惡性胸膜間皮瘤2022.v1-NCCN（英文版）

MalignantPleuralMesotheliomaNCCNClinicalPracticeGuidelinesinOncologyNCCNMalignantPleuralMesotheliomaersionDecemberNCCNGuidelinesforPatients?availableat/patientsVersion1.2022,12/22/21?2021NationalComprehensiveCancerNetwork(NCCN),Allrightsreserved.NCCNGuidelinesandthisillustrationmaynotbereproducedinanyformwithouttheexpresswrittenpermissionofNCCN.loeybiiononooloeydln才91n6lm9bioin9岡6bio才n916qytM9bio6lonooloeyPloeybiiononooloeydln才91n6lm9bioin9岡6bio才n916qytM9bio6lonooloeyP2u1e91y\2u1eio6lonooloeyyelioma*DavidS.Ettinger,MD/Chair?*DouglasE.Wood,MD/ViceChair?JamesStevenson,MD/Lead?DaraL.Aisner,MD,PhD≠WallaceAkerley,MD?JessicaR.Bauman,MD??AnkitBharat,MD?DeboraS.Bruno,MD,MS?JoeY.Chang,MD,PhD§Tn9Univ912i才yotT9x62LucianR.Chirieac,MD≠ThomasA.D’Amico,MD?MalcolmDeCamp,MD?NHughesPhDesPanelDisclosuresThomasJ.Dilling,MD,MS§JonathanDowell,MD?ScottGettinger,MD?TTravisE.Grotz,MD?MatthewA.Gubens,MD,MS?AparnaHegde,MD?RudyP.Lackner,MD?MichaelLanuti,MD?JulesLin,MD?BillyW.Loo,Jr.,MD,PhD§ChristineM.Lovly,MD,PhD?RenatoG.Martins,MD,MPH?ErminiaMassarelli,MD,PhD?DanielMorgensztern,MD?GregoryA.Otterson,MD?JoseM.Pacheco,MD?SandipP.Patel,MD??TGregoryJ.Riely,MD,PhD?TJonathanRiess,MD?StevenE.Schild,MD§resaAShapiroMDPhDAditiP.Singh,MD?TaweeTanvetyanon,MD,MPH?JaneYanagawa,MD?StephenC.Yang,MD?EdwinYau,MD,PhD?ThomasNg,MD?Tn9Univ912i才yotT9nn92299H96l才n2oi9no9euralMesotheliomaPanelMembersfGuidelinesUpdatesPretreatmentEvaluation(MPM-2)ClinicalStageI–IIIAandEpithelioidHistology;SurgicalEvaluation(MPM-2)euralMesotheliomaPanelMembersfGuidelinesUpdatesPretreatmentEvaluation(MPM-2)ClinicalStageI–IIIAandEpithelioidHistology;SurgicalEvaluation(MPM-2)ClinicalStageIIIBorIV,SarcomatoidorBiphasicHistologyorMedicallyInoperable;Treatment(MPM-2)ClinicalStageI–IIIAandEpithelioidHistology;Treatment(MPM-3)PrinciplesofPathologicReview(MPM-A)PrinciplesofSystemicTherapy(MPM-B)PrinciplesofSupportiveCare(MPM-C)PrinciplesofSurgery(MPM-D)PrinciplesofRadiationTherapy(MPM-E)eliomadexlievesthatthebestmanagementforanypatientwithcancerisinaclinicaltrial.Participationinclinicaltrialsisespeciallyencouraged.FindanNCCNMemberInstitution:/home/member-institutions.ofEvidenceandsusAllrecommendationsotherwisedNCategoriesofEvidenceandConsensus.NCCNCategoriesofPreference:Allrecommendationsareconsideredappropriate.SeeNCCNCategoriesofPreference.TheNCCNGuidelinesareastatementofevidenceandconsensusoftheauthorsregardingtheirviewsofcurrentlyacceptedapproachestotreatment.AnyclinicianseekingtoapplyorconsulttheNCCNGuidelinesisexpectedtouseindependentmedicaljudgmentinthecontextofindividualclinicaltancestodetermineanypatientscareortreatmentTheNationalComprehensiveCancerNetworkNCCNmakesnorepresentationsorwarrantiesofanykindregardingtheircontentuseorapplicationanddisclaimsanyresponsibilityfortheirapplicationoruseinanyway.TheNCCNbereproducedinanyformwithouttheexpresswrittenpermissionofNCCN.?2021.Version1.2022,12/22/