healing and has reduced the CSF leak rate.

Positioning The patient is positioned supine on the operating table with the head slightly elevated, extended, and rigidly fixated. Intraoperative image guidance is particularly useful in this approach. Best visualization is obtained by standing on the side opposite the maximum extent of the tumor. For example a clival tumor extending posteriorly and to the left is best approach through the right maxilla.

Incision and Soft Tissue Dissection

Figure 5 (A) Axial T2-weighted MRI, (B) sagittal postcontrast T1-weighted MRI identify a lesion of the posterior nasal cavity, sphenoid and ethmoid sinuses, and clivus with minimal lateral extension. This tumor was accessed and resected with an entirely endoscopic technique. A chronic dural perforation was identified and repaired. Despite this primary repair, postoperative CSF leakage was noted. The patient was taken back to the operating room where a repeat endoscopic procedure was performed. The dural defect was widened and an intra- and extradural repair was performed with an “onlay” technique with fascia and fat, which resulted in resolution of the spinal fluid leakage. Source: From The Department of Neurosurgery, M.D. Anderson Cancer Center. Used with permission.

The upper lip is retracted and a sublabial incision is made along the gingival sulcus extending to the lateral maxillary buttress. The soft tissues of the face are then elevated subperiosteally to expose the piriform aperture, infraorbital foramen, and floor of the nasal cavity.

Bony Dissection, Osteotomies, and Tumor Resection A complete anterior maxillary antrotomy is performed preserving the infraorbital nerve. The medial wall of the antrum, the palatine bone, and the posterior wall of the antrum are removed exposing the pterygopalatine/pterygomaxillary fossa. The sphenopalatine artery is identified and coagulated if necessary. The frontal process of the maxilla is divided as close to the alveolar ridge as possible and as superiorly as possible (Fig. 8). The nasal mucosa is opened and the turbinates

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Figure 6 (A) Sagittal postcontrast T1-weighted MRI reveals a small enhancing lesion in the lower clivus. Biopsy confirmed it as a chordoma. (B) Intraoperative photograph of a transoral approach and resection of this small clival lesion. The oral retractor is in place and the pharyngeal mucosa and musculature is being retracted laterally. The tumor was resected in its entirety. (C) Intraoperative frameless stereotactic navigation was utilized and found to be helpful in the localization and resection of this lesion. Source: From The Department of Neurosurgery, M.D. Anderson Cancer Center. Used with permission.

dislocated anteriorly or removed. It is preferable to try to preserve the turbinates in order to keep the option of a turbinate flap. The nasal septum is dislocated to the opposite side and the vomer and sphenoid rostrum identified. The vomer is then removed facilitating entry into the sphenoid sinus. The entire anterior wall and floor of the sphenoid sinus is removed. The pharyngobasilar fascia and overlaying nasopharyngeal mucosa are elevated with cautery and flapped inferiorly. Using the operating microscope, the infraorbital nerve is followed to the pterygomaxillary fissure, which lies just behind the posterior wall of the maxillary sinus. The nerve is dissected free of the adipose tissue and followed to the foramen rotundum. The foramen is located at the top of the pterygoid plate, just lateral to the sphenoid sinus. The foramen is widened with a high-speed drill to expose the dura of the temporal fossa floor lateral to the foramen and the dura of the medial cavernous sinus medially. Removing the bone superomedial to the foramen rotundum unifies the foramen rotundum and superior orbital fissure [Fig. 9(A) and 9(B)]. Removal of the lateral wall of the sphenoid sinus connects this expo-

Figure 7 (A) Postcontrast T1-weighted MRI at the level of the petrous carotid, (B) postcontrast T1-weighted MRI at the level of the cavernous carotid. This patient presented with diplopia. Biopsy was consistent with a primary low-grade adenocarcinoma. The patient underwent resection via a left transmaxillary approach. Source: From The Department of Neurosurgery, M.D. Anderson Cancer Center. Used with permission.

sure to the midline exposure of the sellar region. The bone of the lateral sphenoid sinus is removed to expose the medial CS further. The clivus is thus fully exposed. Clivectomy is performed to the extent needed [Fig. 10(A) and 10(B)].

Reconstruction and Closure If the dura has been penetrated, dural closure is enhanced by placement of a fascial graft in addition to fat and fibrin glue. This repair is reinforced with vascularized nasal wall, floor, and septal flaps. A turbinate flap can also be used. The nasal septum is relocated and the frontal process of the maxilla is plated into its normal anatomic position. As with all of the anterior transfacial approaches, intermittent graduated lumbar spinal drainage may be used.

Figure 8 In this surgical photograph, the antrum of the left maxilla has been widely opened by a large anterior antrotomy. The maxillary antrum and medial maxilla have been unified with the nasal cavity by removal of the medial antral wall and of the medial maxilla. The septum has been displaced to the right and the vomer removed. The face of the sphenoid has been opened and surgical hemostatic agent is on the clival dura following resection of the primary adenocarcinoma identified in Figure 7(A) and 7(B). Source: From The Department of Neurosurgery, M.D. Anderson Cancer Center. Used with permission.

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Figure 9 (A) Artist’s representation of the expansion of the transmaxillary approach to the anterior cavernous sinus and infratemporal fossa. Under the operating microscope, the foramen rotundum is opened both medially, unified with the sphenoid sinus, and laterally to expose the temporal dura. Continued removal of the pterygoid plate opens the foramen ovale and allows access to the infratemporal fossa. With complete removal of the pterygoid plate, the entire sphenoid sinus is accessed and the entire anterior wall and floor are removed. The pharyngobasilar fascia can be detached and thus the entire clivus is within the surgical field. (B) Intraoperative photograph shows the orbital tissues being protected by the brain retractor. The suction is in the sphenoid sinus, palpating the medial cavernous sinus wall. The foramen rotundum has been widened to expose the temporal dura lateral to it and superior to it. Source: From The Department of Neurosurgery, M.D. Anderson Cancer Center. Used with permission.

Transmandibular, Circumglossal, Retropharyngeal, Transpalatal Approach to Clivus and Upper Cervical Spine Initially described by Biller et al. (22) and popularized by Krespi (23–25) and later by Ammirati (26,27), the transmandibular approach to the skull base provides simultaneous exposure of the middle and lateral compartments of the skull base, allows excellent vascular control and access to cranial nerves IX–XII, and by straight forward expansion allows an exposure that extends from the ipsilateral ITF to the contralateral medial pterygoid plate, from the anterior cranial fossa to the lower clivus and the anterior cervical spine down to C7 (28). The main indications for this approach are large tumors involving both the middle and lateral compartments and tumors of the craniocervical junction and upper cervical spine. Ideally suited for extradural pathology, intradural extensions can be removed by this approach, although the risk of CSF leakage and meningitis increases (28). Even though dural repair is, as already mentioned, rarely water-

tight in this region, the elevation and subsequent replacement of the laterally based pharyngeal flap helps buttress any needed dural repairs. Along with the judicious use of subcutaneous fat and fascial grafts, fibrin glue, and lumbar spinal drainage, this minimizes the incidence of CSF leakage. A good deal of anatomic dissection is required for this approach, which results in predictable morbidity. A temporary tracheostomy is required. Conductive hearing loss and serous otitis media result from section of the Eustachian tube. Temporary swallowing difficulties induced by the circumglossal and palatal incisions, the extensive retropharyngeal dissection, and the section of the tensor and levator palatini muscles occasionally necessitate the insertion of a gastrostomy. Preoperative consultation with dentistry should be obtained to fashion a palatal stent to be used for support of the palatal mucosa after closure. This stent allows for improved apposition of the mucosa against the residual hard palate. This helps to prevent acute mucosal loss.

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Figure 10 (A and B) Postcontrast axial MRI imaging following resection of a primary adenocarcinoma via a left transmaxillary approach. Note complete removal of the tumor from the medial cavernous sinus wall and carotid artery. Source: From The Department of Neurosurgery, M.D. Anderson Cancer Center. Used with permission.

Due to this inherent morbidity, long and careful consideration should be given to the use of this approach. It should be reserved for instances where surgical cure or significant palliation are likely (Fig. 11) (28).

Positioning, Incision, and Soft Tissue and Bony Dissection With the patient in rigid cranial fixation in the supine position with the head slightly extended, a tracheostomy is performed (Fig. 12). A curvilinear incision is then begun just below the mastoid and extended inferiorly and medially along a skin crease to the mentum and through the lip split (Fig. 13). Subplatysmal flaps are elevated to expose the upper neck and submandibular gland and surrounding tissues. A selective neck dissection allows for the clear identification and preservation of the lingual and hypoglossal nerves. The ICA and IJV are identified and vessel loops are placed. Continued elevation of the flap exposes the mandible. The mandibulotomy site is carefully marked and an internal fixation plate is placed. The plate position is carefully marked,

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Figure 12 Positioning for patient undergoing a transmandibular, circumglossal retropharyngeal approach to the clival chordoma illustrated in Figure 11. Use of intraoperative frameless stereotactic navigation aids in surgical planning and execution. The incision begins at the tip of the mastoid, curves forward to the midline and curves around the chin and then terminates in a midline lip split. Source: From The Department of Neurosurgery, M.D. Anderson Cancer Center. Used with permission.

and the plate removed and saved for closure. A stair-step mandibulotomy is performed between the lower medial two incisors (Fig. 13). Dissection follows the floor of the mouth posteriorly towards the glossopharyngeal sulcus. This allows the mandible to swing laterally and the tongue medially. The styloid process is palpated and the muscular attachments are separated. The ICA, IJV, and CNs IX–XII are traced superiorly to the skull base. As the incision approaches the anterior tonsillar pillar, it splits into two limbs. The upper limb extends to the soft palate, which is separated from its lateral attachments (Fig. 14). This incision is then carried onto the hard palate approximately 1 cm medial to the alveolar ridge. It then passes anteriorly around to the contralateral hard palate. The base of the hard palate is resected as needed for

Figure 11 Sagittal postcontrast T1-weighted MR imaging of a patient with a large and complex clival chordoma. Panel A reveals the tumor prior to any surgical intervention. Panel B reveals residual tumor following first stage transcondylar resection of the portion of the tumor, which was causing marked neural compression. Panel C reveals the final appearance following transmandibular, circumglossal retropharyngeal resection of the anterior components of the tumor. It is complex tumors, like this, that may require extensive and multi-staged procedures to maximize resection. Source: From The Department of Neurosurgery, M.D. Anderson Cancer Center. Used with permission.

