HistologicalTypirg of OdontogenicTumours I. R. H. Kramer,J.J.Pindborg, andM. Shear SecondEdition
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HistologicalTypirg of OdontogenicTumours I. R. H. Kramer,J.J.Pindborg, andM. Shear SecondEdition
With142Fisures
Springer-Verlag Berlin Heidelberg NewYork London Paris Tokyo HongKong Barcelona Budapest
I. R. H. Kramer Emeritus Professorof Oral Pathology,University of London, England J. J. Pindborg Professorof Oral Pathology,Royal Dental College,Copenhagen,Denmark (WHO Collaborating Centre for the Histological Classification of OdontogenicTumours) M. Shear Deputy Vice-Chancellorand Honorary Professorof Oral Pathology University of the Witwatersrand,Johannesburg,South Africa
ln this series,colour illustrations will be limited in number in order to maintain a reasonable salesprice In the present volume. we are greatly rndebted to a number of donors, including the Intcrnational Association ol Oral Pathologists and Kodak Limited. whose generous contributions have made it possible tor all of the photomicrographs to be reproduced in colour
First edition oublished bv WHO in I 971 as No 5 in the International Histolosical Classification of Tumours series
ISBN 3-540-54I42-X Springer-Verlag Berlin Heidelberg NewYork ISBN 0-387-54142-XSpringer-Verlag NewYork Berlin Heidelberg Data Library of CongressCataloging-in-Publication Kramer, Ivor R H (Ivor Robert Horton) Histological typing of odontogenic tumours / I R H Kramer, J J Pindborg,and M Shear 2nd ed p cm - (Internationalhistologicalclassificationof tumours) Rev ed of: Histologicaltyping of odontogenictumours,jaw cysts,and allied lesions/ J J Pindborg. I R H Kramer, in collaborationwith H Torloni. 1971 Includesindex alk paper)I S B N 3 - 5 4 0 - 5 4 1 4 2 -( X (alk paper) ISBN 0-387-54142-X 1 Odontogenictumors Histopathology 2 Odontogenictumors ClassificationI Pindborg,J J (JensJorgen), I 92I Histologicaltyping of odontogenic tumou$. j aw cysts.and allied lesions I I Pindborg,J J (JcnsJorgen), 1921 III Shear,Mervyn IV Trtle V Scrics:lnternational histologicalclassificationof tumours (Unnumbered) [DNLM: 1 OdontogenicTumors classification2 Odontogcnic Tumors pathology WU 280 K89h] forLibraryofCongress 91-4996 CIP RC280M6K73 1991 61699'292-dc20 DNLM/DLC This work is subject to copydght All rights are reserved,whether the whole or part of the malerial is concerned,specilicallythe rights of translation,reprinting,reuseof illustrations,recitation,broadcasting,reproduction on microfilm or in any other way. and storagein data banks Duplication of this publicationor parts thereof is permittcd only under the provisionsof the German Copyright Law of September9, 1965,in its currcnt venion. and permissionfor use must alwaysbe obtained from Springer-VerlagViolations are liable for prosecutionunder the German Copydght Law O Springer-VerlagBerlin Heidelberg 1992 Printed in Germany The use of gcncral descriptivenames,registerednamcs,trademarks,etc in this publicationdocs not imply, even in the absenccof a specificstatement,that suchnamesare exempt from the relevanIprotectivclaws and regulationsand thcrcfore frec for generaluse Product liability: The publisherscannot guarantcethe accuracyof any information about dosageand application containcdin this book In every individual casethc user must check such information by consultingthe relevantlilcraturc Reproductionof the figures:Gustav Dreher GmbH, Stuttgart Typesettingand printing: Appl, Wemding: Binding: Sch.iffcr,Gri.instadt 211311 1-5,13 - Printedon acid-freepaper SPIN:10479455
Consultants Abrams.A.. Dr. Department of Oral Pathology,University of Southern California, Los Angeles,USA Buchner.A.. Dr. Department of Oral Pathology,Schoolof Dental Medicine, University of Tel Aviv, Israel Donath. K^ Dr. Institute of Pathology,University of Hamburg, Germany Esguep,A., Dr. Department of Oral Pathology,Faculty of Odontology, University of Chile. Chile Hansen,L., Dr. Department of Oral Medicine and Hospital Dentistry, University of California, SanFrancisco,USA Nikai, H., Dr. Department of Oral Pathology,Hiroshima University, Japan Radden.8..Dr. Department of Dental Medicine and Surgery, University of Melbourne,Australia
Reviewers Rick, G., Dr. Oral PathologyService,La Jolla, California, USA Lee,K.W., Dr. Department of Oral Pathology,Institute of Dental Surgery,University of London, England van der WaqL1.,Dr. Department of Oral Pathology, Academic Hospital, Free University, Amsterdam, Netherlands
General Preface to the Series
Among the prerequisitesfor comparativestudiesof cancerare international agreement on histological criteria for the definition and classificationof cancertypes and a standardizednomenclature.An internationally agreedclassificationof tumours, acceptablealike to physicians, surgeons, radiologists, pathologists and statisticians, would enable cancer workers in all parts of the world to compare their findings and would facilitate collaboration among them. In a report published in 1952,ta subcommittee of the World Health Organization (WHO) Expert Committee on Health Statistics discussedthe generalprinciplesthat should govern the statistical classificationof tumours and agreed that, to ensure the necessary flexibility and ease of coding, three separate classificationswere neededaccordingto (1) anatomicalsite,(2) histologicaltype, and (3) degreeof malignancy.A classificationaccordingto anatomicalsite is availablein the International Classificationof Diseases.2 In 1956,the WHO ExecutiveBoard passeda resolution3requesting the Director-General to explore the possibilitythat WHO might organizecentres in various parts of the world and arrange for the collection of human tissuesand their histologicalclassification.The main purpose of such centreswould be to develop histological definitions of cancertypes and to facilitate the wide adoption of a uniform nomenclature. The resolution was endorsed by the Tenth World Health Assemblvin Mav 1957.1
1 2 3 4
WHO (1952)WHO TechnicalReportSeries. No.53,1952,p45 WHO (1977)Manualof the internationalstatisticalclassification of diseases, injuries,and causesof death.1975version.Geneva WHO (1956)WHO Official Records.No.68,p 14 (resolutionEB 17.R40) WHO (1957)WHO OfficialRecords. No.79,p467(resolution WHA 10.18)
VIII
GeneralPreface to theSeries
Since1958,WHO hasestablisheda number of centresconcerned with this subject.The result of this endeavourhas been the International Histological Classificationof Tumours, a multivolumed series whose first edition was published between 1.967and 1981.The present revisedsecondedition aims to update the classification,reflecting progressin diagnosisand the relevanceof tumour types to clinical and epidemiologicalfeatures.
Prefaceto the HistologicalTyping of OdontogenicTumours,SecondEdition
The first edition of this book, entitled Histological Typing of Odontogenic Tumours,Jaw Cystsand Allied Lesions,twas the result of a collaborativeeffort organizedby WHO and carried out by the International Reference Centre at the Department of Oral Pathology, Royal Dental College,Copenhagen,Denmark. In order to keep the classificationup to date, and in preparation for this new edition, the text of the first edition was circulatedto the international panel of consultantslisted on page V for their comments and suggestions.These, together with advice received from many other oral pathologists,were taken into accountin the preparation of a new draft. After further preparatorywork and discussion,a revised draft was sent to the three reviewerslisted on page V, and their detailed commentswere of the greatesthelp in the preparation of the final text. The authors would like to expresstheir sincereappreciationof the help sofreelygivenbythe consultantsand reviewers. In this secondedition the title has been modified for the sake of uniformity with other volumes in this series;the scoperemains essentially the sameas that of the first edition. The histological classificationwhich appearson pages7-9 contains the morphology code numbers of the International Classification of Diseasesfor Oncology (ICD-O)2 and the Systematized Nomenclature of Medicine(SNOMED).1
1 Pindborg JJ, Kramer IRH (1971) Histological Typing of Odontogenic Tumours, Jaw Cysts, and Allied Lesions. Geneva, World Health Organiza^ tion (International Histological Classification of Tumours, No.5) ' World Health Organization (1990) International Classification of Diseases ^' for Oncology. Geneva College of American Pathologists (1982) Systematized Nomenclature of Medicine. Chicago
X
Tumours Typingof Odontogenic Preface to the Histological
It will, of course, be appreciatedthat the classificationreflects the presentstateof knowledge,and modificationsare almost certain to be neededasexperienceaccumulates.Furthermore,the classification necessarilyrepresentsa majority view, from which somepathologistsmay wish to dissent.It is neverthelesshoped that, in the interests of international cooperation, all pathologists will use the classificationas put forward. Criticisms and suggestionsfor its improvement will be welcomed, these should be sent to the World Health Organization,Geneva,Switzerland. The publications in the series International Histological Classification of Tumours are not intended to serveas textbooks but rather to facilitate the adoption of a uniform terminology that will facilitate and improve communicationamong cancerworkers. For this reason literature referenceshave been omitted and readersshould refer to standardworks for bibliographies.
Contents
Introduction
1
......
HistofogicalClassificationofOdontogenicTumours . . . . . . DefinitionsandExplanatoryNotes Neoplasmsand Other Tumours Related to the OdontogenicApparatus Neoplasmsand Other LesionsRelated to Bone EpithelialCysts
. ....
.
7 11 11 27
......34
Subject Index
43
Illustrations
47
Introduction
Inter-relationshipsof the Dental Tissues The tooth germ hasthree main components- the enamel organ,the dentalpapillaand the dentalfollicle (Fig.1).The enamelorganis an epithelial structurederived from the ectodermthat lines much of the oral cavity.The dental papilla and the dental follicle are ectomesenchymal (mesectodermal),being partly derived from cells that migrated from the neural crest early in embryogenesis.Both the gross morphology of the tooth germ and the differentiation of its cells depend upon a complex pattern of inductive interactionsbetween the epithelium and the ectomesenchyme. The sites in which the teeth will form appear to be determined before the commencementof epithelial downgrowth from the oral epithelium to form the odontogenic epithelium. This epithelial downgrowth (the dental lamina), the developmentof the enamelorgans of the individual teeth, and the morphology of each enamel organ, are controlled by the ectomesenchyme. The enamelorgan is responsiblefor the formation of enameland comprisesfour layers: outer dental epithelium, stellate reticulum, stratum intermedium and inner dental epithelium (Figs.1 and2a). The dental papilla (Fig.2b) is responsiblefor the formation of the dentine, and contact with epithelium provides the inductive stimulusnecessaryfor the differentiation of odontoblastson the surface of the papilla.When dentineformationstarts(Fig.3).this in turn providesthe stimulusfor the maturation of inner dental epithelial cells into functional ameloblastsand enamel is depositedon the dentine surfacein the crown area. Later. a further extension from eachenamel organ provides the epithelium necessaryfor the induction of odontoblastdifferentiation and dentine formation in the root area.The epithelial extensionfrom the enamelorgan breaksup, and residues(the epithelial rests of Malassez)persist throughout life in
2
Introduction
the periodontal ligament closeto the root surfaceof each tooth. In the formed tooth, the dental papilla remainsas the dental pulp, with the layer of odontoblastsat the periphery (Fig.a). The morphologicaland inductive relationshipsbetweenthe various parts of the normal tooth germ are reproduced,to a greater or lesserextent, in many of the tumours and tumour-like lesionsof the odontogenic tissues.Thus, the observation of these features is important both in the identification of the lesionsand in their classification. For example,normal dentine is easilyidentified becauseof its tubular structure,but if for somereasonthis tubular structureis absent it is difficult to distinguishbetween atypicalpoorly mineralizeddentine (dentinoid) and atypical osteoid. However, if an osteoid-like tissuedevelopsin direct relationshipto odontogenicepithelium, this relationshipprovides strong presumptiveevidencethat the material is, in fact, dysplasticdentine. Cementum,which normally coversthe dentine of the root of the tooth, existsin both acellularand cellular forms. Cementumis essentially a type of bundle bone, and both the cementumof the tooth and the bundle bone lining the tooth socket are produced by cells derived from the dental follicle. Cementum, especiallythe acellular variety,tends to exhibit a characteristicintensebasophilia(Fig.5). However, when cementum is depositedother than in its normal location on the root of a tooth, it may be difficult to distinguishfrom bone (seebelow). Cementum and dentine, like bone, have a substantialcollagenous matrix. The organic component of enamel is non-collagenous and is presentin suchsmall amountsthat, when a specimenis demineralizedbefore sectioning,the tenuousmatrix of the enamelmay be lost. However, in somecircumstances(especiallywhen enamelis enclosedby other tissues)the matrix may be retained (Fig.6). Globules of basophilicmineralized material in contact with ameloblasticepithelium may representdysplasticenamel.
