Flistological Typing of Bone Tumours

FlistologicalTyping of BoneTumours

F, Schajowicz In Collaboration with Pathologistsin 9 Countries

SecondE,dition

With 166Figures, Mostly in Colour

Springer-Verlag Berlin Heidelberg NewYork London Paris Tokyo HongKong Barcelona Budapest F.Schajowicz f Head, WHO CollaboratingCentre for the Histological Classificationof Bone Tumours Italian Hospital, Buenos Aires, Argentina andDepartment of Orthopedic Surgery and Pathology St. Louis University Medical Center, St. Louis, Missouri, USA

Series Editor L. H. Sobin Head, WHO Collaborating Centre for the International Histological Classificationof Tumours Armed Forces Institute of Pathology,Washington, DC, USA

In this series,colour illustrations will be limited in number in order to maintain a reasonablesales price.

The printing of additional colour figures was made possible by financial support from Prof. F.J.Martinez-Tello, Madrid, Dr. T.Matsuno, Kita-Ku Sapporo, Prof. Dr. M. Salzer-Kuntschik, Yienna and the following Japanese companies: Daiichi Pharmacological Co., Howmedica, Mitsubishi Yuka Bio-clinical Laboratories Inc., Roussel Morishita KK, Taisho Pharmacological Co.

Firstcdition publishcd by WHO in 1972 as No 6 in thc IntcrnationalHistological Classificat ion of Tumours scncs

ISBN 3-540-56460-8Springer-Verlag Berlin HeidelbergNewYork ISBN 0-387-56460-8Springer-Verlag NewYork Berlin Heidelberg

Library of CongressClatalogrng-in Publication Data Schalowicz.Fnlz Histologicaltyprngofbonetumors/F.Schajowicz.incollaborationwithpathologistsin9countrics 2ndedpcm (lnternationalhrstologlcalclassrticationoftumors)lncludcsbibliographrcalreferencesandrndex ISBN 3-540-56,160-lJ(alk paper) ISBN 0-387-56460-8(alk papcr) I Bones Tumors Histopalhology 2 Bones Tumors Cllassit'ication I litlc II Series:lnternationalhistonalclas- - sification of tumors (Unnumbered) [DNLM: I Bof,c Ncoplasms classrfication 2 Bone Neoplasms pathology WE258S296h19931RC280865318 199361699'271 0014 dc20 DNLM/DLClorLibraryofCongrcss93 17622CIP

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Reproduction of Lhefigures: Gustav Dreher GmbH. Sluttgart Typesettrngand printing: Appl. Wemdrng: Binding: SchiifTcr,Griinstadt 21131455 4 3 2 1 0 Prinledonacid keeDaDer Participants

Ackerman,L.V., M. D. Department of Pathology,State University of New york at Stony Brook, StonyBrook, New York, USA

Adler C. P.,M. D. PathologischesInstitut der Universit?itFreiburg (Ludwig-Aschoff Haus),Freiburg i. Br.,FRG

Bertoni,F., M. D. AnatomiaPathologia Malpighi, Bologna, Italy

Donato de Pr6spero,J., M. D. DepartamentoPatol6gica Anatomfa, Faculdade de Ciencias Medicasde SantaCasa de S5oPaulo. Brazll

Martinez Tello.F.J.. M. D. Hospital"Primero de Octubre,"Departamento de Anatomia Patol6gica,Madrid, Spain

Mazabraud,A., M. D. Pavillon Ollier, Hospital Cochin,Paris, France

Matsuno,7.,M. D. Departmentof Orthopaedics,Hokkaido UniversitySchool of Medicine,Kita-Ku, Sapporo,Japan

Povysil,C., M. D. SecondDepartment of Pathology,Charles University, prague, Czechoslovakia VI Participants

Salzer-Kuntschik,M., M. D. Institut fiir PathologischeAnatomie, Vienna,Austria

Schajowicz,F, M. D. t Head,WHO CollaboratingCentre forthe Histological Classificationof BoneTumours, Italian Hospital, Buenos Aires, Argentina,andDeparrment of OrthopedicSurgery and Pathology,St. Louis University Medical Center,St. Louis, Missouri.USA

Slssorzs.H.4.. M. D. Departmentof Pathology,Hospital for JointDiseases, Orthopedic Institute, New York, USA, Presentaddress: Histopathology Unit, Imperial CancerResearch Fund Laboratories, Royal Collegeof Surgeonsof England,London, UK

Sobin,L. H., M. D. Head,WHO CollaboratingCentre for InternationalHistologica- Classificationof Tumours,Armed ForcesInstitute of Pathology, Washington,DC, USA

Unni.K. K.. M.8.. B. S. Department of SurgicalPathology, Mayo Clinic, Rochester, Minnesota.USA General Prefaceto the Series

Among the prerequisitesfor comparativestudies of cancerare international agreementon histologicalcriteria for the definition and classificationof cancertypes and a standardizednomenclature. An in- ternationally agreed classificationof tumours, acceptablealike to physicians,surgeons, radiologists, pathologists and statisticians, would enable cancer workers in all parts of the world to compare their findingsand would facilitatecollaboration among them. In a report published in 7952,1a subcommittee of the World Health Organization(WHO) Expert Committee on Health Statistics discussedthe general principles that should govern the statistical classificationof tumours and agreed that, to ensure the necessary flexibility and ease of coding, three separate classificationswere neededaccording to (1) anatomicalsite, (2) histologicaltype, and (3) degreeof malignancy.A classificationaccording to anatomicalsite is availablein the InternationalClassification of Diseases.2 In 1956,the WHO ExecutiveBoard passeda resolution3request- ing the Director-Generalto explore the possibilitythat WHO might organizecentres in variousparts of the world and arrangefor the col- lection of human tissuesand their histological classification.The main purposeof suchcentres would be to develophistological definitions of cancertypes and to facilitate the wide adoption of a uniform nomenclature. The resolution was endorsed by the Tenth World Health Assemblyin May 7957.4

I WHO (1952)WHO TechnicalReport Series. No.53, 1952,p 45 2 WHO (1977)Manual of the internationalstatistical classification of diseases. iniuries,and causes of death,1975 version. Geneva 3 wHo (1956)WHO OfficialRecords. No.68, p 14(resolution EB 17.R40) 4 wHo (1957)WHO OfficialRecords. No.79, p467 (resolution WHA 10.18) VIII General Prefaceto the Series

Since1958, WHO hasestablished a numberof centresconcerned with this subject.The resultof this endeavourhas been the Interna- tional HistologicalClassification of Tumours,a multivolumedseries whosefirst edition waspublished between 1967 and 1981.The pre- sentrevised second edition aimsto updatethe classification,reflect- ing progressin diagnosisand the relevanceof tumour typesto clinical and epidemiologicalfeatures. Preface to Histological Typittg of Bone Tlrmours.Second Edition

The first edition of HistologicalTyping of Bone TumoursI wasthe result of a collaborativeeffort organizedby WHO and carried out by the International Reference/CollaboratingCentre for the Histologi- cal Classificationof Bone Tumours at the Osteo-Articular Pathology Centre,Italian Hospital,Buenos Aires, Argentina.The Centrewas establishedin 1963,and the classificationwas publishedin7972. In order to keepthe classificationup to date,the Centrecirculated a setof revisionproposals to the participantslisted on pagesV andVI. Their reponsesprovided the basisfor a new draft. After further com- municationsamong the participants, the present classification, definitionsand explanatory notes were recommended for publication. ProfessorSchajowicz, Head of the WFIO Centre,died suddenly during the final stagesof preparation of the publication. His former pupil and colleague,Dr. H. Gallardo, SpanishHospital, Buenos Aires, Argentina,helped to completethe selectionof illustrations. Dr. K. Shanmugaratnam,Singapore, Head of the WHO Centrefor Upper Respiratory Tract Tumours, and Dr. Sharon Weiss,Ann Ar- bor, Head of the WHO Centrefor Soft TissueTumours, reviewed the final draft of the manuscriptand provided valuablecomments. The histologicalclassification of bonetumours, which appears on pages3-6, containsthe morphology code numbers of the Inter- national Classificationof Diseasesfor Oncology(ICD-O)2 and the SystematizedNomenclature of Medicine(SNOMED).3

I Schajowicz F, Ackerman VL, SissonsHA, Sobin LH, Torloni H (1972) Histo- logical Typing of Bone Tumours. Geneva, World Health Organization (Interna- tional Histological Classificationof Tumours, No. 6) 2 World Health Organization (1990) International Classification of Diseasesfor Oncology. Geneva 3 College of American Pathologists (1982) Systematized Nomenclature of Medicine. Chicago X Preface to Histological Typing of Bone Tumours, Second Edition

It will, of course,be appreciatedthat the classificationreflects the present state of knowledge,and modificationsare almost certain to be neededas experienceaccumulates. Although the presentclassifi- cationhas been adopted by the membersof the group,it necessarily representsa view from which somepathologists may wish to dissent. It is neverthelesshoped that, in the interestsof international cooper- ation, all pathologistswill usethe classificationas put forward. Criti- cism and suggestionsfor its improvementwill be welcomed;these shouldbe sentto the World Health Organization,Geneva, Switzer- land. The publicationsin the seriesInternational Histological Classifi- cation of Tumoursare not intended to serveas textbooks but rather to promote the adoption of a uniform terminology that will facilitate communicationamong cancer workers. For this reasonthe literature referenceshave intentionally been omitted and readersshould refer to standardworks for bibliographies. Contents

Introduction

Histological Classificationof Bone Tumours 3

Definitions and Explanatory Notes 7 Bone-FormingTumours. . . . 7 Cartilage-FormingTumours . 74 Giant-Cell Tumour . 20 Marrow Tumours 22 VascularTumours 26 Other ConnectiveTissue Tumours 29 OtherTumours . . . -)+ UnclassifiedTumours 36 Tumour-like Lesions 36

Illustrations 4-)

Subjectlndex 127 Introduction

During the two decadessince rhe publication of the first edition of Histological Typingof Bone Tumours,new methodsof diagnosis,es- peciallyradiological imaging techniques (computed tomography and magnetic resonanceimaging), associatedwith advancesin the new cytomorphologicalmethods including immunohistochemistry,DNA ploidy analysis,cytogenetic chromosomal investigation,etc., have greatly improved our diagnostictools and treatment results.These advancesare reflected by the publication of new editions of various important textbooks in recent years.In thesepublications classification criteria differed. In contrast,the WHO classificationhas been relatively unaltered, and hasintroduced a limited numberof new entitiesand subdivided others becauseof distinct histologicalfeatures and biologicalbehaviour. In generalthe framework and the conceptof the original classification,as it hasbeen widely accepted, remains essentially unchanged. The classificationis basedon the line of histologicaldifferentiation, in many instancesreflecting the type of intercellular matrix material produced.This approachis justified because it avoidstheoretical his- togeneticcontroversies. The classificationincludes benign and malignant neoplasmspri- maryin bone,together with certain"tumor-like" lesions that werein- troduced becauseof their importance in differential diagnosisand becauseof uncertainty regarding their neoplasticnature. It is true that the number of lesionsin this category could be widened to include an endlessnumber of lesionssimulating bone tumoursbased on clinical-radiographicfindings. Some of theselesions are relatively common (Pagetdisease, fracture callus, osteomyelitis, osteonecro- sis)and othersare extremelyrare (melorheostosis,congenital or ac- quiredosseous dysplasia, massive osteolysis, etc.). In orderto simpli- fy the classification,only a reduced group of relatively frequent 2 Introduction lesionslocated within bone or on its surfacewhich may presentprob- lems of differential diagnosisare included.Metastatic and soft tissue tumourshave been excluded. The diagnosisof a bone lesion should be establishedby a combination of clinical, radiological and pathological studies.Therefore, the typical radiographic imagesare included with the pathological findings. Most bone tumours can be diagnosedby routine haematoxylin- eosin stains, but in some casesimmunohistochemical studies are needed. Although this revised classificationreflects the present state of knowledge,modifications undoubtedly will be neededin the future' Hopefully the adoption of a uniform terminology will continueto facilitate communicationamong oncologists. HistologicalClassification of BoneTirmours

I Bone-formingtumours

1.1 Benign 1.1.1 Osteoma. 9180/0" 1,.1,.2 Osteoidosteoma and osteoblastoma r.1.2.7 Osteoidosteoma 9197t0 1.1.2.2Osteoblastoma. . 9200t0 1,.2 Intermediate 7.2.1 Aggressive(malignant) osteoblastoma . . 9200tr l.J Malignant 1.3.1 Osteosarcoma.... 9180/3 1.3.1.1 Central(medullary) osteosarcoma . . . . . 9180/3 1.3.1.1.1Conventionalcentralosteosarcoma. . . . 9180/3 r.3.7.1.2Telangiectaticosteosarcoma . . 9183t3 1.3.1.1.3Intraosseouswell-differentiated (low-grade) osteosarcoma..... 91B0/31 1.3.r.7.4Round-cellosteosarcoma. . . . 9t85t3 7.3.1.2 Surfaceosteosarcoma. . . . 9190t3 7.3.1.2.7Parosteal(juxtacortical) osteosarcoma . 9790t31 7.3.1.2.2Periostealosteosarcoma. . . . 9790t32 7.3.1.2.3High-gradesurfaceosteosarcoma. . . . 9790t33

2 Cartilage-forming tumours 2.1 Benign 2.7.7 Chondroma 9220t0 2.7.1.7 Enchondroma. . . 9220t0 2.7.7.2 Periosteal(juxtacortical) chondroma . . . 9227t0 u Morphology code of the International Classification of Diseasesfor Oncology (lCD-O) and the SystematizedNomenclature of Medicine (SNOMED).

