chondrosarcoma: an overviewwhat is a chondrosarcoma? • chondrosarcoma is a malignant tumor of bone...
TRANSCRIPT
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Chondrosarcoma:Anoverview
AliNajefiST6BTUTeaching19/04/2018
Introduction• Defini-ons• Epidemiology• Types• Radiology• Histology• Treatment• Prognosis• Futuredirec-ons
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WhatisaChondrosarcoma?• Chondrosarcomaisamalignanttumorofbonethatischaracterizedbytheproduc7onofcar7lagematrixbytumorcells• Diversehistopathologyandclinicalbehavior• CategorisedtogetherintheWHOclassifica7onasatypicalcar7laginoustumour/chondrosarcomagradeI.
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WHOclassi:ication
Epidemiology • 9%ofallbonetumours• UKagestandardisedratesreport0.19/100,000popula-on• 2ndmostcommonprimarymalignancyofbone(non-haematological)
• PrimaryandSecondary• Primarypeaksaround30-60yearsofage• Secondarybetween25-45yearsofage
• Slightlyhigherincidenceinmales• NoRacePredelic-on• 100-120newcasesperyearintheUK
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Location-Primary• Pelvis• ProximalFemur• ProximalHumerus
• Canoccurinribsandscapula
• Althoughrareinhand,mostcommonprimarymalignancyofbonehere.
Location–Secondary(Peripheral)
Secondarylesionsoccuratsitesofbenigncar-lagelesions• Mul-pleenchondromas• Ollierdisease–25%byage40• Maffucci-higher
• Mul-pleHereditaryExostoses• Around5%life-merisk• 1%riskforsolitaryenchondromas(Referralbias–trueincidenceunknown)
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SecondaryChondrosarcomaAssociatedwith• Enchondromas• Osteochondromas• Synovialchondromatosis• Chondromyxoidfibroma• Periostealchondroma• Chondroblastoma• Previousradia-ontreatment• Fibrousdysplasia
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TypesofPrimaryChondrosarcoma
• Conven-onal(90%)• Centralorperipheral
• ClearCell• Mesenchymal• Dedifferen-ated
ClearCellCS• Slowgrowing• Epiphyseal(especiallyproximalfemur)• Locallyrecurrenttumour• Itiso^enconfusedwithchondroblastomaorGCT.• Metastasesoccuronlya^ermul-plelocalrecurrences.• Primarytreatmentiswideexcision.• Systemictherapyisnotrequired.
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MesenchymalCS• Highgrade• Predilec-onforflatbones;longtubularbonesarerarelyaffected.
• Ittendstooccurinyoungerindividualsandhashighratesofmetasta-cpoten-al.
• The10-yearsurvivalrateis28%.• Thisen-tyrespondsfavorablytoradiotherapy.• Treatmentissurgicalremovalcombinedwithadjuvantchemotherapy.
• Radiotherapyisrecommendedifthetumorcannotbecompletelyremoved.
DedifferentiatedCS• Approximately10%ofchondrosarcomasmaybededifferen-atedintoafibrosarcomaorosteosarcoma.
• Thisoccursinolderindividualsandishighlyfatal.• Surgicaltreatmentiswideexcision• Adjuvanttherapyiswarranted.
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ClinicalFeatures• IncreasingPain• Palpablemass• Slowgrowing–symptomsmaybepresentformanyyears• Painwithoutpathologicalfracture–differen-atesenchondromaandchondrosarcoma
RadiographicAppearance
• Margin/paeernofbonedestruc-on • Presence/typeofmatrixmineraliza-on• Cor-calresponse• So^--ssuemass• Presence/typeofperiostealreac-on
• Thesiteofthelesionandageofthepa-entmustbeconsidered
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Radiographicappearance• Arisesinthemedullarycavity• Irregularmatrixcalcifica-on.• Thepaeernofcalcifica-onhasbeendescribedas“punctate,”“popcorn,”or“commashaped.”
• Moreaggressiveappearancethanenchondroma• Bonedestruc-on,• Cor-calerosions,• Periostealreac-on• So^--ssuemass.
Radiographicappearance• CTcanbehelpfultoshowendostealerosions]• MRIshowsso^-ssuecomponent• Sizeofthecar-laginouscapofanosteochondromawithCTorMRI• >2cminaskeletallymaturepa-ent
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Enchondroma
Juxtacorticalchondroma
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Osteochondroma
Chondromyxoid:ibroma
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Grade2Chondrosarcoma
Chondrosarcoma
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Chondrosarcoma
Chondrosarcoma
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DedifferentiatedCS
DedifferentiatedCS
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Histology• GradeI,II,orIII.• Theaggressivenesspredictedbyhistologicgrade.• Gradingsystemisbasedonthreeparameters• Cellularity• Degreeofnuclearatypia• Mito-cac-vity.
EnnekingStaging
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AJCC/UICC
HistologyGrade1
• Verysimilartoenchondroma.• Cellularityishigher,andthereismildcellularpleomorphism.