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Figure 13 Artist’s representation of the incisions and stair-step mandibulotomy necessary for the transmandibular, circumglossal retropharyngeal approach to the clivus. Source: From The Department of Neurosurgery, M.D. Anderson Cancer Center. Used with permission.

visualization into the sphenoid sinus. The lower limb of the incision extends into the hypopharynx passing lateral to the tonsil and the orifice of the Eustachian tube. The Eustachian tube is transected and retropharyngeal dissection follows the subperiosteal plane to expose the clivus and upper cervical spine. This pharyngeal flap is elevated and rotated medially. The clivus and upper cervical spine are covered by the longus capitis muscles and the prevertebral fascia. Removal of the posterior hard palate reveals the posterior bony nasal septum (vomer) and the anteroinferior face of the sphenoid sinus (Fig. 15). Removal of this bone allows wide exposure of the sphenoid sinus and the sella turcica and upper clivus. At this point, clivectomy may be performed and may extend from the sella turcica to the foramen magnum (Fig. 16).

Figure 14 Artist’s representation of the transmandibular, circumglossal retropharyngeal approach to the clivus. In this illustration, the mandible has been reflected laterally keeping the lingual and hypoglossal nerves intact. The mucosal incisions at the level of the anterior tonsillar pillar extend superiorly onto the soft palate and subsequently onto the hard palate and inferiorly along the lateral pharynx in order to rotate the pharynx medially. Source: From The Department of Neurosurgery, M.D. Anderson Cancer Center. Used with permission.

The mandible is reapproximated and the reconstruction plate secured. Drains are placed in the neck and a nasogastric tube is inserted. Precise alignment of the vermilion border is assured during lip closure and the platysma and skin are closed in a standard fashion. Graduated, intermittent lumbar spinal drainage may be utilized if the dural closure is tenuous.

Reconstruction and Closure If the dura is deficient, repair with fascial and subcutaneous fat grafts and fibrin glue is performed. In this case, a layer of fascia is placed intradurally with its edges extending beyond the dural opening. If possible, this is tacked down with sutures. A second extradural fascial layer is placed and reinforced with fibrin glue and autologous fat. This can be reinforced with vascularized nasal septal flaps. Closure begins by reattaching the superior constrictor muscle to the muscles at the base of the skull. The palatal flap is reapproximated and the soft-palate and hard-palate mucosae are sutured. The preoperatively fashioned palatal stent is placed to support the palatal mucosa. The floor of the mouth is closed in a double layer. The pharyngeal flap is allowed to return to its normal position and closure is by careful reapproximation of the posterolateral mucosal edges.

Figure 15 Intraoperative photograph following completion of the approach phase of the transmandibular approach to the clivus. The mucosa of the palate is being retracted laterally and the hard palate has been resected in order to access the sphenoid sinus. The tumor is identified deep to the pharyngobasilar fascia and longus coli muscles. Source: From The Department of Neurosurgery, M.D. Anderson Cancer Center. Used with permission.

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teotomy (removal of supraorbital bar), ethmoidectomy, sphenoidectomy, and the extradural resection of the clivus. The limits of exposure are the foramen magnum inferiorly and the hypoglossal canals inferolaterally, while the intracavernous carotid arteries form the superolateral limits. The posterior clinoids, dorsum sella, and the region behind and above the pituitary gland are obscured by the gland, rendering this a blind area via the extended transbasal approach (Fig. 18).

Positioning, Incision, and Soft Tissue Dissection

Figure 16 Artist’s representation of the transmandibular approach to the clivus following clivectomy. The bone has been removed from the sella and from the undersides of the optic nerves. Bone removal can continue inferiorly down to the foramen magnum. At this point, it can be extended laterally to the hypoglossal canals bilaterally. Source: From The Department of Neurosurgery, M.D. Anderson Cancer Center. Used with permission.

Extended Transbasal Approach Developed by Tessier and Derome, the transbasal approach to the clivus has subsequently been modified to incorporate orbital osteotomies in an effort to reduce frontal lobe retraction and to allow exposure of more posteriorly and laterally related structures such as the medial walls of the cavernous sinus and the hypoglossal canals (Fig. 17) (12,29–34). The approach consists of a bifrontal craniotomy, bilateral orbital os-

The patient is placed in rigid cranial fixation in the supine position with the head slightly extended. Following a bicoronal scalp incision, the scalp is elevated sharply from the periosteum and loose connective tissue layers (collectively named the pericranium) immediately deep to the galea in order to maintain the maximal thickness and vascularity of the pericranium medial to the superior temporal lines bilaterally. Separation of these layers should only be taken to a level 1 cm above the supraorbital bar to preserve the rich vascular supply to the pericranium. Both superficial and deep layers of the temporalis fascia are incised. Dissection deep to the deep fascial layer minimizes the risk of injury to the frontalis branches of the facial nerve. Lateral subperiosteal dissection exposes the zygomatic process of the frontal bones, frontozygomatic sutures, and the upper lateral orbital rims. Medially, the subperiosteal dissection exposes the glabella, the frontonasal suture, and the superior orbital rims (Fig. 19).

Bone Dissection and Osteotomies Following a bifrontal craniotomy, the dura is dissected from the posterior wall of the frontal sinuses. The frontal sinuses are then cranialized and demucosalized with the high-speed drill and rongeurs. Careful dissection of the dura from the orbital surface of the frontal bones allows access for the orbital osteotomies. The orbital periosteum is dissected down from the roof and walls of the orbit. It has not been necessary in our experience to free the medial canthal ligaments. With protection of the orbital contents and dura, osteotomies are placed in the lateral wall, roof, and upper medial walls of the orbits and across the nasal bones to just in front of the crista galli. This bifronto–orbital osteotomy piece is freed with an osteotome and removed (Fig. 20).

Figure 17 Sagittal, coronal, and axial postcontrast T1-weighted MRI imaging of a patient with a low-grade, metastatic leiomyosarcoma to the sphenoid sinus and upper clivus presenting with progressive visual loss. This lesion was felt to be best approached via a transbasal route. Source: From The Department of Neurosurgery, M.D. Anderson Cancer Center. Used with permission.

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Figure 18 Artist’s representation of the improvement in the angle of vision following removal of the supraorbital osteotomy. This added 1.5 cm allows for a much greater angle of dissection, extending from the tip of the foramen magnum to the floor of the sella. There remains an area that is not well seen posterior and superior to the sella turcica. Source: From The Department of Neurosurgery, M.D. Anderson Cancer Center. Used with permission.

If an attempt at olfactory sparing is to be made, the dura is dissected along the side of the cribriform plate bilaterally to the level of the posterior ethmoidal artery. Under the microscope, a reciprocating saw is used to cut across the anterior planum sphenoidale at the level of the frontosphenoid suture. A generous cuff of nasal mucosa is preserved with the cribriform plate (12,29). Olfactory sparing is contraindicated for nasopharyngeal malignancies due to the neurotropism that many of these neoplasms exhibit. If, as is most often the case, olfactory preservation is not an issue the crista galli is removed and the dural sleeves of the olfactory groove are cut on either side and closed primarily. The planum sphenoidale is then opened and a wide sphenoidotomy is performed with a high-speed drill. The medial wall of the orbit is removed anteromedially to the optic nerves. One or both of the optic nerves may require decompression (Fig. 21). All but the lateral wall of the optic canal can be removed from this approach. The walls of the sphenoid are progressively removed from anterior to posterior. The sellar floor is removed. Access to the dorsum sella is blocked by the pituitary gland, and tumor in this area is not well seen although some degree of extradural elevation of the gland is possible. The cavernous sinuses and intracavernous ICA are exposed by the complete removal of bone on their medial aspects (Fig. 22). Although covered by a thin periosteal layer, bleeding from the cavernous plexus may occur and is

Figure 19 Artist’s representation of the skin incision and bifrontal craniotomy and biorbital osteotomy needed for the extended transbasal approach. The incision extends from the root of the zygoma bilaterally in a bicoronal fashion behind the hairline. The bifrontal craniotomy is created by placing entry holes at the keyhole region bilaterally and at the midline. Orbital osteotomies are raised by dividing the lateral orbital rims at the frontal zygomatic suture, the orbital roof, with protection of the dura and of the periorbital membrane and with divisions in the medial orbits under direct vision superiorly and medially. The final osteotomy is just in front of the crista galli and this frees the bilateral osteotomy. Source: From The Department of Neurosurgery, M.D. Anderson Cancer Center. Used with permission.

controlled by tamponade. Similarly, bleeding from the clival basilar venous plexus can be considerable but controlled with surgical packs. The clival tumor and bone are progressively removed in a superior to inferior direction with the foramen magnum being the lower limit of resection. At the level of the foramen magnum, the resection can be carried laterally up to the hypoglossal canals. Clival bone removal continues to include a margin of normal appearing bone if possible.