Histological Classificationof Bone Tumours

6 Other connectivetissue tumours

6.7 Benign 6.t.7 Benign fibroushistiocytoma 8830/0 6.1,.2 Lipoma 8850/0 6.2 Intermediate 6.2.r Desmoplasticfibroma 8823/0

6.3 Malignant 6.3.1, Fibrosarcoma 8810/3 6.3.2 Malignant fibroushistiocytoma.... BB30/3 6.3.3 Liposarcoma 8850/3 6.3.4 Malignantmesenchymoma 8990t3 6.3.5 Leiomyosarcoma 8890/3 6.3.6 Undifferentiatedsarcoma. . . . 8800/3

7 Other tumours

7.1 Chordoma 9310t3 7.2 Adamantinomaof longbones 9261t3 7.3 Neurilemoma 9560t0 1.4 Neurofibroma 9540t0

8 Unclassifiedtumours

9 Tirmour-likelesions

9.7 Solitary bone cyst(simple or unicameralbone cyst) . 33400

9.2 Aneurysmal bone cyst . . 33640 9.3 Juxta-articularbone cyst (intraosseous ganglion) 33600 9.4 Metaphysealfibrous defect(nonossifying fibroma) 74940 9.5 Eosinophilicgranuloma (histiocytosis X, Langer- hanscell granulomatosis). . 7j860 6 HistologicalClassification of Bone Tumours

9.6 Fibrous dysplasiaand osteofibrousdysplasia 9.6.1 Fibrous dysplasia 7491,0 9.6.2 Osteofibrousdysplasia

9.7 Myositis ossificans(heterotopic ossification) ' . . 73410

9.8 Browntumourofhyperparathyroidism..'. '. '. 74840 g.g Intraosseousepidermoid cyst . 33410

9.10 Giant-cell (reparative)granuloma 44170 Definitions and ExplanatoryNotes

1 Bone-Forming Tlrmours

1.1 Benign

1.1.1Osteoma(Figs. 1-3)

A benign,slowly growing lesionconsisting of well-dffirentiated mature bone,with a predominantlylamellar structure. These lesionsare regardedby some as hamartomasrather than true neoplasms.Three different types of osteomaare distinguished: conventionalosteoma ("ivory exostosis"),parosteal (juxtacortical) osteoma,and medullary osteoma (bone island or enostoma). Conventionalosteoma is almostentirely restrictedto bonesof in- tramembranous(direct) bone formation, that is, the externaltable of the skulland the paranasalsinuses, where it appearsas a denseivory- like bony mass.The locationat the inner tableand maxillary bones is lessfrequent and only rarely is the external surfaceof a long or flat boneinvolved (parosteal or juxtacorticalosteoma). Lesionswith similar histologicalfeatures found in the medullary cavity of other bones are called "medullary osteomas"(or "enos- tomas" or "bone islands").They generallypresent as radiological findings without clinical relevanceor growth potential and are con- sideredas hamartomas.

1.1.2 Osteoid Osteoma and Osteoblastoma

Osteoidosteoma and osteoblastoma are closely related entities of os- teoblastictype and appear under a commonheading. At onetime, the term "giantosteoid osteoma" was used (but laterabandoned) for benign osteoblastomato conveythe relationshipbetween the lesions. U Definitions and ExplanatoryNotes

Although there are no specifichistological criteria to distinguish betweenthem, the two termsare retainedbecause of their wide ac- ceptancebased on differencesin the size,site, radiological appearance,clinical presentationand surroundingbony reaction.It is possible that thesedifferences are relatedto the respectivesites of the two lesions:cortical for osteoid osteoma and medullary for osteoblastoma. Consideringboth lesionsas closely related tumours of osteoblastoma derivation.the terms"circumscribed" or "cortical" osteoblastoma for conventionalosteoid osteoma, and "genuine" or "spon- gious"osteoblastoma for osteoblastomahave been proposed. l.l.2.l Osteoid Osteoma(Figs. a-8) A benign osteoblasticlesion characterizedby its small size (usually lessthan 1 cm), a clearlydemarcated outline, and usuallythe presence of a surrounding zone of reactivebone formation. Histologically,it consistsof immature bone and osteoidwithin a cellular,highly vascu- larizedstroma. An arbitrary criterion generallyused to determine whether a lesion is diagnosedas osteoid osteomaor osteoblastomais the sizeof the nidus:lesions less than 1,or 2 cm in diameter are classifiedas osteoid osteoma;those larger are osteoblastoma.Others have useda dividingline of 1.5cm for lesionsindistinguishable by all other criteria. Osteoid osteomatypically occursin the shaft of long bones,particularly the tibia and femur, the femoral neck and intertrochanteric region accountingfor most of them. Unlike osteoblastoma,osteoid osteomais infrequent in the spine.The majority of osteoidosteomas occur during the seconddecade of life with a predilection for males (3:1). Painis the mostcommon clinical manifestation, often worse in the eveningand relieved by salicylates.Osteoid osteoma may have an intrarticular location and present as synovitis of the involved joint. Multiple loci or a subperiosteallocation are extremelyrare. Radioisotopeimaging and computedtomography are very useful in both anatomicallocalization and diagnosis.

1.1.2.2 Osteoblastoma(Figs. 9-11 ) A benign or locally aggressivetumour with a histologicalstructure similar to that of osteoidosteoma, but characterizedby its larger size (usuallymore than1.5 cm) and typicallyby theabsence of a surrounding zoneof conspicuousreactive bone formation. Bone-FormingTumours 9

Osteoblastomasare lessfrequent than osteoidosteomas. They most frequently occur in the vertebrae and flat bones, and in the bonesof the hand or foot; they do not, asa rule,produce the intense pain commonly associatedwith osteoid osteoma.They occur more frequently in males,and during the first three decadesof life. There is a diversityin the natural history,i. e. malignantpotential, of osteoblastoma;conventional osteoblastoma should be considered an unpredictablelesion. The term "benign" thereforeshould not be used.

1.2 Intermediate

1.2.1Aggressive (Malignant) Osteoblastoma (Figs. 12-14)

An osteoblastomawith abundantand large hypertrophicosteoblasts, often havingplump or bizarre hyperchromqticnuclei and alternating ',blue fields of giant cells of osteoclastictype. These lesions contain spiculatedbone" produced by typicalosteoblasts. Conventional osteoblastomashave a significantrecurrence rate of approximately15 7o , especiallyafter intralesional excision (curettage).Although very rare, caseshave been reported of malignant transformationto typical osteosarcoma. The histologicaldistinction from osteosarcomamay be difficult. However, in the type of osteoblastomadesignated ,,malignant osteoblastoma"(Schajowicz and Lemos), the areasof necrosis,atypical mitosis and malignant cartilage so evident in osteosarcomaare lacking. Lesions with similar distinctive histological features have beendesignated " aggressiveosteoblastoma" (Dorfman). In spite of their more aggressiveclinical courseand frequent recurrence,none of the lesionsreported as "malignant" or ,,aggressive" osteoblastomahave metastasized.Therefore. as the lesions appear to have no metastatic potential, the name "aggressiveosteoblastoma"seems more appropriate.The term "osteosarcomain situ" hasrecently been suggested. Wide excision,preferably en bloc, is the indicatedtreatment. 10 Definitions and ExplanatoryNotes

1.3Malignant l.3.L Osteosarcoma (Figs.15-aa)

A malignanttumour characterizedby the directformation of bone or osteoidby thetumour cells. The term "osteosarcoma"is now increasinglybeing usedby most centres,replacing the older term "osteogenicsarcoma". Osteosarco- ma is the most common primary malignant tumour of bone apart from myeloma.It coversa wide spectrumof lesionswith distinct clinical and pathological features, associatedwith different biological behaviours.Two fundamental groups can be clearly separated,the central (medullary) and the surface(peripheral) osteosarcomas.In- tracortical osteosarcomasare extremely rare and only isolated caseshave been reported.

1.3.1.1 Central (Medullary) Osteosarcoma(Figs. 15-21) Besides the more common conventional or classicosteosarcoma, severalvariants of central osteosarcomahave been described:the telangiectaticosteosarcoma, the well-differentiated (low-grade) osteosarcoma,and the small-cellosteosarcoma simulating Ewing sarcoma.With the exceptionof the well-differentiatedosteosarcoma, all are highly malignant.

1.3.1.1.1Conventional Central Osteosarcoma An osteosarcomathat arisescentrally and after destroying the cortex invadesthe surrounding tissues,but generallyrespects the adjacent growth cartilage. Grossly and radiographically,an almost purely sclerosingand an osteolyticvariety may be distinguished;however, a mixture of these featuresis rnorecommon. Osteosarcomasshow considerablevariation in gross and histological pattern, differing greatly in the amount of tumour bone or osteoid present, in the pleomorphism of the tumour tissue and in the number of atypical mitoses and extent of necrosis.In addition to bone and osteoid, the tumour cells may produce cartilage, fibrous tissueor myxoid tissue;many areasof tumour tissuemay have an undifferentiated spindle-celled structure without any specific type of intercellular material. Subdivisionof osteosarcomason the basisof a predominantly osteoblastic,chondroblastic, fibroblastic or fibrohistiocytic structure can be useful for recognition but does not Bone-FormingTumours11 seemto be of importance as far as prognosisand treatment are concerned. Most tumours occur in patients between the ages of 10 and 20 years;they are relatively infrequent below the ageof 10 yearsand exceptionalunder 5 years and over 40 years of age.Many of the tumours developingafter middle ageare associatedwith Pagetdisease of bone (Figs.22-24) or, more rarely, following irradiation or secondary to fibrous dysplasia.Males are more frequently affectedthan females.The metaphysisof the long bones,particularly the lower end of the femur, the upper end of the tibia and the upper end of the humerus(that is, areasnear the most activelygrowing epiphysis)are the sitesof predilection.

1.3.I.1.2 TelangiectaticOste osarcoma (Figs. 25 -28) An osteosarcomacharacterized by numerouslarge spaces filled with blood and separatedby fibrous septa. There are areasof conspicuouscellular anaplasiafrequently associatedwith giant cellsof the osteoclasttype or with atypicalmultinu- cleatedgiant cells.Tirmour osteoidor bone is often scarceand may be difficult to find. Therefore, this lesion is often mistaken for an aneurysmalbone cystor a malignantgiant cell tumour. Radiological- ly, telangiectaticosteosarcoma appears as a moth-eaten or perme- ative radiolucent lesion,most commonly locatedin the metadiaphy- seal region. On gross examination the tumour is a haemorrhagic multiloculated mass.Following these criteria this neoplasmis relatively rare (approximately 77" of all osteosarcomas).The particularly poor prognosis associatedwith this tumour in earlier times has improved due to new pre- and postoperative chemotherapeutic methods.

1.3.1.1.3Intraosseous Well-Differentiated (Low'Grade) Osteosarcoma(Figs. 29 -31) An osteosarcomacomposed mainly of fibrous and osseoustissue with little cellularatypia or mitotic activity. This hasbeen identified in recent yearsas a distinct entity with a better prognosisthan the conventionalcentral osteosarcoma.It has many histologicalsimilarities to parosteal(uxtacortical) osteosarcoma and sharesits biologicalbehaviour. In somecases the histological featuresmay simulatefibrous dysplasiaor aggressiveosteoblastoma. This variant of osteosarcomais rare and comprisesapproximately 1 % of all osteosarcomas. 12 Definitions and ExplanatoryNotes

1.3.1.1.4Round-Cell Osteosarcoma(Figs. 32-34) An osteosarcomawith thehistological features of both Ewing sarcoma and osteosarcoma. This rarevariant (about I"h of osteosarcomas)has been labelled "small-cellor round-cellosteosarcoma simulating Ewing sarcoma,,. Recognitionof this rare entity is important becauseof possiblediffer- encesin responseto treatment.

