胰腺癌.上海.课件

PANCREATICNEOPLASMAPKU.FH2015年6月，上海IntroductionTheseareextremelyexcitingtimesforpancreaspathology,theexomesofallofthemajortumortypesthatariseinthepancreashavebeensequenced,andeachtumortypeappearstohaveadistinctmutationalprofileEvenhistologicallysimilarneoplasmsofductallineage,suchasconventionalductaladenocar.,mucinouscysticneoplasms,andintraductalpapillarymucinousneoplasms,havesomedistinctgeneticfeatures,despitesharingcertainkeymutationsthatcharacterizeductaltypeInfiltratingDuctalAdenocarcinomaneoplasticglandscanberemarkablywell-differentiated,andcanbedifficulttodistinguishbetweenreactivenon-neoplasticglandandinvasiveadenocar.,despitethehighlylethalnatureofthiscancer（oneofthemostdeadlyofallofthesolidmalignancies）ductaladenocar.elicitanintensedesmoplasticreaction,especiallywithinthepancreasitselfRe-endothelializeSMAD418q，肿瘤抑制基因，TGF-B超家族成员，细胞内信号传导inactivatedin55%ofIDA,onlyrarelytargetedinothertumortypesImmunolabelingforSmad4accuratelyreflectsgenestatus.LossofSmad4immunoexpressionwouldsupportadiagnosisofcarcinomaratherthanreactiveatypiaSmad4losscanalsopointtoapancreaticprimaryinametastasisofunknownoriginInaddition,SMAD4genestatushasprognosticsignificance,withlossofSmad4beingassociatedwithaworseprognosisandmorewidespreadmetastasesinpatientswithductaladenocar.IntraductalNeoplasmsofthePancreas3types：

intraductalpapillarymucinousneoplasms(IPMNs)(common,cystic)

intraductaltubulopapillaryneoplasms(ITPNs)

(rare,

solid)intraductaltubularpyloricgland-typeadenomaFeaturesoftheinvasiveadenocarcinomacomponentsTheoverallincidenceofanassociatedinvasivecarcinomainIPMNsisrelativelylow:branchduct-typeIPMNs15%;mainducttype30%;intestinaltype(colloidcarcinoma)pancreatobiliarytype(tubular-typeadenocarcinomas)MucinousCysticNeoplasm(MCN)2components:mucin-producingneoplasticepithelialcells:low-,intermediate-,high-gradecharacteristicnon-neoplastic“ovarian-type”subepithelialstromaUncommon(1-2%),low-grademalignant(10%havemalignantbehavior)mostlyinyoungwomenDespitenumerousstudies,thehistogenesisremainsunclear,havenotanormalcounterpartinthepancreasMacroscopylocatedinanypartlarge（mean7.5cm）highlyvariablecysticdegenerationGrosslywell-circumscribed,thereisnorealfibrouscapsule（neoplasticcellsmayinfiltratethesurroundingpancreaticparenchyma,andevenadjacentorgans）MicroscopycordsofmonomorphiccellsseparatedbysmallvesselsexhibitingavariabledegreeofperivascularcollagendepositionThemostcharacteristicfeature:pseudo-papillaryareaswithfibrovascularstalksorrosette-likestructuressecondarytopoorcohesionoftheneoplasticcellsneoplasticcells:smallandregularwithclearoreosinophiliccytoplasmvariants:clearcell,pleomorphic,oncocyticNuclei:uniform,ovoidwithfinelydispersedchromatin,inconspicuousnucleoli;longitudinalnucleargrooves(characteristic);RaremitosesImmunohistochemistryhighlydistinctivefromotherpancreaticneoplasmsThemostsensitiveandspecificmarkeristheabnormalintensenuclearexpressionofbeta-catenin,observedinnearlyallcaseswhichsecondarytoconstitutiveactivationofWntpathwaycausedbybeta-cateningene(CTNNB1)mutations.ThereisalsoalossorabnormalcytoplasmicexpressionofE-cadherinImmunolabelingofSPNwithanantibodytobeta-catenin.Strongcytoplasmicandnuclearlabelingwasobservedinneoplasticcells(right)ascomparedwiththemembranouslabelingfoundinnon-neoplasticexocrinecells(left).Theneoplasticcellsconsistentlyexpressvimentin,whereasstainingforkeratinsistypicallyeithernegativeoronlyveryfocal(30%)OtherdiagnosticmarkersincludeCD10,CD99(dot-like),PR,ER,galectin-3andalpha-1-antitrypsindifferentialdiagnosiswithneuroendocrinetumorsissometimesdifficultsynaptophysincanbefocally(31%)orevendiffusely(10%)positivechromograninisconsistentlynegative,asarestainsforpancreaticexocrineenzymessuchastrypsinandchymotrypsinMolecularCharacteristicsmaingeneticevent(90%)associatedtothetumorogenesisofSPNisalterationoftheWnt/beta-catenin(amultifunctionalproteinwithbothadhesiveandtranscriptionalactivationfunctions)signalingpathwayduetoactivatingpointmutationswithinexon3ofbeta-cateningene(CTNNB1)thiscanthereforehelpestablishthediagnosisofSPNHistogenesisAcinar,ductal,neuroendocrine,andprimordialcelloriginshavebeenproposed,butthephenotypeofthistumordoesnotspecificallyresembleanyofthesecellsneuroendocrinedifferentiation:+:ultrastructurallypresenceofrareneurosecretorygranules;positiveimmunostainingforsynaptophysin

-:negativityforchromograninandpositivityforAATandvimentinBasedontheprevalenceofSPNsinfemales,theexpressionofP