21?2021NationalComprehensiveCancerNetwork(NCCN),Allrightsreserved.NCCNGuidelinesandthisillustrationmaynotbereproducedinanyformwithouttheexpresswrittenpermissionofNCCN.UPDATESVersion1.2022,12/22/21?2021NationalComprehensiveCancerNetwork(NCCN),Allrightsreserved.NCCNGuidelinesandthisillustrationmaynotbereproducedinanyformwithouttheexpresswrittenpermissionofNCCN.PrintedbyMinTangon3/14/20227:06:33AM.Forpersonaluseonly.Notapprovedfordistribution.Copyright?2022NationalComprehensiveCancerNetwork,Inc.,AllRightsReserved.eliomadexrsionoftheNCCNGuidelinesforMalignantPleuralMesotheliomafromVersionincludeMPM-2?ClinicalassessmentmodifiedpClinicalstageI–IIIAandepithelioidorbiphasichistology.(alsoappliestoMPM-3)pClinicalstageIIIBorIV,sarcomatoidorbiphasichistology,orMedicallyinoperable?SurgicalEvaluationpBullet3modified:MediastinoscopyorEBUS/EUSFNAofmediastinallymphnodes?Footnotebadded:SeePrinciplesofPathologicReview(MPM-A)?Footnotecmodified:Surgeryshouldmaybeconsideredforbiphasichistologyifthepatienthasearly-stagedisease.(alsoappliestoMPM-3)?Footnoteremoved:IfN2diseaseisidentified,prognosiswithsurgery(andothertherapy)issubstantiallydiminished.SurgicalresectionshouldonlybeconsideredinthesettingofaclinicaltrialoratacenterwithexpertiseinMPM.(alsoappliestoMPM-3)MPM-3?AdjuvantTreatmentpUnresectableaftersurgicalexplorationandchemotherapy:SystemictherapyConsiderRTpUnresectableaftersurgicalexploration:SystemictherapyandconsiderRTMPM-A?NewsectionaddedforPrinciplesofPathologicReviewMPM-B1of2?First-LineSystemicTherapyRegimens;PreferredpBullets1and2:carboplatinAUC5addedasanalternatetocisplatinpBullet3modified:Nivolumab360mgevery3weeks(or3mg/kgevery2weeks)andipilimumab1mg/kgevery6weeksuntildiseaseprogression,unacceptabletoxicity,orupto2yearsinpatientswithoutdiseaseprogression(category1)(preferredinnon-epithelioid).?First-LineSystemicTherapyRegimens;OtherRecommendedpPemetrexed/carboplatin±bevacizumabmovedtopreferredregimens?SubsequentSystemicTherapypPembrolizumabandassociatedreferences(MPM-A2of2)removed?Footnoteamodified:ThePemetrexed-basedchemotherapymayalsobeusedformalignantperitonealmesothelioma,Allregimensmayalsobeusedforpericardialmesotheliomaandtunicavaginalistestismesothelioma.?Footnotebadded:Broadmoleculartumorprofilingisrecommendedwiththegoalofidentifyingraredriveralterations(eg,NTRKorALK)forwhicheffectivedrugsmaybeavailableortoappropriatelycounselpatientsregardingtheavailabilityofclinicaltrials.?Footnotecadded:Carboplatinisrecommendedforpatientswhoarecisplatinineligible.?Footnotegadded:Pemetrexedcombinationregimensusedinthefirst-linesettingareoptionsforsubsequentsystemictherapyifimmunotherapyisadministeredasfirst-linetreatment.MPM-B2of2?Referencesadded:16,21PrintedbyMinTangon3/14/20227:06:33AM.Forpersonaluseonly.Notapprovedfordistribution.Copyright?2022NationalComprehensiveCancerNetwork,Inc.,AllRightsReserved.eliomadexrsionoftheNCCNGuidelinesforMalignantPleuralMesotheliomafromVersionincludeMPM-E1of3?GeneralPrinciplespBullet7modified:Whenthereislimitedornoresectionofdisease,deliveryofhigh-doseRTtotheentirehemithoraxinthesettingofanintactlunghasnotbeenshowntobeassociatedwithsignificantsurvivalbenefit,andthetoxicityissignificant.RTundersuchcircumstancesafterP/Disusuallynotrecommended.ArandomizedphaseIIItrialinpatientswithnon-metastaticMPMwhounderwentnon-radicallung-sparingsurgeryfoundsubstantiallygreateroverallsurvivalwithradicalhemithoracicintensity-modulatedRT(IMRT)comparedtopalliativeRT.HemithoracicpleuralIMRTafterP/Dinthepresenceofanintactlungmaybeconsideredincenterswithexperienceandexpertiseinthesemethods,giventhetechnicaldifficultyofthistreatment.pBullet9modified:Advancedtechnologiesmaybeused,suchasimage-guidedRT(IGRT)fortreatmentinvolvingIMRT/stereotacticradiosurgery(SRS)/stereotacticbodyRT(SBRT),andintensity-modulatedprotontherapy(IMPT).MPM-E2of3?Bullet1added:AminimumtechnologicalstandardisCT-planned3D-CRTusingphotonorphoton/electronbeams.?Bullet2modified:Useofhighlyconformalradiationtechnology(IMRT)isthepreferredchoicebasedoncomprehensiveconsiderationoftargetcoverageandclinicallyrelevantnormaltissuetolerance.AdvancedtechnologiesareappropriatewhenneededtodelivercurativeRTsafely.Thesetechnologiesinclude(butarenotlimitedto)4D-CTand/orPET/CTsimulation,IMRT/VMAT,IGRT,motionmanagement,andprotontherapy.?Bullet3modifiedwithremovalofthistext:CTsimulation-guidedplanningusingeitherIMRTorconventionalphoton/electronRTisacceptable.10IMRTisapromisingtreatmenttechniquethatallowsforamoreconformalhigh-doseRTandimprovedcoveragetothehemithorax.IMRTorothermoderntechnology(suchastomotherapyorprotons)shouldonlybeusedinexperiencedcentersoronprotocol.WhenIMRTisapplied,theNCIandASTRO/ACRIMRTguidelinesshouldbestrictlyfollowed.MPM-E3of3?Referencesadded:8,11,12PrintedbyMinTangon3/14/20227:06:33AM.Forpersonaluseonly.Notapprovedfordistribution.Copyright?2022NationalComprehensiveCancerNetwork,Inc.,AllRightsReserved.eliomadexINITIALEVALUATIONaandorlthickening?ChestCTwithcontrast?Thoracentesisforcytologicassessment?Pleuralbiopsy(eg,thoracoscopicbiopsy[preferred],Abramsneedle,CT-guidedcorebiopsy,openbiopsy)(minimizenumberofports)ublemesothelinrelatedMalignantpleuralidisciplinarymwithperienceinMPMmmendedeatmentPMaTherearenodatatosuggestthatscreeningimprovessurvival.bSeePrinciplesofPathologicReview(MPM-A).Note:Allrecommendationsarecategory2Aunlessotherwiseindicated.ClinicalTrials:NCCNbelievesthatthebestmanagementofanypatientwithcancerisinaclinicaltrial.Participationinclinicaltrialsisespeciallyencouraged.Version1.2022,12/22/21?2021NationalComprehensiveCancerNetwork(NCCN),Allrightsreserved.NCCNGuidelinesandthisillustrationmaynotbereproducedinanyformwithouttheexpresswrittenpermissionofNCCN.MPM-1PrintedbyMinTangon3/14/20227:06:33AM.Forpersonaluseonly.Notapprovedfordistribution.Copyright?2022NationalComprehensiveCancerNetwork,Inc.,AllRightsReserved.eliomadexPATHOLOGICDIAGNOSISPRETREATMENTEVALUATIONCLINICALASSESSMENTSURGICALEVALUATIONTREATMENTsotheliomabsotheliomabtabdominalCTwithcontrastClinicalstageI–IIIAandTdIfsuggestedTdIfsuggestedbyimagingstudiesuspicionofcontralateralorealdisease?MediastinoscopyorEBUS/EUSFNAofmediastinallymphnodes?Perfusionscanning(onlyifFEV1<80%)ChestMRIwithChestMRIwithcontrast(optional)eClinicalstage,IIIBorIV,sarcomatoidorbiphasichistology,orMedicallyinoperableorapygapygstsupportivecarehSeePrimaryTreatment(MPM-3)apygbSeePrinciplesofPathologicReview(MPM-A).cSurgerymaybeconsideredforbiphasichistologyifthepatienthasearly-stagedisease.dIfPET/CTistobedone,recommendobtainingPET/CTbeforepleurodesis.ConfirmdiagnosisofMPMpriortopleurodesis.IfMPMissuspected,considerevaluationbyamultidisciplinaryteamwithexpertiseinMPM.eForfurtherevaluationofpossiblechest,spinal,diaphragmatic,orvascularinvolvementbasedonCTimaging.fObservationmaybeconsideredforpatientswhoareasymptomaticwithminimalburdenofdiseaseifsystemictherapyisplannedatthetimeofsymptomaticorradiographicprogression.gSeePrinciplesofSystemicTherapy(MPM-B).hSeePrinciplesofSupportiveCare(MPM-C).Note:Allrecommendationsarecategory2Aunlessotherwiseindicated.ClinicalTrials:NCCNbelievesthatthebestmanagementofanypatientwithcancerisinaclinicaltrial.Participationinclinicaltrialsisespeciallyencouraged.Version1.2022,12/22/21?2021NationalComprehensiveCancerNetwork(NCCN),Allrightsreserved.NCCNGuidelinesandthisillustrationmaynotbereproducedinanyformwithouttheexpresswrittenpermissionofNCCN.MPM-2tageioidcPrintedbyMinTangon3/14/20227:06:33AM.Forpersonaluseonly.Notapprovedfordistribution.Copyright?2022NationalComprehensiveCancerNetwork,Inc.,AllRightsReserved.tageioidceliomadexCLINICALSTAGEPRIMARYTREATMENThADJUVANTTREATMENTjInductionchemotherapygwithpemetrexedandcisplatin(orcarboplatin)ChestCTwithcontrast?PET/CTformediastinalassessmentbasedonCTorotherevidenceofadvanceddiseaseResectableexplorationiorExtrapleuralorExtrapleuraleumonectomyireuraleuralIMRTkthoracicRTkConsiderRTkexplorationiumonectomyiumonectomyiChemotherapygandconsidersequentialeuraleuralIMRTkalchemotherapyg+alchemotherapyg+andConsiderRTkandConsiderRTkcSurgerymaybeconsideredforbiphasichistologyifthepatienthasearly-stagedisease.gSeePrinciplesofSystemicTherapy(MPM-B).hSeePrinciplesofSupportiveCare(MPM-C).iSeePrinciplesofSurgery(MPM-D).jSeeNCCNGuidelinesforSurvivorship.kSeePrinciplesofRadiationTherapy(MPM-E).Note:Allrecommendationsarecategory2Aunlessotherwiseindicated.ClinicalTrials:NCCNbelievesthatthebestmanagementofanypatientwithcancerisinaclinicaltrial.Participationinclinicaltrialsisespeciallyencouraged.MPM-3Version1.2022,12/22/21?2021NationalComprehensiveCancerNetwork(NCCN),Allrightsreserved.NCCNGuidelinesandthisillustrationmaynotbereproducedinanyformwithouttheexpresswrittenpermissionofNCCN.PrintedbyMinTangon3/14/20227:06:33AM.Forpersonaluseonly.Notapprovedfordistribution.Copyright?