1.3.1.2Surface Osteosarcoma (Figs. 3544) An osteosarcomathat arises from thesurface o.f the bone. Surfaceosteosarcomas occur mostly in long bonesand are far less common than thosearising within bone.They canbe subdividedinto three categories:parosteal (juxtacortical), periosteal and high-grade surfaceosteosarcoma. This division isjustified becauseof differences in histological features, biological behaviour and prognosis. Parostealosteosarcoma is associatedwith the best prognosis;high- gradesurface osteosarcoma has a poor prognosis,almost identical to that of conventionalcentral osteosarcoma.The prognosisof periostealosteosarcoma is intermediate.

1.3.1.2.1Parosteal (Juxtacortical) Osteosarcoma (Figs. 35-38) A distinct type of osteosercoma,characterized by an origin on the externalsurface of a boneand a high degreeof structuraldifferentiation. Thesetumours grow relativelyslowly and havea better prognosis than the ordinary type of osteosarcoma.Histologically, the tumour consistsof a massof bone trabeculae,often mature and lamellar.The trabeculaeare separatedby fibrous tissuecomposed of spindle cells that are minimally pleomorphic and have few mitoses.Occasionally, at the periphery of the tumour, smallareas of cartilageshow the histological pattern of low-grade chondrosarcoma.The distinction from myositis ossificansmay be difficult, particularly with a parostealos- teosarcomaat an early stageof development. The term "parostealosteosarcoma" is at presentpreferred to the older term "juxtacortical osteosarcoma"used by Jaffe. This is to avoid confusion,since some authoritieshave grouped all surfaceos- teosarcomasunder the singletitle of "juxtacorticalosteosarcoma". Parostealosteosarcoma usually sparesthe medullary cavity un- lessthe lesionis of long duration or hashad surgicaltreatment. These tumours usually occur in young adults and involve the shaftsof long bones,most commonly the lower andposterior part of the femur and the upper part of the humerus.They are circumscribedand some- Bone-FormingTumours13 times lobulated lesions,adherent to or surroundingthe cortex of the bone.They are relativelyinfrequent tumours (10 % of all osteosarcomas). According to the above definition, highly malignant surfacetu- mours, previouslyregarded as gradeIII parostealosteosarcomas, shouldbe classifiedas high-grade surface osteosarcomas. In sometumours,especially after a recurrence,areas of high-grademalignancy may be found in an otherwisewell-differentiated lesion: these lesions havebeen called "dedifferentiated" parosteal osteosarcomas.

1.3.1.2.2Periosteal Osteosarcoma (Figs. 3941) A surfaceosteosarcoma that containspredominantly low- or medium- grade malignant cartilage, often undergoing calcification or enchondral ossification.In focal areas,the tumour producesfine lace-likeos- teoid. Although long recognized,periosteal osteosarcomahas been more clearlydefined in the lastdecade. It occursmost often in adolescentsand hasa predilectionfor the diaphysesof the femur and tibia. There is only occasionalinvolvement of the underlying cortex, and penetration of the medullary cavity is rare. In at leastsome patients the tumour resemblesperiosteal chondrosarcoma, an entity with similar clinical and radiographicfeatures. Areas that havebeen inter- preted aslace-like osteoid or tumour bone may actuallybe strandsof cartilageor areasof enchondralossification.

1,.3.1.2.3High-Grade SurfaceOsteosarcoma (Figs. 4244) A surfaceosteosarcoma with highly malignanthistological features. This lesion occursmost frequently in adolescentsand is predominantly locatedin the diaphysesof long bones,mostly in the femur or humerus.The radiographicfeatures may be similar to those of periostealosteosarcoma. The prognosisis almost as bad asthat of a conventionalcentral osteosarcoma. 14 Definitions and ExplanatoryNotes 2 Cartilage-FormingTumours

2.1 Benign

2.1.1 Chondroma (Figs.a5-a7)

A benigntumour characterizedby theformation of mature cartilage, but lacking the histologicalcharacteristics of chondrosarcoma(high cellularity,pleomorphism and presenceof largecells with double nuclei or mitoses). Benign cartilagetumours are relatively common lesions.Typical- ly, they involve the short tubular bonesof the handsand feet, and less commonly the ribs or the major long bones.They are usuallysituated centrally (enchondroma) ; periosteal(juxtacortical) chondromasare lessfrequent. The lesionsmay be solitaryor part of the condition multiple enchondromatosis,in which severalor many bones are af- fected. Casesof multiple enchondromatosiswith a predominantly unilateral distribution are generallyreferred to as "Ollier disease"or "dyschondroplasia".When multiple enchondromasare accompa- nied by multiple hemangiomasof soft tissues,the term "Maffucci syndrome"is used. Grossly,chondromas have a lobulated cartilaginousappearance. They often show necrosisand calcification,with or without enchondral ossification, and this may be evident radiologically. Myxoid changeis common. The histologicaldistinction between chondroma and chondrosarcoma is sometimesdifficult, particularly when only a limited sample of tissue is available. Lack of high cellularity, pleomorphism and plump cells with large or double nuclei favour a benign lesion.The site of the tumour and the radiologicaland clinical featuresare often helpful in making the distinctionbetween benign and malignant cartilage tumours. Radiologically,enchondroma is radiolucent, often well-definedround or ovoid, expandingand slightly thinning the cortex. The lesionis usuallylocated in the metaphysis,extending toward the diaphysis.Varying degreesof mottled calcificationare common. There are often discrepanciesbetween biological behaviour and histological appearance,depending on the clinical symptoms and the anatomicalsite of the lesion. Thus, solitary tumours of the tubular bones of the hands and feet and some periostealtumours, although showing cytological features of low-grade malignancy,behave in a benignfashion. Cartilage-FormingTumours15

Heavily calcifiedcartilaginous lesions that sometimesoccur in the metaphysesof long bones,often without symptoms,have been referred to as "calcifying and ossifyingchondromas". They are probably chondromatoushamartomas and not true neoplasms. Malignant changeis rare in a solitary enchondroma,particularly in the hands or feet, but occursmore frequently (in approximately 307" ofcases)in casesof multiple enchondromatosis,particularly in casesof Ollier or Maffucci syndrome.

2.I.2 Osteochondroma (Osteocartilaginous Exostosis) (Figs.48-51) A cartilage-cappedbony projection on theexternal surface of a bone. This is a frequent type of bone lesion.It may be solitary or part of the generalizedcondition multiple hereditaryexostoses ("diaphyseal aclasis"or "hereditary deforming chondrodysplasia").Osteochon- dromas are commonly located in the metaphysealregions of long bones,particularly the lower femur, upper tibia and upper humerus, but are alsofound in other bonessuch as the scapulaor ilium. Solitary lesionsmay haveeither a broador a narrowbase (i. e.they may be either sessileor pedunculated),while multiple lesionscan involve the whole metaphysisof a bone. Osteochondromasoccur most frequently in children;their growth usuallyceases at the time of skeletalmatu- ration. They are probably disordersof growth rather than true neoplasms. Malignant changeis rare in solitary osteochondromas,but occurs more frequently (approximately5 % ) in casesof multiple hereditary osteochondromas.

2.1.3 Chondroblastoma (Epiphyseal Chondroblastoma) (Figs.52-55) An uncommon benign tLtmoLtr,characterized by highly cellular and relatively immature, rounded or polygonal, chondroblast-likecells with distinct outlines, together with multinucleated osteoclast-like giant cellsarranged singly or in groups.On the whole,there is little in- tercellularmaterial, but small amounts of cartilaginousintercellular matrix with areasof focal calcificationare typicaL The lesionsare almostinvariably situatedin the epiphysesof long bonesadjacent to the epiphysealcartilage plate;they sometimes extend into the adjacentmetaphysis. The upper tibia, femur and upper humerusare common sites.The tumours usuallyoccur in patientsun- 16 Definitions and ExplanatoryNotes der20 yearsof age.Codman in 1931was the first to givea detailedac- count of this tumour, which he regardedas an "epiphysealchondro- matous giant cell tumor". In 7942,Jaffe and Lichtenstein suggested that the lesion was a specifictype of tumour, distinct from giant cell tumour,and proposed the name"benign chondroblastoma". The distinction between chondroblastomaand chondromyxoid fibroma is not alwaysclear, inasmuch as cases with someof the histologicalfea- turesof both havebeen reported. Cases with someof the histological features of aneurysmalbone cyst have been referred to as "cystic chondroblastoma". A few casesof chondroblastomamay pursue a more aggressive course and recur locally with invasion of joint spacesand adjacent boneand/or soft tissue, but manyof thesedevelopments are to be at- tributed to incorrect initial treatment. The existenceof a "primary malignant chondroblastoma"is still questionable.The exceptional casesof malignantevolution which have been reported may be divided into the following categories:(1) Chondroblastomawith sarcoma- tous transformation,with or without prior radiationtherapy ("secondary" malignant tumours). (2) Chondroblastoma exhibiting benign-appearinglung metastases. These metastases usually develop subsequentto surgery.They usuallybehave in a relativelybenign fashion,with the exceptionof the one reportedby Kyriakos et aI.,1 which pursueda malignantcourse. Unfortunately there are asyet no histologicalparameters that permit determinationof which metas- taseswill ceasetheir growth or which will progressand kill the host. (3) Chondroblastoma-likechondrosarcoma, i. e. a chondrosarcoma resemblinga chondroblastoma.

2.I.4 Chondromyxoid Fibroma (Figs.56-5 9)

A benign tumour characterizedby lobulatedareos of spindle-shaped or stellatecells with abundantmyxoid or chondroid intercellularmate- rial, separatedby zonesof more cellular tissuerich in spindle-shaped or roundedcells with a varyingnumber of multinucleatedgiant cellsof differentsi7es. Large pleomorphic cellsmay bepresent and can result in confusion with chondrosarcoma.However, atypical mitosesare lacking.

I Kyriakos M, Land VJ, PenningL et al. (1985)Metastatic chondroblastoma: report of a fatal casewith a review of the literature on atypical, aggressive,and malignant chondroblastoma. Cancer 55: 1770-1'189 Cartilage-FormingTumours17

Theselesions are usuallysituated in the metaphysealregion of a long bone,particularly the uppertibia, and producean expansionof part of the cortex.Lesions of the tarsaland metatarsalbones are not infrequent.The patientsare adolescentsor youngadults, males and femalesbeing affectedin equal numbers.Radiologically, the lesions appear as eccentric,sharply outlined, radiolucent areas that often causeexpansion of the bone.They have a thin scleroticinner border. Prior to the descriptionof chondromyxoidfibroma thesecases were often diagnosed as myxomas or chondromyxomas.Except in the jaws,true myxomasof bone very rarely,if ever,occur. As noted, occasionaltumours show a combination of the histologicalfeatures of chondromyxoidfibroma and chondroblastoma. The lesionsmay recur after curettage,but malignantchange is extremelyrare.

2.2 Malignant

2.2.1 Chondrosarcoma(Figs. 60-69)

A malignant tumour characterizedby theformation of cartilage,but not of bone,by thetumour cells.It is distinguishedfrom chondromaby itshigher cellularity,greater pleomorphism and appreciabrenumbers of plump cells with large or double nuclei. Mitotic cellsare infrequent. chondrosarcomasshow wide variation in their clinical and histological featuresand behaviour,and severaldifferent variantsbesides the conventionalcentral chondrosarcoma may be observed. Chondrosarcomasare relatively common. They usually occur in patientsbetween 30 and 60 yearsof age,and arerare in individualsun- der20 years.In contrastto benigncartilaginous tumours, the majority of which occurtoward the peripheryof the limb, chondrosarcomasare found mainly in the pelvis,femur, ribs, shoulder girdle and humerus. chondrosarcomasusually originate in the centraltissue of a bone (however,see Sect.2.2.2 on juxtacorticalchondrosarcoma). Some arise de novo; others, sometimes referred to as secondary chon_ drosarcomas,have their origin in a pre-existingbenign cartilagetu- mour, most frequently in multiple hereditary exostoses(peripheral or exostoticchondrosarcoma) or multiple enchondromatosis(ollier disease)Figs.68,69). The histologicaldistinction betweenbenign and malignant cartilagetumours is sometimesdifficult. The following criteria are helpful 18 Definitions and ExplanatoryNotes in diagnosingchondrosarcoma: plump and multinucleatedcartilage cells, the permeation of the tumour through host cancellousbone' replacingmarrow and trapping or encasingthe host bone'slamellar trabeculaeon all sidesand endostealscalloping and/or focal cortical destruction,often associatedwith cortical thickening. Chondrosar- comasare quite variablein their histologicalstructure and behaviour, and an attempt should alwaysbe made to distinguishbetween slowly growing and relatively benign, well-differentiated lesions on one hand,and rapidly growing,more malignant,poorly differentiatedtumours on the other. Tumourswith more or lessconspicuous myxoid areasshould not be confusedwith the so-calledmyxoid chondrosarcoma'an entity with distinctive histological and ultrastructural features not infrequently found primarily in the deepsoft tissuesof the extremities,but extremelyrare within bone.They havealso been referred to as"chot- doid sarcoma". The tissueof a chondrosarcomafrequently showsareas of calcification and enchondral ossification,but bone formation by the tumour cellsis seenonlv in osteosarcoma.

