不明原发灶肿瘤的诊断2-ed.

MetastaticCancerUnknownPrimarySite中国医学院肿瘤医院内科王宏羽MetastaticCancerUnknownPrimarySiteSynonymsandrelatedkeywords◆tumorofunknownprimary◆cancerofunknownorigin◆carcinomaofunknownorigin◆unknownprimarycancerMetastaticCancerUnknownPrimarySite◆unknownprimarycarcinoma◆carcinomaofunknownprimaryoriginMetastaticCancerUnknownPrimarySite◆cancerofunknownprimarysite(cups)◆carcinomaofunknownprimaryorigin(CUP)MetastaticCancerUnknownPrimarySite◆metastaticcancer◆metastaticcarcinoma◆metastatictumor◆metastases◆occultprimarymalignancyCUPBackground(intheUnitedStates)◆32,100patswithCUPSin2007(15,720males;16,380females)◆About2%ofallcancersCUP◆DeathsduetoCUPS:45,230(24,440males;20,790females)CUP◆ThisdiscrepancybetweenincidenceandmortalityisbelievedtobeduetoalackofspecificityinthelistingofcauseofdeathondeathcertificatesCUP◆Itstrueincidenceismostprobablybetween2%and6%◆In15-25%ofcases,theprimarysitecannotbeidentifiedevenonpostmortemCUPPathophysiology◆Cancersarethoughttoarisefromasinglecellthatescapesthecontrolsofnormalcellreplication◆Formsatumoratthesiteoforigin◆UltimatelymetastasizestootherorgansCUPPathophysiology◆Insomecasestheoriginaltumormayremainsmallorundetectableatthetimeofmetastasis◆LeadingtotheclinicalpresentationofCUPCUPFrequency◆UnitedStates:2-6%◆International:2-9%CUPMortality/Morbidity◆Mediansurvivalrangesfrom11weeksto11months◆The5-yearoverallsurvivalrateisabout11%CUPSex◆AnapproximateequalincidenceformenandwomenCUPAge◆Themedianageonpresentationforbothmenandwomenrangesfrom59-66yearsCUPCLINICAL(History)◆Becausemostpatientswithcuphavefairlyadvanced-stagedcancers◆Theconstitutionalsymptomsofmalaise,weakness,fatigue,andweightlossarepresentinnearlyallpatientsCUPCLINICAL(Physical)◆Theclinicalpresentationofcupisextremelyvariable◆DependsontheextentandtypeoforganinvolvementCUP◆一群异源发生的肿瘤◆除外淋巴瘤、转移性黑色素瘤和转移性肉瘤◆集中于上皮细胞组织，包括腺癌、鳞状上皮细胞癌、分化不良上皮癌和神经内分泌癌CUPCUP的诊断标准◆组织活检证实为恶性肿瘤(活检部位不能检出原发灶)◆经过彻底地收集病史或物理检查(包括女性盆腔检查和男性睾丸及前列腺触诊)未发现原发性肿瘤CUP◆CUP实验室检查结果正常，包括完整的血细胞计数、血液生化、胸部X线、腹部和盆腔CT、乳房影像学检查或前列腺特异性抗原(PSA)检查等等CUPCLINICAL◆完整的病史和彻底的体格检查是诊断CUP的基本前提，尤其是既往组织活检结果◆家族史很可能提示遗传性非息肉病性结肠癌或乳腺癌易感性CUP◆彻底的体检可能会发现特异性原发肿瘤◆左侧锁骨上淋巴结肿大(Virehow’S结节)(胃Ca?)