Tumor Resection The tumor is removed in an intralesional fashion. Depending on the consistency and vascularity, the tumor removal may be accomplished with microdissection and suction, ultrasonic aspiration, or with a high-speed diamond drill (Fig. 23).

Reconstruction and Closure Reconstruction begins by closure of any dural defects. Temporalis fascia or fascia lata are used as dural patches as necessary if primary closure is not possible. Usually, it is difficult if

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Figure 21 Intraoperative photograph of the transbasal approach in a patient with an extensive juvenile nasopharyngeal angiofibroma of the sphenoid sinus and clivus. The two orbits are anteriorly and laterally placed and all bone has been removed including that overlying the optic nerves bilaterally. The tumor is immediately anterior and inferior to the optic nerves. Source: From The Department of Neurosurgery, M.D. Anderson Cancer Center. Used with permission. Figure 20 Artist’s representation of the bifrontal craniotomy and biorbital osteotomy necessary for the extended transbasal approach. At this stage, the cribriform plate and ethmoid sinuses are removed and a wide sphenoidotomy performed to access the clivus. Source: From The Department of Neurosurgery, M.D. Anderson Cancer Center. Used with permission.

not impossible to get a watertight closure of the clival dura. In this case, as described above, a layer of fascia is placed intradurally with its edges extending beyond the dural opening and tacked down with sutures or hemoclips. A second extradural fascial layer is placed and reinforced with fibrin glue and autologous fat. The open ethmoid sinuses are packed with fat and then the pericranial flap is turned down to cover and reinforce the exposed dura and separate it from the paranasal sinuses. The bifronto–orbital osteotomy is replaced in its anatomic position and rigidly fixated with titanium plates. Care is taken not to compress the pericranial graft as it passes over the orbital soft tissues and nasal bones. The remainder of the closure follows standard techniques. Graduated, intermittent lumbar spinal drainage may be employed if the dural closure is tenuous.

Of the posterior transpetrous approaches, the petrosal or subtemporal–retrolabyrinthine approach is best suited for large posterolateral intradural tumor extensions [Fig. 24(A)– 24(C)] (39), while the ITF approach can be used for both extraand intradural tumor extensions (8). In the later approach, the structures of the jugular foramen can be identified and skeletonized with the high-speed drill. The extradural removal of tumors from around the exiting lower cranial nerves can result in neurologic improvement. The approach can be extended inferiorly by the posterior mobilization of the vertebral artery from the foramina transversaria of C1 and C2. In this way, the region of the odontoid process and arch of C1 can be exposed (40–43). Craniospinal fixation may be necessary. Total petrosectomy allows access from the sphenoid sinus to the foramen magnum and from the upper cervical spine to the intradural structures of the middle and posterior fossae. Destruction of the inner ear and complete mobilization of the facial nerve with their attendant morbidities are consequences of this approach. The problem of limited midline access remains (35).

Transpetrous Approaches In the presence of clival tumors with lateral extensions, adequate access for tumor resection may necessitate the use of a variety of transpetrous approaches. The amount of petrous bone resection is tailored to the location of the tumor. Anterior, posterior or rarely, total petrosectomy may be necessary (35). An anterior petrosectomy will access tumor extensions in and around the petroclival synchondrosis, the posterior cavernous sinus, and the prepontine and cerebellopontine cisterns. The limits of bone removal include the ICA laterally, the superior petrosal sinus medially, the inferior petrosal sinus inferiorly, and the internal auditory canal posteriorly (36). Sacrifice of the mandibular nerve and anterolateral displacement of the ICA allows for further inferior exposure of the clivus (37,38). Although a few appropriately located small tumors can be resected through this surgical corridor, an anteriorly based approach is typically required as a second stage.

Transcondylar Approach Tumors of the lower clivus with lateral extension to the atlanto–occipital joint, jugular foramen, or upper cervical spine are well addressed via this approach (44–50). Important advantages of the transcondylar approach include a short and wide surgical field, vascular control of the vertebral artery and an uncontaminated surgical field. The direct lateral exposure of the craniocervical junction afforded by this approach allows for a direct line of sight to the structures ventral to the cervicomedullary junction and upper cervical cord (51). This is an excellent approach for large lower clival chordomas. Neural decompression can be directly confirmed and craniocervical fixation performed should it be necessary. This typically saves the patient from immediate danger and allows time for a staged anterior approach, which in most cases is required for maximal tumor removal. The region of the occipital condyle may be accessed through either a posterolateral or an anterolateral approach (40,43). The

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Figure 22 Artist’s representation of the upper clivectomy that can be achieved via the transbasal approach. Both optic canals and medial cavernous sinus walls can be opened as can the anterior wall and floor of the sella turcica. Source: From The Department of Neurosurgery, M.D. Anderson Cancer Center. Used with permission.

posterolateral approach affords excellent anterior intradural midline access but does not allow a surgical corridor to the anterior extradural region. It is an excellent approach for clival tumors that penetrate the dura and extend posteriorly to compress the cervicomedullary region [Fig. 25(A)–25(D)]. It is typically used as a staged procedure, with a secondary anterior approach. The posterior midline access afforded allows for immediate craniocervical stabilization if necessary (Fig. 26). The posterolateral approach, sometimes called the far or extreme lateral approach is described elsewhere in this book. The anterolateral approach will be described below.

Positioning and Incision The patient is positioned in the supine position with the head slightly elevated and turned to the opposite side or in the direct lateral position. There are several options for the incision. We have used a large retroauricular C-shaped incision although an incision that begins along the upper anterior bor-

der of the sternomastoid muscle, curves across the mastoid process and then travels along the occipital crest to the external occipital protuberance can also be used. The exact choice of skin incision will be dependent on the extensions of the tumor, the need to combine this with another approach for resection or for concurrent occipitocervical fusion.

Soft Tissue Dissection Once the flap is elevated, the sternomastoid muscle is dissected along its anterior border to identify the jugular vein. The dissection continues superiorly and the sternomastoid muscle is detached from the mastoid tip and reflected posterolaterally (Fig. 27). The accessory nerve is identified in relation to the jugular vein and dissected superiorly as far as possible towards the skull base. Its distal portion, just prior to its penetration of the sternomastoid is also freed in order to mobilize the nerve inferiorly. The fatty tissue around the mid portion of the nerve is left undisturbed as a

Figure 23 Sagittal, coronal, and axial postcontrast MRI imaging following resection via a transbasal approach of the metastatic, low-grade leiomyosarcoma illustrated in Figure 17. Source: From The Department of Neurosurgery, M.D. Anderson Cancer Center. Used with permission.

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Figure 24 (A) Axial T2-weighted MRI reveals a large, intradural, laterally extending chordoma. The trigeminal nerve is displaced laterally. (B) Intraoperative photograph following completion of the petrous exposure. The petrous vein, trigeminal nerve, and VII–VIII nerve bundle are well identified as are the anterior inferior cerebellar artery and the tumor between the VII–VIII nerve complex and the trigeminal nerve. (C) Axial T2-weighted image following resection via the petrosal approach of this large intradural extension of chordoma. A secondary transmaxillary approach completed the resection in this patient. Source: From The Department of Neurosurgery, M.D. Anderson Cancer Center. Used with permission.

protective cushion around the nerve. The transverse process of the atlas is palpated just below and anterior to the tip of the mastoid process. The rectus minor, superior, and inferior oblique and the levator scapulae muscles are detached from the transverse process with attention to the vertebral artery,

which lays immediately deep to these muscles. As described by George, the vertebral artery is first exposed inferiorly between the transverse processes of C1 and C2. Here it is crossed anteriorly by the anterior branch of the C2 nerve root. The vertebral artery is then exposed above C1 and dissection

Figure 25 (A) Axial postcontrast MRI revealing a large intra- and extradural chordoma. (B) Intraoperative photograph of the posterolateral exposure of the condyle. The tumor is well identified as is the overlying hypoplastic vertebral artery. (C) Following resection and direct and complete decompression of the cervicomedullary junction. (D) Confirms neural decompression and removal of the posterolateral component of the tumor. A secondary transmandibular approach accessed and resected the remaining anterior disease. Source: From The Department of Neurosurgery, M.D. Anderson Cancer Center. Used with permission.

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Figure 28 This intraoperative photograph was taken following resection of the tumor identified in Figure 27. The vertebral artery is entirely skeletonized and the capsule of the atlantoaxial joint has been removed completely to identify the occipital condyle. A mastoidectomy and retrosigmoid craniectomy have been performed in order to achieve total tumor removal in this case of radiation-associated, osteogenic sarcoma. Source: From The Department of Neurosurgery, M.D. Anderson Cancer Center. Used with permission.