2.2.2 J uxtacortical ( Periosteal) Chondrosarcoma (Figs. 7 0-72 )

A malignant cartilage-formingtumour arisingfrom the externaLsur- face of a bone,possibly of periostealorigin, usually characterizedby welt-differentiatedlobulated cartilagewith extensiveareas of spotty calcificationand enchondralossification; however, tumour osteoidor boneis absent. Lesions of this type are rare, and possiblyrepresent a cartilage counterpartof periostealosteosarcoma. The lesioninvolves the shaft of a long bone,most often the femur,and occursin adolescents'with a predominancein males. Characteristically,the tumour is small and adjacentto the cortex; sometimesit showsareas of spotty calcification, radiating bone spiculesand often a typical Codman triangle. Thesetumours have a better prognosisthan the similar central type of chondrosarcoma.A juxtacortical (periosteal) chondrosarcoma must be distinguishedfrom a chondrosarcomaarising as a result of malignant changein the cartilageof an osteochondroma(peripheral or exostoticchondrosarcoma), a changemore commonly associated with multiple hereditaryosteochondromas. Cartilage-FormingTumours 19

2.2.3 Mesenchymal Chondrosarcoma (Figs.73-75)

A malignant tumour, characterizedby thepresence of scatteredareas of more or lessdifferentiated cartilage together with highly vascular spindle-cellor round-cell"mesenchymal" tissue, often with a haeman- grcpe r r c y lo ma lous p oI lern. These tumours are relatively rare, but have characteristichisto- logical featureswhich justify their separationas a distinctive malignant cartilage tumour. They are generally highly malignant; nearly one-third originate in juxtaosseoussoft tissue;multifocal lesions haverarely beenreported.

2.2.4 Dedifferentiated Chondrosarcoma (Figs.76-78)

A highly anaplasticsarcoma juxtaposed to a borderlineor low-grade malignantcartilage tumour. Thereis typicallyan abrupt transitionbe- tweenthecomponents. "Dedifferentiation" of a histologicallylow gradeand clinicallyin- dolent cartilage tumour occurs in approximately 1.0"/"of all chon- drosarcomas.Although there is a question over the accuracyof the concept of dedifferentiation in the pathogenesisof this tumour, the term "dedifferentiatedchondrosarcoma" continues to be usedas a distinct,well-defined entity becauseit remainsuseful to indicate the tumour's more aggressiveand malignant behaviour and poor prognosis.The tumour involvesmost frequently the long bones,particularly the femur, humerus,and pelvis;almost all are associatedwith a central chondrosarcoma.There is a wide range of age from 20 to 80 years.

2.2.5 Clear-Cell Chondrosarcoma (Figs.79-81 ) A tumour of low-grade malignancy characterizedby rounded cells with conspicuousclear or vacuolatedcytoplasm and by a cartilaginous or chondroid matrix in at leastsome areas.Scattered osteoclast-type giant cells,occasional bone trabeculaeand aneurysmalbone cyst-like areasmay bepresent. Clear-cellchondrosarcoma is consideredby someas a rare variety of chondrosarcoma,and by others as an atypical,more aggressive chondroblastoma or its malignant counterpart. It usually affects adults, most commonly involving the proximal part of the femur, humerus or tibia. These are sites similar to those of chondroblas- 20 Definitionsand Explanatory Notes toma, which often showssimilar radiographicfeatures. Clear-cell chondrosarcomasoften recur after simple curettage but rarely metastasize,therefore a more aggressivetreatment (resection) than that usedfor chondroblastomahas been advocated.

2.2.6 Malisnant Chondroblastoma (Figs.82-84)

The existence of this entity is questionable. For discussionsee Sect.2. 1.3, chondroblastoma.

3 Giant-Cell Tumour (Osteoclastoma)(Figs.85-95)

An aggressivetumour, characterized by richly vascularizedtissue consistingof ratherplump spindle-shapedor ovoid cellsand by thepresence of numerous giant cells of osteoclasttype, which are uniformly distributedthroughout the tumour tissue.There is relativelylittle collagen.Areas ofhaemorrhage and ofregressivechanges, such as necrosis, fibrosis andfibrohistiocytic reaction, are frequently present, especially in largeror longstandingtumours. Most giant-celltumours occur in patientsbetween 20 and 40 years of age.They arerarely seen in patientsbelow the ageof 15 yearsand areextremely rare underthe ageof 10 years;this helpsto distinguish them from certainbenign lesions that were previouslyregarded as giant-cell tumours or variants (chondroblastoma,chondromyxoid fibroma, aneurysmalbone cyst, metaphysealfibrous defect), but are now regarded as separateentities. Giant-cell tumours typically involve the endsof the long bones,common sitesbeing the lower end of the femur, the upper end of the tibia and the lower end of the radius. The tumours are osteolytic.They originate towardsthe medial or lat- eral aspectsof the endsof the bones,close to the articularcartilage; later the tumour occupiesand even expandsthe entire end of the bone and the adjacentmetaphysis. Men and women are affectedwith about equalfrequency. Giant-cell tumours can no longer be considered innocent growths.They presentwith few exceptionsas aggressive,potentially malignant lesionsthat recur in about 20%-50% of patientsafter in- cisional excision (curettage),undergo sarcomatoustransformation in about 57"-10"h of patients, and even produce in rare instances Dulmonarv metastaseswithout histolosical evidence of malisnant Giant-CellTumour 27

changes.Synonyms have been "low-gradeneoplastic giant cell tumour" or "semimalignantgiant-cell tumour,'. Casesof apparentlymetaphyseal origin in adolescentpatients with an immature skeletonoccur rarely.There are also some exceptionalcases with a diaphyseallocation. In the past, attemptswere made to histologically,,grade" the tumours into benign, aggressiveand malignant variants.These criteria have not proved to be satisfactory,however, and there is today no agreementon specifichistological features that dependablyin_ dicate the likelihood of malignant behaviour.In this sense,all giant- cell tumours are potentially malignant.At present it is not possible to predict clinical behaviour on the basis of histological strucrure, and thus distinguishbetween "benign,, and ,,malignant"varieties. The radiographic features dividing giant-cell tumours into three categories(grade I, quiescent;grade II, active,and grade III, aggressive) seem to be more important than histology for prognosisand treatment.Many casesof the quiescentradiological type, which gen_ erally have a more favourable prognosis, show a predominantly fibroxanthomatoushistological pattern, and rarely if ever recur after excision. So-calledprimary malignant giant-cell tumours seem to be extremely rare, and no clearhistological criteria for their diagnosishave been established.The apparentincidence varies widely in different institutions.In most casesmalignant change has occurred subsequent to the presence of a histologically verified benign tumour (,,secondary"malignant giant cell tumour). The therapyhas included irradiation in almostevery instance; only in exceptionalcases has the malignant tumour, usually a fibrosarcomaor osteosarcoma,developed ,,primary after curettage only. Most other casesreported as malignant giant-celltumour", in which zonesof typicalbenign giant-cell tumour tissue are present in associationwith some other type of clearly malignant neoplasm,are more likely other types of sarcoma that happen to be richly endowedwith multinucleatedgiant cells of the osteoclastictype. The majority of theseneoplasms appear to be telangiectaticor giant-cell-richosteosarcomas, fibrosarcomas or malignant fibrous histiocytomas.Primary diffusely malignant giant-cell tumourwith a roentgenogramconsistent with the diagnosisof typical giant-celltumour is extremelyunusual. Multicentric bone involvement by giant-cell tumours is unusual and may appearsimultaneously or metachronously.It is necessaryto excludehyperparathyroidism. 22 Definitionsand Explanatory Notes

The histogenesisof giant-cell tumour is still unclear.The giant cellsof the giant-celltumour and its so-calledvariants are similar to normal osteoclasts,and their identical histochemicalbehaviour and ultrastructuralsimilarity indicate a closerelationship; hence the use of the term "osteoclastoma"seems to be justified.Most authorities agree that the multinucleated giant cells are derived from mono- nuclear stromal cells,possibly of undifferentiatedmesenchymal cell origin, or from cellsof histiocyticmacrophage origin, either by agglu- tination or conglomeration.Much lesslikely is an origin of the giant cellsby mitotic division of stromal cellsin the absenceof cytoplasmic segmentation. The formation of bone or osteoidtissue is occasionallyseen in giant-celltumours. It usuallyappears to be reactivein nature' although the possibilitythat the tumour cellscan themselves form bone hasnot beencompletely excluded.

4 Marrow Tlrmours(Round-Cell Tirmours)

4.1 Ewing Sarcoma (Figs.96-103)

A malignant tumour with a rather uniform histologicalappearance composedof denselypacked, glycogen-rich small cellswith round nuclei but without prominent nucleoli or distinct cytoplasmicoutlines. The tumour tissueis typicallydivided into irregular strandsor lobules by fibrous septa,but theintercellular network of reticulinfibres, which is a featureof malignantlymphoma, is not seen.Mitoses are generally infrequent. Haemorrhageand extensiveareas of necrosisare common. The nature and origin of this tumour have been debated since Ewing (192\) describedit asan "endothelial myeloma". The difficulties of differential diagnosiswithin the group of malignantround-cell tumours of bone, and specificallyof separationbetween Ewing sarcoma,malignant lymphoma and metastaticneuroblastoma, are well known. The presence of intracellular glycogen in alcohol-fixed specimensand evenafter neutral formalin fixation aidsthe diagnosis of Ewing sarcoma, as glycogen is typically absent in lymphoma and most cases of neuroblastoma. The urinary excretion of catecholaminesshould be determined in all casesof this type, as it is increasedin a high proportion of cases(approximately 80o/o) MarrowTumours 23 of neuroblastoma.Silver stains show a lobular distribution of the reticulin fibres circumscribing large areas of tumour cells. In the zones of necrobiosisthe nuclei of the tumour cells are often small and pyknotic,about the sizeof a lymphocyte.Pseudorosettes or tumour cellsof larger sizeare presentin sometumours, making the distinction from primitive neuroectodermaltumours of bone (PNET) difficult. Ewing sarcomausually occursin patients between the agesof 5 and 15 years.The commonsites are the shaftsand metaphysesof long bones (femur, tibia, humerus and fibula) although some flat bones (pelvis or scapula)may alsobe involved. On X-ray examinationthe tumours are usuallyseen to be osteolyticbut the bone destructionis often associatedwith patchy reactive bone formation or with periosteal bone formation, which may show a characteristic"onion- skin" appearance. Ewing sarcoma metastasizesearly, to the lungs and to other bones.The strikingtendency to involveother boneshas suggested a multicentricorigin. Metastasis in regionallymph nodesor to the central nervoussystem is infrequent.

4.2 Primitive NeuroectodermalTumour of Bone (PNET) (Figs.104-106)

A rareand highly malignanttumour thatresembles the peripheral neu- roepithelioma of soft tissues. Its distinction from Ewing sarcoma, whenbased solely on routinemicroscopy, is difficult and uncertain. PNET is characterizedhistologically by the presenceof numerous Homer-Wright rosettesor pseudorosettesdistributed in a hap- hazardfashion, and by a greater degreeof cellular and nuclearpleo- morphism than in Ewing sarcoma.Glycogen depositsare presentin abouthalf the cases.Electron microscopy shows the presence of neu- rosecretorygranules, intermediate filaments and neurotubule-like structures. However, unlike in metastatic neuroblastoma,urinary catecholamineexcretion is negativein PNE! and this helpsto distin- guishthese lesions. In recent yearsthe distinction between PNET and Ewing sarcoma has also been basedparticularly on the resultsof immunohisto- chemicalstaining with neuron-specificenolase (NSE) and other neural markers(HNK-1, HBA-71 and others).These can be expectedto be positive in PNET. However,they have alsobeen found positivein 24 Definitions and ExplanatoryNotes severalcases in whichthe otherhistological features are those of Ew- ing sarcoma.Moreover, the presenceof a reciprocal 11:22 chromo- some translocationshared by both tumours suggestsa histogenetic relationship.At presentit is a matter of debatewhether all Ewing sar- comasare actuallyPNET, or whether the diagnosisof PNET should be restrictedonly to atypicalEwing sarcomasdisplaying morphological evidenceof neural differentiation.

4.3 Malignant Lymphoma of Bone (Figs.107-110)

A malignantlymphoid tumour consideredto beprimary in the bone. There can be a rather varied histologicalstructure. The tumour cellsare usuallyrounded and rather pleomorphic and may havewell- defined cytoplasmic outlines; many of their nuclei are indented (cleaved)or horseshoe-shapedand have prominent nucleoli. In most casesnumerous reticulin fibres are present and are distributed uniformly betweenthe tumour cells. This tumour was formerly referred to as "reticulum-cell sarcoma", first describedby Parker and Jacksonas a primary lesion to be regardedas distinct from Ewing sarcomabecause of its characteristic histology and better prognosis.The tumour cells were then considered of histiocytic origin. Since the advent of newer classifications (Lennert, Lukes and Collins) of the non-Hodgkin lymphomas,it has beenshown that the majority of "histiocytic" tumours were in fact B- or T:cell lymphomas,and that true "histiocytic" lymphomasare rare' Although the classificationof nodal lymphomas has undergone great changes,no definite and universally accepted classification schemehas been developed,particularly for the rare primary lym- phomasofbone. "Primary" lymphoma of bone is defined as a solitary osseousle- sionwithout involvement of otherosseous or nonosseoussites within 6 months on the onset of symptoms.The involvement of regional lymph nodesdoes not excludethe diagnosisof primary lymphoma of bone. Given this definition it becomesevident that many of the lym- phomasreported in the older literature as "primary" in bone cannot be acceptedas such by presentstandards because they were not ade- quatelystaged. Furthermore, they did not havethe benefit of the new staging procedures such as radionuclide scanning, computed to- mographyand magneticresonance imaging. Most of thesecases were MarrowTumours 25 probably secondarydeposits in bone derived from tumours of lymph nodesor from other extranodallesions, which, althoughmorphologi- cally indistinguishable,have a different clinical behaviour and a worseprognosls. Malignant lymphoma of bone can occur at any age,but is most common in patientsover 20 yearsof age,differing from Ewing sarcoma in this respect.The long bones,ilium and spineare commonly af- fected.The lesionsare most often ill-defined, mixed lytic-blasticto purely lytic; however,sometimes there is widespreadinfiltration of bonewithout much alteration in radiographicappearance. Histologically,all reported casesof primary lymphoma of bone are of the diffuse type. The tumour cells are generallysubclassified accordingto nuclearsize and shapeas cleaved, non-cleaved or pleomorphic. The great majority are large cleavedcells. The prognosis seemsto be more favourable in tumours with a predominantly cleaved cell population. Very rarely primary bone lymphomas are composed predominantly of well-differentiatedlymphocytic cells. These must be distinguishedfrom secondaryinvolvement from a nodal lymphoma.In either type, primary or secondary,leukaemic changesin the peripheralblood frequently develop.

4.4 Myeloma (Figs.711-Il4)

A malignant tumour, usually with multiple or diffuse bone involvement,by neoplasticplasma cells showing varying degrees of immaturi- ty, including atypical forms. The lesions are often associatedwith the presenceof abnormalproteins in the blood and urine,and occasionally with thepresence of amyloid or para-amyloidin thetumour tissueor otherorgans. Most casesof myelomapresent with multiplebone lesions ("multiple myeloma", "myelomatosis"),this being one of the most frequent malignantconditions of the skeleton.It usuallyoccurs in patientsbetween 50 and 70 yearsof age;the commonsites are the spine, pelvis,ribs, sternum, skull andthe metaphysisof the longbones, that is,the bonesthat containred marrow in the adult. The lesionsappear either asfocal osteolyticareas or as areasof diffuse marrow replace- ment without alterationin bone structure.Exceptionally, myeloma may appearas a sclerosingdense radiographic lesion, either solitary or disseminated,which is associatedin aboutone-third of the patients with progressiveperipheral neuropathy. 26 Definitionsand E,xplanatory Notes

Abnormal valuesfor certainlaboratory tests (anaemia, increased plasma globulin, elevated erythrocyte sedimentation rate, monoclonal spike in globulin fraction of serum electrophoresis,Bence Jonesproteins in the urine, hypercalcaemia)are generallydiagnostic for myelomatosis.These tests are usuallynegative in patientswith solitary myeloma. In the later stagesof the diseaserenal insufficiencymay occur, due to deposits of Bence Jones protein in the renal tubules, nephrolithiasissecondary to massiveosteolysis and hypercalcaemia and amyloidosis.This is the most seriousand lethal complication- Much more rarely, an apparently single bone lesion is found to havethe histologicalstructure of myeloma.These cases usually occur in a younger age group than multiple myeloma. A diagnosisof solitary myelomamust alwaysbe approachedwith caution,as the majority of casesprogress to generalizedmyelomatosis. Waldenstrommacroglobulinaemia is a rare neoplasticdisease of the haematopoieticsystem, related to multiple myeloma, differing only in that the cells are plasmacytoidwith lymphocyte-like nuclei and produce a monoclonal high molecular weight protein, the IgM macroslobulin.

5 VascularTumours

Vasculartumours of bone show a wide range of histologicalappearance,varying from well-differentiatedvasoformative lesions to highly anaplastictumours. It is sometimesdifficult to make a cleardistinc- tion between the relatively common haemangiomasand the rare angiosarcomas.The existing nomenclature of malignant vascular tumours is confusing. The terms "haemangiosarcoma","haemangioendothelioma"and "haemangioendotheliosarcoma"have been usedas synonyms,and havebeen applied to a wide variety of malignant vasculartumours. At the sametime, theseentities are generally divided into different grades,from well-differentiated (grade I haemangioendothelioma)to poorly differentiated (grade III haemangioendothelioma). The rare haemangiopericytomaoriginating in bone is consideredin all reports a distinct entity. In view of the confusion still prevailing, the present schemeof classificationseparates malignant vascular lesions of bone into an intermediateor indeterminategroup (essentiallylow-grade tumours), VascularTumours 27 which includeshaemangioendothelioma and the rare haemangiopericytoma, and a clearly malignant group, angiosarcoma(haemangiosarcoma).Some casesof haemangiopericytomamay present frankly ma'lignanthistological features and a metastatic potential, and are alsoincluded in the malignantgroup. An indisputablecase of lymphangiosarcomaof bonehas not yet beenreported.

5.1 Benign

5.1.1Haemangioma (Figs. 115, 116)

A benign tumour or malformation consistingof well-formed blood vesselsof eithera capillaryor a cavernoustype. A clear distinction between some capillary haemangiomasand well-differentiatedhaemangioendotheliomas may sometimesbe difficult. Some of these lesionsare clearly malformations; others, because of their growth potential, are regarded as benign tumours. They occur most commonly in the vertebrae,often without clinical symptoms,and also in the skull, where they commonly produce a characteristic"sun-ray" radiologicalappearance. Multiple haemangiomas("systematized haemangiomatosis") of bone are encountered;they may or may not be associatedwith soft tissuehaemangiomatosis. So-called massive osteolysis ("disappear- ing" or "phantom" bone disease)is a rare conditionpossibly related to haemangiomatosis.

5.1.2 Lymphangioma

A benign tumour or malformation consistingof lymph vessels,usually in theform of dilated cysticspaces. Theselesions are extremelyrare. Virtually all casesshow multiple skeletalinvolvement. They often occur in associationwith soft tissue lesionsof the sametype.

5.1.3 Glomus Tumour (Glomangioma)

A benign lesion consistingof uniform cells with round regular nuclei, sharply definedcell bordersand pale cytoplasm,intimately associated with vascularstructures and probably derivedfrom theneuromvoarte- rial glomus. 2U Definitions and ExplanatoryNotes

The occurrenceof glomus tumours of the skeleton is extremely rare, but authenticatedcases have been describedwithin a terminal phalanx.More common is the erosion of bone by a glomus tumour originatingin the adjacentsoft tissues.

5.2 Intermediateor Indeterminate

5.2.1Haemangioendothelioma (Figs. 117-120)

An aggressive,but virtually nonmetastasizingtumour characterized by thepresence of solid cell cordsand vascularendothelial structures. The endothelialcells are oftenprominent and plump, but thefrankly malignanthistological features of angiosarcomaare lacking. A reticulin stain is important for the recognition of this entity. Haemangioendotheliomasare rare tumours.Those with a predomi- nance of epithelioid or histiocytoid endothelial cells have been referred to as "epithelioid haemangioendotheliomas","histiocytoid haemangiomas"and "myxoid angioblastomas".In general,they havethe samehistological features as the soft tissuetumours that are referred to by the samename. They commonly recur locally after excision,but rarely metastasize.In about one-third of cases,multiple bone lesions,usually in the sameextremity, may be present. The terms "haemangioendothelioma"(graded I-III) and "haemangiosarcoma"are usedinterchangeably by someauthors.

5.2.2 Haemangiopericytoma (Fig. 121 ) An aggressivetumour characterizedby a pattern of vascularspaces lined by a singlelayer of endothelialcells surrounded by zonesof pro- liferating cells. Only a small number of tumourswith a histologicalstructure similar to that of haemangiopericytomaof soft tissueshave been reported in the skeleton.The exacthistological criteria for the recognition of haemangiopericytoma,and for the separationof low-grade and malignant variants, have not yet been satisfactorily defined. The perivascularpattern of thesetumours canbest be recognizedin reticulin preparation. Other ConnectiveTissue Tumours 29

5.3 Malignant

5.3.L Angiosarcoma(F igs. 122-725)

A malignanttumour characterized by theformation of irregularanas- tomosingvascular channels lined by oneor morelayers of atypicalen- dothelial cells,often of immature appearance,and accompaniedby solid massesof poorly differentiatedor anaplastictissue. Angiosarcomasof bone are rare, and it must be emphasizedthat other highly vascular tumours, particularly the relatively common telangiectaticosteosarcoma, are sometimeserroneously diagnosed as angiosarcoma.A positive immunocytochemicalreaction for factor VIII or for (Jlexlectin canbe usefulin identifying the vascularna- ture of a poorly differentiatedmalignant tumour. Angiosarcomasare highly malignant tumours that metastasize rapidlyto the lungs.Multiple angiosarcomasof bone,or of bone and soft tissues,can occur.Synonyms include "haemangiosarcoma"and "malignanthaemangioendothelioma".

5.3.2 Malignanthaemangiopericytoma

Somecases of haemangiopericytomashow evident features of malignancy,frank anaplasiaand metastatic potential, associated with a bad prognosls.

6 Other Connective TissueTumours

6.L Benign

6.1.1Benign Fibrous Histiocytoma

A benignlesion characterized by thepresence of spindle'celledfibrous tissuewith a storiform pattern and containing a variable number of multinucleatedgiant cells,hemosiderin pigment and lipid-bearinghis- tiocy te s (xanthoma cells ). Thesehistological features are identical to those of metaphyseal fibrous defect (fibrous cortical defect and nonossifying fibroma). However, almost all authoritiesconsider metaphyseal fibrous defect a non-neoplasticlesion (possibly a developmentalanomaly), since it 30 Definitionsand Explanatory Notes is often self-limitedor may becomeossified and disappear.The term "benign fibrous histiocytoma" implies a neoplasm,and its existence as a separateentity is basedon clinical differencesfrom metaphyseal fibrous defect.These clinical differencesinclude an older age of the patientsand the lesionbeing confined to the diaphysisor epiphysisof long bones,or to the pelvisand ribs,clavicle or spine.Moreover, the lesion is generallypainful even in the absenceof fracture. Some exceptional casesof atypicalfibrous histiocytomahave been reported, but their histologicalfeatures are not yet clearlydefined.