Cementum-ContainingLesions Within the normal periodontal ligament, next to the cementum covering the root of the tooth and sometimesfused to the cementum, it is not uncommon to find occasionalrounded, strongly baso-
Introduction 3 philic calcified masses.In this location it is reasonableto suppose that thesemassesare derived from the type of cell that forms the adjacent cementum,and they are termed 'cementicles'.When similar massesare found in certain tumours and tumour-like lesionsof the jaws, often fused into larger aggregatesand sometimesintermingled with depositsof bone, it is reasonableagainto regard them asa form of cementum; this supposition is reflected in the names by which theselesionsare known (eg. 'cementifyingfibroma', 'cemento-ossifying fibroma'). However, it must be recognizedthat similar cementum-likematerial may be found in lesions of parts of the craniofacial skeleton other than the jaws, and occasionallyin other parts of the skeletonlocations in which it is not possibleto envisagederivation from the odontogenictissues.These observationsmay be attributable to the fact that, although formed by cells of the odontogenic apparatus, cementumis a form of bundle bone. Therefore, it is understandable that sometimestissue of similar appearancemay be found in locations other than the jaws. The classificationof odontogenictumours has to include provision for lesionsin which there is hard tissuethat may be cementum, or bone, or a mixture of the two - lesionswhich might be described under the heading 'Neoplasms and other tumours related to the odontogenicapparatus'or in the categoryof 'Neoplasmsand other lesions related to bone'. In this revision, the one neoplasm that is generally accepted as being essentiallycementogenic(the benign cementoblastoma)has been included in the former category,whilst the cemento-ossifyinglesions (both neoplastic and dysplastic)are listed in the category of 'Neoplasms and other lesions related to bone'.
Scope of the Classification The primary purpose of the following classificationis to list and define neoplasms,tumour-like lesions and cysts arising from the odontogenic apparatus. However, the classification also includes some distinctivejaw lesionsthat are of uncertain status,and others that are clearly non-neoplasticbut must be distinguishedfrom odontogenic neoplasms.The classificationincludesa few types of odontogenic tumours that have been described quite recently, so that
4
Introduction
only a preliminary picture is available of their clinical and histopathological characteristics.It is hoped that including reference to them here will make possiblethe identification and description of further cases,so that a more detailed knowledge of their characteristicscan be achieved. Types of bone tumour that also occur in other parts of the skeleton and do not show specialfeatureswhen occurring in the jaws are not included, although certain bone tumours and tumour-like lesionsthat are distinctivewhen occurring in the jaws are discussed' Similarly, soft tissuetumours that are not peculiarto the jaws but may occur within the jaws are not considered,unlessthey present specialproblems in differential diagnosis.Metastaticdepositsin the jaws are also excluded. Other volumesin this seriesthat will be helpful in the identification of tumours of the orofacial region include Soft TissueTumours Oral and OropharyngealTumours Bone Tumours SalivaryGland Tumours Classification of Odontogenic Tumours Over the yearstherehavebeenmany attemptsto producea'logical' classificationof tumours and tumour-like lesionsof the odontogenic tissues.Recent advancesin our understandingof the origins and the interactionsof thesetissueshave provided a sounderscientificbasis for classification,but uncertainties remain, partly becauseof the complexity of the tissuesinvolved and partly becausethe rarity of some lesionsmakes it difficult to accumulatea large seriesfor study and comparison. The classificationusedhere is basedfirstly on tumour behaviour, 'benign' and with a broad division into lesionsgenerallyregardedas 'benign' 'malignant', categoryincludesa numthe thoseregardedas non-neoplastic. certainly probably or ber of entities that are 'benign' based on the types of lesions are then Subdivisionsof the odontogenic tissues involved: odontogenic epithelium without odontogenic ectomesenchyme;odontogenic epithelium with odontogenic ectomesenchyme;odontogenic ectomesenchymewith or 'included' in without included odontogenic epithelium. The word the latter group is intended to indicate that, although epithelium
Introduction 5 may be present,it sometimesappearsto be included by chance rather than playing any essentialrole in the pathogenesisof the leslon. Lesions made up of odontogenic epithelium with odontogenic ectomesenchymehave the elementsnecessaryfor inductive interactions leading to the formation of dentine and then enamel.Whether or not thesedental hard tissuesare found in any individual casedepends in part on the stageat which the lesion is excised,and in part on factorsthat are not yet understood.It is possiblethat someof the lesionsgiven separatedesignationsin the present classificationare simply chronological stagesin the evolution of a single type of tumour; until larger numbers of exampleshave been studied,it is suggestedthat they should be placed into the separatecategoriesprovided, so that differences in presentation and behaviour may be more easilyassessed. Notes on Terminology 1. Where there is good evidencethat a lesion is neoplastic,this will be statedin the brief definition of the lesionthat precedesthe detailed description. 2. Where there is good evidencethat a lesion representsa developmental anomaly or malformation, this will also be stated in the brief definition. 3. In accordancewith common practice,the terms 'lesion' and 'lesionaltissue'will be usedfor both neoplasticand non-neoplastic disorders. 4. Synonymsare given where they havebeen widely usedin the literature; the preferred term is given first, followed by the synonym in brackets.
HistologicalClassification of OdontogenicTumours
1
Neoplasms and Other Tumours Related to the Odontogenic Apparatus
1.1 1.1.1
Benign Odontogenicepitheliumwithout odontogenic ectomesenchyme 1.1.1.1 Ameloblastoma 9310/0, 7.7.1.2 Squamousodontogenictumour . 937210 1.1.1.3 Calcifyingepithelialodontogenictumour (Pindborgtumour) . . . 934010 1.7.1.4 Clear cell odontogenictumour . 927010 I.I.2 Odontogenicepitheliumwith odontogenic ectomesenchyme, with or without dentalhard tissueformation I.1.2.f Ameloblasticfibroma 933010 I.I.2.2 Ameloblasticfibrodentinoma(dentinoma) and ameloblasticfibro-odontoma 9290t0 1 . 1 . 2 . 3Odontoameloblastoma 931710 1 . I . 2 . 4Adenomatoid odontosenrctumour 9300/0 7 . 1 . 2 . 5Calcifying odontogeniccyst 9301,t0 1 . 1 . 2 . 6Complexodontoma . . . 928210 1 . I . 2 . 7Compound odontoma . 928110 1 . 1 . 3 Odontogenicectomesenchyme with or without included o dontogenic epithelium 1.1.3.1 Odontogenicfibroma Seenote 1 1.7.3.2Myxoma (odontogenicmyxoma, myxofibroma) . . 932010 1.1.3.3Benigncementoblastoma (cementoblastoma,true cementoma) . . 9Lj3l0 Morphology code of the International Classification of Diseasesfor Oncology (ICD-O) and the SystematizedNomenclature of Medicine (SNOMED) Central odontogenic fibroma 932110,peripheral odontogenic fibroma 932210
8
Histological Classification of Odontogenic Tumours
1,.2
Malignant
1.2.1 Odontogeniccarcinomas 937013 1.2.1.1 Malignantameloblastoma 921013 carcinoma 1.2.1,.2Primaryintraosseous 1.2.1.3 Malisnantvariantsof other odontogenic See note 2 epithelial tumours 927013 Malignant changesin odontogeniccysts 1.2.1.4 r.2.2 Odontogenicsarcomas (ameloblasticsarcoma) 933013 1.2.2.1, Ameloblasticfibrosarcoma 7.2.2.2Ameloblastic fibrodentinosarcoma 9290t3 and ameloblasticfibro-odontosarcoma 8980/3 Odontogeniccarcinosarcoma l at I.Z.J
2
Neoplasmsand Other LesionsRelated to Bone
2.1. 2.1,.I
Osteogenicneoplasms Cemento-ossifyingfibroma (cementifyingfibroma, ossifyingfibroma)
Seenote 3
2.2 Non-neoplasticbone lesions 2.2.1 Fibrous dysplasiaof the jaws dysplasias 2.2.2 Cemento-osseous 2.2.2.1 Periapicalcementaldysplasia (periapicalfibrous dysplasia) dysplasia(gigantiform 2.2.2.2 Florid cemento-osseous cementoma,familial multiple cementomas) dysplasias 2.2.2.3 Other cemento-osseous 2.2.3 Cherubism (familial multilocular cysticdisease of the jaws) . Z.L.+ Central giant cell granuloma 2.2.5 Aneurysmal bone cyst 2.2.6 Solitary bone cyst (traumatic,simple,haemorrhagic bone cyst)
74910
927210 927510
70980 44130 33640 33404
2 Use appropriatetumour codingfrom 1.1above,with behaviourcode/3' 3 Ossifyingfibroma926210, cementifyingfibroma927410'
fibroma is recommendedfor cemento-ossifying 926210
HistologicalClassification of OdontogenicTumours L.J
9
Other tumours
2.3.1 Melanotic neuroectodermaltumour of infancy (melanoticprogonoma)
3
9363t0
Epithelial Cysts
3.1 Developmental 3.1.1 Odontogenic 3.1.1.1 "Gingival cysts"of infants(Epsteinpearls) 3.1.1.2 Odontogenickeratocyst(primordialcyst) 3.1.1.3 Dentigerous(follicular)cyst 3.1,.1.4Eruption cyst 3.1.1.5 Lateral periodontalcyst 3.1,.1,.6Gingival cyst of adults 3.7.7.7 Glandularodontogeniccyst;sialo-odontogenic cyst 3.1.2 Non-odontogenic 3.7.2.1 Nasopalatineduct (incisivecanal) cyst 3.1.2.2 Nasolabial(nasoalveolar)cyst 3.2 Inflammatory 3.2.1 Radicularcyst 3.2.7.7 Apical and lateral 3.2.1,.2Residual 3.2.2 Paradental(inflammatorycollateral, mandibular infected buccal) cvst
26540 26530 26560 26550 26520 26540 26520 26600 26500
43800
26520
Definitions and ExplanatoryNotes
1 Neoplasmsand Other Tumours Related to the Odontogenic Apparatus
1.1 Benign 1.1.L Odontogenic Epithelium without Odontogenic Ectomesenchyme 1.1.1.1Ameloblastoma A benign but locally invasivepolymorphic neoplasm consistingof proliferating odontogenicepithelium, which usually has a follicular or plexiform pattern, lying in a fibrous stroma. Most ameloblastomasoccur asintraosseousgrowthsarisingfrom remnantsof odontogenicepithelium, although as they enlargethere may be secondaryfusion with the oral epithelium. Usually the ameloblastomasare diagnosedin the 4th and 5th decadesof life, except the unicystic variety, which is usually found in the 2nd and 3rd decades. Over 80% of ameloblastomasoccur in the mandible and the remainder in the maxilla. In the mandible, about 70oh arein the molar region and the ascendingramus, 20"/" in the premolar region, and l0% in the incisorregion. Radiographically, the ameloblastoma may show considerable variation. The typical picture is of a multilocular destructionof bone (Fig.7), but unilocular ameloblastomasalso occur. Embedded teeth may be presentin a variety of relationshipsto the tumour. Histologically, the ameloblastomaoccurs in two main patterns: follicular and plexiform. However, not infrequently both patterns are presentin the sametumour.