2022NationalComprehensiveCancerNetwork,Inc.,AllRightsReserved.eliomadexPRINCIPLESOFPATHOLOGICREVIEWPathologicEvaluation?Malignantmesotheliomaoriginatesfromthecellsintheserosalliningthatsurroundsthebodycavities.Ofallmesotheliomas,~85%arisefromthepleura,~15%arisefromtheperitoneum,andtheremainder(<1%)originatesfromthepericardiumorthetunicavaginalis.1?IntheUnitedStates,diffuseMPMaffects~3,000patientseachyear,withanannualincidenceof~1in100,000.2,3?Thepurposeofthepathologicevaluationofmalignantmesotheliomaisbasedonthepathologicassessmentoftumortissue,whichcanbeobtainedfromcorebiopsysampling,pleurectomy,orothermoreextensiveresectionssuchasextrapleuralpneumonectomy.Givenitsrarityandoverlappingmicroscopicfeatureswithotherconditions,thehistologicdiagnosisofdiffusemalignantmesotheliomacanbechallenging.?Toestablishapathologicdiagnosisofmesothelioma,diagnostictoolsthatareusedclinicallyincludehistologicassessment,immunohistochemistry(IHC),cytogenetics,andmoleculartechniques(suchastargetednext-generationsequencing[NGS],fluorescenceinsituhybridization[FISH],andsingle-nucleotidepolymorphismarrays).Despitethemultiplediagnostictoolkits,thediagnosisreliesprimarilyonproperhistologicassessmentandIHC.?TheneweditionoftheWorldHealthOrganization(WHO)ClassificationofThoracicTumorsbytheInternationalAgencyforResearchonCancer(IARC)introducedthefollowingchangesfromtheprevious2015edition:pNewentity:MesotheliomainSitupNewterminology:DiffusePleuralMesothelioma(insteadofDiffuseMalignantPleuralMesothelioma)pNewterminology:LocalizedPleuralMesothelioma(insteadofLocalizedMalignantPleuralMesothelioma)pNewterminology:Well-differentiatedpapillarymesothelialtumor(WDPMT,insteadofWell-differentiatedpapillarymesothelioma)pGenetictumorsyndromesinvolvingthethorax:BAP1tumorpredispositionsyndromeisahereditarycancersyndromecausedbyheterozygousgermlinepathogenicvariantsintheBAP1(BRCA1associatedprotein1)gene.?Thedescriptionsbelowrefertodiffusemesothelioma,whichwillbenamedmesotheliomaforthepurposeofsimplicity.assification?Mesotheliomaisclassifiedintothreehistologictypes:epithelioid,biphasic(mixed),andsarcomatoid,whichhavesignificantprognosticvalue.1?Thedeterminationofhistologictypesisbasedonthecytologicfeaturesofthetumor:pEpithelioidmesotheliomaischaracterizedbyepithelioid-to-roundcells.pSarcomatoidmesotheliomaischaracterizedbyspindledcellswithtaperednuclei.pBiphasicmesotheliomacontainsbothepithelioidandsarcomatoidcomponentsinvariousproportions,witheachcomprisingatleast10%ofthetumor.Note:Allrecommendationsarecategory2Aunlessotherwiseindicated.ClinicalTrials:NCCNbelievesthatthebestmanagementofanypatientwithcancerisinaclinicaltrial.Participationinclinicaltrialsisespeciallyencouraged.Version1.2022,12/22/21?2021NationalComprehensiveCancerNetwork(NCCN),Allrightsreserved.NCCNGuidelinesandthisillustrationmaynotbereproducedinanyformwithouttheexpresswrittenpermissionofNCCN.MPM-AOF8PrintedbyMinTangon3/14/20227