6.1.2 Lipoma

A benigntumour of matureadipose tissue with no evidenceof cellular atypm. There are two types of lipoma, an intraosseousand a periosteal type,the latter usuallyinducing new bone formation. Although these lesionsconstitute an establishedentity, they are rare. They usually occurin adults,and may be mistakenfor other more serioustypes of lesions,or maybe associatedwith a boneinfarct. A varietyof skeletal sitesare involved,most commonly long bonesand calcaneus. Angiolipomatous malformations,usually of the vertebral bodies, havebeen described, but they shouldbe distinguishedfrom true lipo- mas.

6.2 Intermediate

6.2.1Desmoplastic Fibroma (Figs. 126-128)

A benignbut locally aggressivetumour characterizedby theformation of abundant collagenfibres by the tumour cells. The tissueis sparsely cellular,and the nuclei are ovoid or elongated.The cellularity,pleomorphism and mitotic activity which arefeatures of fibrosarcoma are lacking. The term "desmoplasticfibroma" was appliedby Jaffe in 1958to describea group of rare fibrous tissuelesions in bone,distinct from fi- brosarcomaon the one hand and from variousbenign lesionson the other,presenting often a locally aggressivebehaviour. Histologically, the lesionsresemble "desmoid tumours" of soft tissues.The tumours usuallyoccur in adolescentsor young adults and involve a variety of skeletalsites, including long bones,vertebrae and pelvis.Local recur- OtherConnective Tissue Tumours 31 rence sometimesfollows excision.but no metastaseshave been reported. The distinction between desmoplasticfibroma and well-differentiatedfibrosarcoma is often difficult. A small lesion originating beneath the periosteum and eroding the underlying cortex is referred to asa "periostealdesmoid", which thoughconsidered to be a periostealvariant of desmoplasticfibroma, is a reactiverather than a neoplasticlesion.

6.3 Malignant

6.3.1Fibrosarcoma (Figs. 129-131)

A malignant tumour characterizedby the formation by the tumour cells of interlacing bundles of collagenfibres, and by the absenceof other typesof histologicaldifferentiation, such as cartilage or bone. Fibrosarcomasof bone were originally classifiedwith osteosarcomas,but the view that they should be regarded as a separategroup hasbecome generally accepted. Fibrosarcomasusually involve long bones,particularly the lower part of the femur and the upper part of the tibia. They occur in older patients than do osteosarcomas,mostly in persons from 20 to 60 yearsof age.Radiologically, they appearas osteolytic,poorly defined lesions.Fibrosarcomas are a variablegroup asfar astheir histologicalstructure is concerned.Some are highly differentiated,rich in collagen,and show only slight mitotic activity or cellular pleomorphism,while others are relatively undifferentiated.There is someev- idencethat the highly differentiatedtumours havea better prognosis thanthe others. It may be difficult, particularlyin limited biopsyspecimens, to distinguish between poorly differentiated fibrosarcomas,osteosarcomas containingonly a small amount of tumour bone, and poorly differentiated or undifferentiated tumours of other types. Similarly, it may be difficult with a limited sampleof tissueto distinguisha highly differentiatedfibrosarcoma from a desmoplasticfibroma. Many cas- esformerly classifiedas pleomorphic fibrosarcomaare at presentre- ferred to as"malignant fibrous histiocytoma". 32 Definitions and ExplanatoryNotes

6.3.2 Malignant Fibrous Histiocytoma (Figs.732-735)

A rather infrequenthighly malignant tumour of bone with the same vqriablestructure as the more common tumour of soft tissue.It is characterizedhistologically by bundles of collagenfibres and spindle- shapedfibroblast-like cells arranged in a storiform or " cartwheel"pattern togetherwith rounded cellsshowing features of histiocytes.The latterhave ovoid, indentednuclei and cytoplasmwith phagocytic activity and can transform into foam cells. The tumours frequently contain cellswith bizarre,pleomorphic and multiple nuclei. Typicalmultinu- cleatedgiant cells of osteoclastictype as well as atypical onesare often found. Mitotic activityand cellularatypia are common. Relatively con- spicuousinflammatory cells,predominantly lymphocytes, are charac- ter6trc. Radiographsshow a radiolucent lesion with poorly defined per- meative margins destroyingthe cortex and often extensivelyinvad- ing extraosseoussoft tissues.Malignant fibrous histiocytomausually occursin adultsand commonly involvesthe long bones,predomi- nantlythe metaphysealregion of the femur or the tibia. An associa- tion with boneinfarct is not infrequent,and a possibleaetiologic relationship has been suggested.Some authorsaccept the presenceof infrequent areasof bone or cartilageas consistent with the diagnosis of malignantfibrous histiocytoma,but this is not acceptedby others, who classifysuch a lesion asosteosarcoma with a predominant fibro- histiocyticpattern. Malignant fibrous histiocytomaof bone seemsto be overdiag- nosed.A wide biopsy or thorough study of the operativespecimen is often necessary.Immunohistochemical studies and electron mi- croscopymay be helpful by excludingother lines of specificdifferen- tiation.

6.3.3 Liposarcoma

A malignant tumour characterizedby lipoblastic differentiation,as shownby thepresence of atypicallipoblasts. This is an exceedinglyrare type of bone tumour, althoughauthen- ticated caseshave been reported. They almost invariably occur in long bones,usually in tibia and femur. Other ConnectiveTissue Tumours 33

6.3.4 Malignant Mesenchymoma (Figs.136-138)

A malignanttumour characterizedby thepresence of multiple typesof connectivetissue differentiation,particularly those not usually en- counteredin theskeleton. This is an exceedinglyrare type of tumour and needs further study.The few reported casesshow a combination of osteosarcoma- tous and liposarcomatouscomponents. These tumours havebeen re- ferredto as"primary osteoliposarcomaof bone".

6.3.5 Leiomyosarcoma

A rare malignant tumour characterizedby intersectingbundles of spindle-shapedcells with elongated,blunt-ended, central nuclei and scant fib rillar cyto p lasm, r esembling smo oth muscle differentiation. Thereare variabledegrees of nuclearatypia and pleomorphism,with thepresence of hyperchromaticor bizarre nuclei and generallyin.fre- quentmitotic activity.The stroma variesfrom areaswith scarcefibres to broad hyalinizedfibrous zones. Leiomyosarcomaof bone is more common in elderly patientsand involvespredominantly long tubular bones,especially the femur and tibia.about the knee. Radiographically,leiomyosarcoma appears as an ill-defined osteolytic lesion, with features very similar to those of fibrosarcoma. Electron microscopyand immunohistochemicalstudies with smooth musclemarkers (actin and desmin) aid in diagnosisand separation from fibrosarcoma. The courseof osseousleiomyosarcoma is variable and seemsre- lated to the gradeof histologicaldifferentiation.

6.3.6 Undifferentiated Sarcoma (Fig. 139)

A malignant tumour with a pleomorphic spindle-celledstructure but devoid of any specificpattern of histological differentiation. In a limited biopsy specimen,a poorly differentiated fibrosarcoma, an osteosarcomawith relatively little tumour bone,a lymphoma, or even an undifferentiatedmetastatic carcinoma can posepractical difficulties of identification and thus be confusedwith casesproperly belongingto this group. Even after the study of adequatesamples of tissue, including cytomorphological and immunohistochemical methods,and subsequentfollow-up investigation, rare casesremain 34 Definitionsand ExplanatoryNotes in whichthe tumour isregarded as primary in bonebut whereno specific pattern of differentiationcan be detected.Consequently, this groupis regarded as an essentialpart of the classification.

7 OtherTumours

7.1 Chordoma (Figs.140-143)

A locally aggressiveor malignant tumour characterizedby a lobular arrangementof tissue,which is usuallymade up of cordsand sheetsof highly vacuolatedcells ("physaliphorous cells") and mucoid intercellular material. Thesetumours are almostalways restricted to the axialskeleton; this,together with their histologicalstructure, suggests that theyorig- inate from notochordal tissue.Although often regarded as arising from developmentalremnants of notochord, chordomasare usually found in patients over 40 yearsof age.Men are more commonly af- fected than women. The sacraland spheno-occipitalregions are the commonestsites. The interveningvertebrae are involved only rarely. Half the vertebral lesionsoccur in the cervicalspine. Chordomasare slowly growing tumours.They infiltrate adjacent structuresand recur after local resection.Although thesetumours almost invariably prove fatal, metastasesdevelop rarely and then usually at a late stageafter many attemptsat local surgicaltreatment. The histologicaldistinction between chordoma and chondrosar- comais sometimesdifficult. Somechordomas of the spheno-occipital region contain more or less extensivechondrosarcoma-like areas, and are known as"chondroid chordomas". The positiveimmunocy- tochemical reaction for cytokeratin identifies them as chordomas, chondroid variant. A mucin-secretingcarcinoma may mimic the histological appearanceof chordoma,but the cells of a chordoma contain glycogenand not mucin. Somechordomas have a more cellular and pleomorphic histologicalstructure than others,but this pattern does not appear to show any clear correlation with either rate of growth or frequencyof metastasis.However, it seemsthat the chondroid chordomashave a much better prognosisthan classicchordo- mas. OtherTumours 35

7.2 Adamantinoma of Long Bones (Figs. 1a4-Ia6)

A malignant, or at least locally aggressive,tumour characterizeclby a widerange of morphologicalpatterns, most commonly thepresence of circumscribed massesor tubular formation of apparently epitheliat cellssurrounded by spindle-celledfibrous tissue. This is a well-establishedbut rare tumour that almost invariably involvesthe shaftof the tibia at its anterior aspect.Radiographs show a lucent,frequently multilocular lesionwith scleroticbordeis. It usually occursin adults,although it seemsnot to be asrare in children under 10years of ageas was formerly reported.The peripheralcells of the supposedepithelial formations are columnar and palisaded, while the centralcells have a stellatearrangement and areieparated by spaces;this givesthe lesionsome degreeof resemblanceto the ameloblastoma("adamantinoma") of thejaw, and to other epithelial tumoursof the basal-celltype. The histogenesisis uncertain.The histologicalsimilarity to ameloblastomahas suggested an epithelialorigin, despite the para- dox of the intraosseoussituation of the tumours,and this appeirsto be confirmed by the resultsof electron microscopyand of immunohistochemicalstudies (keratin positiveand factor vIII negative). Not infrequently,adamantinoma may be associatedwith or mimic fibrous dysplasiaor osteofibrousdysplasia, and this hassuggested a closerelationship between these entities.

7.3 Neurilemoma

A benigntumour of nervesheath origin, having thesame morphologi- calfeatures as soft tissueneurilemomas, but originatingwithin a bone. Intraosseousneurilemomas are very rare, but a small number of authenticatedcases, most frequently involving mandible and sacrum and presumably arising from intraosseousnerves, have been reported.

7.4 Neurofibroma

A benign neurogenictumour of schwann celtsand fibroblasts having the same morphological features as soft tissueneurofibromas, but originating within a bone. 36 Definitions and ExplanatoryNotes

It is composedof spindle-shapedor stellatecells with elongated wavy nuclei.The stromais oedematouswith diffuselydistributed collagen fibres. Occasionally,cells with large pleomorphic nuclei are present,but mitotic activity is absent' Benign nerve sheath tumours associatedwith von Reckling- hausendisease are almost alwaysneurofibromas. Only a few casesof intraosseousneurofibroma appear to have been authenticated,although the term is more frequently usedin the radiologicalliterature. It is well known, of course,that other typesof skeletalchange, including scoliosis,growth disorders,congenital bowing and pseudarthro- sis,commonly occur in neurofibromatosis,but theseare not associated with the presenceof neurofibromatoustissue actually within the involved bones.Similarly, no casesof intraosseousmalignant neuro- genic tumours ("malignant schwannoma","neufosarcoma") have beenauthenticated.

8 UnclassifiedTirmours

Any large seriesof bone tumours includeslesions for which a specific classificationis not possible,either becausethe lesionsin question show featuresthat apparentlybelong to more than one group or because they show features that have hitherto been unrecognized. Thesecases, which make up a diversegroup and include both benign and malignanttumours, are regardedas unclassifiable. It is hoped,of course, that further study and experiencewill ultimately result in their more preciserecognition and classification.

9 Tumour-likeLesions

9.1 SolitaryBone Cyst (Simple or UnicameralBone Cyst) (Figs.147,148) by A unicameralcavity fitled with clearor sanguineousfluid and lined a membraneof variable thickness,which consistsof loose vascular connectivetissue showing scatteredosteoclast giant cells and some- timesareas of recentor old haemorrhageor cholesterolclefts' Solitarybone cystsare most frequently locatedin the metaphyses at the upper end of the humerusand the femur;they occurin children TumourlikeLesions 37 and adolescents.Bands or massesof fibrin-like material resembling odontogeniccementum, or of hyalinized or calcified connectivetissue, are commonly present in the tissueof the wall, and occasional bone trabeculaemay alsobe present.The grossand microscopicfea- tures are often modified by fracture.Based on the similarity between the bone cystfluid and seruma transitory circulatorydisturbance due to a developmentalvenous anomaly has been proposed as aetiology.