• Thenucleiaresmallbuto^enshowopenchroma-npaeernandsmallnucleoli.
• Binucleatedcellsarefrequent.• Mitosesareveryrare.
Grade1chondrosarcomasarelocallyaggressiveandpronetorecurrences,butusuallydonotmetastasize.
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HistologyGrade2• ThecellularityishigherthaninGrade1tumors.
• Characteris-cfindingsaremoderatecellularpleomorphism,plumpnuclei,frequentbi-nucleatedcells,andoccasionalbizarrecells.
• Mitosesarerare.• Fociofmyxoidchangemaybeseen.
UnlikeGrade1tumors,about10%to15%ofGrade2chondrosarcomasproducemetastases.
HistologyGrade3
• Characteris-cfindingsare• highcellularity• Markedcellularpleomorphism
• HighN/Cra-o• Manybizarrecells
• Frequentmitoses
ThesearehighgradetumorswithsignificantmetastaNcpotenNal.
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Management
Low-grade• Extendedcureeagewiththeuseofintraopera-veadjuvanttreatments(phenol,cement,cryotherapy).
• Low-gradeperipheralchondrosarcomas(arisingfromosteochondromas)shouldbesurgicallyexcised,aimingtoexcisethetumourwithacoveringofnormal-ssueoverit.
• Thosewithso^--ssueextensionshouldbetreatedsimilartohigh-gradelesions.
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HighGrade• Wideorradicalresec-onoramputa-on.• Endoprosthesis• Thelocalrecurrenceratea^erintraopera-vetumorcontamina-onishigh.
• Pulmonarymetastasescanbetreatedwithsurgicalresec-onifpossible.
Chemotherapy• Noroleinthetreatmentofconven-onalchondrosarcoma• Frequentlyusedfortreatmentofdedifferen-atedandmesenchymalchondrosarcomas.
• Recentevidencesuggeststhatmesenchymalchondrosarcomamayberesponsivetochemotherapyandmaybeconsideredforadjuvantorneoadjuvanttherapy
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Radiotherapy• Limitedrole• Unresectableorinoperable• Inadequatemargins• Axialskeletonandpelvicorshouldergirdle,orboth,canbecontrolledbyradia-ontherapy.
• Chondrosarcomasofthefacialbonesandskullaresuccessfullytreatedwithcombina-onofradiotherapy]
• MesenchymalChondrosarcoma
Prognosis• Dependsmostlyonthesize,grade,andloca-onofthelesion.• Ifincompleteresec-on(usuallybecauseofitssizeorloca-on),localrecurrenceislikely.
• Low-gradelesionshaveagreaterthan90%10-yearsurvivalrate
• High-gradeconven-onalchondrosarcomaarereportedtohavea20%to40%10-yearsurvivalrate.
• The5-yearsurvivalrateislessthan15%forpa-entswithdedifferen-atedchondrosarcoma,withmostdeathsoccurringinthefirst2years.
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Futuredirections
PolychronidouG,KaravasilisV,PollackSM,HuangPH,LeeA,JonesRL.NoveltherapeuBcapproachesinchondrosarcoma.FutureOncol.2017Mar;13(7):637-648.
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Futuredirections• Theiden-fica-onofIDH1andIDH2muta-onsinchondrosarcomahasledthesetobetargetedwithnew,specificagents,althoughtheeffec-venessandfutureroleofsuchagentsareunclear.• AmaryMF,BacsiK,MaggianiF,etal:IDH1andIDH2muta7onsarefrequenteventsincentralchondrosarcomaandcentralandperiostealchondromasbutnotinothermesenchymaltumours.JPathol224:334-343,2011
• Iden-fica-onofMesenchymalchondrosarcomaissupportedbyiden-fica-onofanHEY1-NCOA2fusion,whichcanoccurinbothboneandso^-ssue.Adjuvantchemotherapymayprovideasurvivaladvantage.• FrezzaAM,CesariM,BaumhoerD,etal:Mesenchymalchondrosarcoma:Prognos7cfactorsandoutcomein113pa7ents.AEuropeanMusculoskeletalOncologySocietystudy.EurJCancer51:374-381,2015
Summary• Olderagegroup• Centralorperipheral• Mul-pletypes• Canbedifficulttodis-nguishfrombenigncar-lagetumours• Matrixcalcifica-on,aggressiveappearance• Surgeryismainstayoftreatment• MesenchymalchondrosarcomarespondstoCT/RT
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ThankYou
• UKguidelinesforthemanagementofbonesarcomas,Gerrandetal.ClinSarcomaRes(2016)6:7
• Campbells13thedi-on,2017• SarcomasoftheSo^TissueandBone,Mar-nM.Malawer,LeeJ.Helman,and
BrianO’Sullivan,2008• ImagingofBonetumoursandtumourlikelesions,Baerth,Knaut.Springer.