外科学教学课件：Gestational Trophoblastic Diseases (GTDs)

GestationalTrophoblastic

Diseases(GTDs)22023/3/234IntroductionGTDsincludeadiseasespectrumofhydatidiformmole,invasivemole,choriocarcinoma,andplacental-sitetrophoblastictumor.Theyarisefromfetaltissuewithinthematernalhost.ThefirstandonlydisseminatedsolidtumorshighlycurablebychemotherapyUniqueandcharacteristictumormarker:hCGClassification

invasivemolechoriocarcinomaplacentalsitetrophoblastictumor(PSTT)GTDsHydatidiformmole(HM)(completeandpartial)GestationalThrophoblasticneoplasia(GTN)7HydatidiformmoleMolarpregnancyHydatidiformmoleisanabnormalpregnancycharacterizedgrosslybymultiplegraplikevesiclesfillinganddistendingtheuterus,usuallyintheabsenceofanintactfetus.IncidenceandepidemiologyItsincidencevariesworldwidefrom1in125deliveriesinMexicoandTaiwanto1in1500deliveriesintheUS.Highriskfactorswomen<20and>35-40yearsLoweconomicstatusNutrition:dietsdeficientinprotein,folicacid,andcaroteneEtiologyCompletemolesarealwayseuploid,paternalinorigin,andabsenceorinactivationoftheovumnucleus.Partialmolesaretriploid

细胞遗传学研究表明:

因染色体变异、卵子不正常，致受精缺陷，空卵受精，双精子受精

2023/3/2142023/3/2152023/3/216PathologyCompletegrape-likemassesPartialgrape-likemasseswithembroyorfetus2023/3/218Completehydatidiformmoledemonstratingenlargedvilliofvarioussize2023/3/2192023/3/220Hydatidiformmole:specimenfromsuctioncurettage2023/3/221Alargeamountofvilliintheuterus.2023/3/2222023/3/223Hereisapartialmoleinacaseoftriploidy.Notethescatteredgrape-likemasseswithinterveningnormal-appearingplacentaltissue.PathologymicroscopicallycharacteredemaofthevillousstromaAvascularvilliNestsofproliferatingtrophoblasts2023/3/225Themicroscopicappearanceofhydatidiformmole:HyperplasiaoftrophobasitccellsHydropicswellingofallvilliVesslesareusuallyabsent2023/3/226ComparisonofcompleteandpartialHMCompleteIncompleteKaryotypeDiploid46XX(90%)Triploid69XXY(90%)EmbryoAbsentPresentVillihydropicFewhydropicTrophoblastsDiffusehyperplasiaMildfocalhyperplasiaImplantation-sitetrophoblastDiffuseatypiaFocalatypiaβ-hCGHigh(>50000)SlightelevationFrequencyofclassicclinicalsymptomscommonrareRiskforpersistentGTN20%-30%<5%ComparisonofcompleteandpartialHM2023/3/229Theca-luteincystsatypeofbilateralfunctionalovariancystfilledwithclear,straw-coloredfluid.Tobeclassifiedafunctionalcyst,themassmustreachadiameterofatleastthreecentimeters.OverstimulationofthecaluteincellsbylargeamountsofHCGsecretedbyproliferatedtrophoblast2023/3/231Largebilateralthecaluteincystsresemblingovariangermcelltumors.Withresolutionofthehumanchorionicgonadotropin(HCG)stimulation,theyreturntonormal-appearingovaries.ClinicalmanifestationSymptomsandsignsAmenorrheaandVaginalbleedingThemostcommonsymptom,8-12weeksVaryfromspottingtoprofusebleeding,irregularUterusenlargementandsoftDisproportionateuterinesize50%haveexcessiveuterinesizeforgestationaldate33%theuterusissmallerthanexpectedAbdominalpainExcessiveuterineenlargement,rupture,hemorrhageandinfectionofovariancystHyperemesisgravidarumSeverenauseaandvomitingPreeclampsiaInthefirstorearlysecondtrimester,10%-12%PathognomonicofHMOvarianthecaluteincystsRegressspontaneouslyseveralweeksafterevacuation,parallelingthedeclineofhCGlevelRupture,bleedingandinfectioncauseacuteabdominalsymptomsandrequiressurgeryGreaterlikelihoodofdevelopingmalignantsequelaeHyperthyroidismProductionofTSHbymolartissue,10%Disappearfollowingevacuationofthemole,anoccasionalpatientmayrequireantithyroidtherapyLaboratoryfindingsβ-hCGRadioimmunoassayinserumandurineAbnormalelevatedleveldeclinetonormalwithin14weeksfollowingevacuationHCG测定：HCG异常增高受精6日→8~10到最高峰→12W↓较低水平→妊娠→产后2W消失有时需动态监测比较Ultrasound-----diagnosticmethodReliable,safe,economical,simple,specificCharacteristicpattern:multipleechoesformedbytheinterfacebetweenthemolarvilliandthesurroundingtissue,nonormalgestationalsacorfetus2023/3/2372023/3/2382023/3/2392023/3/240落雪样图象蜂窝状图象2023/3/241Transvaginalsonogramdemonstratethe“snowstorm”appearance2023/3/242ColorDopplerimageofahydatidiformmoleandsurroundingvessels.2023/3/243DiagnosisandDifferentialdiagnosisDiagnosisClinicalfindings,expulsingofgrape-likevesicles,-hCG,ultrasoundDifferentialdiagnosisAbortion:ultrasoundTwinpregnancy:nobleedingPolyhydramnios:nobleedingTreatment