9.2 Aneurysmal Bone Cyst (Figs.149,150)

An expanding osteolytic lesion consisting of blood-filled spacesof variablesize separated by connectivetissue septa containing trabeculaeof boneor osteoidtissue and osteoclastgiant cells. Prior to its recognition by Jaffe in 1950 and by Lichtenstein in 1950,examples of aneurysmalbone cystwere usuallyregarded as giant-celltumours or telangiectaticosteosarcomas. It hasbeen accepted asan entity,although in somecases its histologicaldistinction from giant-celltumour may be difficult or evenimpossible. Aneurysmal bone cysts are usually seen in patients under 30 yearsof ageand involve either the shaftsof long bonesor the vertebral column, generally arising in the posterior osseouselements. They often have an eccentriclocation, which, with the "ballooned- out" distensionof the periosteum,was responsiblefor their name. Their rapid developmentand large sizemay suggesta malignant lesion,but in fact they are benign. Cystic changes,apparently secondary and closely resembling those of aneurysmal bone cyst, are sometimes present in benign chondroblastoma,giant-cell tumour, osteoblastomas,osteosarcoma and other lesionsand mav involve substantialareas of tissue.

9.3 Juxta-articularBone Cyst(Intraosseous Ganglion) (Figs.151,152)

A benign, cystic, and often multiloculated lesion, made up of fibrous tissue,with extensivemucoid change,situated in thesubchondral bone adjacentto a joint. The juxta-articularbone cystis a fairly common lesion,occurring in patientsof middle age.It usuallyinvolves the bonesadjacent to the hip joint, knee joint, ankle and carpal bones.In radiographs,it ap- 38 Definitionsand Explanatory Notes pears as a well-defined osteolytic area with a surrounding zone of sclerosis.It hasbeen described as a "synovialcyst", but it lacksa syn- ovial lining; the histologicalstructure resemblesthat of a soft tissue ganglion. Similar cysts occur in osteoarthritis, and more rarely in rheumatoid arthritis.

9.4 Metaphyseal Fibrous Defect (Nonossifying Fibroma) (Figs.153,154)

A well-defined,benign, non-neoplastic bone lesion,characterized by essentiallythe same histological features described in benign fibrous histiocytoma, that is,spindle-celled fibrous tissuewith a storiform pattern and containing a variable number of multinucleatedgiant cells, hemosiderinpigment and lipid- bearing histiocytes (xanthoma cells ). The term "metaphysealfibrous defect" has been used for many years and is purely descriptiveand noncommittal with respectto its histogenesis.Lesions ofthis type are alsoreferred to as"fibrous cortical defects","nonossifiying fibroma", "fibrous xanthoma" or "histiocytic xanthogranuloma". The lesionsusually involve the metaphysealregion of long bones in children or adolescents,most commonly at the lower end of the femur or the upper or lower end of the tibia. The fibrous cortical defect is a fairly common, small lytic intracortical lesion of children which often disappearsin a few yearsor may progressoccasionally, extending to the medullary cavity, representing the typical features of nonossifyingfibroma. It is characterizedas an eccentric,sharply outlined, osteolyticdefect surrounded by a thin shellof reactivebone. As growth proceedsit becomesprogressively more separatedfrom the growth plate. It is usually symptomlessand in some casesmay ultimately disappear.It may become painful only after a pathological fracture or when it occasionallyshows a progressive,conspicuous en- largement. Metaphysealfibrous defect may involve multiple bones and on rare occasionspresent extraskeletal anomalies (Jaffe-Campanacci syndrome). Tumour-likeLesions 39

9.5 EosinophilicGranuloma (Histiocytosis X, LangerhansCell Granulomatosis)(Figs. 155, 156)

A non-neoplasticlesion of unknown aetiology,characterized by an in- tenseproliferation of histiocyteswith varying numbers of eosinophilic leucocytes,neutrophilic leucocytes, lymphocytes, plasma cells and multinucleategiant cells.Zones of necrosisare frequent, as is thepresence of lipid-bearing foam cells, especially in multiple and older lesions. Either solitary or multiple lesionsmay occur,the latter aspart of the Hand-Schiiller-Christiansyndrome or of Letterer-Siwedisease. Theseall seemtobemanifestations of thesamebasicdisorder,which is sometimesreferred to as"histiocytosis X" or "reticuloendotheliosis". The histiocyteshave indented or lobulatednuclei, often with longitu- dinal groovesand abundant eosinophiliccytoplasm that containsS- 100protein.The cellsfrequently contain cytoplasmicinclusions called "Bierbeck granules",shaped like tennisrackets. They arecharacteris- tic of the Langerhanscells of the epidermis,and someauthors use the term "Langerhans histiocytosisor granuloma" for histiocytosisX. Children and adolescentsare usuallyinvolved, and common sitesfor bone lesionsin eosinophilicgranuloma include the skull, mandible, ribs, femur, vertebrae and flat bones.The lesionsare osteolytic,and may be associatedwith periostealreaction. Radiological distinction fromEwing sarcomaor osteomyelitisis sometimes difficult. When large numbers of eosinophilicleucocytes are present,the histologicaldiagnosis is usuallyobvious. Occasionally, however, particularly when eosinophilsare relatively infrequent and histiocytic cellspredominate, the histologicalappearance may resemblethat of Hodgkin diseaseor evenof non-Hodgkin lymphoma.

9.6 FibrousDysplasia and OsteofibrousDysplasia

9.6.1Fibrous Dysplasia (Figs. 157, 158)

A benign lesion, presumably developmental in nature, characterized by the presence of fibrous connective tissue with a characteristic whorled pattern and containing trabeculaeof immature nonlamellar (woven) bone, typically not lined by osteoblasts. Lesionsof fibrous dysplasiamay be solitary (monostotic)or multiple (polyostotic).The latter are occasionallyaccompanied by cuta- 40 Definitionsand Explanatory Notes

neouspigmentation and, in females,by precociouspuberty (Albright syndrome).Cartilage may be rarely presentin solitary and more frequently in multiple lesions.Rare solitary lesionswith considerable amountsof cartilageare referred to as"fibrocartilaginous dysplasia". Fibrous dysplasiausually presentsclinically during childhood or adolescence.Bones commonly involved include the femur, tibia, fa- cial skeletonand ribs. Radiographically,the lesionsoften havea characteristic"ground glass"appearance. Malignant changehas been reported in fibrous dysplasia,but is very rare.

9.6.2 Osteofibrous Dysplasia (Figs.159,160)

A rare benignlesion, almost exclusively localized in the tibia andfibu- la of young children.As in fibrous dysplasiathe lesionsare characterized by thepresence of fibrous connectivetissue and trabeculaeof im- maturenonlamellar bone. In contrastto fibrous dysplasia,the surfaces of the bone trabeculaeare usually covered by rows of active osteoblasts. The term "osteofibrousdysplasia" was introduced by Campanac- ci in 1976,replacing the designation"ossifying fibroma" which had been usedby Kempsonin 1966to describethese lesions in analogyto the processin maxillary bones, which presentssimilar histological features.Osteofibrous dysplasia involves predominantly the cortex of the tibia, showinga characteristicradiological loculated to bubbly appearance,with bowing of the anterior cortex. Some authors refer to this lesion as "cortical fibrous dysplasia",a more activeor aggres- sivetype of an otherwisetypical fibrous dysplasia.

9.7 MyositisOssificans (Heterotopic Ossification) (Figs.161,162)

A non-neoplasticlesion, sometimes associated with trauma,characterized by proliferation of fibrous tissue and by formation of large amountsof new bone.Cartilage may also bepresent. The lesionsmay occur on the externalsurface of a bone or in soft tissuesat a distance from theperiosteal surface. The abnormal tissuemay be highly cellular.When the lesion involvesthe externalsurface of a bone,the radiologicaland histological distinction from juxtacortical osteosarcomamay be difficult. In the soft tissues,distinction from the rare osteosarcomaof soft tissuesmay TumourlikeLesions 41 alsopresent problems, although in myositisossificans the maturation of the abnormal tissuecharacteristically results in a peripheral shell of mature bone surrounding a central massof more cellular tissue. Muscle is not necessarilyinvolved. The lesion is not inflammatory in nature,but the term myositisossificans is retainedas it is widely used. The designationheterotopic ossification has been proposedbecause of its wider applicationto traumatic and nontraumaticlesions. Some lesionsoccurring on the surfaceof bone are referred to as"periostitis ossificans"or "reactiveperiostitis" and thoseoccurring in soft tissues are at times referred to as "pseudomalignantosseous tumours of soft tissues".These local lesionsmust be distinguishedfrom the rare generalizedcondition myositis ossificansprogressiva. Periostitis ossificans is the periosteal equivalent of myositis ossificanswith clinico- pathological features similar to myositis ossificansor of fracture callus.

9.8 Brown Tumour of Hyperparathyroidism (Figs.163,164)

A circumscribednon-neoplastic lesion characterizedby thepresence of large numbers of osteoclastgiant cells, usually arranged in groups and separatedby richly vascularizedfibrous tissuewith areasof new bone and osteoidformation. The surrounding bone tissuefrequently shows evidenceof increasedosteoclastic resorption. Areas of recent and old haemorrhageare common. The brown tumour of hyperparathyroidism is easily confused with giant-celltumour, althoughthe typical spindle-shapedmononu- clearcells of a giant-celltumour are not usuallypresent and the tissue is often more fibrous. The distinction between the two types of le- sionsis aidedby their different skeletaldistribution: in long bones,lesionsof hyperparathyroidismusually involve the shafts,and not the endsof the bone asin giant-celltumour. The presenceof radiological and biochemicalevidence of hyperparathyroidismis also important in making the diagnosis.In the jaw bones,the brown tumour of hy- perparathyroidismmay be histiologicallyindistinguishable from giant-cellgranuloma. 42 Definitions and E,xplanatoryNotes

9.9 IntraosseousEpidermoid Cyst (Fig.165)

A relativelyinfrequent non-neoplastic lesion, also called "keratin or squamous-epithelialcyst", which involves the iaws, the distal pha- langesand the skull. It is characterizedhistologically by a membrane consistingof squamousepithelium, covered by laminatedmasses of keratinthqt may occupypart of thecavity. The great majority occurin malesbetween 20 and 50 yearsof age. The phalangeallesions are most frequent in manual workers: their appearancefollowing trauma is strong evidencefor a traumatic aetiology. Epidermoid cysts involving the skull, also referred to as "cholesteatoma",are lessfrequent and radiographicallyshow a ra- diolucentappearance, as do the phalangealcysts, with sharplyde- marcated,often slightlysclerotic margins. The aetiologyis probably a developmentaldefect, rather than post-traumatic.

9.10 Giant-Cell (Reparative) Granuloma (Fig.166)

An uncommon non-neoplasticlesion distinctfrom true giant-celltumour, characterizedhistologically by a prominentfibrous stromawith areasof haemorrhageand nestsof multinucleatedgiant cells.The giant cellsare smaller than thoseo.f true giant-cell tumours. These lesions are histologicallyindistinguishable from the similar lesions("brown tumour") in hyperparathyroidism.Conspicuous new boneformation is common. Giant-cell (reparative) granuloma involves primarily the jaw bone but alsothe tubular bonesof handsand feet, and exceptionally carpal,tarsal and other bones. The adjective "reparative" has been dropped by many authors, becausea history of trauma is infrequent. Giant-cell granulomasof handsand feet, sometimesreferred to as"giant-cell reactions", occur more commonly in males,at agesranging widely from 6 to 53 years. Radiographically,the lesionsare osteolyticand trabeculated,slightly expandingthe thinned cortex and commonly involving the diaphysis and metaphysis.