Figure 26 Lateral radiograph of the spine following occipital–cervical fusion in a patient who underwent complete condylar resection for removal of a clival chordoma. Used with permission.

of the C1–C2 joint. This fully exposes the lateral foramen magnum.

Bony Dissection and Osteotomies is carried posteriorly along the arch of C1 in a subperiosteal plane. The foramen transversarium of C1 is opened and the vertebral artery dissected free and translocated posteriorly. The C1 transverse process is resected and then the anterior arch of C1 is exposed and cleared off subperiosteally. Finally, the vertebral artery in its periosteal sheath is separated from the atlanto–occipital membrane and capsule

A standard mastoidectomy is performed and bone should be removed to unroof the lower half of the sigmoid sinus and jugular bulb. The superior extent of exposure is the jugular foramen. Tumor extensions above this level will require the addition of a transpetrous approach. A retromastoid craniotomy may be added if needed (Fig. 28). The extent of condylar resection depends on the extent of the tumor. Care must be taken in the identification of the hypoglossal nerve, which passes through the mid-portion of the condyle. Resection of greater than 50% of the condyle typically necessitates occipitocervical fixation. This can be performed at the same operation or at a secondary procedure with the patient maintained in a rigid collar in the interim.

Tumor Resection The tumor is resected using standard intralesional ultrasonic aspiration or suction and bipolar cautery. When significant encasement of the lower cranial nerves and the vertebral artery exists, cranial nerve monitoring serves as a useful adjunct. The dissection plane should proceed from normal to abnormal anatomy, especially in cases where prior surgery and treatment have created distorted anatomy and scar tissue.

Reconstruction and Closure Standard techniques for dural closure including primary dural closure and/or patch duraplasty are used to facilitate watertight dural closure in order to prevent CSF leak. Figure 27 Intraoperative photograph of a patient operated on via the anterolateral approach. The sternocleidomastoid muscle is reflected posteriorly. The accessory nerve is protected and the jugular vein is controlled in the vascular loop. The tumor is identified just below the tip of the mastoid overlaying the region of the condyle and vertebral artery. Source: From The Department of Neurosurgery, M.D. Anderson Cancer Center. Used with permission.

POSTOPERATIVE CARE AND FOLLOW-UP The most important aspect of the patients’ postoperative care is the identification and aggressive management of lower cranial neuropathy. All patients are evaluated by a speech

Chapter 18: Clival Tumors

pathologist in the immediate postoperative period and a swallowing evaluation performed. A modified barium swallow or direct laryngoscopy may be recommended. Only when deemed safe, oral intake is allowed. Disturbances of ocular movement are managed initially by patching and subsequently by prisms and extraocular muscle surgery under the supervision of an ophthalmologist. A noncontrast CT of the brain is done on the first postoperative day to identify any subclinical complications. A baseline postoperative MRI is done within 48 hours after surgery. If clinically indicated, dynamic imaging of the craniocervical junction with flexion– extension radiographs is obtained. Close follow-up with clinical evaluation and imaging is essential, the frequency of which is dependent on tumor pathology. For patients with chordoma or chondrosarcoma, if no tumor is visualized on baseline postoperative imaging, additional imaging is obtained at 3-month intervals for the first year and then every 6 months for the next 2 years and yearly thereafter. When residual disease is identified, the patient should be referred to a specialized radiation treatment facility, ideally one that has proton beam capability as well as radiation oncologists familiar with the treatment of disease processes that affect the clivus. Referral to medical oncology may also be necessary. Management algorithms for residual or recurrent local disease is complex and beyond the scope of this chapter. Multiple variables should be analyzed including the clinical condition of the patient; the size and location of the recurrence; the tumor histology at the initial operation; the extent of the previous resection; and the dose, field, and fractionation scheme of prior radiation therapy. REFERENCES 1. Alfieri A, Jho HD. Endoscopic endonasal cavernous sinus surgery: An anatomic study. Neurosurgery. 2001;48:827–836. 2. Cavallo LM, Messina A, Cappabianca P, et al. Endoscopic endonasal surgery of the midline skull base: Anatomical study and clinical considerations. Neurosurg Focus. 2005;19:E2. 3. Cavallo LM, Messina A, Gardner P, et al. Extended endoscopic endonasal approach to the pterygopalatine fossa: Anatomical study and clinical considerations. Neurosurg Focus. 2005;19:E5. 4. De Oliveira E, Rhoton AL, Peace DA. Microsurgical anatomy of the region of the foramen magnum. Surg Neurol. 1985;24:293– 352. 5. Oot RF, Melville GE, New PF, et al. The role of MR and CT in evaluating clival chordomas and chondrosarcomas. Am J Roetgeol. 1988;151:567–575. 6. Meyers SP, Hirsch WL Jr, Curtin HD, et al. Chordomas of the skull base: MR features. Am J Neuroradiol. 1992;13:1627–1636. 7. Maira G, Pallini R, Anile C, et al. Surgical treatment of clival chordomas: The transsphenoidal approach revisited. J Neurosurg. 1996;85:784–792. 8. Laws ER Jr. Transsphenoidal surgery for tumors of the clivus. Otolaryngol Head Neck Surg. 1984;92:100–101. 9. Lalwani AK, Kaplan MJ, Guti PH. The transsphenoethmoid approach to the sphenoid sinus and clivus. Neurosurgery. 1991;31:1008–1014. 10. Crockard HA, Sen CN. The transoral approach for the management of intradural lesions at the craniovertebral junction: Review of 7 cases. Neurosurgery. 1991;28;88–98. 11. Menezes AH, VanGilder JC. Transoral-transpharyngeal approach to the anterior craniocervical junction. Ten-year experience with 72 patients. J Neurosurg. 1988;69:895–903. 12. Beals SP, Jogannic EF, Hamilton MG, et al. Posterior skull base transfacial approaches. Clin Plast Surg. 1995;22:491–511. 13. Catalano PJ, Biller HF. Extended osteoplastic maxillotomy. A versatile new procedure for wide access to the central skull base and infratemporal fossa. Arch Otolaryngol Head Neck Surg. 1993;119:394–400.

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14. James D, Crockard HA. Surgical access of the base of the skull and upper cervical spine by extended maxillotomy. Neurosurgery. 1991;29;411–416. 15. Wei WI, Lam KH, Sham JS. New approach to the nasopharynx: The maxillary swing approach. Head Neck. 1991;13:200–207. 16. Couldwell WT, Sabit I, Weiss MH, et al. Transmaxillary approach to the anterior cavernous sinus: A microanatomic study. Neurosurgery. 1997;40:1307–1311. 17. Rabadan A, Conesa H. Transmaxillary-transnasal approach to anterior clivus: A microsurgical model. Neurosurgery. 1992:30(4):473–481. 18. Sabit I, Schaefer SD, Couldwell WT. Extradural extranasal combined transmaxillary transsphenoidal approach to the cavernous sinus: A minimally invasive microsurgical model. Laryngoscope. 2000;110;286–291. 19. Uttley D, Moore A, Archer DJ. Surgical management of midline skull base tumors: A new approach. J Neurosurg. 1989;71:705– 710. 20. DeMonte F, Hanna EY. Transmaxillary exploration of the intracranial portion of the maxillary nerve in malignant perineural disease. J Neurosurg. 2007;107:672–677. 21. Sabit I, Schaefer SD, Couldwell WT. Modified infratemporal fossa approach via lateral transantral maxillotomy: A microsurgical model. Surg Neurol. 2002;58:21–31. 22. Biller HF, Shugar JM, Krespi YP. A new technique for wide-field exposure of the base of the skull. Arch Otolaryngol. 1981;107:698– 702. 23. Krespi YP, Har-El G. Surgery of the clivus and anterior cervical spine. Arch Otolaryngol Head Neck Surg. 1988;114:73–78. 24. Krespi YP, Sisson GA. Skull base surgery in composite resection. Arch Otolaryngol. 1982;108:681–684. 25. Krespi YP, Sisson GA. Transmandibular exposure of the skull base. Am J Surg. 1984;148:534–583. 26. Ammirati M, Bernardo A. Analytical evaluation of complex anterior approaches to the cranial base: An anatomical study. Neurosurgery. 1998;43:1398–1407. 27. Ammirati M, Ma J, Cheatham ML, et al. The mandibular swingtranscervical approach to the skull base: Anatomical study. [technical note] J Neurosurg. 1993;78:673–681. 28. DeMonte F, Diaz E, Callender D, et al. The transmandibular, circumglossal, retropharyngeal approach for chordomas of the clivus and upper cervical spine. Neurosurg Focus. 2001;10:1–5. 29. Feiz-Erfan I, Spetzler RF, Horn EM, et al. Proposed classification for the transbasal approach and its modifications. Skull BaseInterdisciplin Approach. 2008;18:29–48. 30. Fujitsu K, Saijoh M, Aoki F, et al. Telecanthal approach for meningiomas in the ethmoid and sphenoid sinuses. Neurosurgery. 1991;28:714–719. 31. Gay E, Sekhar LN, Rubinstein E, et al. Chordomas and chondrosarcomas of the cranial base: Results and follow-up of 60 patients. Neurosurgery. 1995;36:887–896. 32. Kawakami K, Yamanouchi Y, Kawamura Y, et al. Operative approach to the frontal skull base: Extensive transbasal approach. Neurosurgery. 1991;28:720–724. 33. Sekhar LN, Nanda A, Sen CN, et al. The extended frontal approach to tumors of the anterior, middle and posterior skull base. J Neurosurg. 1992;76:198–206. 34. Terasaka S, Day JD, Fukushima T. Extended transbasal approach: Anatomy, technique, and indications. Skull Base Surg. 1999;9:177–184. 35. Leonetti JP, Reichman OH, Al-Mefty O, et al. Neurotologic considerations in the treatment of advanced clival tumors. Otolaryngol Head Neck Surg. 1992;107:49–56. 36. Kawase T, Shiobara R, Toya S. Anterior transpetrosal transtentorial approach for sphenopetroclival meningiomas: Surgical method and results in 10 patients. Neurosurgery. 1991;28:869– 876. 37. Harsh GR IV, Sekhar LN. The subtemporal, transcavernous, anterior transpetrosal approach to the upper brain stem and clivus. J Neurosurg. 1992;77:709–717. 38. Sen CN, Sekhar LN. The subtemporal and preauricular infratemporal approach to intradural structures ventral to the brain stem. J Neurosurg. 1990;73:345–354.