A.EvacuationWhendiagnosisisconfirmed,molarpregnancyshouldbeterminated.Suctioncurettage:safe,rapid,effective,withgentlesharpcurettageIntravenousoxytocinshouldbegivenafteramoderateamountoftissuehasbeenremovedtopreventhemorrhageandperforationTissuefromthedeciduabasalisforpathologicstudyPreparingforbloodtransfusion,laparotomyRarely,molartissuecouldnotberemovedatonetime,after1week,again2023/3/246B.ProphylacticchemotherapyhCG>100000U/LPatientwithextremelylargeuterusorpoorfollow-upThecaluteinovariancyst>6cmwomen<20and>35-40yearsMTX,5-Fu,Dactinomycin,singleagentchemotherapymonitortoxicityC.SurgeryAge>40years,highrisk,nodesireofpregnancy----hysterectomyThecaluteincysts:ovariesshouldremainintact,becauseregressionspontaneously.oraspirateunderultrasound,iftorsionforalongtime,necrosis,removeFollow-upTheincidenceofmalignantdiseaseis20%-30%.TimeWeeklyintervalsafterevacuationuntilserumhCGdeclinestonondetectablelevelson3successiveassaysThenmonthlyfor6monthsandoncehalfayearforatotal2yearsContentsSymptom:abnormalvaginalbleeding,cough,hemoptysisPelvicexaminationSerial-hCGdeterminationUltrasoundChestX-rayorbrainCTContinuecontraceptionduringsurveillancefor1year,condomororalcontraceptive,notIUDGestationalTrophoblastictumorOneoftheraremalignanciesthatarehighlycurableevenwithwidespreadmetastasisMostcommonlyfollowamolarpregnancy,buttheymayfollowanytypesofpregnancy.InvasivemoleInvasivemoleisahydatidiformmolethatinvadesmyometriumoradjacentstructure.Itmaypenetratethemyometriumandcauseuterineruptureandhemoperitoneum.In10~15%ofpatientswhohavehadprimarymolarpregnancy,oftenwithin6monthsaftermolarevacuationChoriocarcinoma2-5%ofallcasesofGTN.Antecedentgestation:molarpregnancy(60%),abortion(30%),termpregnancyandlesscommonlyectopicpregnancyEarlyvascularinvasionwithwidespreaddissemination,causehemorrhageandnecrosisoftissuesororgans.Themostcommonsiteofmetastasisislung,andthenvagina,pelvis,liver,brainThetimebetweenantecedentgestationandchoriocarcinomaisvariable.2023/3/255侵蚀性葡萄胎及绒毛膜癌来源及发生时间

1.Pathology

InvasivemoleIngross(picture)Vesicles,locallyinvasiveMicroscopically,proliferativetrophoblast,invasionofthemyometriumwithidentifiablevillousstructureChoriocarcinomaGrosslyredandgranular,extensivenecrosisandbleedingMicroscopically,