Unless otherwise stated,all the preparations shown in the photomicrographs re- produced on the following pageswere stained with haematoxylin-eosin' Fig.1a,b. Osteoma. a Male, 36 years. Frontal sinus. Radiograph. b Female, 9 years. Medullary tumour, upper third femur. Radiograph

Fig.2. Osteoma.Frontal sinus Fig.3. Osteoma.Same case as in Fig' 2

Fig.4a,b. Osteoid osteoma Male, l8years Shaft of tibia aRadiograph b Photograph of sPecimen 45

Fig.5a,b. Osteoidosteoma.a Radiographof specimenoftibia. b Samecaseasa

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Fig.6, Ostettido.\tt'(,mo. Same casc us Fig.5

Fig.9a-c. Osteoblastoma. a Male, 29 years. Talus. Radiograph. b,c Female, 23 years.Ninth rib b Photograph of specimen. c Radiograph of specimen

Fig.10. Osteoblastoma.Same caseas Fig.9b

Fig.13. Aggressive(malignant) osteoblastoma.Same case as Fig. 12

Fig. 14. Aggressive(malignant) osteoblastoma.Same caseas Fig. 12

Fig. 18. Central (medullary) osteosarcoma.Same caseas Fig. 15.Tumour bone

'.:.Y,,

Fig.21. Central (medullary) osteosarcorza.Sclerosing pattern

Fig.22a-c. Osteosarcoma in Paget disease Male, 71 years. Shaft of humerus. a Radiographs.b Photographofspecimen. c Radiograph of specimen

Fig.25a-c. Telangiectatic osteosarcoma. Female, 6 years. Upper third of humerus. a Radiograph. b Photograph of specimen c Radiographof specimen

Fig.26. Telangiectaticosteosarcoma. Same case as Fig.25. Large blood-filled spaces

Fig.29a-c. Intraosseous wett-diJferentiatetlosteosarcoma. Femare, 15 years. shaft of photograph humerus. a Radiograph b of specimen. c Radiographof speclmen

Fig.30. IntraosseotLs well-differentiatetlosteosarcoma. samecase as Fig 29. sim_ ulatesfibrous dysplasiaat low power Fig.32a,b. Round-cell osteosarcoma.Male' 13 years' Distal end of ulna' a Radiograph. b Photographof specimen 59

Fig.33. Round-cell osteosarcoma Samecase as Fig.32.Simulates Ewins sar_ coma at low power

Fig.34. Round-cell osteosarcoma.Same case as Fig.32. Bone formed by round cells humerus' Fig.35a-c. Parosteal osteosarcoma.Female, 17 years' Upper shaft of a iadiograph. b Photograph of specimen' c Radiograph of specimen

Parostealosteosarcoma. Same caseas Fig' 35' Sclerotic bone of tumour Fig.38. Parosteal osteosarcoma. Same case as Fie.35. Chondrosarcomatous tissue 6l

Fig.39a-d. I'ariottt'trl()st(()\(r(otnLt Malc. 19veilrs Lowcr mctaphvsisof l'c mLlr.a Racliouraphb'lirnoqrr-nm c Photographol spccimcn d lLadiogt'ltph of soccirlcrr

Fig.40. I'triottt,ul ostr'orur(otno.Samc case as Fig 39 Fig.41. Periostealosteosarcoma. Same caseas Fig. 39. Lace-like femoral bone

Fig.42a-c. High-grade surface osteosarcoma.Female, 13 years. Shaft of femur. a Radiograph. b Photograph of specimen. c Radiograph of specimen High-grade surlace osteosarcoma.Same case as Fig.42

s 65

Fig.45a-d. Enchondroma. a-c Male, 64 years. Metacarpal. a Radiograph. b Photograph of specimen. c Radiograph of specimen. d Photograph of an- other soecimen

Fig.46. Chondroma Samecase as Fig.45 a-c

Fig.49a,b. Osteochondroma.Male,l3 years.Ilium. a Radiographof specimen b Samecase as a

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Fig.53. Chondroblastoma. Samecase as Fig.52 b

Fig.54. ChondroblastomaSame case asFig.52b

Fig.57. Chondromyxoid fibroma Male, 10years. Upper metaphysisof tibia. Radiograph

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Fig. 58 a,b. Chondromyxoid fibroma. Same caseas Fig. 57. Chondroid stroma

Fig.61. Chondrosarconza.Well-differentiated tumour

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Fig.66. Chondrosarcona Pleomorphic cartilage l6

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Fig.6tla-c. ()hontlrosurt:onruin 0lliar tlrsca,rcMale.2l ycars a Hancirvitl'r rnul- tiplc cnchondrcmiis Radioglaph b,c Ilutrerus with chonclros:lrcorlaRadio- graDhs 77

l'ie.70a-d..ltt.rttrtrtrtit'ulL'ltpnrlrlsurt6nra Malc. 17vcars LJppershaltollemur a,b Radiographs.c Photosr-aphof spccimen.d Racliographol speclrrcn

years Distal end of femur Fig.73 a-c. Mesenchymalchondrosarcoma' Male,36 a iadiograph. b Tomogram. c Photograph of specimen

Fig.74. M esenchymalchontlrosarco'ma' Same case as Fig' 73 80

Fig. 75. M esenchymalchondrosarcoma Samecase as Fig.73 poorly difTerenti_ ated cells

Fig'76a-c. Dedifferentiatetr chondrosarcoma. Mare,49 years. upper shaft of femur. a Radiograph. b Tomogram. c photograph of spetimen 81

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Fig.77. Dedifferentiated chondrosarcoma. Same case as Fig.76. Abrupt transi- tion between low-grade cartilage tumour and dedifferentiated cells

Fig.78. Dedifferentiatedchondrosarcoma. Samecase as Fig. 76

Fig.81. Clear-cell chondrosarcoma.Same caseas Fig. 79 b. c

Fig'82a'b. Malignant chondrobrastoma? Female,32 years. Distal epiphysis of secondmetatarsal. a Radiograph. b Radiograph. Reclrrence 5 .onit, tut", ?tt Fig' it2 b Fig. 83. M alignant chondroblastttmaZSame caseas

Fig.84.Malignantchonclroblastoma?SamecaseasFig.t]2b.Giantcellsbetween round cells are PleomorPhtc 85

Fig.85a-c. Giant-cell tumour. Male, 56 years. Lower end of femur. a,b Radio- graphs. c Photograph of specimen

Fig.86. Giant-cell tumoar. Same caseasFie g5 86

Fig.88a-d. Giant-cell tumour. Fema1e,30years. Upper end of tibia. a,b Radio- griphs. c Photograph of specimen. d Radiograph of specimen Fig.89. Giant-cell tumotr Samecaseas Fig.tlt3

Fie.90. Giant-cell tumoar Fibrous stroma

Fig.93. Giant-cell tumoui: Same caseas Fig.92. Original biopsy

Fig.94. Giant-cell tumour. Same case as Fig.92. A metastasisis present in the lower lobe of the right lung. Radiograph

Fig.97a-c. Ewing sarcoma. Male, 25 years. Upper end of humerus. a Radio- graph. b Photograph ofspecimen. c Radiograph ofspecimen

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Fig.98. Ewing sarcoma. Same case as Fig. 96 a. Periosteal reactive bone forma- tlon Fig.99. Ewing sarcoma.Same caseas Fig. 96 a

Fig.100. Ewing sarcoma.Same case as Fig.96 a 93

Fig.101. Ewingsarcoma

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Fig.102. Ewing sarcomri.Tumour divided into lobules by reticulin fibres

Fig.105. Primitive neuroectodermal tumour of bone' Same case as Fig.104. Prominenl rosetleformation

Fig.106.Primitive neuroectodermaltumour of bone Same caseas Fig' 104 Fig.107a-c. Malignant lymphoma of bone. Male, 61 years. Lower end of humerus. a,b Radiographs. c photograph of specimen

Fig.108. Malignant lymphoma ofbone Samecaseas Fis. 107 Fig. 109. M alignant lymp homa of bone. Large lymphoid cells

Fig.110. Malignant lymphoma of bone. Same caseas Fig. 107.Heavy reticulin fibre formation Fig.111a-d. MyelctmaFemale, 42 yearsMultiple lesions.Radiographs. a up- perfemur, at time of presentation.b, c Lumbarspine, 2 yearsafteipresentatlon. d Skull..lyears after presentation Fig.112. Myeloma. Same caseas Fig. 11 1

,st

101

t. '1ii'.

Fig.116. Haemangioma Samecase asFig. 115

Fig.117a-c. Haemangioendothelioma. Male, 63 years. Multiple lesions of right tibia and femur a Radiographs. b Photograph of specimen. c Radiograph of speclmen

103

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Fig.120. Haemangioendothelioma Same case as Fig. 117. Heavy reticulin fibre formation

Fig. l2L. H aemangiop ericy toma

Fig,l2{. Angiosarcoma

Fig.l25. Angiosarcoma l06

Fig. 126a'b. Desmoplustit:f'ibronn Male. -56years Lowcr end .f humcrus. Ra- diographs

,l' t) I Fig.129 a' b. Fibrosarcoma.Female. 67 years.Upper end of tibia. Radiographs

109

Fig.132a,b. Matignantfibroushistiocytoma.Female,T0years.Upperendoffe- mur. Radiographs

Fig.133. Malignant fibrous histiocytoma. Samecase as Fig' L32

Fig.136a,b. Malignant mesenchymoma.Female, 32Years Upper end of humerus. a Radiograph b Photograph of specimen

Fig.137. Malignant mesenchymoma. Liposarcomatous pattern' Same case as Fie.136

113

Fig. 140. Chordoma. Female,62 years.Sacrum. Radiograph

Fig.141a,b. Chorrktma. Same case as Fig.140. aPhotograph of specimen b Radiographof specimen

Fig.144a'b. Adamantinoma of long bones Male,12 years. shaft of tibia. a Ra- diographs (initial presentation). b Radiographs (1 year after curettage)

Fig. 145 Adamantinoma of long bones.Same caseas Fie. 144 116

Fig.146. Adamantinoma of long bones

Fig.147a,b. Solitarybone cyst.a Female,8 years'Upper shaftof femur' Radio- graph. b Female,6 years.Upper shaftof humerus.Radiograph 117

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Fig. 148a,b. Solitury bone cyst

Fig.149a,b. Aneurysmal bone cyst. a Male, 3-5years. Calcaneus. Radiograph. b Female,10 years. Metaphysis of ulna.Radiograph

Fig. 152. Juxta-articular bone cysl

Fig.153. Metaphyseal fibrous defect. Female, 15 years. Lower metaphysis of femur. Radiograph 120

Fig.154a, b. Metaphysealfibrous de.fecl

Fig.155a,b. Eosinophilic granuloma a Male, 20 years. Frontal bone. Radio- graph. b Male,6 years.Shaft of femur.Radiograph *'

Fig. t56a. b. Eosinophilic granulomu

Fig. 157. Fihrorrsdysplasio Female, 14 years. Upper shaft of femur. Radiograph

Fig. 160 a,b. O steofibrous dysplasia

r0r. Myositis !s. ossificans.Male, 13 years.Soft tissuesof trochantericregion. Radiograph Fig.162 a, b. Myositis ossificans.Same case as Fig' I 61

Multiple Fig.163a,b. Browntumour of hyperparathyroitlism' Female,60 years' boie lesions, parathyroid adenoma removed. a Tibia and fibula. Radiograph' b Hand RadiograPh t25

Fig. 164a, b. B r o wn tumo ur of hyp erparathy ro idlsn. Samecase as Fig. 163

Fig. 165a, b. Intraosseousepidermoid cyst a Female, 38 years.Distal phalanx of finger. Radiograph. b Intraosseousepidermoid cyst t26 SubjectIndex

Page Figures Adamantinomaof lons bones 35 14+146 Angiosarcoma 29 1,22725

Brown tumor of hyperparathyroidism 4I 1,63,164

Chondroblastoma(epiphyseal) 15 <') << Chondroblastoma,malignant 20 82-84 Chondroma 14 45-47 Chondromyxoidfibroma 16 56-59 Chondrosarcoma l'7 60-69 Clear-cell 19 79-81, Dedifferentiated 19 76-78 Juxtacortical(pe riosteal) 18 70-72 Mesenchymal 19 73-75 Chordoma )4 t40-143 Cyst Aneurysmalbone cyst 37 149,150 Intraosseousepidermoid cyst 42 165 Juxta-articularbone cyst 37 751,752 Solitarybone cyst(simple or unicameral) 36 747,748

Desmoplasticfibroma 30 126 1,28

Eosinophilicgranuloma (histiocytosis X) 39 155 156 Ewing sarcoma 22 96-103

Fibrosarcoma 31, 1,29-731, Fibrousdysplasia 39 157,158 Fibroushistiocytoma (benign) 29

Giant-cell(reparative) granuloma 42 r66 Giant-celltumor (osteoclastoma) 20 85-95 Glomus tumor (glomangioma) 27

Haemangioendothelioma 28 117-720 Haemangioma 27 115,116 Haemangiopericytoma 28 1,27