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39. Blevins NH, Jackler RK, Kaplan MJ, et al. Combined transpetrosal-subtemporal craniotomy for clival tumors with extension into the posterior fossa. Laryngoscope. 1995;105:975– 982. 40. Carpentier A, Blanquet A, George B. Suboccipital and cervical chordomas: Radical resection with vertebral artery control. Neurosurg Focus. 2001;10(3):1–6. 41. George B, Dematons C, Cophignon J. Lateral approach to the anterior portion of the foramen magnum. Application to surgical removal of 14 benign tumors: Technical note. Surg Neurol. 1988;29:484–490. 42. George B, Laurian C. Surgical approach to the whole length of the vertebral artery with special reference to the third portion. Acta Neurochir. 1980;51:259–272. 43. George B, Lot G. Anterolateral and posterolateral approaches to the foramen magnum: Technical description and experience from 97 cases. Skull Base Surg. 1995;5:9–19. 44. Babu RP, Sekhar LN, Wright DC. Extreme lateral transcondylar approach: Technical improvements and lessons learned. J Neurosurg. 1994;81:49–59.

45. Borba LA, Al-Mefty O. Skull-base chordomas. Contemp Neurosurg. 1998;20:1–6. 46. Canalis RF, Martin N, Black K, et al. Lateral approach to tumors of the craniovertebral junction. Laryngoscope. 1993;103:343–349. 47. George B, Archilli M, Cornelius JF. Bone tumors at the craniocervical junction. Surgical management and results from a series of 41 cases. Acta Neurochir (Wien). 2006;148:741–749. 48. Lang DA, Neil-Dwyer G, Iannotti F. The suboccipital transcondylar approach to the clivus and cranio-cervical junction for ventrally placed pathology at and above the foramen magnum. Acta Neurochir (Wien). 1993;125:132–137. 49. Sen CN, Sekhar LN. An extreme lateral approach to intradural lesions of the cervical spine and foramen magnum. Neurosurgery. 1990;27:197–204. 50. Sen CN, Sekhar LN. Surgical management of anteriorly placed lesions at the craniocervical junction—An alternative approach. Acta Neurochir. 1991;108:70–77. 51. Wen H, Rhoton AL Jr, Katsuta T, et al. Microsurgical anatomy of the transcondylar, supracondylar, and paracondylar extensions of the far-lateral approach. J Neurosurg. 1997;87:555–585.

19 Tumors of the Anterior Skull Base Vijayakumar Javalkar, Bharat Guthikonda, Prasad Vannemreddy, and Anil Nanda

SURGICAL ANATOMY

noidale, anterior clinoid process, diaphragma sellae, orbital roof, and tuberculum sellae. The most common sites are the olfactory groove or tuberculum sellae. Any of these locations can give rise to meningiomas that invade the underlying bone and paranasal sinuses. Malignant meningiomas comprise approximately 1% to 7% of all meningiomas with another 5% being atypical (3). There are nine subtypes of meningioma with low risk of recurrence (WHO grade I). Rhabdoid, papillary, and anaplastic (malignant) are classified as WHO grade III tumors and signify a higher likelihood of aggressive behavior and recurrence. Atypical, clear cell, and chordoid are intermediate grade tumors (WHO grade II). Unlike meningiomas with low risk of recurrence, malignant meningiomas are more common in males.

The floor of the anterior cranial fossa is formed by the orbital plates of the frontal bone, the cribriform plate of the ethmoid bone, and the lesser wings and anterior body of the sphenoid. Posteriorly, it is bounded by the lesser wings of the sphenoid and anterior margin of the chiasmatic sulcus. It typically contains irregular crevices upon which the frontal lobes rest. The medial portion of the anterior cranial fossa is the barrier between the intracranial space superiorly and the nasal cavity inferiorly. The medial anterior cranial fossa (Fig. 1) is bordered by the paranasal sinuses: anteriorly by the frontal sinus, laterally by the ethmoid sinuses, and posteriorly by the sphenoid sinus (1). The central part of the floor of the anterior cranial fossa is formed by the ethmoid bone. Tumors arising from the skull base may erode this part of the anterior skull base resulting in intracranial or sinus extension. The cribriform plate is the perforated central portion of the ethmoid. It contains 30 to 50 foramina (ranging 0.1–0.5 mm in diameter), which transmit the olfactory nerves (1). The crista galli is a sharp projection of the ethmoid bone in the midline, which gives attachment to the falx cerebri. The olfactory grooves on either side of the crista galli support the olfactory bulbs. Lateral to the olfactory grooves, the floor continues as the roof of the ethmoidal sinuses (fovea ethmoidalis). The foramen caecum is a small aperture situated between the crista galli and frontal crest, through which a small vein from the nasal cavity traverses to the superior sagittal sinus. The dura mater over the cribriform plate is thin, and care should be taken when reflecting the dura from this part of the floor. Lateral to either olfactory groove are the internal openings of the anterior and posterior ethmoidal foramina. The anterior ethmoidal foramina transmit the anterior ethmoidal vessels and the nasociliary nerve. The posterior ethmoidal foramen transmits the posterior ethmoidal vessels and nerve.

Esthesioneuroblastoma Esthesioneuroblastoma was first described by Berger et al. in 1924 (4). Schall and Lineback described the first cases in America in 1951 (5). They arise from the olfactory neuroepithelium, and the incidence is 3% of all intranasal tumors (6). Esthesioneuroblastoma can invade the cribriform plate, paranasal sinuses, intracranial cavity, and orbits. The most common site of metastasis is cervical lymph nodes, while sites of distant metastasis such as lungs, brain and bone are less common (7). It is most common in the fifth decade of life (8). A bimodal distribution has been shown at peaks in age groups 11 to 20 and 51 to 60 years (9,10). The sex distribution is almost equal. The Kadish staging system is the most commonly used system (Table 1) (11). Surgery followed by radiation has been widely adopted as the standard of care in Kadish stages A and B disease. For patients with Kadish C disease, the use of combined modality treatment with surgery followed by radiation and chemotherapy has been adopted (12). In patients with advanced and high-grade esthesioneuroblastoma, the option of platinum-based chemotherapy should be considered (13).

Chondrosarcoma

REGIONAL PATHOLOGY AND DIFFERENTIAL DIAGNOSIS

Chondrosarcoma constitutes about 6% of all the skull base tumors (14). They are thought to arise from the persistent islands of embryonal cartilage that occur near the cranial base synchondroses (15). The majority of them arise from the middle cranial fossa (64%) followed by the anterior cranial fossa (14%) and 7% originate from the posterior fossa (16). They should be distinguished from chordomas, especially the chondroid variety of chordoma, which may mimic a chondrosarcoma (17). Staining for epithelial membrane antigen and cytokeratin (chondrosarcomas do not stain positive) should be carried out to distinguish them from chordoma. Four primary histologic types have been reported: conventional (hyalin and myxoid), dedifferentiated, clear cell, and mesenchymal (18,19). Most cranial base chondrosarcomas

The anatomic structures that are intimately related to the anterior cranial fossa are the frontal bone; frontal, ethmoid, and sphenoid sinuses; nasal cavity; nasopharynx; and orbit and its contents. Any tumor, either benign or malignant, arising from these anatomic structures can erode through the anterior cranial fossa floor. The following is a summary of pathologies that often affect the anterior skull base.

Meningioma Meningiomas often arise from the dura mater of the anterior cranial fossa. Anterior cranial fossa meningioma constitutes about 40% of all the intracranial meningiomas (2). They originate from the dura of the olfactory groove, planum sphe293

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cases and 26% recurrence-free survival for reoperated cases at 10 year follow-up (22). Various forms of radiation treatment like high-dose protons or charged particles, such as carbon ions, helium or neon and radiosurgery using the gamma-knife or cyber knife is used to complement surgery. Chemotherapeutic trials with agents such as imatinib have also been tried and the results of a phase II study on imatinib are awaited (30).