novilli,butinsteadsheetsoftrophoblastsonabackgroundofhemorrhageandnecrosis.2023/3/257Invasivehydatidiformmoleinfiltratingthemyometrium2023/3/258Invasivemole:thetissueinvadesintothemyometriallayer.Noobviousborderline,withobviousbleeding.2023/3/259子宫肌层深部受水泡状绒毛侵犯，滋养叶细胞轻度增生，并有异型。HE×402023/3/260Microscopicimageofchoriocarcinoma2023/3/261Microscopicimageofchoriocarcinomaabsenceofchorionicvilli2.ClinicalfindingsNonmetastaticgestationaltrophoblastictumor------invasivemoleorchoriocarcinomaafterHM,confinedtotheuterusVaginalbleeding:irregularEnlargementorsubinvolutionofuterusThecaluteincystsAbdominalpain:rarely,perforationofuteruscausepainandhemorrhage,torsionorruptureofcystsSymptomsofpregnancy:pseudopregnancyMetastaticgestationaltrophoblastictumor----choriocarcinoma(picture)Localhemorrhage:destroybloodvesselsLungmetastasis:chestpain,cough,dyspnea,hemoptysis

Vagina:anteriorwallandfornix,violetbluenodular

LiverBrain:headache,vomiting,dizziness,coma,deathOtherorgans:spleen,kidney,bladderandetal3.DiagnosisSymptomsandsignsAftermolarevacuation,>1year,choriocarcinoma;<6months,invasivemole;betweenthem,botharepossibleSerum-hCG>9weeksaftermolarevacuation;>4weeksafterabortion,delivery,ectopicpregnancy,titerishigh,ordecreasethenincreaseUltrasoundHighechoesinmyometrium,nocapsuleX-rayPulmonarymetastasisCT,MRIBrain,lung,liverandrenalmetastasisHistology:withvilli------invasivemolewithoutvilli----choriocarcinoma2023/3/266Acaseofinvasivemole:insidetheuterinecavitythetypical“snowstorm”appearancecanbedetected,Thelocationofbloodflowsuggestaninvasivemole.2023/3/267Dopplerimageofinvasivemole.Dopplerwaveformanalysisdepictslowvascularresistance(RI=0.35)2023/3/268Dopplerimageofchoriocarcinoma2023/3/269Dopplerimageofchoriocarcinoma4.DifferentialdiagnosisInvasivemoleandchoriocarcinomaTimeandnatureofpreviouspregnancyHistology:villipresentornottermpregnancyabortionectopicpregnancy<6mchoriocarcinomainvasivemole>1yafterevacuationhydatidiformmoleDifferentiationfromotherdiseasesHMInvasivemolechoriocarcinomaPSTTReactionofplacentaRetainedplacentaPreviouspregnancynoHMvariousvariousvariousAbortion,termLatentphaseno<6m>12m<1ynonovillihavehavenononoHave,degenerationProliferativetrophoblastSlightsevereSlightsevereclusterSever,clusterIntermediatetrophoblastDispersed,noproliferationnoDepthofinfiltrationdeciduamyometriummyomyoSuperficialmyometriumdeciduanecrosisnohavehavenononometastasisnohavehavealittlenonometastasisofliver,brainnoalittleeasilyalittle+orHCG++++or

+or5.Stagingaccordingtoanatomy

Istage:confinedtotheuterusIIstage:extendsoutsideoftheuterusbutislimitedtothegenitalstructuresIIIstage:extendstothelung,withorwithoutknowngenitaltractinvolvementIVstage:allothermetastaticsite2023/3/2742023/3/2752023/3/2762023/3/2776.ClinicalstagingandPrognositicscoring0124age<4040--AntecedentpregnancyHMabortionterm-Interval(m)<44~<77~<1313hCG(IU/ml)BT<1,0001,000-10,00010,000-100,000100,000Largesttumor-3~<5cm5cmSiteofmetastaseslungSpleen,kidneyGItractLiver,brainNumberofmetastases-1-45-8>8Priorfailurechemotherapy--OnedrugTwoormoredrugs6lowrisk,7highrisk7.Treatment

Principle:chemotherapyisthefirstchoice,sometimesaccompaniedwithhysterectomyorradiotherapyMortalitydecreaseddramatically,from90%to20-30%Chemotherapy

Medicines5-fluorouracil(5-Fu)Methotrexate(MTX),LeucovorincalciumDactinomycinCyclophosphamide(CTX)Vincristine(VCR)Cis-platinum(CDDP)Etoposide(VP-16)Single-agentchemotherapy:MTXordactinomycin,lowriskCombinedchemotherapy:EMA-CO,highriskSideeffectsBonemarrowdepressionDigestivesystemsymptomsLesionofliverandrenalfunctioncalvitiesJudgmentoftherapeuticeffectDetermine-HCGeveryweekafteronecourseoftreatment,decreaseonelogarithmIndicationofdrugwithdrawTillsymptomandsigndisappear,primarya