72
Definitions andExplanatory Notes
In the follicular pattern (Fig.8) the tumour epithelium is in the form of more or lessdiscreteislands.Theseconsistof a centralmass of polyhedral cells, or loosely connected angular cells resembling stellate reticulum, surrounded by a layer of cuboidal or columnar cellsresemblinginternal dental epithelium or preameloblasts.Commonly, cystsform within the epithelialislands(Fig.9). In the plexiform pattern (Fig.10) the tumour epithelium is arranged as a network which is bounded by a layer of cuboidal to columnar cells and includescells resemblingstellatereticulum. The latter are often lessnumerousthan in the follicular type. Cyst formation occursbut is usually due to stromal degenerationrather than to a cysticchangewithin the epithelium. Unicystic Ameloblastoma.Three histologicalvariants of the unicystic ameloblastomahave been described.In the first, a relativelyinnocuousepithelial lining may, in parts, show transformation to one with cuboidal or columnar basalcells with hyperchromaticnuclei, nuclearpalisadingwith polarization,cytoplasmicvacuolizationwith intercellular spacing,and subepithelialhyalinization. In the second variant the cystlining is similar to that of the first (Fig. 11a), but a localizednodule arisesfrom part of this lining and projects into the lumen of the cyst. The nodule comprisesodontogenic epithelium with a plexiform pattern resembling that seen in the plexiform ameloblastoma(Fig.11b). This variety is sometimesreferred to as the plexiform unicysticameloblastoma.In the third variety, sometimes referred to as mural ameloblastomq somepart of the wall of the cyst is infiltrated by typical plexiform or follicular ameloblastoma. Sectioningat many levelsis essentialto ascertainthe presence of mural involvement. The first and secondvariants appear to require nothing further than enucleation,whereasin the third variant there may be infiltration of adjacentbone as in other forms of ameloblastoma. The diagnosisof unicysticameloblastomais made histologically, and cannot be predicted preoperatively on clinical or radiographic grounds. Cellular variants of the two main patternsof ameloblastomaare: a) Acanthomatous(Fig.12). This term is applied when there is extensivesquamousmetaplasia,sometimeswith keratinformation, within the islandsof tumour cells.Usuallythe generalpattern of the tumour is that of the folliculartype.This varietymust be dis-
Tumours 13 Odontogenic tinguishedfrom the squamousodontogenictumour (page 14),in which the peripheral cells are flat rather than columnar. b) Granularcell type (Fig.13).Ameloblastomassometimesshow a granular transformation of groups of the epithelial cells. Occasionally,a tumour is seenin which almost all of the epithelium is of this type, and when the granular cell changeis extensivethe tumour is referred to asthe granular cell type. The cellsare large and may be cuboidal, columnar or rounded. Their bulky cytoplasm is filled with acidophilic granules,which resemble lysosomesultrastructurallyand histochemically. It should be noted that, in a variety of other lesionswhich contain odontogenicepithelium, a granular changemay be seenin some of the epithelialcells. Other Variations. In any ameloblastoma,but especiallyin the follicular type, there may be marked hyalinization of the connective tissueadjacentto the epithelium(Fig.l ). The stroma of ameloblastomasusuallyconsistsof relatively acellular loose connectivetissue.Sometimesit is more collagenous,and may be frankly desmoplasticwith small nests and strandsof odontogenic epithelium. This has been described as the desmoplastic ameloblastoma (F ig. 15). Rarely, an ameloblastomamay show a predominantly basaloid pattern (Fig. 16), and this type of tumour is sometimesreferred to as a basalcell ameloblastoma.When a basalcell type of growth occurs in the jaws,specialcareis necessary to distinguishbetweenthis type of ameloblastomaand an intraosseousadenoid cysticcarcinoma. Sometimesan ameloblastomawill show a limited amount of dystrophic mineralization.This occurswithin the epithelium and should be distinguishedfrom the mineralized massesin the calcifying epithelial odontogenictumour, and from the dental hard tissueformation in the adenomatoidodontogenictumour and other lesions. In most ameloblastomaskeratinizarion is absentor limited. Occasionallythere is more extensivekeratinization (keratoameloblastoma) and in a very rare variant (papilliferouskeratoameloblastoma) some microcystsare lined by parakeratinizedepithelium and contain keratin, whilst others have a non-keratinizedepithelium with a p a p i l l i f e r o upsa t t e r n( F i g s 1. 7 .l 8 ) . As indicated earlier. most ameloblastomasarise from intraosseousresiduesof odontogenicepithelium. However, some ameloblastomas(peripheralameloblastoma)appearto arise directly from
14
Definitions and Explanatory Notes
the surfaceepitheliumor from residuesof the dental lamina lying outsidethe bone (Fig.19). It is also generallyagreedthat ameloblastomasmay also arise as a resultof a neoplasticchangein the wall of a non-neoplasticodontogeniccyst,but opinions differ regardingthe proportion of tumours that arise in this way. Figure 20 illustratesthe developmentof an ameloblastomain a dentigerouscyst. Although the above list of types, or variants, of ameloblastoma gives the main histological patterns that may be encountered, it should be noted that, with the exception of the unicystic and the peripheral lesions and the desmoplasticameloblastoma,there appear to be no consistentvariations in clinical behaviour associated with thesepatterns. In general,thesetumours tend to spreadthrough the cancellous bone (Fig.21).They may causeresorptionof compactbone but do not infiltrate the Haversiancanals. peripheralameloblastomas Unicysticameloblastomas, and possiblydesmoplastic ameloblastomas havelower recurrenceratesthan other ameloblastomas. l.l.LZ SquamousOdontogenicTumour A benign but locally infiltrative neoplasm consisting of islands of well-differentiatedsquamousepitheliumin a fibrous stroma. The epithelial islandsoccasionallyshowfoci of centralcysticdegeneration. The squamousodontogenictumour probably arisesfrom residues or derivativesof the dental lamina or from the restsof Malassez. The tumour has been found from the 2nd to the 7th decadesof life, with most occurring in the 3rd. There is no sex predilection,the maxilla and mandible are equally affected,and in someinstancesthe lesion is multicentric. Most caseshave shown a unilocular radiolucency. The main histologicalfeatures are islandsof well-differentiated squamous epithelium set in a mature connective tissue stroma (Fig.22).Theseepithelial islandshave a peripheral layer of flattened or cuboidal cells,and lack the columnar cells that are typical of the ameloblastoma.In about half of the casesthere are microscopicfoci of degenerationand/or calcified areaswithin the tumour islands. Someof the caseshave an aggressiveclinicalbehaviour,but it appearsthat curettageis the treatmentof choice,and there havebeen few recurrences.
Tumours 15 Odontogenic 1.1.L.3Calcifying Epithelial OdontogenicTumour (Pindborg Tumour) A locally invasiveepithelialneoplasmcharacterizedby the development of intraepithelialstructures,probably of an amyloid-like nature, which may becomecalcified and which may be liberatedas the cells break down. The calcifying epithelial odontogenic tumour has been found with approximately the same frequency in the 4 decadesbetween the agesof 20 and 60 years.In two-thirds of the casesthe mandible is affectedand in one-third the maxilla. The prevalencein the molar region is three times that in the premolar region,whereasin the other sitesof the jaws there is a fairly even distribution. Among extraosseouscasesthere seemsto be a predilection for the anterior region. Most of these tumours are intraosseous,and in about half of the casesthe lesion hasbeen associatedwith an uneruptedor embeddedtooth or teeth. The calcifying epithelial odontogenic tumour most commonly presentsas a painlessmassthat hasbeen slowly enlarging. The characteristicradiographic appearanceis of an irregular radiolucent area, containing radiopaque masses of varying size which tend to be located closeto the crown of the unerupted tooth (Fig.23).At the peripherythe radiolucentzone may or may not be clearly demarcatedfrom the normal bone. Histologically,the tumour showsa considerablevariation. There are sheetsor strandsof polyhedral epithelial cells which have welldefined cell borders and which often show distinct intercellular bridges (Fig.24), and a fibrous stroma that may show degenerative changes.There is usually pleomorphism of the tumour epithelium (Fig.25);giantnuclei,multinucleatedcellsand cellswith prominent nucleoli are often a feature of the epithelium, but mitosesare rarely seen.Variants showinga preponderanceof clear cellshave alsobeen reported. Within the sheetsof tumour cellsare rounded, acidophilic, homogeneousmasseswhich commonly calcify and may show Liesegang rings (Fig.26), although in a few instancesno calcificationsare found. Special staining techniques,especiallythioflavine T, show that the homogeneousmaterial gives reactions similar to those of amyloid (Fig.27). There is some controversy as to the nature of the amyloid-like material:whether it is a degenerationproduct or is activelysecreted. The surroundingepithelial cellsmay degenerate,with the result that
l6
Definitions and Explanatory Notes
the acidophilicand mineralizedmassesare liberated.The stroma may containstronglybasophilicbodies,which are irregularor angular and which sometimesfuse to form complex masses. In the peripheral or extraosseoustype the neoplasticepithelium appearsto be lessactive (Fig.28), and there are fewer foci of calcificationthan in the intraosseous type. In a few tumours, part of the lesion has the pattern of the calcifying epithelial odontogenictumour and part has the pattern of the adenomatoidodontogenictumour. 1,.1,.L4Clear Cell OdontogenicTumour A benignbut locally invasiveneoplasmoriginatingfrom odontogenic epitheliumand characterizedby sheetsand islandsof uniform, vacuolatedand clear cells. This neoplasmhas been describedonly recentlyand few cases have been published;it is therefore too early to give a comprehensivepicture. The clear cell odontogenictumour probably arisesfrom residues or derivativesof the dental lamina or from rests of Malassez.It occursas a centraltumour in eitherjaw, in the form of a radiolucent lesion often with poorly defined margins. The main histologicalfeatures are sheets,strandsand islandsof uniform vacuolated,clear or finely stippled cellswithout evidenceof glandular differentiation (Fig.29).Many tumour cells contain abundant glycogengranules.Ultrastructurally, many cells exhibit prominent vacuolizationand a paucity of cytoplasmicorganelles.The mature fibrous stroma is scanty,and there is no evidence of amyloid depositionor calcification. The tumour has some similarity in appearance to clear cell adenocarcinoma.It seemsto be more locally aggressivethan ameloblastoma. 1.1.2 Odontogenic Epithelium With Odontogenic Ectomesenchyme, With or Without Dental Hard Tissue Formation Ameloblastic Fibroma and Related Lesions Neoplasms composed of proliferating odontogenic epithelium embeddedin a cellular ectomesenchymal tissuethat resemblesthe dental papilla, and with varying degreesof inductivechangeand dentalhard tissueformation.
Odontogenic Tumours 11 There is a variety of lesionsthat consistsof a disorderly mixture of odontogenic epithelium and odontogenic ectomesenchyme. Some are developmental anomalies (see complex and compound odontomata):in their later stagesthesewill show inductive changes and lay down increasing amounts of dental hard tissuesuntil the growth of the lesion is completed. Other lesions, grouped here under the heading 'ameloblastic fibroma and related lesions', are benignneoplasms.All of theseare rare, and until more experience hasbeen gainedit may be worthwhile separatelyidentifying the differing patterns or types,even though someof thesemay later prove to be nothing more than stagesin the evolution of a single type of tumour. These neoplasmstend to occur in children. As developingodontomata are also usually found in children, specialcare is needed to distinguish such self-limiting developmental anomalies from the neoplasmsdescribedhere. I.1,.2.1Ameloblastic Fibroma This tumour usually occursin a much younger age group than does the ameloblastomaand is not commonly seen in individuals over 21.yearsof age. Ameloblastic fibroma shows a well-defined cystic radiolucency, usually in the premolar-molar region of the mandible, and radiographic differentiation from ameloblastomamay be impossible. The epithelial componentis usuallyin the form of strandsand islands,often consistingof a peripheral layer of cuboidal or columnar cells which may enclosea small number of cells resemblingstellate reticulum (Fig.30). Cyst formation within the epithelium is not common, and the cystsremain small.In sometumours the epithelial cells are mainly rounded or cuboidal and arrangedin slenderstrands The connectivetissuecomponent is much more cellular than in ameloblastoma;the cells are rounded or angular, and there is little collagen(Fig.31).There may be a narrow cell-freezone bordering the epithelium, and sometimesjuxtaepithelial hyalinization of the type seenin the ordinary ameloblastoma.Occasionallythe hyalinizationis more diffuse. In a few instancesa variable proportion of the stromal cells exhibit a finely granular cytoplasm,and such tumours are sometimes termed granular cell ameloblasticfibroma. There is evidence that both the epithelial and the connective tissuecomponentsof ameloblasticfibroma are neoplastic.