:06:33AM.Forpersonaluseonly.Notapprovedfordistribution.Copyright?2022NationalComprehensiveCancerNetwork,Inc.,AllRightsReserved.eliomadexPRINCIPLESOFPATHOLOGICREVIEWMesotheliomaClassification(continued)?Withineachhistologictype,mesotheliomacanbedividedintoseveralsubtypesandpatternsbasedonitscytologic,architectural,andbackgroundstromalfeatures.4pOtherrarevariantsofepithelioidmesotheliomaincludeclear-cell,signetring-cell,rhabdoid,deciduoid,andsmall-cell.5-7Tumorcellsarearrangedindiversearchitecturalpatternsthatincludetubulopapillary,trabecular,solid,acinar,micropapillary,oradenomatoid.pInsarcomatoidmesothelioma,subtypesdescribedincludeconventional/spindlecell,desmoplastic,8,9andlymphohistiocytoid.10-12Asubsetofsarcomatoidmesotheliomaexhibitsheterologousdifferentiationwithosteosarcomatous,chondrosarcomatous,and/orrhabdomyosarcomatouselements.9pTheassignmentofhistologictypecanbechallenging,giventheinter-tumoralandintra-tumoralmorphologicheterogeneity.Appropriatetypeclassificationofmesotheliomaisnonethelessimportant,giventheprognosticsignificanceofdifferenthistologictypes.pStudiescomparingtheconcordancebetweenhistologictypeininitialbiopsieswithsubsequentresectionshaveshownthattheaccuracyoftypingincreaseswithahighernumberofbiopsies.13Whilesarcomatoidhistologyinbiopsiesishighlypredictiveofsarcomatoidhistologyinresections,epithelioidhistologyinbiopsiesisnotentirelyspecificandischangedtobiphasicorsarcomatoidtypesinresectionsinupto20%ofpatients.13HistologicCriteriaforMesothelioma?Inmesothelioma,thegoalsofhistologicassessmentaretoconfirmthepathologicdiagnosisandtodeterminethehistologictype,whichallowsforprognosticationandtreatmentplanning.Forthediagnosisofmesothelioma,oneneedstoestablisheachofthethreeconditionsbelow:pThelesionisdiffuseandnotsolitary.Correlationwithclinicalandradiologicfindingsisneededtoconfirmthatthedistributionofthetumorisdiffuseratherthansolitary.Whilealmostall(>99%)mesotheliomasarediffuse,rarecasesoflocalizedpleuralmesotheliomahavebeendescribed,whicharesolitary,haveadifferentpathogenesis,andharborarelativelylessaggressiveclinicalcourse.14-17pThelesionalcellsaremesothelial.Giventhemorphologicoverlapbetweenmesotheliomaanddiversemimicssuchascarcinomas,IHCcanbeusedtoconfirmthepresenceofmesothelialdifferentiationinthetumorcells.Othertoolssuchascytogeneticsandmolecularanalysismayalsobehelpfulinsomeinstances(seenextpage).pThelesionalcellsaremalignant.Histologicassessmentisintegraltoestablishthatthemesothelialcellsaremalignant.Morphologicfeaturesthatdistinguishmesotheliomafromreactiveconditionsinclude:1)invasionintoadjacenttissue,suchasadiposeorfibroustissue,andskeletalmuscle;2)full-thicknessserosalinvolvement;and3)formationofexpansilenodules(consideredasatypeoffibroustissueinvasion).Thepresenceoftissueinvasionisconsideredtobethemostreliablecriterionindistinguishingmesotheliomafromreactivemesothelialproliferations.18,19Ontheotherhand,“worrisome”featuressuchasnecrosis,cytologicatypia,andmitosesshouldbeinterpretedwithcaution,sinceeachcanbepresentinreactivepleuritisanddonotnecessarilyindicatemalignancy.?Interpretationcanbedifficultwhenthereislimiteddiagnostictissue,tangentialsectioning,artifactsfromhistologicprocessing,and/orentrapmentofadjacentstructuresmimickinginvasion.18,20Foramesothelialproliferationthatissuspiciousfor,butnotdefinitiveformalignancy,onemayreportthefindingsas“atypicalmesothelialproliferation”andrecommendre-biopsyand/orclosefollow-up.Note:Allrecommendationsarecategory2Aunlessotherwiseindicated.ClinicalTrials:NCCNbelievesthatthebestmanagementofanypatientwithcancerisinaclinicaltrial.Participationinclinicaltrialsisespeciallyencouraged.?Inthedistinctionbetweenmesotheliomaandbenign,reactivemesothelialproliferations,theroleofNote:Allrecommendationsarecategory2Aunlessotherwiseindicated.ClinicalTrials:NCCNbelievesthatthebestmanagementofanypatientwithcancerisinaclinicaltrial.Participationinclinicaltrialsisespeciallyencouraged.MPM-AVersion1.2022,12/22/21?2021NationalComprehensiveCancerNetwork(NCCN),Allrightsreserved.NCCNGuidelinesandthisillustrationmaynotbereproducedinanyformwithouttheexpresswrittenpermissionofNCCN.2OF8PrintedbyMinTangon3/14/20227:06:33AM.Forpersonaluseonly.Notapprovedfordistribution.Copyright?2022NationalComprehensiveCancerNetwork,Inc.,AllRightsReserved.eliomadexPRINCIPLESOFPATHOLOGICREVIEWImmunohistochemistryMarkerstoconfirmmesothelialdifferentiation?IHCisintegraltothepathologicdiagnosisofmesotheliomainclinicalpractice.?Usefulimmunohistochemicalmarkersinclude:1)positivemarkerstoconfirmmesothelialdifferentiation,suchasWT1,calretinin,andD2-40;and2)negativemarkerstoexcludemimics,suchaspolyclonalCEA,TTF-1,andclaudin-4.22-24Oneofthecaveatsisthatnoindividualimmunohistochemicalmarkerisentirelysensitiveandspecific.Therefore,itisrecommendedthatapanelincludingatleasttwomesothelialmarkers(calretinin,WT1,D2-40)andtwocarcinomamarkers(claudin4,TTF-1,polyclonalCEA)shouldbeusedtoestablishthediagnosis.25?Broad-spectrumkeratins(AE1/AE3,pancytokeratin,MNF116)arenotspecificandareexpressedinbothmesotheliomaandcarcinomas.?Sarcomatoidmesotheliomaoftenshowsfocaltoabsentexpressionformostmesothelialmarkers,withthemostsensitivemarkerbeingD2-40/podoplanin.26?Recently,GATA3hasbeenexploredasapotentialdiagnosticmarkerforsarcomatoidmesotheliomassinceGATA3isexpressedinonly~10%–20%ofsarcomatoidcarcinoma27andstronglyexpressedinallsarcomatoid/desmoplasticmesotheliomas.28Markerstoconfirmamesothelialmalignantproliferation?Althoughthedistinctionbetweenmesotheliomaandreactivemesothelialproliferationsprimarilyreliesonhistologicassessment,thiscanbechallenginginsomecases.?Atpresent,onlyBRCA-1relatedprotein-1(BAP1)andmethylthioadenosinephosphorylase(MTAP)IHC,andcyclin-dependentkinaseinhibitor2A(p16)FISHhavesufficientpublicationsandreproducibilityofresultstobeconsideredasestablishedmarkers.21pBAP1IHCisaspecif