◆脐周淋巴结肿大或包块(SisterMaryJosph’S结节-由恶性腹水造成的腹胀以及脐周肿块{脐孔肿大变硬,产生冰山样脐部肿块})(低分化癌-胃肠道)◆腹股沟淋巴结肿大、肛周包块(肛门肿瘤)CUPCLINICAL(Physical)◆Themostcommonsitesofinvolvementbeinglung,bone,lymphnodes,andliverCUPCLINICAL(Physical)◆Includingheadandneck,rectal,testicular,pelvic,andbreastexaminationsCUPCLINICAL(Physical,Labandradiologicalstudies)◆Acompletebloodcellcount(irondeficiencymaypointtowardanoccultgastrointestinalmalignancyleadingtochronicbloodloss)CUPCLINICAL(Physical,Labandradiologicalstudies)◆urinalysis(microscopichematuriamaybeasignofoccultgenitourinarymalignancy)CUPCLINICAL(Physical,Labandradiologicalstudies)◆liverandrenalfunctiontests◆stoolforoccultblood◆chestradiographCUPCLINICAL(Physical,Labandradiologicalstudies)◆abdomenandpelvisCT◆mammographyinwomen◆measurementofPSAinmenCUPPhysical•AscitesshouldleadonetoevaluateforaGIoranovarianprimary•Anaxillarymassinafemaleshouldmakethecliniciancheckforbreastcancer•AcervicalnodeshouldleadtoathoroughENTexaminationCUPPhysical•Abrainmetastasisshouldleadtoasearchforalung,breast,orkidneyprimary•Bonemetastasisshouldleadtoevaluationforprostate,breast,lung,renal,orthyroidprimaryCUPPhysical•Atesticularmassshouldleadtomeasurementoftumormarkerssuchasbeta-HCGandAFPCUPPhysicalDependingontheclinicalsituation,thesemayincludechestCT,breastMRI,upperorlowerendoscopyCUPCLINICAL(Physical)◆Insuspectedheadandneckmalignancies,panendoscopyoftheupperaerodigestivepathwaysshouldbeperformedwithevenasindicatedblindbiopsiesofthelymphoidtissueintheseareasCUPCLINICAL(Physical)◆DiagnostictonsillectomymaybewarrantedCUPCLINICAL(Physical)◆IntensivetestingalsoaddstothemorbidityfortheweakandfrailpatientCUPCLINICAL(Physical)◆Alargenegativecost-to-benefitratioexistsforanextensiveunguidedclinicalevaluationCUPCLINICAL(Physical)◆Onestudyquotinga9.5%increasein1-yearsurvivalatacostof2-8milliondollarsCUPCLINICAL(Physical)◆Whentheseinvestigationsfailtorevealapotentialprimarylesion,acancerofunknownprimaryoriginisassumedCUPWORKUP(ImagingStudies)◆18F-FDG-PETisincreasinglybeingusedintheevaluationofmetastaticmalignanciesCUPWORKUP(ImagingStudies)◆ThismaybeespeciallythecaseinsuspectedheadandneckmalignanciesCUPWORKUP(ImagingStudies)◆ThistestinglacksspecificityandmayonlybeusefultoidentifypromisingsitesforbiopsyCUPWORKUP(ImagingStudies)◆18氟-脱氧葡萄糖(18F-FDG)-PET可辅助指导活组织检查，确定疾病程度和辅助选择恰当的治疗CUPWORKUP(ImagingStudies)◆Althoughpromising,highcostandfalsepositiveratesof20%limititsutilityincasesofCUP◆ThecombinationofPET/CTmayreducethefalse-positiverateCUPOtherTests◆TheroleoftumormarkerslikeAFP,beta-HCG,CA125,CA27.29,CA19.9,andCEAtoestablishaspecificprimarysiteCUPOtherTests◆Mosttumormarkersarenonspecific◆ItmaynotbeusedtoestablishdefinitivediagnosesCUPOtherTests◆男性腺癌和骨转移，常规检查血清PSA◆男性未分化癌和低分化癌，检测B-HCG和AFP,AFP也用于诊断HCC◆B-HCG和AFP水平并不能预测化疗效果或生存期CUPOtherTests◆CEA、CA125、CA19-9和CA15-3对于确定原发灶没有帮助◆大多数血清肿瘤标记物是非特异性的，可判断预后CUPProcedures◆Abiopsyofthemetastaticsite◆Acarefulevaluationofthe