18
Notes Definitions andExplanatory
1.1.2.2 Ameloblastic Fibrodentinoma (Dentinoma) and Ameloblastic Fibro-odontoma Lesions similar to ameloblasticfibroma, but also showing inductive changesthat lead to the formation of dentine,and, in ameloblastic fibro-odontoma, enamelas well. Radiographically, ameloblastic fibrodentinoma appears as a well-defined radiolucency containing varying amounts of radiopaque material. The epithelium is usually in the form of slender strandsconsisting of no more than a doublelayer of roundedor cuboidalcells,and much of the connectivetissuemay resemblethat of the dental papilla. In addition, a poorly organizeddentine is deposited(Fig.32); strands of the odontogenic epithelium are closely associatedwith this dentine and some may become incorporated. Usually the dentine is poorly mineralized, and it contains entrapped mesenchymal cellsin addition to the entrappedepithelium. Relatively well-formed tubular dentine is a rare finding, but the margins of the massesof forming dentine often show radially arranged coarsefibre bundles with elongated cells lying between and parallel to the bundles (Fig.32). Most ameloblasticfibrodentinomasoccur within bone, but a few lie outside, and occasionallythe contained epithelium may have been derived directly from the oral mucosa. Ameloblastic fibro-odontoma is similar to ameloblastic fibrodentinoma, with the same associationof odontogenic epithelium and cell-rich mesenchyme,but here the inductive changesare further advancedand enamelis presentin additionto dentine(Fig.33). The radiographic appearance,like that of ameloblastic fibrodentinoma,is of a well-definedradiolucencycontainingvarying amountsof radiopaquematerial (Fig.3a). As in the caseof the other lesionsdescribedin this section,distinction from a developingodontoma is important but may be difficult. In addition to the histological features,careful considerationmust be given to the age of the patient and to the location of the lesion (for example, if it is directly overlying the crown of an unerupted tooth in a young subject,it is likely to be a developingodontomarather than a neoplasm). 1.1.2.3 Odontoameloblastoma A very rare neoplasmwhich includeso donto genic ecto mesenchy me, in addition to odontogenicepitheliumthat resembles an ameloblasto-
Tumours 79 Odontogenic ma both in structureand in behaviour.Becauseof thepresenceof the odontogenicectomesenchyme, inductivechangestakeplace leadingto theformation of dentineand enamelin parts of the tumour. Radiographicallythe tumour presentsas a radiolucencysimilar to that of an ameloblastoma,but within which mineralizedtissuecan be detected. Histologically the tumour epithelium is typical of an ameloblastoma,but in addition to fibrous stroma there is a variable amount of typically cellular odontogenicectomesenchyme(Fig.35), and both dentine and enamelwill be formed. 1.1.2.4Adenomatoid OdontogenicTumour A tumour of odontogenic epithelium with duct-like structuresand with varying degreesof inductive changein the connectivetissue.The tumour may bepartly cystic,and in some casesthe solid lesion may be present only as massesin the wall of a large cyst. It is generally believedthat the lesionis not a neoplasm. The tumour is seenmore frequently in female patients,it usually occursin the 2nd decadeof life, and presentsasa slow-growing,painlessswelling.The maxilla is involved nearly twice asfrequently asthe mandible, the anterior part of the maxilla, especiallythe canine region, being the most common site. The tumour is commonly associated with an uneruptedtooth and may closelysimulatea dentigerous cyst both radiographically (Fig.36 a) and at operation, but in some casesthe presence of calcified material within the adenomatoid odontogenictumour may be a usefuldiagnosticfeature(Fig.36b). Histologically,the tumour may be solid or there may be more or lessextensivecyst formation (Fig.37). The epithelium is in the form of whorled massesof spindle cells as well as sheetsand plexiform strands.Rings of columnar cells give rise to a duct-like appearance (Fig.38),but suchstructuresmay be scanty.Betweenopposingrows of columnar cellsthere is often an acidophilicmaterial that is usually periodic acid-Schiff (PAS) positive. Immunohistochemicalstudies have shown this to be basementmembrane-likematerial. The connective tissue component includes varying amounts of acidophilic hyaline material, often containing strandsof entrapped epithelium. This hyaline material appearsto be dysplasticdentine (Fig.39),and occasionallya tubular pattern is seenin some areas. Very rarely the formation of enamel matrix has been observed,and amyloid-like material may also be present. Calcification is sometimes seenand may be extensive.
20
Notes Definitions andExplanatory
The adenomatoid odontogenic tumour is usually encapsulated and is readilyenucleated. L.I.2.5 Calcifying OdontogenicCyst A cystic lesion in which the epithelial lining shows a well-defined basal layer of columnar cells,an overlying layer that is often many cells thick and that may resemblestellatereticulum, and massesof 'ghost'epithelialcellsthat may be in the epithelialcystlining or in the 'ghost' epithelial cells may become calcified. .fibrous capsule. The Dysplasticdentinemay be laid down adjacentto the basallayer of the epithelium,and in someinstancesthe cystis associatedwith an areaof more extensivedentalhard tissueformation resemblingthat of a complex or compound odontoma. The lesion is most commonly found in the 2nd decade of life, with an almost equal sex distribution and a similar incidencein the mandibleand the maxilla. Radiographically, the lesion appears as a well-defined radiolucencycontainingvarying amountsof radiopaquematerial (Fig. a0). Calcifying odontogeniccyst usually occurswithin bone but may also occur in the soft tissuesof the tooth-bearing area. Parts of the lesion often bear a striking resemblance to an ameloblastoma(Fig.41) and previouslymost caseswere diagnosed as atypical ameloblastomas.'Ghost' epithelial cells (Figs.41.,42), often calcified like those seenin pilomatrixoma, are one of the most distinctivefeaturesof the calcifyingodontogeniccyst,although such cellsmay also occur in the ameloblastomaand in certain other odontogenicepithelialIesions. Various stains,e.g. Goldner stain, van Gieson, and fluorescence microscopyafter stainingwith rhodamine B (Fig.43), may be useful in distinguishing between the ghost cells and other acidophilic masses.The stainingreaction of the ghostcellssuggeststhat they are keratinizing,and they are entirely thioflavine T-negative. The cyst wall showsareaswith more or lessextensiveproliferation, which may extendinto the cystcavity.As indicatedearlier, dental hard tissueformation may be minimal or extensive(Fig.aa). Most lesionswith the featuresdescribedaboveappearto be nonneoplastic.An exceptionis when the lesion also has ameloblastomalike areas.Suchtumours may have an infiltrative pattern of growth. The terms dentinogenicghost cell tumour or odontogenicghost cell tumour have been proposed for a predominantly solid lesion with
OdontogenicTumours
2I
features of ameloblastoma, ghost cells and dentinoid. This tumoul
usually occursin older Patients. There is a rare variant of calcifying odontogenic cyst in which melanin forms in the ePithelium. I.1.2.6 Complex Odontoma A malformation in which atl the dental tissuesare represented,individual tissuesbeing mainly well formed but occurring in a more or lessdisorderly pattern. The lesion occursmost commonly in the premolar or molal region. The active growth phaseis during the formation of the dentiiion, and those lesionsthat causeexpansionof the bone are usually diagnosedduring the first 2 decadesof life. Smaller lesionsmay be an incidental radiographicfinding in adults. Radiographically,the lesion commencesas a well-definedradiolucency in which there is progressivedeposition of radiopaquematerial of a nodular nature (Fig.a5). Although complex odontoma consistsprimarily of a disordered mixture of dental tissues (Fig.46), some examples include betterordered. tooth-like structures.As already mentioned, during its development complex odontoma may be difficult to distinguishfrom ameloblasticfibroma or fibro-odontoma, and evenwhen growth has been completed,residuesof the odontogenicepithelium may still be identifiable (Fig.a7). Although the growth is self-limiting,the lesion may recur if it is incompletely removed at its early, predominantly soft tissue,stage. 1.L2.7 Compound Odontoma A malformation in which alt the dental tissuesare representedin a more orrlerly pattern than in the complex odontoma, so that the lesion consistsof many tooth-likestructures.Most of thesestructuresdo not morphologically resemblethe teeth of the normal dentition, but in eachone enamel,dentine,cementumand pulp are arrangedos in the normal tooth. The distinction between compound and complex odontomas is arbitrary, being based on a preponderanceof well-organizeddenticles as against a preponderance of disorganized dental tissues rather than on any absolute difference. An example of the radiographic appearanceis shown in Fig' 48 a, and Fig.48b showsthe contents of the samelesion separatedinto its individual denticles.
22
Definitions and Explanatory Notes
1.1.3 Odontogenic Ectomesenchyme With or Without Included Odontogenic Epithetium 1.1.3.1 OdontogenicFibroma A fibroblastic neoplasmcontainingvaryingamountsof apparentlyinactiveo dontogenicepithelium. This neoplasmis relatively rare and controversyexistsas to the conceptand the definition.At presentthe term 'odontogenicfibroma' appearsto be appliedto varioustypesof lesion.one resembles dental follicle both in location and in structure;tissueof this type is referred to later under the heading ,,Myxoma". Another and lesscommon lesion is composedof a more cellular fibrous tissue,containingislandsand strandsof odontogenicepithelium (Fig.49).However,the epithelialcomponentmay be so ub.rndant that it is temptingto considerthe lesionan epithelialtumour. This secondtype, which is usually encapsulatedor sharply demarcated, may contain varying amounts of hard tissue resemblingdysplasticcementumor bone (Fig.50). occasionally,the fibrous component of an odontogenicfibroma will show variable numbers of cells with an acidophilic granular cytoplasm.The term granular cell odontogenictumour is sometimes applied to tumours of this type, and to ameloblasticfibromas showing similar granular cells (see page 77). Further subdivisionof this group may become necessary,but at present criteria have not been agreed and differencesin behaviour havenot been established. Not all central fibromas of the jaws contain epithelium, and in some the epithelial component is sparse.In the absenceof epithelium, the diagnosisof odontogenic fibroma should be made with caution. Extraosseouslesions exist (peripheral odontogenicfibroma) that have similar patterns to those describedabove.Sometimesthe proliferation of odontogenicepithelium is so marked (Fig.51) that it may be difficult to distinguishfrom a peripheral ameloblastoma. There is also a distinctive gingival lesion, composedof strands and islands of epithelium in a mature fibrous stroma (Fig.52), that rarely exceeds1 cm in diameter and does not causedestruction of the underlying bone. This lesion appearsto be non-neoplastic,and is known as odontogenicgingival epitheliathamartoma.
Tumours 23 Odontogenic 1.1.3.2Myxoma (OdontogenicMyxoma, Myxofibroma) A locally invasiveneoplasmconsistingof rounded and angular cells lying in an abundantmucoid stroma. Radiographically, myxoma commonly shows multiple radiolucent areasof varyingsize(Fig.53a) separatedby straightor curved bony septa ('soap-bubble' appearance).This picture may be indistinguishablefrom that of an ameloblastoma.It may also present as an ill-defined radiolucency. Myxoma of the jaws is a tumour that showslittle encapsulation. It often extendsthrough the bone (Fig. 53b) and into the soft tissues without any well-defined margin, so that complete removal is difficult and recurrencesare common. Growth may be quite rapid and is probably due mainly to the accumulation of mucoid ground substance (Figs.54,55), as mitoses are rarely seen. Atypical nuclei (Fig.56) are occasionallyseen,but thesetumours do not metastasize. Most odontogenicmyxomascontain little collagen,but some contain a moderate amount. often in the form of isolated thick hyalinizedbands.Depending upon the amount of collagen,some of these neoplasms are called myxofibromas. Scattered islands or strands of inactive-looking odontogenic epithelium, occasionally surroundedby a zone of hyalinization,may be found in some of the myxomas. When a tooth fails to erupt, the follicle surrounding the crown may become thickened. Histologically, this thickened follicular fibrous tissue is often myxoid, with an abundant slightly basophilic ground substance,and commonly islandsof odontogenicepithelium are also present (Fig.57). Thus, the thickened follicle may have an appearancesimilar to that of odontogenicfibroma or myxoma, but if the tissueis from a relatively narrow zone surrounding the crown of an unerupted tooth it is likely to be a non-neoplasticthickened follicle rather than a fibroma or myxoma. 1.1.3.3Benign Cementoblastoma (Cementoblastoma,True Cementoma) A neoplasmcharacterizedby the formation of sheetsof cementumlike tissuecontaininga large number of reversallines and being unmineralizedat theperiphery of the massor in the more activegrowth area. The benign cementoblastoma occurs almost always in the premolar or molar region, more commonly of the mandible than the
24
Definitions andExplanatory Notes
maxilla, and there is a slight preponderancein males.Most casesare found in the 2nd and 3rd decadesof life. Almost always,the tumour is closelyrelated to and partly surroundsthe root or roots of a single tooth. Radiographically, the tumour is well defined and the central radiopacityis generallysurroundedby a radiolucentzoneof uniform width (Fig.58)representingthe peripheralunmineralizedtissueand the formative cellular layers. Usually, the root of the associated tooth is shortenedby resorption and the tumour hard tissueis fused to the root (Fig.59).In the more maturepartsof the growth the hard tissuecontainsa small number of entrappedcells,and the numerous stronglybasophilicreversallines (Fig.60) give an appearancesimilar to that seenin Paget disease.The soft tissuecomponent consistsof vascular,loose-texturedfibrous tissuecontaininglarge,deeplystaining cells with a single nucleus and multinucleated cells. At the periphery (Fig.61) and in other areas of active growth, extensive sheetsof unmineralizedtissuemay be seenwhich show no remodelling. The newly formed unmineralizedtissueat the periphery is often arrangedin slenderradiatingcolumns(Fig.61). The lesion appearsto be a benign neoplasmand is readily enucleated. Histologically, however, it may sometimes resemble an atypical osteosarcoma,and may also be difficult to distinguishfrom osteoid osteoma or osteoblastoma.However, it has the distinctive relationshipto the root of a tooth and doesnot show the tendencyto recur that has been found with osteoblastoma.