Nasopharyngeal Carcinoma

Figure 1 Anterior cranial fossa floor. Neural–dural transition at the medial anterior cranial base. Source: From Ref. 1.

are of the low-grade variety and grow slowly. Dedifferentiated and mesenchymal chondrosarcomas are much more aggressive, but fortunately are rare (20,21). Magnetic resonance imaging (MRI) is the best study for preoperative diagnosis. On short repetition time (TR)/echo time (TE) MRI scans, chondrosarcomas generally exhibit low signal intensity. However, on long TR/TE MRI scans, they generally have very high signal intensity. After the administration of gadolinium, they show a marked enhancement in either a heterogeneous or homogeneous pattern. In one study, with particularly long follow-up, a recurrence free survival of 32% at 10 years was reported (22).

Chordomas Chordomas are slow-growing neoplasms arising from the remnants of primitive notochord. They are predominantly located in the sacrococcygeal region and the clivus. Fifty percent of chordomas involve the sacrococcygeal region, 35% occur at skull base near the spheno–occipital area, and 15% are found in the vertebral column (23). Chordomas typically present in adult males. Chordomas in children and adolescents are very uncommon, and account for ≤5% of all chordomas (24). Craniocervical chordomas most commonly involve the dorsum sellae, clivus, and nasopharynx. Chordomas are divided into conventional, chondroid, and dedifferentiated types. Conventional chordomas are the most common. Chondroid chordomas contain both chordomatous and chondromatous features and this histology is associated with better prognosis (25,26). Dedifferentiation or sarcomatous transformation occurs in 2% to 8% of chordomas and this can develop at the onset of the disease or later (27,28). Surgical treatment plays a major role in the management of chordoma. The main prognostic factor for local failure, and possibly survival, is quality of surgical margins (29). Tzortzidis et al. reported a 42% recurrence-free survival for primary Table 1 Kadish Staging—Esthesioneuroblastoma Stage A Stage B Stage C

Tumor confined to the nasal cavity Tumor confined to the nasal cavity and paranasal sinuses Tumor extends beyond the nasal cavity and paranasal sinuses, including involvement of cribriform plate, base of skull, orbit, or intracranial cavity

Nasopharyngeal carcinoma is a nonlymphomatous squamous cell carcinoma, which is uncommon in most countries and its age-adjusted incidence for both sexes is less than one per 100,000 population (31). In endemic areas like southern China, the incidence is much higher at 15–50/100,000 per year (32). The incidence is high among Chinese people who have immigrated to Southeast Asia or North America, but is lower among Chinese people born in North America than those born in China (31). Epstein-Barr virus is implicated in the pathogenesis of nasopharyngeal carcinoma and even the premalignant lesions harbor EBV (33). According to WHO classification, these are classified into three types. Type I includes typical keratinizing squamous cell carcinoma, type II includes nonkeratinizing squamous cell carcinoma, and type III includes undifferentiated carcinoma (34). Definitive diagnosis is made by endoscopic guided biopsy (32). Disease staging is based on the International Union against Cancer and American Joint Committee on Cancer staging system (AJC/UICC). The extent of nasopharyngeal carcinoma as per the TNM staging is the most important prognostic factor (31). Radiation treatment is the mainstay of treatment. Stage I and IIA lesions are treated by RT alone, while stages III and IVA, B lesions are treated by RT with concurrent chemotherapy followed by adjuvant chemotherapy [I, A]. Concurrent chemotherapy could also be considered for stage IIB disease [III, B]. The standard agent used in concurrent chemotherapy is cisplatin [I, A]. Adjuvant chemotherapy on its own has not been documented to confer survival advantage, adjuvant cisplatin and 5-fluorouracil combined with concurrent cisplatin RT has been demonstrated to be beneficial [I, A] (34). Gene therapy and immunotherapy are also being studied (35,36).

Malignant Melanoma Mucosal malignant melanoma (MM) accounts for 1% of all melanomas (37). Of all the mucosal malignant melanomas, sinonasal melanoma is the most common site. The most common sinonasal malignant melanoma sites are the lateral wall and the inferior turbinate of nasal cavity, maxillary sinus, and the ethmoid sinus (38). It is seen in fifth to eighth decade and occurs equally in men and women (39). Prognosis is poor, and the 3-year overall survival for malignant melanoma was only 28.2% in one study (38).

Lymphoma Non-Hodgkin lymphomas of the sinonasal tract are uncommon malignancies in the United States, representing approximately 1.5% of all lymphomas (40). The incidence has been reported to be higher in Asians and South American countries (41). Diffuse large cell B-cell lymphoma is the most common variety (42). Skull base involvement associated with sinonasal lymphoma is rare (43). It is associated with Epstein–Barr virus, and is also known as lethal midline granuloma syndrome (44). Lymphoma usually presents as a midfacial destructive lesion with nasal obstruction, epistaxis, ulceration, fever, chills, and weight loss (39). Fine needle aspiration or

Chapter 19: Tumors of the Anterior Skull Base

biopsy can reveal the diagnosis. If fine needle aspiration or biopsy is unavailable or if the fine needle aspiration is insufficient for diagnosis, then nasal biopsy is suggested (42). T-cell lineage extranodal NHL is associated with poor prognosis (45). Traditionally, radiation was considered the main stay of treatment for low-grade histology and stage I and stage II disease. In recent studies, combined treatment with chemotherapy and radiation has shown to improve survival (40,46–48).

Angiofibroma Angiofibromas are benign highly vascular tumors that occur in adolescent males. The classical presentation is nasal obstruction and epistaxis. The common routes of invasion are anterior infiltration of nasal cavity, anterolateral erosion of the posterior maxillary sinus, and anterosuperior destruction of the ethmoid air cells (49). They may also extend laterally into the pterygopalatine fossa (42). Imaging studies may reveal classical anterior bowing of the posterior wall of maxillary sinus (Holman–Miller sign). MRI better delineates the extent of tumor and spatial relationship with surrounding vital structures. Surgical resection after preoperative embolization is the main stay of treatment. Combined approaches are needed for those with intracranial extension. Radiation treatment has also been used as a treatment modality for angiofibromas (50).

Adenoid Cystic Carcinoma Adenoid cystic carcinoma is a malignant tumor that occurs most frequently in the parotid gland. They account for 10% to 15% of paranasal sinus malignancies (42). They have a high propensity for perineural spread. These tumors grow silently and present at a late stage due to submucosal extension. Adenoid cystic carcinoma usually arises in the sixth decade of life with nearly equal occurrence in males and females (51). Hematogenous metastasis is known to occur to the lungs after clinical progression of several years (52,53). Histologically, three growth patterns are recognized: cribriform, tubular, and solid. Solid growth pattern is associated with worse prognosis (54). Indeed, the worst prognostic factor in patients with adenoid cystic carcinoma is involvement of the skull base (55). Aggressive treatment with combined surgery and irradiation therapy is often inadequate to achieve local control (56). High-dose, conformal proton beam radiation therapy has been tried in patients with adenoid cystic carcinoma of the skull base with some success (55). Other modalities like Gamma Knife radiosurgery has been tried in the management of recurrent salivary gland tumors involving the skull base (57,58).

CLINICAL ASSESSMENT Clinical assessment should include detailed clinical history and physical examination including a comprehensive head and neck examination. The presence or absence of palpable lymph nodes in the neck should be determined. If the lymph nodes are palpable, then the location, size, mobility, and relationship to the carotid and other adjacent structures should be noted. Anterior skull base tumors have a propensity to involve the olfactory nerves, the visual system, including the orbit, optic nerves, and optic chiasm. Commonly overlooked, anosmia can be associated with significant lifestyle modifications for the patient and the family (59). A formal visual acuity assessment, funduscopic evaluation, and visual field testing are essential upon diagnosis. Surgery or radiation treatments

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can both lead to worsening of visual function and thus pretreatment assessment is crucial. Preoperative full extraocular motility correlates well with the likelihood of preserving orbital function (42). Evaluation by a multidisciplinary team consisting of neurosurgeon, head and neck surgeon, medical oncologist, and radiation oncologist is essential for delivery of optimal care for anterior skull base malignancies.

DIAGNOSTIC IMAGING MRI High quality MRI scan is the examination of choice. The advantages with MRI are superior soft tissue resolution, multiplanar imaging, and no ionizing radiation. It not only shows the extent of tumor, but also the relationship with important neurovascular structures like cranial nerves and blood vessels. Thin section, coronal, fast, spin echo T2-weighted images are useful for assessing the presence or absence of subtle anterior skull base penetration, whereas coronal postgadolinium T1-weighted images with fat saturation most sensitively assess dural, leptomeningeal, and parenchymal extension (42). MRI allows evaluation of the potential perineural spread of tumor along the branches of the trigeminal nerve (60,61). Even though nerve enhancement and thickening is not specific to perineural spread, such an observation is more likely in the setting of head and neck cancer due to perineural spread rather than inflammation. MRI has a higher sensitivity and specificity in detecting perineural spread than CT (62). MRI appearances may indicate the origin of anterior skull base tumors (63). MRI is especially useful in evaluating the orbit and its contents, but peritumoral edema can lead to abnormal signal intensity within ocular muscles and abnormal contrast enhancement of muscles, which may simulate neoplasm on MR imaging. This false-positive result is less commonly seen with a CT scan (64). Orbital infiltration is generally limited by the tough fibrous periorbita, which functions as an excellent barrier against the spread of neoplasm. Unfortunately, the periorbita is not readily identifiable even in high-resolution MR imaging or thin-section CT. MR imaging is also useful to study vascular encasement. In one study, the authors found that a single criterion of involvement of 270 degree or more of the circumference was accurate in predicting the surgeon’s ability to peel the tumor off the carotid artery (65).

