恶性胸膜间皮瘤2022.v1-NCCN（英文版）

MalignantPleuralMesotheliomaNCCNClinicalPracticeGuidelinesinOncologyNCCNMalignantPleuralMesotheliomaersionDecemberNCCNGuidelinesforPatients®availableat/patientsVersion1.2022,12/22/21©2021NationalComprehensiveCancerNetwork(NCCN),Allrightsreserved.NCCNGuidelinesandthisillustrationmaynotbereproducedinanyformwithouttheexpresswrittenpermissionofNCCN.loeybiiononooloeydln才91n6lm9bioin9冈6bio才n916qytM9bio6lonooloeyPloeybiiononooloeydln才91n6lm9bioin9冈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†ÞTravisE.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‡†ÞGregoryJ.Riely,MD,PhD†ÞJonathanRiess,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