1.2 Malignant L.2.1OdontogenicCarcinomas Most carcinomasfound in the jaws have invaded from lesionsof the oral mucosa. Some may be metastatic deposits from primary tumours in distant sites. Primary endosteal carcinoma of the jaws arisesfrom epithelial residuesin the jaws. As such epithelial remnants are of odontogenicorigin, primary endostealcarcinomasof the jaws are referredto asodontogeniccarcinomas. Odontogeniccarcinomasmay developby malignant transformation of an ameloblastomaor directly from residuesof odontogenic epithelium following tooth development (so-called primary intraosseouscarcinoma) or from the epithelial lining of odontogenic
Tumours 25 Odontogenic cysts.Subclassificationof odontogenic carcinomasinto these three categoriesis probably of academicand researchinterest only: from a clinicopathologicalpoint ofview they are best consideredtogether. Only by careful analysisof well-documentedexamplesof eachof the three categorieswould it be possibleto determinewhether there are any differencesin their prognoses. 1,2.L1 Malignant Ameloblastoma A neoplasmin which thepattern of an ameloblastomaand cytological featuresof malignancyare shown by the primary growth in theiaws and/or by any metastaticgrowth. Tumours meeting thesecriteria may ariseas a resultof malignantchangein a pre-existingameloblastoma, or possibly as a primary malignant ameloblastomanot precededby an ordinary ameloblastoms. The histologicalfeatures of a primary and a metastatictumour are shown in Figs.62-64. The term'malignant ameloblastoma'should not be applied to an ordinary ameloblastomathat endangerslife through direct extension of the growth involving vital structures(e. g. extensioninto the baseof the skull from a tumour of the maxilla). Special care is needed in distinguishing between malignant ameloblastomaand intraosseoussalivarygland tumours. 1.2.1.2Primary IntraosseousCarcinoma A squamouscell carcinomaarising within the iaw, having no initial connectionwith the oral mucosa,and presumably developingfrom residuesof the odontogenicepithelium. Someof the reported casesof primary intraosseouscarcinomaof the jaws have shown histological features of squamouscarcinoma which were indistinguishablefrom squamouscarcinomaof the oral a definitivediagnosismay be immucosa(Fig.65).In suchinstances, radiologicaldata.In other cases, and reliable clinical possiblewithout however,the tumours have a distinctly odontogenicpattern (Fig.66) with basal-typecells forming alveoli or arrangedin a plexiform patternwith palisadingof the peripheralcells.The nuclei of the latter are often orientated away from the basementmembrane.There may be foci of squamousmetaplasiaor keratinizationin thesealveoli,similar varietyof ameloblastoma. to thoseseenin the acanthomatous Within the group of odontogeniccarcinomasit is sometimesdifficult to decidewhether a tumour should be classifiedas a malignant
26
Definitions andExplanatory Notes
ameloblastomaor as a primary intraosseouscarcinoma.If there is histologicalevidenceof a previousameloblastomaat the site. the diagnosisof malignant ameloblastomacan be made with more confidence. These lesions should not be difficult to distinguish from carcinomas arising from salivary tissue (particularly from intraosseous mucoepidermoidcarcinoma). L2.1.3 Malignant Variants of Other OdontogenicEpithelial Tumours whilst malignant ameloblastomasand primary intraosseouscarcinomas are well documented,there is less evidenceavailableconcerning malignant variants of calcifyingodontogeniccyst,calcifying epithelialodontogenictumour and clearcell odontogenictumour. Tumours are known to occur which have features of calcifying odontogenic cyst, including varying numbers of ghost cells, and which also show cytologicalfeaturesand an infiltrative pattern suggestiveof malignancy(odontogenicghostcell carcinoma). Calcifyingepithelial odontogenictumours commonlyshow cellular and nuclear pleomorphism,but thesefeaturesdo not necessarily indicate malignant behaviour with metastaticpotential. 1.2.1.4Malignant Changesin OdontogenicCysts Although it has been suggestedthat keratinizing odontogeniccysts are more likely to becomemalignant than are non-keratinizingcysts, this hasnot been proven. It is clear,however,that malignant change in any form of odontogeniccyst is rare. Figures67 and 68 illustrate epithelialdysplasiain a residualradicularcyst. L2.2 O dontogenic Sarcomas L2.2.1 Ameloblastic Fibrosarcoma(Ameloblastic Sarcoma) A neoplasm with a similar structureto ameloblasticfibroma, but in which the ectomesenchymal componentshows the featuresof a sarcoma. In the past, some of theserare tumours have been reported as 'malignant ameloblastomas'. However,the term 'ameloblasticfibrosarcoma' should be applied to those tumours in which it is the mesenchymalcomponent,and not the odontogenicepithelium, that appearsto be malignant(Figs.69,70).
Neoplasms andOtherLesionsRelatedto Bone 27 1.2.2.2Ameloblastic Fibrodentinosarcoma and Ameloblastic Fibro-odontosarcoma Neoplasmssimilar to ameloblasticfibrosarcoma, but in which limited amounts of dysplastic dentine (dentinoid) have formed, and, in ameloblasticfibro-odontosarcoma,enamelas well. In the rare ameloblasticfibro-dentinosarcomaand fibro-odontosarcoma,parts of the odontogenicepithelium have exertedsufficient inductive influence to result in dentine formation, followed, in the odontosarcoma,by the deposition of enamel matrix, even though the ectomesenchymalcomponent is sarcomatous.The presenceof induceddentine and enameldoesnot appearto alter the basicnature of this neoplasm.Figure 71 showsthe hard tissueformation and Figure 72 the sarcomatousmesenchymalcomponent. 1.2.3 Odontogenic Carcinosarcoma A very rare neoplasm, similar in pattern to ameloblasticfibrosarcoma, but in which both the epithelialand the ectomesenchymal componentsshow cytological features of malignancy.
2 Neoplasmsand Other Lesions Related to Bone
2.1 OsteogenicNeoplasms 2.Ll Cemento-ossifying Fibroma (Cementifying Fibroma, Ossifying Fibroma) Demarcated or, rarely, encapsulatedneoplasmsconsisting of fibrous tissuecontainingvarying amountsof mineralizedmaterialresembling bone and/or cementum. Theselesionsmay be difficult to distinguishfrom fibrous dysplasia, but they are sharply demarcatedor rarely encapsulatedmasses that behaveasbenignneoplasms. Radiographically,theseneoplasmsare well defined and contain varying amounts of radiopaque material (Fig.73). The sharply defined character of the lesions is also apparent at operation (Fig.74), and histologically the presenceof this demarcation from
28
DefinitionsandExplanatory Notes
the adjacenttissuesis an important feature in distinguishingthe tumours from fibrous dysplasia(Fig.75). In the latter condition it is common to find that the metaplasticbone of the lesion is fused directly to the surrounding bone. In contrast, the hard tissues of cemento-ossifyingfibromas do not fuse with the surrounding bone, except,occasionally,in limited areas. Referencewas made earlier to the difficulty of distinguishingbetween bone and cementum,and to the fact that both cementumand part of the bone of the jaws have a similar origin. Thus, the lesionsin the cemento-ossifyingfibroma group may be regardedas forming a continuousspectrum.The soft tissuecomponentis a cellular fibrous tissue.Some of the lesions contain rounded or lobulated, strongly basophiliccalcified masses(Fig.76) with only occasionalentrapped cells;these massesresembleatypical cementum.Other lesionscontain trabeculaewith the typical appearanceof metaplasticbone, indistinguishablefrom that seenin fibrous dysplasia(Fig.77).Some tumours in the group contain both cementum-like material and metaplasticbone in varying proportions.However, presentevidence suggeststhat they all behavein a similar manner:unlike fibrous dysplasia,they continue to enlargeuntil removed. The term juvenile (aggressive)ossifyingfibroma is used for an actively growing lesion mainly affecting individuals below the age of 15 years. Juvenile ossifying fibroma consistsof a cell-rich fibrous tissue containing bands of cellular osteoid without osteoblastic rimming togetherwith trabeculaeof more typical woven bone. Small foci of giant cells may be present, and in some parts there may be abundant osteoclastsrelated to the woven bone. Usually no fibrous capsule can be demonstrated, but like the ossifying fibroma described above (and unlike fibrous dysplasia), juvenile ossifying fibroma is well demarcatedfrom the surroundins bone.
2.2 Non-neoplasticBone Lesions 2.2.1 Fibrous Dysplasia of the Jaws lesionoccurring mainly A benign,self-limitingbut non-encapsulated in young subjects,usually in the maxilla, and showing replacementof the normal bone by a cellular fibrotts tissuecontaining islands or trabeculaeof metaplasticbone.
Neoplasms andOtherLesionsRelatedto Bone 29 Radiographically,the appearancedependsupon the stageof the lesion. In the osteolytic stage there is an ill-defined radiolucency (Fig.78), and in the later stagesthe progressivedeposition of Ieappearance(Fig.79)'There is sionalbone resultsin a ground-glass no sharp line of demarcationbetween lesional tissueand surrounding bone. The histological pattern of the lesion varies with its age and stage of development.In the early lesion the tissue is fibroblastic, richly cellular (Fig.80), and often shows a whorled pattern; there may be little bone. As the lesion progresses,the amount of bone increases(Fig.81) and gradually the fibrous tissue decreasesboth in amount and in cellularity. The newly formed bone at the periphery fuses directly with the surrounding bone (Fig.82), so that there is no capsuleor line of demarcation except in limited areas. There may be cyst formation, and at some stages osteoclasts may be fairly numerous,but it is unusual to see substantialcollections of multinucleated giant cells other than those directly related to the bone trabeculae.Some cementum-liketissue may be deposited, but cartilage is rarely, if ever, seen in fibrous dysplasiaof the jaws. Although fibrous dysplasiais self-limiting,the affectedarea does not return to normal. Radiographic change persists,and although the metaplasticbone of the active lesion will gradually be replaced by lamellar bone, this may have an abnormal and distinctive arrangement.The trabeculaeof lamellar bone are slender,they tend to run parallel to one another, and they lie abnormally close together in a fibrous stroma that remains moderately cellular (Figs.83,84). The term osseouskeloid has sometimesbeen used for lesionsof this type. Fibrous dysplasiaof the jaws is usually a monostotic lesion, but may occasionallybe part of a polyostotic process. 2.2.2 Cemento-osseous Dysplasias There is a variety of jaw lesions that are characterizedhistologically by the presenceof cementum-like tissue, and which (unlike cemento-ossifyingfibroma) appear to be dysplasiasrather than dysplasiaspresent both clinineoplasms.These cemento-osseous cally and histopathologicallyin a number of forms, and the relationship between them is uncertain; some authorities regard them as forming part of a continuous spectrum,and others regard them
30
Definitions andExplanatory Notes
as separate entities. Whilst recognizing these differing points of view, in the context of the presentpublication it is useful to describe certain more or lesswell-defined clinicopathologicalpresentations, without rejecting the possibility that they may be related to one another. 2.2.2.1 PeriapicalCemental Dysplasia (PeriapicalFibrous Dysplasia) A non-neoplasticlesionaffectingtheperiapical tissuesof one or more teeth,and with histological features similar to those of the lesions of the cemento-ossifying fibroma group, but without a sharply defined marSrn. This lesionis most easilyrecognizedwhen it affectsthe periapical areasof severalteeth (Fig.85),which may be adjacentto one another or in different parts of the jaws. A common presentationis in the mandibular incisor region in middle-agedwomen. Mainly fibroblastic in the early stages,there is progressivedeposition of metaplasticbone,cementum-liketissueor both (Fig.86).Each periapical lesionis self-limiting,rarely exceeds1 cm in diameter,and ultimately becomesa densemineralizedmass(Fig.85). 2.2.2.2 Florid Cemento-osseous Dysplasia (Gigantiform Cementoma,Familial Multiple Cementomas) Lobulated massesof dense, highly mineralized, almost acellular cemento-osseoustissuetypically occurring in severalparts of thejaws. Black persons are affectedmore commonly than white, and sometimesthereis a familial distribution. These radiographically dense masses (Fig.87) are sometimes distributed more or less symmetrically in the jaws, which supports the view that they representsomeform of dysplasiaor developmental anomaly.However, the massesmay attain a considerablesizeand cause expansion of the jaw. Histologically, the lesion consistsof large sheetsor fused globulesof cemento-osseous tissue(Fig.88), sometimesstrongly basophilic,which may be fused to the roots of one or more teeth or may lie separately.When fused to the roots, florid cemento-osseous dysplasiamust be distinguishedfrom hypercementosis,in which abnormal amounts of cellular cementum are laid down in an orderly manner on the root of the tooth. It should be noted that massessimilarto thoseof florid cemento-osseous dysplasia may form in the jaws in somecasesof Pagetdisease.