CT A thin-section, coronal CT scan can be helpful in evaluating the cribriform plate for invasion (42). The following findings might suggest skull base invasion by tumors on CT scan: foraminal enlargement, bony thinning, erosion, and displacement (65). Perineural spread on a CT is demonstrated by the enlargement of the neural foramina and or soft-tissue infiltration of the fat adjacent to or within the neural foramina (66– 68). CT evidence of perineural spread is often an inference whereas there can be direct visualization of enhancement of the nerve with MR imaging (69). CT images can be fused with PET scans and the PET-CT fusion technique might be useful in evaluating skull base malignancies (70).

PET Scan Preoperative PET scan in anterior skull base tumors has a very low yield (71). PET-CT scan may show better results for the detection of lymph node metastasis than PET or CT alone (72,73). In long-term surveillance of patients, obtaining a preoperative PET scan may be helpful in that any increase in

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unexpected activity can be evaluated (42). The important limitations associated with PET scans are due to false-positive and false-negative results following treatment. During the first three months following radiotherapy, there is false-negative uptake of FDG (74). False-positive results may be due to early postoperative changes, inflammation at the primary site, or regional lymph nodes (71).

Vascular Encasement In cases where the major blood vessels are involved by the tumor, resection carries a risk of cerebrovascular insufficiency. The imaging studies that are useful in such cases are MR angiograms, conventional angiography, temporary balloon occlusion, and Xe-CT CBF studies (69). Anatomic imaging techniques like conventional angiogram and MRI are less reliable in predicting the risk of stroke. Preoperative carotid artery temporary balloon occlusion with Xe-CT CBF scanning provides the most reliable measure of the collateral carotid artery circulation (75). Even in cases where a successful preoperative assessment is completed, the risk of developing stroke is 3% to 8% (59). Conventional angiography is also used to study the overall vascularity of the tumor and occasionally endovascular embolization of the arterial tumoral feeders is helpful.

Biopsy Whenever possible, an endoscopic transnasal biopsy is obtained (59,75). This will help to differentiate certain tumors, like primary lymphomas, which have a nonconventional or highly specific treatment strategy (42).

SURGICAL TECHNIQUE The goals of anterior skull base surgery are resection of tumor with negative margins. Occasionally, en-bloc resection is sought (especially for primary bone lesions); however, this is rarely practical in anterior skull base tumors. Minimal brain retraction, preservation of neurologic function, and improved aesthetic outcome are essential tenets to anterior skull base surgery (42). Reconstruction of the anterior cranial base is also an extremely important part of the surgical strategy to reduce postoperative CSF leak and infections. The preoperative plan for closure is equally important to the plan for approaching and resecting the tumor. The concept of clear margins applies to anterior skull base malignancies similar to the other head and neck malignancies. If possible, negative margins should be obtained; however, given the critical structures in the area, this is often not feasible (76). The importance of histologically negative margins is universally accepted (38,77).

APPROACHES FOR ANTERIOR SKULL BASE MALIGNANCIES Craniofacial Resection Surgery remains the main modality of treatment for anterior skull base malignancies. The craniofacial approach constitutes the main surgical strategy. In 1954, Smith reported a case in which the craniofacial approach was used for the first time (78). It was only after Ketcham’s publication in 1966 that the craniofacial approach became the standard for the surgical treatment of malignancy of the anterior skull base reaching the lamina cribrosa (79). The important contraindications for craniofacial resection are significant invasion of the brain, invasion of the optic chiasm, invasion of both orbits,

Figure 2 Bicoronal skin incision extending from one zygomatic arch to the other. Source: From Ref. 89.

invasion of the internal carotid artery, cavernous sinus extension, and elderly patients with associated comorbid medical illness (42,80,81). The advances in imaging techniques, neuronavigation, operating microscope, sophisticated skull base approaches, and reconstructive techniques have all contributed to the overall improvement of results. Craniofacial resection is safe and effective treatment option for patients with malignant tumors of the skull base. In the International Collaborative Study of Craniofacial Surgery for malignant skull base tumors, the mortality rate was 4% and postoperative complications were noted in 33% of cases (77).

Preoperative Preparation Broad-spectrum antibiotics are administered at the time of induction of general anesthesia. The use of broad-spectrum antibiotics in craniofacial resections has been shown to reduce the incidence of infectious complications (82–86). There are no definite guidelines regarding the use of lumbar drains at the time of surgery. Most feel that drainage of CSF achieves brain relaxation and thus reduces the retraction of the brain (75,87). Others believe that routine lumbar drain is not recommended and sacrifice of the nerves and fenestration of the peri-olfactory cisterns enable adequate drainage of CSF (88).

Incision The standard bicoronal frontal incision extends from the tragus of one ear to the other behind the hairline (Fig. 2). The scalp incision is extended down to the plane between the epicranial aponeurosis and the pericranium. The posterior scalp flap is retracted several centimeters to expose extrapericranium for reconstruction so that sufficient length of flap can be harvested. The scalp edges are secured with Raney clips. The pedicled galeal-pericranial flap is considerably stronger than the pericranial flap and it is the local flap of choice when reconstructing a skull base defect (75).

Soft Tissue Dissection The anterior flap is elevated to expose the supraorbital ridge, glabella, and the upper half of nasal bones (Fig. 3). Care should be taken to preserve the supratrochlear and supraorbital vessels, which supply the flap. After elevation of the flap, the galeal-pericranial flap is dissected and wrapped in bacitracin-soaked gauze throughout the procedure. A 1 cm

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Figure 3 Dissection of pericranium in preparation for bifrontal craniotomy. Source: From Ref. 89.

cuff of galea should be preserved on the anterior flap for subsequent scalp closure. After reflection of the scalp flap, proposed bony cuts are marked on the anterior wall of frontal sinus and bone.

Bony Dissection and Osteotomy A single burr hole is made in the midline 5 cm above the glabella. Bone cuts are made with a drill bilaterally up to the midorbit without entering the frontal sinus. Frontal sinus cuts are made using 2 mm cutting burr through the anterior and posterior wall of the frontal sinus. This strategy reduces the incidence of dural tears adjacent to the frontal sinus (75). A small frontal craniotomy is largely favored. After the bony cuts, the frontal bone flap is elevated. The remainder of the posterior wall of the frontal sinus is removed using a rongeur. Care should be taken to remove mucosa of the sinus and cranialize the frontal sinus by excising the posterior wall. Any bleeding from the sagittal sinus can be controlled with tamponade and gelfoam. The technique of the craniotomy might vary. While elevating the dura from the base of anterior cranial fossa, care must be taken, especially while separating it from the crista galli. Once the dura is separated, the crista galli can be excised by a rongeur. The dura is further separated from the cribriform plate and planum sphenoidale. Undue retraction should be avoided. If a lumbar drain was instituted, draining 30 cc of CSF will relax the brain at this stage, allowing for easier extradural dissection. The bone cuts in the floor of the anterior cranial fossa are completed using a fine cutting burr (Fig. 4). The tumor can be approached from the inferior aspect by transfacial approaches. Modified Weber–Ferguson incision is favored because of the better cosmetic result (75). Facial incision may be avoided in cases of selected tumors of the superior nasal vault or ethmoid sinuses if adequate exposure and resection can be accomplished transcranially. After the appropriate transfacial approach, the tumor is removed, en bloc if possible, using both the transfacial and transcranial routes.

Subcranial Approach The concept of the subcranial approach to anterior skull base was first introduced by Raveh, in 1978, initially for the treatment of trauma to the anterior skull base, and later it was applied to skull base tumors (91,92). This approach combines a bifrontal craniotomy with naso-orbital osteotomies. It provides adequate exposure of the orbital, sphenoethmoidal, and clival regions as well as nasal and paranasal sinuses (93). The

Figure 4 Illustration of the bone cuts around the cribriform plate. Source: From Ref. 90.

advantages of this procedure are minimal frontal lobe retraction and no facial incisions. A potential disadvantage of the subcranial approach, when it is used in resection of malignant tumors, is osteomyelitis or osteoradionecrosis of the disconnected and replaced bones that includes the medial orbital rim, glabella, and part of the nasal bone (42).

Midfacial Degloving Approach Midfacial degloving (MFD) approach avoids facial incisions. It can be combined either with bifrontal craniotomy or subcranial approaches for tumor resection. It provides adequate exposure to nasal cavities, ethmoid complexes, maxillary sinuses, ethmoid roof, cribriform plate, sphenoid sinuses, and nasopharynx (94). Extended unilateral maxillotomy approach to the skull base can be carried out through MFD approach (95).

Orbitozygomatic Approach This approach was first described by Pellerin et al. and Hakuba et al. (96,97). Removal of the zygomatic arch, lateral orbit, and part of the zygomatic body with a standard pterional craniotomy can give access to the parapharyngeal space and the floor of the middle cranial fossa (42). The orbitozygomatic approach is also recommended for skull base tumors that involve the cavernous sinus (98).

