小細胞肺癌診斷治療進展課件

SmallCellLungCancer(SCLC):

Diagnosis,TreatmentandNaturalHistoryGaryL.WeinsteinM.D.小細胞肺癌診斷治療進展SCLCLungcancerepidemiologySCLCPathologyTumormarkersGeneticsClinicalcourseStagingTreatment小細胞肺癌診斷治療進展小細胞肺癌診斷治療進展小細胞肺癌診斷治療進展小細胞肺癌診斷治療進展小細胞肺癌診斷治療進展小細胞肺癌診斷治療進展小細胞肺癌診斷治療進展小細胞肺癌診斷治療進展小細胞肺癌診斷治療進展小細胞肺癌診斷治療進展小細胞肺癌診斷治療進展小細胞肺癌診斷治療進展小細胞肺癌診斷治療進展小細胞肺癌診斷治療進展小細胞肺癌診斷治療進展小細胞肺癌診斷治療進展小細胞肺癌診斷治療進展小細胞肺癌診斷治療進展小細胞肺癌診斷治療進展小細胞肺癌診斷治療進展小細胞肺癌診斷治療進展小細胞肺癌診斷治療進展小細胞肺癌診斷治療進展小細胞肺癌診斷治療進展小細胞肺癌診斷治療進展小細胞肺癌診斷治療進展SCLC,factoids15–25%ofalllungcancersAlmostexclusivelyinsmokersDistinguishedfromNSCLCby:RapiddoublingtimeHighgrowthfractionEarlydevelopmentofwide-spreadmets小細胞肺癌診斷治療進展SCLC,factoids(cont’d)Consideredhighlyresponsiveto“chemsandbeams”BUT…usuallyrelapseswithin2yearsdespitetreatmentOverall,only3–8%ofallpatientssurvivemorethan5yearsMostcommonmalignancyassociatedwithNeurologicparaneoplasticsyndromes小細胞肺癌診斷治療進展SCLC,pathologyMostrecent(1999)WHOclassificationClassicalsmallcellcarcinomaLargecellneuroendocrinecancerCombinedsmallcellcarcinomawithsomeNSCLCCellsareapprox.2X’sthesizeofnormallymphocytes小細胞肺癌診斷治療進展SCLC,pathology

小細胞肺癌診斷治療進展SCLC,pathology

小細胞肺癌診斷治療進展SCLC,clinicalpresentationTypicallyarisecentrallyMostcommonpresentationisalargehilarmasswithbulkymediastinalLANCommonsymptomscough,SOB,wtlossApprox.70%withovertmetsatpresentationCommonlyspreadtoliver,adrenals,boneandbrainCanpresentwithparaneoplasticsyndome小細胞肺癌診斷治療進展SCLC,tumormarkers3maingroups:Neural,Epithelial,NeuroendocrineEpithelial:virtuallyallSCLCsareimmunoreactiveforKeratinandEpithelialMembraneAntigen1ormoremarkersofNeural/Neuroendocrinedifferentiationfoundinapprox.75%ofSCLCs小細胞肺癌診斷治療進展SCLC,tumormarkersLeadstoexpressionofdopadecarboxylase,calcitonin,neuron-specificenolase,chromograninA,CD-56(aneuralcelladhesionmolecule)gastrinreleasingpeptideandinsulin-likegrowthhormoneOccasionallypatientsproduceantibodiesthatcross-reactwithboththeSCLCcellsandtheCNScerebellardegenerationsyndromesSCLCcellscanproduceanumberofpolypeptidehormonesincludingACTHandVasopressin

小細胞肺癌診斷治療進展NeurologicParaneoplasticSyndromes

小細胞肺癌診斷治療進展Lungcancer,ParaneoplasticSyndromes

小細胞肺癌診斷治療進展SCLC,geneticsDevelopmentoflungcancersoccurthroughstimulationofproliferationandmutagenesis,occurringoverYEARSandresultingfromexposuretotobaccoandothercarcinogens小細胞肺癌診斷治療進展SCLC,geneticsThemostcommongeneticsofSCLCare:P53mutationispresentin75-90%Lossofheterozygosityofc-somes9pand10qinthemajorityDeletionof3pinactivationofasmanyas3tumorsuppressorgenesLossoftheretinoblastomagenefunctionisnearlyubiquitousActivationoftelomeraseinapprox.90%(allowscellstodivideforever)小細胞肺癌診斷治療進展小細胞肺癌診斷治療進展小細胞肺癌診斷治療進展小細胞肺癌診斷治療進展小細胞肺癌診斷治療