Neoplasms andOtherLesionsRelatedto Bone 31, 2.2.2.3 Other Cemento-osseous Dysplasias Lesions which share some of thefeatures of periapical cementaldysplasia and,/orflorid cemento-osseous dysplasia,but do not have their characteristicclinicopathological patterns of presentation.
2.2.3 Cherubism (FamilialMultilocularCysticDiseaseof the Jaws) A benign, self-limiting condition in which the lesional tissueconsists of vascular fibrous tissue containing varying numbers of multinucleatedgiant cells arranged diffusely or focally. The lesionsoccur in children, sometimesearly in childhood, and usuallyshow a familial tendency.They affect one or more quadrants of the jaws, forming radiolucent,usually multilocular, areasand expandingthe bone (Figs.89,90). The bone lesions are more active in younger patients;after the age of about 12 years activity usually diminishes and finally the lesionsbecomeinactive.Consequentlythe histologicalfindingsvary. The more activelesionis cellularwith many giant cells(Fig.91)and may contain multiple foci of extravasatedblood. In somecasesa cuff of acidophilic van Gieson-positivematerial is seen around the vessels(Fig.92).As activitydiminishesthe lesionaltissuebecomesprogressivelymore fibrous, the number of giant cells diminishes,and new bone is laid down. 2.2.4 Central Giant Cell Granuloma An intraosseouslesion consistingof more or less cellular fibrous tissue containing multiple foci of haemorrhage, aggregations of multinucleatedgiant cells,and sometimestrabeculaeof woven bone forming within the septa of more mature fibrous tissue that may traversethe lesion. Giant cell granulomamay occur in either jaw and at any age.It is seen most commonly, however, in the tooth-bearingarea of the mandible in the 3rd decadeof life. Radiographically,there is an area of bone destructionwhich has a smoothor lobulatedoutline (Fig.93a) and which may be traversed by slenderbony septaresultingin a multilocularpattern (Fig.93b). The radiographicappearancemay thus bear some similarity to that of an ameloblastoma.The histological pattern varies considerably. In some cases,the focal aggregationof giant cells is clear (Figs.94,
32
Notes Definitions andExplanatory
95) and trabeculae of bone often extend between the foci of giant cells(Fig.96).In others,the tissueis loose-texturedand oedematous and the giant cells may show little evidenceof a focal arrangement. Fresh haemorrhageis a frequent feature and depositsof fibrinoid material may also be seen.Haemosiderinmay be scantyor abundant, and mitosesare not uncommon. The lesion can expand the bone and penetratethe cortex, sometimes presentingas a gingival swelling.In theseinstancesthe superficial aspectappearsencapsulated,but on the deeperaspectthe relationship with the bone is irregular. Removal is sometimesfollowed by recurrence,but the lesion is not invasive and does not metastasize.In somevery cell-richareasthe lesionmay resemblea giant cell tumour, whilst other examplescontain a few relatively large blood spaces,though not so large asthosecommonly found in the aneurysmal bone cyst. It may be impossibleto distinguishon histological grounds between the giant cell granuloma,cherubism,and the brown node of hyperparathyroidism. Distinction between true giant cell tumour and giant cell granuloma may be difficult. Comparisonof the giant cellsin giant cell granuloma of the jaws and in giant cell tumours of long boneshasshown that the giant cellsin giant cell granulomastend to be smaller and to contain fewer nuclei. Well-documented true giant cell tumours do occur in the jaws: like the long bone lesionsthey contain larger giant cellswith greater numbersof nuclei.
2.2.5AneurysmalBoneCyst A benign intraosseouslesion,characterizedby blood-filled spacesof varying size associatedwith a fibroblastic tissuecontaining multinucleatedgiant cells,osteoid,and woven bone. Aneurysmal bone cyst of the jaws usually occurs in individuals below the age of 30 years, more often in the mandible than in the maxilla. There is a slight female preponderance. Radiographically,it is a radiolucentlesion,sometimesof a multiloculatedappearance, which balloonsthe cortex (Fig.97). Histologically,there are many large and small cavernousspaces filled with erythrocytes (Fig.98). The spacesare usually contained within a cellular connectivetissuewith fresh and old haemorrhages, which may show organization,numerousmultinucleatedgiant cells, haemosiderin,and slendertrabeculaeof osteoid(Figs.99,100).The
Neoplasms andOtherLesionsRelatedto Bone 33 solid areaswith large numbersof giant cellsand fibroblasts,together with foci of haemorrhageand of haemosiderindeposition,may look very much like giant cell granuloma of the jaws. Other solid areas may have the appearanceof fibrous dysplasia,cemento-ossifying 'hybrid fibroma, and possibly other jaw tumours. These so-called lesions' give support to the view that aneurysmalbone cyst may representsecondarychangein a pre-existinglesion.
2.2.6 SolitaryBone Cyst (Traumatic,Simple,Haemorrhagic BoneCyst) An intraosseouscysthaving a tenuouslining of connectivetissuewith no epithelium. The solitary bone cyst is most often seen during the seconddecade of life, and casesare rarely seenafter the age of 25 years.The most common locations in the jaws are the body and symphyseal areaof the mandible. Radiographically, the solitary bone cyst presents as a welldefinedunilocularradiolucentarea (Fig.101),often with a scalloping of the margin between the roots of the premolars and molars or in areasremote from the teeth. Histologically,the solitary bone cyst has no epithelial lining. The bony walls are covered by a thin, loose-textured fibrous tissue (Fig.102) that may contain multinucleated giant cells and haemosiderin granules. Although sometimes termed a 'traumatic' or 'haemorrhagic' bone cyst, the pathogenesisof this lesion is unknown.
2.3 Other Tumours 2.3.1 Melanotic Neuroectodermal Tumour of Infancv (Melanotic Progonoma) A tumour arising, typically, in the anterior part of the maxilla in an infant under the age of I year. The tumour consistsof varying proportions of two cell types - epithelium-like cells, often arranged in strands, and small, darkly staining lymphocyte-like cells - in a cellular, fibrous stroma.Melanin is found within the epithelium-likecells, and to a lesserextentwithin the lvmphocvte-likecells.
34
Definitions and Explanatory Notes
On the basis of embryological,ultrastructural and biochemical evidenceit is now assumedthat this tumour is derivedfrom cellsof neural crest origin. The lesion may be present as a pigmentedor non-pigmented exophytic gingival tumour or it may be contained within the bone. The area of bone destruction may be traversedby bone septa, and the associateddevelopingteeth are often displaced(Fig.103).The cut surface of the lesional tissue shows pigmentation varying from mottled grey patchesto a uniform deep black. The epithelium-like cells and the lymphocyte-like cells may appear in separateareasof the lesion,though more commonlythey are together(Fig.10a).The may be arrangedin epithelium-likecellsare often pale-staining;they sheets,cords,or duct-likestructures,and the latter may containlymphocyte-likecellswithin the ducts or clefts(Fig.105).Melanin granulesmay be scantyor the cellsmay be heavilyloaded(Fig.106). The appearanceof the lymphocyte-likecellsvariesconsiderably. In some instancesthey resemblesmall lymphocytes,with a dense, rounded nucleusand little cytoplasm(Fig.10a).In other instances the nucleusis larger, with a finer chromatin pattern. At the margins the tumour sometimesextendsirregularlyinto the bone,so that the lesion appears invasive, but recurrence is very rare. Only a few malignantexampleshavebeenreported. A small number of casesof an apparentlyidentical tumour have been reported in the mandible and in severalother parts of the body.
3 Epithelial Cysts
3.1- Developmental 3.1.1 Odontogenic 3.1.1.1 "Gingival Cysts" of Infants (Epstein Pearls) Small cystsarisingfrom epithelialcell restsin the alveolarmucosaof infants. These lesions,which are commonly present at birth, are seldom seenover the ageof 3 months.They are white or yellow nodulesand are found over the future tooth-bearins areaof the alveolarmucosa.
Epirhelialcysts 35 Histologically there is a thin lining of stratified squamousepithelium with flat basal cells and a parakeratinizedsurface.Keratin fills the cystcavity (Fig.107). 3.1.1.2 OdontogenicKeratocyst (Primordial Cyst) A cystarisingin the tooth-bearingareasof thejaws, or posterior to the mandibular third molar, and characterizedby a thin fibrous capsule and a lining of keratinized stratified squamous epithelium usually about five to eight cells in thicknessand generally without rete ridges. This type of cyst is thought to arisefrom the dental lamina or its remnants, or from offshoots of the basal layer of oral epithelium. The stimulus to cyst formation is unknown, but it is not inflammation. The lesionsoccur over a wide agerangewith a peak frequencyin the 2nd and 3rd decadesand a secondpeak in the 5th decade.They are more common in male than in female subjects. The mandible is involved much more frequently than the maxilla. About half of the casesoccur at the angleof the mandible and extend for varying distancesinto the ramus and forward into the body. There is no specialrelationshipto a tooth. Radiographically,the keratocystmay show a unilocular or multilocular pattern and the cysticspacesmay have a smooth or scalloped border(Fig.108). Histologically, the cyst wall is thin unlessthere is inflammation. The basallayer of the epithelium is well defined and is composedof either columnar or cuboidalcells(Fig. 109).The keratinizationof the epithelium is predominantly of the parakeratotictype, but caseswith orthokeratosisare seen.Often the cyst lining has a corrugated surface (Fig.110),and in somespecimensthe epitheliallining in part of the wall becomesdetachedfrom the fibrouscapsule(Fig.111).Occasionally the epithelium shows features of dysplasia.In some odontogenic keratocysts the connective tissue contains islands of epithelium or separate daughter cysts (Fig.112). It inflammation supervenesthe fibrous capsulebecomesthickened, the epithelium developsreteprocesses, andthe keratinizationmay be lost (Fig.113). The pathologist may also receive material aspiratedfrom a suspected keratocyst.Smearsprepared from this material are likely to show squames;becausethese are not freshly shed but have been trapped within the cyst for a considerabletime, they often show partial breakdown and ill-defined margins (Fig. 11a).
36
Definitions andExplanatory Notes
A keratocyst may envelop an adjacent unerupted tooth (envelopmental keratocyst;Fig. 108a). Sometimesa tooth may erupt into the cavity of a keratocyst(follicular keratocyst).Such casesmay be erroneouslydiagnosedasdentigerouscystwith a keratinizing lining. Most keratocystsare isolatedlesions,but similar cystsalso occur aspart of the multiple naevoidbasalcell carcinomaand jaw cystsyndrome. In this condition the keratocysts are commonly multiple (Fig.11s). Odontogenickeratocystshave a marked tendencyto recur. 3.1.1.3Dentigerous (Follicular) Cyst A cyst which enclosesthe crown and is attachedto the neck of an unerupted tooth. It develops by accumulation of fluid between the reduced enamelepitheliumand the crown, or betweenthe layersof the reduced enamelepithelium. Dentigerous cystsare most often found in relation to the mandibular third molar, the maxillary canine and third molar, and the mandibular second premolar. They occur at all agesbut most frequently in the 2nd, 3rd and 4th decades,and more frequently in male than in female subjects. Radiographically,a dentigerous cyst is seen as a well-defined radiolucent area associatedwith the crown of an unerupted tooth (Fig.116). Often the radiolucent area surrounds the crown, but sometimesit lies mainly or entirely to one side.In Fig.117the cyst associatedwith a maxillary canine has been opened to show the attachment at the neck of the tooth. Histologically,the cystwall is composedof a thin layer of connective tissuelined by epitheliumthat may be only two to three cellsthick (Fig.11Ba)and this resemblesthe reduced enamel epithelium. If there is inflammation the epithelium becomesthicker and more squamous. The lining epithelium may include a variable number of mucus-producing cells(Fig.118b)and sometimesalsociliatedcells. In some casesthe cyst lining is keratinized,although generallysuch keratinization is only in limited areas.In the adjacent connective tissue,islandsof odontogenicepitheliumare often seen,and these appearinactive. 3.1.1.4 Eruption Cyst A cyst thqt surrounds the crown of an erupting tooth, liespartly outside the bone, and is lined by non-keratinizingstratified squamous epithelium.