SURGICAL APPROACHES FOR ANTERIOR SKULL BASE MENINGIOMAS The surgical approach depends on the location of the tumor. The most common surgical approaches are variants of either standard pterional or subfrontal (2,99). Extended frontal approaches to anterior skull base tumors have been proposed (100). This approach is a modification of the transbasal approach of Derome. The addition of bilateral orbitofrontal or orbitofrontoethmoidal osteotomy (Figs. 5–7) improves the exposure of midline lesions, while minimizing

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Figure 5 Extent of bone removal in fronto-orbital osteotomy. Source: From Ref. 89.

the need for frontal lobe retraction. Compared with a conventional bifrontal craniotomy, the addition of fronto-orbital osteotomy increases the surgical exposure while minimizing frontal lobe retraction. In one study, the angle of exposure increased markedly with an average gain of 76% for the anterior cranial fossa (89). Otani et al. proposed selective extradural anterior clinoidectomy for surgical management of tuberculum sellae meningiomas (101). They recommend this procedure for complete resection of tuberculum sellae meningiomas extending to the surrounding anatomic structures. Arai et al. proposed a transcranial–transsphenoidal approach for tuberculum sellae meningiomas (102). They stressed that this approach provides good access to a tumor extending inferomedially to the optic nerve. The other approaches that are published in the literature are frontal sinus approach to olfactory groove meningiomas, and orbital roof craniotomy

Figure 7 Basal view of skull showing the extent of bone removal in orbitofrontoethmoidal osteotomy. Source: From Ref. 89.

via an eyebrow incision (103,104). Endoscopic endonasal and endoscopic glabellar approaches to the anterior skull base has been described as well (105,106).

Endoscopic Approaches Endoscopic resection of anterior skull base tumors was described by Casiano to resect esthesioneuroblastoma (107). This technique has been used to resect other tumors like angiofibromas, ethmoid carcinomas, fibro-osseous lesions, and chondro-osseous lesions. Endoscopic approaches avoid facial incisions and bony cuts thus offering a cosmetic advantage. There are concerns regarding the oncologic safety of endoscopic tumor removal in case of malignancies. Long-term outcome results of endoscopic tumor removal may clarify the doubts regarding oncologic safety. Obviously, each patient should be approached individually with the appropriate surgical plan developed based on tumor type, location, and the clinical presentations. The goal of the surgery also will contribute to this decision making. Not all patients are suitable for endoscopic approaches. Small lesions and those that do not involve the carotid artery are more suitable for an exclusive endoscopic approach (108). Some patients may require combined approaches and in some, an open procedure may be beneficial. In one preliminary study, minimally invasive endoscopic approaches did not differ significantly from traditional craniofacial resection in operative time, blood loss, hospital stay or complication rate, survival, and recurrence rates (109). Larger prospective studies comparing both the techniques are required; the findings of such studies might help in proper selection of patients.

Tumor Resection

Figure 6 Basal view of the skull showing the extent of bone removal in fronto-orbital osteotomy. Source: From Ref. 89.

The idea behind the evolution of so many different cranial approaches has been to reduce brain retraction with improved visibility and accessibility of the tumor topography. Occasionally, however, it has been pointed out by us that extensive bony removal does not improve the visibility beyond a certain point and is thus unwarranted (110). Most extracranial tumors with intracranial extension would be exposed during the operative dissection itself, while they occupy the paranasal sinuses or the nasopharyngeal cavity. Tumors such

Chapter 19: Tumors of the Anterior Skull Base

as angiofibrolipoma, angiolipoma, and fibromatous tumors could be removed en bloc along with their attachment to the sinus mucosa. However, careful dissection is required in cases with dural attachment or infiltration. Discretion is required in radical resection of these tumors, keeping in mind that they could be invasive and malignant. In such instances, frozen section histopathology is helpful in decision making. Intracranial tumors with extracranial extension often require the detachment of the falx at the cribriform plate and division along the sagittal axis. Dural opening with adequate margin for closure allow for a good closure. The pterional approach with an orbital extension, would also afford an excellent view of planum sphenoidale and ACF when the Sylvian fissure is adequately split (100,111,112). The extent of craniotomy thus depends upon the size and location of the lesion as well as the clinical presentation of the patient (113). The principle behind safe removal of the intracranial tumor is maintaining the dissection within the arachnoid planes and avoiding pial breach. At places, this plane maybe eroded by the tumor, in which case, the pia has to be followed carefully to avoid injury to brain parenchyma and perforators from the anterior cerebral arteries (114). Cavitron ultrasonic aspirator has been a remarkable aid in achieving intratumoral resection and debulking. This also offers relaxation of the intracranial structures enabling clear visualization of neurovascular structures. Tumor debulking and periodical dissection around the tumor usually separates the surrounding structures away from the lesion. Attention is required in case of large tumors to save the perforators from the anterior communicating artery and the anterior cerebral arteries. In large tumors, these small vessels may be encased in the tumor or hidden on the other side of the tumor capsule. Endoscopy is an excellent accessory during surgery for large tumors that cross the midline. The bony part of the tumor or the hyperostotic bone in some meningiomas could pose difficulties. Most often, the exophytic part of the bone can be safely drilled away or completely removed if in close proximity to the craniotomy for the ease of subsequent reconstruction. Involved bone in the craniotomy flap should be excised and the bone flap reconstructed with methylmethacrylate or titanium mesh. Reconstruction En bloc removal of anterior skull base tumors may create defects in the anterior skull base and allow direct communication between the intracranial space and paranasal sinuses. Adequate reconstruction is essential to create a barrier between these two compartments, which will reduce the incidence of infection, CSF leak, and pneumocephalus. Small dural tears can be closed primarily or with fascia lata, temporalis fascia, or pericranium. Flaps for reconstruction of the anterior skull base can be classified as local flaps, pedicled myocutaneous flaps, and free tissue transfer. The most commonly used flap is the pericranial-galeal flap. The blood supply is derived from the supraorbital and supratrochlear arteries. These flaps are sufficient to repair small defects. If the orbital roofs are intact, the pericranial flap may be sufficient in achieving adequate support without formal bone reconstruction (115). Local flaps, like pericranial flaps, are difficult to harvest following previous surgery and prior radiotherapy. Galeal flaps may not be adequate to cover defects of bone like burr holes and craniotomy bony cuts. Loss of galea and frontalis muscle from the undersurface of the frontal scalp makes it thin and poorly vascularized and this might be problematic after radiotherapy (116,117). They can also cause functional and cosmetic com-

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plications including sensory motor loss and regional alopecia (118). Medial transposition of the temporalis muscle is useful in reconstructing anterolateral skull base defects (115). The temporalis muscle flap derives its blood supply from the maxillary artery (119). In order to preserve the blood supply, the muscle should remain attached to the coronoid process (115). The temporalis muscle flap has a reliable blood supply while maintaining an effective arc of rotation of 120 to 130 degrees (120,121). Temporalis muscle can cover ipsilateral defects of the orbitofrontal region, maxilla, temporal bone, and infratemporal fossa. For reconstructing the orbit following exenteration, the temporalis muscle can be transposed into the orbit through a subcutaneous tunnel or through an opening in the lateral orbital wall (122). For maxillary reconstruction, the flap is transposed into the maxilla under the zygomatic arch. For more medially situated defects, temporalis muscle flaps are less reliable (115). Extensive skull base defects require either free tissue transfer from distant donor site or regionally transferred pedicled flaps. Regional myocutaneous flaps are an option in many skull base defects but free tissue transfer is more reliable (123). Regional pedicle flaps are often reserved for patients who are poor candidates for free flaps (124). The pectoralis major flap is widely used to repair extensive anterior and lateral skull base defects (124,125). Trapezius mycocutaneous flap is favored for reconstruction of lateral defects of the posterior skull base (115). Myocutaneous flaps may not always provide a watertight seal of the nasopharynx (126,127). Free tissue transfer is considered to be the best to repair extensive defects of the skull base by many authors (114,123,127–138). The success rates for free tissue transfer ranges from 86% to 100% (126,139–141). These free flap survival rates compare favorably to pedicled flaps used for similar conditions (142). The most common free flaps that are used in the reconstruction of anterior skull base defects are: rectus abdominis flap, the radial forearm flap, the latissimus dorsi flap, and the anterolateral thigh flap (123). Rectus abdominis is the most extensively used free flap for skull base reconstructions. It provides a bulky muscle that can obliterate dead space (115). Not only the defect size but individual characteristics of the defect and donor sites must also be taken into consideration when choosing the appropriate reconstruction source (123). For example, in obese patients, the anterolateral thigh flap is frequently used since it provides appropriate volume with a reliable skin paddle (143). Frequently used vessels for anastomoses include the facial, lingual arteries, and superior thyroid artery. The preferred recipient veins include the internal jugular, external jugular, and facial veins (123,137). End-to-end anastomoses are ordinarily performed with the exception of end-to-side anastomoses, which are performed when using the internal jugular vein (137). The incidence of complications following reconstruction of anterior skull base with free flaps is 10% to 42% (126,128,137,139,141,144,145). The risk of infection with flap reconstruction is approximately 1.4% to 7.4% (137). CSF leak following free flap transfer is about 0% to 8% (146). The advantage with free flap is the flexibility in flap content, and it is possible to introduce a large quantity of wellvascularized tissue in a single stage operation (117). High rate of complications are documented in elderly patients (147) in whom pedicled myocutaneous flaps are an alternative when large defects need reconstruction (124). The common complications are flap loss from ischemia and necrosis, flap failure resulting in CSF leak, meningitis, epidural abscess, empyema, and neurologic injury. Another concern is that the bulk of the

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free flap may mask local recurren