EpithelialCysts 37 The eruption cyst is a form of dentigerouscyst lying in soft tissuesexternal to the bone. Clinically it presentsasa bluish swellingin an area where a tooth will erupt. The histologicalappearanceis shownin Fig.119.The chronicinflammatory infiltrate adjacentto the epithelium is a result of occlusal trauma and leadsto proliferation and thickening of the epithelial lining. 3.1.1.5 Lateral Periodontal Cyst A cyst occurring on the lateral aspector betweenthe roots of vital teeth and arising from odontogenic epithelial remnants, but not as a result of inflammatory stimuli. The lateral periodontal cyst must be distinguishedfrom a collateral odontogenickeratocyst,from a gingival cyst of adults and from a cyst of inflammatory origin lateral to the root of the tooth. The most frequent location is the premolar areaof the mandible, followed by the anterior region of the maxilla. There is a wide age distribution. Radiographsshow a well-definedround or ovoid radiolucentarea,occasionally with a scleroticmargin (Fig.120). Lateral periodontal cystsarisefrom odontogenicepithelium,but preciselyfrom which part is controversial.Reduced enamel epitheIium, remnantsof dentallaminaand cell restsof Malassezhavebeen implicated. The cysts are lined by a thin, non-keratinizing squamous or cuboidal epithelium, ranging from one to five cell layers thick (Fig.121).Nucleiaresmallandpyknotic.Localizedepithelialplaques or thickenings,which may be rounded or flattened, and consistingof fusiform or water-clearcells,are frequently seen(Figs.721,122). The so-calledbotryoid odontogeniccys/ is probably a multilocular variant of the lateralperiodontalcyst(Fig.123). 3.1.1.6 Gingival Cyst of Adults A cystarisingfrom odontogenicepithelialremnantsand involving the gingiva of adults. The cystsare well-circumscribedswellings,usuallylessthan 1 cm in diameter,which occur in the attachedgingivaor interdental papilla and almost alwayson the facial aspect.They are most commonly seenin the canine-premolarregion of the mandible.There may be no radiographic change or only a faint round shadow indicative of superficialbone erosion.
38
Definitions andExplanatory Notes
Their origin is controversial,but remnants of dental lamina and junctionalepitheliumfrom adjacentteeth havebeenimplicated.The lining of the cyst varies from an extremely thin epithelium with one or two layers of flat or cuboidal cells, to a rather thicker stratified squamousepithelium without rete ridges (Figs.124.125).In some cysts, localized epithelial plaques of fusiform or water-clear cells have been described,similar to those found in the lateral periodontal cyst. 3.1..I.7Glandular OdontogenicCyst; Sialo-odontogenicCyst A cystarising in the tooth-bearingareasof thejaws and characterized by an epitheliallining with cuboidal or columnar cellsboth at thesurface and lining crypts or cyst-like spaceswithin the thickness of the epithelium. This type of cyst has been characlerizedonly recently, and few exampleshave been reported. As yet there is no generalagreement are given on the most suitablename for the lesion;two suggestions jaw. It grows slowabove.The lesion ariseswithin the bone of either ly but may reach a considerablesize,and with the larger examples there appearsto be a tendencyto recurrence. The fibrous capsuleis usually free from inflammatory cells.The lining epithelium may be partly squamousand without distinctive features.However, in more or lessextensiveareasthe stratified epithelium has a surfacelayer of acidophiliccuboidal or columnar cells, often forming irregular papillary projections.Thesesurfacecells include a variable number that are ciliated, and similarly variable numbers are mucus-producing.Within the thicknessof the epithelium there may be crypts or cyst-like spaceslined by cells like those seenat the epithelialsurface(Figs.126,127).Mucin may be demonstrablewithin the intraepithelial spacesand within the main cyst cavity. Epithelial plaquesmay be present,similar to those seenin the lateral periodontal cyst and the gingival cyst of adults. Multilocular or botryoid varietiesalso occur. It should be emphasizedthat many types of odontogenic cyst show areasof mucouscell or ciliated cell metaplasia;in the absence of the pattern described above, the presenceof such areas should not lead to the diagnosisof glandularodontogeniccyst.
EpithelialCysts 39
3.1.2 Non-odontogenic 3.1.2.1NasopalatineDuct (Incisive Canal) Cyst A cyst arising from the epithelial residues in the nasopalatine (incisive)canal. Most casesoccur in the 4th, 5th and 6th decades,and there is a three-to-onepreponderancein malesascomparedto females. Radiographically,the cyst is found in the midline of the maxilla as a well-defined round, ovoid or heart-shaped radiolucency (Fig.128).On occlusalradiographsthe cystappearsbehind the inciSOTS.
Histologically,the cyst may be lined by stratified squamousepithelium, pseudostratifiedciliated columnar epithelium (Fig. 129),or both. Transitional types of epithelium may alsobe found, depending upon the presenceof inflammation in the adjacentconnectivetissue. The connectivetissuein the wall of nasopalatineduct cystscharacteristicallycontainslarge nervesand vessels;mucousglandsand adipose tissue may also be present (Fig.130),and a small island of hyaline cartilageis sometimesincluded. An extraosseouspresentationof this lesion, which arisesin the sameepithelial residuesbut superficialto the nasopalatinecanal,is termed cystof thepalatinepapilla. 3.1.2.2Nasolabial(Nasoalveolar)Cyst A cystsituatedon the alveolarprocessnear the baseof the nostril. There is a wide age distribution of this lesion, with a peak frequency in the 4th and 5th decades.There is a considerablepreponderancein females. The cyst doesnot arisewithin the bone,but may causesuperficial erosion of the outer surfaceof the maxilla. Radiographically,it may not be recognizedunlessdemonstratedby injection of radiopaque material. The most likely origin of the nasolabialcyst is thought to be remnants of the embryonic nasolacrimalduct or the lower anterior portion of the mature duct. The wall of the enucleated cyst is commonly corrugated (Fig.131).The cyst is most frequentlylined by non-ciliatedpseudostratified columnar epithelium (Fig.132), which may contain abundant mucouscells(Fig.131).There may be localizedareasof squamous epithelium or cuboidal epithelium.
40
Definitions and Exolanatorv Notes
Note Various non-odontogenic cysts of the mouth and jaws were thought to arise from epithelium trapped in the lines of fusion of the embryonic processes.Now, however, it is generally believed that the grooves between the processesare not eliminated by side-to-side fusion, and that epithelium is unlikely to become trapped. Critical re-examination of the so-called 'fissural' cysts suggeststhat many of the types previously recognized do not exist as separate entities. These debatablelesionsare listed and commentedon below, but they are not included in the formal classification. Median Palatine, Median Alveolar and Median Mandibular Cysts Midline cysts of the maxilla and mandible, previously thought to be entities derived from epithelium entrapped during the fusion of embryonic facial proCESSES
The existence of these cysts as entities derived in this way has been seriously questioned by embryologists and pathologists. It is now felt that those in the maxilla represent a posterior extension of a nasopalatine duct cyst in the caseof a median palatine cyst and an anterior extension in the case of a median alveolar cyst. Occasionally, a cyst in the median alveolar position is a keratocyst. Cysts in the midline of the mandible may be radicular cysts,lateral periodontal cysts or odontogenic keratocysts. Globulomaxillary Cyst A cyst found within the bone between the maxillary lateral incisor and canme, previously thought to be a fissural cystarising from non-odontogenic epithelium included at the site of fusion o,f the globular process of the frontonasal process and the maxillary process. Radiographically, a cyst in the globulomaxillary area shows a characteristic inverted pear-shapedradiolucency between the lateral incisor and canine, occasionally causing divergence of the roots. The concept of a globulomaxillary cyst formed by the entrapment of epithelium during development of the face has been seriously questioned. Cysts undoubtedly occur in this region, and the majority probably represent a range of other varieties, such as the odontogenic keratocyst, lateral radicular or residual cysts,and lateral periodontal cysts.However, a few cysts in this particular location are not readily placed in any of these other categories.
3.2 Inflammatory 3.2.1 Radicular Cyst A cyst arising from the epithelial residues (rests of Malassez) in the periodontal ligamentas a consequenceof inflammation, usuallyfollowing the death of the dental pulp.
EpithelialCysts 4I 3.2.IJ Apical and Lateral Radicular Cyst These radicular cystsare the most common cystsfound in the jaws. They develop when a pulpal inflammation spreadsto the periapical or lateral radicular area and givesrise to the formation of an apical or lateral granuloma.Within a granuloma,epithelial residues(rests of Malassez),stimulated by the inflammation, may proliferate and lead to the formation of an epithelium-lined cysticcavity. The radicular cystmay occur in relation to any tooth, but few are associatedwith the deciduousdentition. The highest incidenceis in the anterior region of the maxilla. They are found over a wide age range,with a peak in the 3rd and 4th decades.Male subjectsare affected more frequently than female. Radiographically,it is not always possible to differentiate between a radicular cyst and an apical granuloma,although cyststend to be larger and to havewell-definedmargins(Fig.133). Histologically, most radicular cystsare lined by non-keratinized stratified squamousepithelium (Fig.13a).The morphology of the epithelium is dependent upon the degree of inflammation. In the presence of inflammation, the cyst epithelium will show proliferatingrete processes(Fig.135).When inflammationis absent,the epithelium tends to be thin with no rete processes,and there may be more or lessextensivejuxtaepithelial hyalinization (Fig.136).When the hyalinization is extensive,the epithelium becomestenuous and degenerate(Fig. 137).Occasionallythe cyst epithelium containsmucous or ciliated cells, even in mandibular radicular cysts.Hyaline bodiesof characteristicappearanceare seenin somecases(Figs.138, 139) and may becomecalcified. Foam cells may be seenin the cystic cavity (Fig.1a0). In the fibrous cyst wall there are often heavy depositsof cholesterolcrystals with an associatedforeign-body giant cell reaction. The inflammatory cell infiltrate is mixed and may include foam cells and plasma cells with prominent Russell bodies. Commonly, the wall of the radicular cyst has a zoneheavily infiltrated with inflammatory cells, between the epithelial lining and an outer fibrous zone with fewer inflammatory cells. 3.2.I.2 ResidualRadicular Cyst A radicular cyst which is retained in the iaws after removal of the associatedtooth (Fig.141).
42
Definitions and Explanatory Notes
3.2.2 Paradental (Inflammatory Collateral, Mandibular Infected Buccal) Cyst A cyst occurring near to the cervical margin of the lateral aspectof a root as a consequenceof an inflammatory processin a periodontal pocket (Fig.1a2). The paradental cyst arisesfrom odontogenic epithelium in the superficial part of the periodontal ligament; the involved tooth is vital. A distinctive form of the paradental cyst occurs on the buccal and distal aspectsof erupted mandibular molars, most commonly the third molars, where there is an associatedhistory of pericoronitis. Similar cysts,almost all of which occur on the buccal surfaceof the mandibular first molars in children around 6-8 yearsof age,have been describedas the mandibular infectedbuccalcyst. The histologicalfeaturesof the inflammatory paradentalcyst are the sameas those of the radicular cvst. Note As previously indicated, the lining of many cysts of the jaws, both odontogenic and developmental, may include ciliated epithelium. However, when a specimen from a suspectedcyst of the maxilla is mainly lined by ciliated epithelium, consideration should be given to the possibility that the material is antral lining, or the lining of a postoperative maxillary cyst (surgicaL ciliated cysf formed at the site of a previous operation involving the antrum.
SubjectIndex
Adenomatoidodontogenictumour Ameloblasticfibroma Ameloblastoma,benign malignant Calcifyingepithelialodontogenictumour Carcinoma odontogenic odontogenicghostcell primaryintraosseous Carcinosarcoma,odontogenic C e m e n t o b l a s t o m a , ( b e n i g n ,.t r u e ) Cementoma,familialmultiple gigantiform Cemento-osseousdysplasia Cemento-ossifyingfibroma Cherubism Clearcell odontogenictumour Cyst bone aneurysmal solitary botryoidodontogenic calcifyingodontogenic collateral dentigerous epithelialdysplasia eruption follicular gingival adults inlants glandularodontogenic globulomaxillary incisive canal keratocyst, odontogenic
Page Figures .....19 36-39 ...16 30.31 .......11 7-21 ....25 62-64 .......
15
23-28
.......24 ...... 26 .......25 . .. . .. 27 ...... 23 . . . . 30 ...30 .. .. . 29 .....27 .....31 . . 16
62-66
.......32 ....33 .......37 .......20 ....42 ...36 ....24 .....36 ....36
37 34 38 40 39 35
65,66 58-61 87,88 87,88 73-77 89-92 29
97-100 l}l,l02 123 40-44 142 116-118 67,68 119 116-118 r24, r25 107 126,127 128-130 108-115
44
Subject Index Page Figures
lateral periodontal mandibular infected u ' * a . . median alveolar mandibular palatine nasoalveolar nasolabial nasopalatine duct odontogenic malignant change in palatinepapilla .. . . paradental postoperative maxillary primordial radicular apical and lateral residual sialo-odontogenic surgical ciliated Cystic disease,familial multilocular
............
Dentinoma Dysplasia cemento-osseous epithelial, in cyst wall fibrous florid cemento-osseous periapical cemental Fibrodentinoma, ameloblastic Fibrodentinosarcoma, ameloblastic Fibroma
ameloblastic rng cemento-ossify odontogenic ossifying,juvenile(aggressive). . . Fibro-odontoma. ameloblastic
ameloblastic Fibro-odontosarcoma. Fibrosarcoma, ameloblastic Follicle,dental,simulatingmyxoma Ghost cell dentinogenic (odontogenic) tumour Granuloma,giantcell,central Granularcellodontogenictumour Hamartoma,odontogenicgingivalepithelial
'^l
120-122
40 40 40 39 39 39
131,132 t31,132 128-130
24 39 42 42 35 40 41 38 42 31 18 29 24 28 30 30 18 27 16 21 22 28 18 27 26 23
142 108-115 133-740 r4l 126,727 89-92 32
67,68 78-84 87,88 85,86 32
30,31 73-77 49-51 33,34 7 1 ,72 69,l0
57
. . . . 20 .... 31 ... .22
93-96
. . . . . 22
52
SubjectIndex
Page Figures 83,84 29
Keloid,osseous Keratoameloblastoma Keratocyst,odontogenic
1J
35
tumour of infancy Melanoticneuroectodermal Myxoma
JJ L-)
t7,18 108-115 103-106 53-56 t-o
Normal structures Odontoameloblastoma Odontogenicfibroma Odontoma complex compound Ossifyingfibroma,juvenile(aggressive) Progonoma,melanotic Sarcoma,ameloblastic Squamousodontogenictumour
'..18 ..'22
35 49-51
.....2I ...2I . . . 28
45-47 48
33
103-106
'..26 . ' . 14
69'70 22
79 15
36-39 2328 29
Tumour adenomatoid odontogenic calcifying epithelial odontogenic clear cell odontogenic ghost cell (dentinogenic, odontogenic) granular cell odontogenic melanotic neuroectodermal squamous odontogenic
45
lo
.
20 22 JJ
T4
103-106 22
Unlessotherwisestated,all the preparationsshownin the photomicrographs on the followingpageswerestainedwith haematoxylinand eosin.
47
8r
Fig.1. Tooth germ in a fetus of about 4.5 months of age. Developing deciduous lower central incisor. x 20
ii
{ q. * - r . . 1 ^
@
s.
Fig.2. a Stellatereticulumof enamelorgan.Stellatereticulumwith stratumintermediumandameloblast layerbelow.x 320.b Dentalpapilla.x 320
4B rr*
ss.
i{
**i
'sr r$& s
'* *
tr.t
&, ** " I
t*
Fig.3. Enamel organ (above) and dental papilla (below). Odontoblasts have differentiated and some dentine has formed. x 320
Fig.4. Dentine and pulp in fully formed tooth. The pseudostratified odontoblast layer lies at the surface of the pulp. x 200
49
Fig.5. Acellular cementum. From left to right: bone, periodontal ligament, cementum and dentine x 80
Fig.6. Enamel matrix. Tenuous matrix remaining after demineralization shows ouilines of enamel prisms cut in varying directions. x 320
-50
Fig.1. Ameloblustomo, mandible Resection specimen showing multilocular radiolucencyand displacementof a molar tooth
L*x 200
"-
r
Fig.9. Ameloblastoma, follicular. Many epithelial islands show early cyst formation. x 80
Fig.10. Ameloblastoma, plexifbrm. Continuous meshwork of epithelium and cysts resulting from stromal degeneration. x 80
53
Fig.13. Amekthlastoma, granular cell type. Rounded cells packed with acidophilic granules.Columnar cells are still presentat the margin x 2(X)
!'t
a
lt.
Fig. 14. AnteloLtlustonu, Jolliculor Markcd juxtaepithelialhyalinization x 2(X)
t,
s
Fig. 15. Ameloblustoma, tlesmoplastic x 160
Fig.16. Ameloblastoma, basaloid pattern x200
-5-5
Fig.17. I'apilli.ferouskcrotoumeloblustontu. x 80
F i g . 1 8 . P t t l ,i l I i . l rt', , t r . :k t r L r lttt r m r lr t l tl r t .t\( , m t t . , . \ 2 l l
Fig.21. Amebblastoma, Jollicular. Typical pattern of extension through cancellous bone. x 32
Fig.22. Squamous odontogenic tumour Islands of squamous epithelial cells. with no columnar cells at the periphery. x 50
Fig. 25. Calcify ing epit helial o do nto genic tumour Marked cellular and nuclear pleomorphism. x 510
Fig.26. Catcifying epithetial odontogenic tumour. Abundant rounded massesot amvloid-like material within the tumour. Some are calcified' x 160
60
Eig.27. Calcifying epithelial odontogenic tumour. Fluorescenceof amvloid-like matcrial stainedwith thioflavine T. x 160
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Fig.29. Clear cell odontogenic tumour Sheets of clear cells, some with a faintly stippled cytoplasm. x 200
Fig.30. Ameloblastic fibroma. Proliferating odontogenic epithelium and cellrich mesenchyme. x 80
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Fig.31. Ameloblastic fibroma. The cell-rich mesenchymal component resembles dental papilla (seeFig.2b). x 200
Fig.32. Ameloblastic fibrodentinoma. Islands of dysplastic and poorly mineralized dentine. x 200
Fig.33. Ameloblastic fibro-otlontoma. Odontogenic epithelium and cell-rich mJsenchyme at upper right; dentine (acidophilic) and enamel (basophilic) at lower left. x32
Fig.34. Ameloblastic fibro-odontoma, right maxilla' L e s i o n e x t e n d s1 o o r h i t a i floor and contains radiopaque areas of varying size
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Fig.36a,b. Adenomatoid odontogenic tumour. a Radiolucent lesion associated with crown of embedded tooth. b Similar lesion, but with areas of mineralizatlon.
65
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Le Fig.38. Adenomatoid odontogenic tumour. The epithelium shows multiple duct-like structures. x 200
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Fig.42. Calcfying odontogenic cys/' Ghost cells lying individually and in small groups. x 200
68
Fig.43. Calcfying odontogenic cysr. Ghost cells showing fluorescence alter stainingwith rhodamine B. x 130
Fig.44. Calcifying odontogenic c/.rr A band of dentine has been formed by odontogenicmesenchymelying beneath the epithelium. x 130
Fig.45. CompLexodontoma. Dense radiopaque mass lying next to an impacted molar
Fig.46. Complex odontoma. Disordered mixture of dental tissues' x 32
71
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Fig.49. Odontogenit:fibromu Cellular fibroblastictissuccontaining strandsof odontogenicepithelium. x 20i)
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Fig.50. Otlontogenic.fibromuFibrous tissuecontaining epithelium and islands of dysplasticcementum or bone x 180
73
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Fig.54. NIy'totnu x32,
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Fig.58. Benign cementoblastorza.Rounded mass related to roots of mandibular first permanent molar
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Fig.62. Malignctnt ameloblustoma. x 160
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Fig.63. Malignant ameloblastoma crowdecl epithelial cells and mitotic activity
x200
Fig.64. M alignant ameloblastoma Same patient as Figs.62and 63. Tumour in regionallymph node. x 45
79 ;,
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Fig.65. Primnry intruosscot.rs carcinonta Intraosscoussquamouscell carcinoma No conncction to surface epithelium or cvidcnce of turnour elsewhere. x 200
*:: Fig.66. Primury intruosseou.scurctnomu Tumour pattern suggestsorigin from odontoscnic eoithelium. x 200
BO
Fig.67. Epithelial dysplasia in cyst wall. x 200
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Fig.6tt. Epithelial dysplusiu in cyst wall. x 2(X)
81
Fig.69. Ameloblastic fibrosarcoma. Odontogenic epithelium lying in richly cellular odontogenic mesenchyme. x 80
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Fig. 70. Ameloblastic fibrosarcoma Malignant features in mesenchymal component. x320
Fig.73. Cemento-ossifyingfibromu, mandible. Well-defined lesion with patchy mineralization
Fig.74. Cemento-.ssi.fvinglibroma, mandible. The tumour has a smooth surface and is well demarcated from the bone
Fig.77. Cemento-ossifyingfibroma. Typical metaplastic bone. x 80
Fig.78. Fibrous dysplasia,mandible. The lesion has ill-defined margins
87
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89
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Fig.85a,b. Periupical cemental dysplasia a Radiolucent lesions at apices of three manclibularincisors b Mineralized massesat apicesof mandibular inciSOTS
Fig.86a,b. Periapical cementaldysplnsia. a Metaplasticbone. x 80 b Cementum-like tissue. x 80
90
Fig.87a'b. Florid cemento-osseoh\dysplasia a Lobulated dense mass in maxillary molar region. b Same patient; smaller mass in incisor/canine region
Fig.88. Florid cemento-osseousdysplasia. Basophilic cementum-like material partly fused to root surface. x 30
Fig.89. Cherubism All four quadrants of the jaws are afTected
Fig.90. Cherubism. occlusal radiographs of mandible. Multilocular ,cystic' aopearance and expansion of bone
Fig.91. Cherubism x80
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Fig.92. Cherubism. Perivascular cuff. x 200
Fig.93a,b. Giant cell granuloma. aMaxilla; loculated radiolucency. bMandible: slenderbonv seotawithin lesion
95 :--:-:.r,'tl-:N::.,!
Fig.96. Giant cell granuloma. New bone formed within the lesion. x 80
Fig.97a,b. Aneurysmal bone cyst, mandible
Fig. 100, Aneurysmal bone cyst.Margin of cavernous space. x 150
Fig.101a'b. solitary bone cysts.Typical scalloped margins between roots of teeth
98
Fig.103. Melanotic neuroectodermaltumour of infancy,maxilla. Developing teeth are disolaced
Small. round, darkly
Fig. 105. Melunotic netrroectoclermaltumour of in.fancy.Strand of pale cells with lymphocyte-likecells within cleft. x 320
101
Fig.108a,b. odontogenic keratocysts,mandible Both examples show scalloped borders
102
Fig. 110. odontogenic keratocyst.corrugated appearance of cyst wall. x g0
l
103
Fig. ll2. Orlontogenickerctlot:ystEpithelial islandsor daughtcr cvstsin wall of main cvst x 80
Fig. 113. Odorttogenickerttlor:vstTr.v0sidcs of samc cyst shorvinglossof kcratinization in areasoI inflirmrnation.x [10
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l gG. Fig.114. odontogenic keratocyst. Smear from aspirated cyst contents. parakeratinized squameswith ill-defined mareins. x 320
$ti. Fig.115. odontogenickeratocyst. Multiple keratocystsin patientwith multiple
naevord basal cell carcinoma Jaw cyst syndrome. x 32
105
Fig. 116a'b. Dentigerous cysts.a Maxillary lesion; typical enclosure of crown of tooth. b Large mandibular cyst
Fig.117. Dentigerous cysr.cyst opened to show relationship to crown of tooth
106
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Fig.119. Eruption cysl. Cyst lining beneath oral mucosa' x 32
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Fig. 120a,b. Lateral periodontal cysts
Fig.121. Lateral periodontal cyst Characteristic plaques in epithelial lining
x200
x 100 Fig.l2\. Lateral periotlontul cltst Plaques partly composed of clear cells
Fig. 123. Botryoid odontog,eniccys/' x 50
Fig.l24. Gingival cystof adult. x 40
Fig.125.Gingivalcystof adult. x320
110
Fig.l26. Glandular odontogenic cyst. Multiple cyst-like spacesor crypts within lining epithelium. x 160
Fig.lZ1. Glandular odontogenic cyst. Cuboidal cells at surface and bordering spaceswithin epithelial cyst lining x 320
Fig.128a,b. Nasopalutineduct cysts
Fig.131. Nasolabial c'y.r/.corrugated lining and abundant mucous cells. x g0
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Fig.133a,b. Radicular cyst aFrom root-filled maxillary incisor. b From mandibular molar
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Radicular clsl. Hyaline bodies.
Fig.140. Radicular cysl Foam cells and cholesterol crystal clefts in cyst contents. x 200
Fig.141.Residualcyst
Big.l42. Paradental cysL Cyst (cut open) on distal aspect of mandibular third molar