FallopianFallopian TTuubebe CancerCancer FredFred UelanUelandd,, MMDD UniversiUniversityty ofof KentucKentuckkyy GynGynecolecoloogicgic OncolOncolooggyy AnatoAnatommyy Three layers of the fallopian tube: • Internal mucosa (endosalpinx) • Intermediate muscular layer (myosalpinx) • Outer serosa, peritoneum of the broad ligament and uterus (mesosalpinx) Tubal mucosa: 1. The endosalpinx has primary folds, increasing in number toward the fimbria 2. Lined by columnar epithelium of three types: o Ciliated o Secretory o Peg cells. BenignBenign TuTubbalal NeoplasmsNeoplasms Adenomatoid tumors Lipoma Leiomyoma Hemangioma Teratomas Lymphangioma Fibroma Mesothelioma Fibroadenoma Mesonephroma Papilloma PrePre--invasivinvasivee DiseaseDisease Carcinoma in situ (CIS) Papillary endosalpingeal lining with cytologically malignant, mitotically actice nuclei Intact basement membrane Often incidental finding at segmental salpingectomy BSO recommended – Fertility is not an issue if recent sterilization PrimaryPrimary TuTubbalal MalignanciesMalignancies AdenocarcinAdenocarcinomomaa SarcSarcomomaa ChoriocarcinChoriocarcinomomaa OtherOther – Metastases to tubes are common FallopianFallopian TTuubebe CancerCancer One of the rarest malignancies of the female genital tract – 0.3% of all gyn malignancies – 3.6 per million women Mean age at diagnosis in the 50’s – ⅔ are menopausal Risk factors – Nulliparity – Chronic salpingitis – Infertility 70% of cases FallopianFallopian TTuubebe CancerCancer PresentationPresentation Delay of diagnosis common – Only 6% were actually asymptomatic – 23% with (+) cervical cytology, including psammoma bodies Triad 1. Vaginal bleeding Present in more than 50% Postmenopausal bleeding, (-) D&C 2. Hydrops tubae profluens Colicky pain Profuse serosanguinous vaginal discharge 3. Adnexal mass AgeAge DistributionDistribution 30 25 20 15 No Patients 10 5 0 <40 40-49 50-59 60-69 70-79 >80 FIGO Report, J Epidemiol Biostat 3:99, 1998 DiagnosisDiagnosis Preoperative diagnosis is rare – 80% have known pelvic or abdominal mass noted before surgery – 10-25% have cancer on cervical cytology Sonography Serum CA-125 – London Trial, 20% of cancers detected were fallopian tube cancers – 25-fold greater than expected PathologyPathology Almost exclusively adenocarcinoma – Endometrioid – Papillary serous – Clear cell 10-25% bilaterality Peritoneal disease common before ovarian spread 87% stain for CA-125 Propensity for lymphatic spread PathologyPathology 1. MainMain ttumumoorr shoulshouldd bebe visualizedvisualized inin ttuubebe 2. TubalTubal mmucosaucosa shouldshould bebe involvedinvolved wwiithth aa papillarypapillary patpattternern wwithith histologichistologic characcharactteristieristiccss ofof thethe endosalpinx.endosalpinx. 3. IfIf thethe tubaltubal wallwall iiss involved,involved, transititransitioonn frfroomm benignbenign toto mmaalignantlignant tubaltubal epitepithhelieliumum shouldshould bebe ddeemonsmonsttratedrated Hu, AJOG 1950 CACA--125125 StaStaiiningning FallopianFallopian TTuubebe EpitheliumEpithelium LowLow MaligMalignnantant PotentialPotential SerousSerous CaCanncercer FallopianFallopian TTuubebe CancerCancer GeneticsGenetics SSimimilailarr toto ovarianovarian andand endendoomemettrialrial ccaancersncers OncogenesOncogenes – K ras, c-crb, erb b2 TTuummoorr SuppressorSuppressor GenesGenes – p53 StagingStaging FIGOFIGO establishedestablished ttubalubal carcincarcinomaoma stagingstaging systsysteemm inin 19919911 StageStage II ConfiConfinneded toto FaFallloplopiianan TubesTubes StageStage IAIA:: ConfinConfineedd toto oneone tubetube StageStage IB:IB: BothBoth tubestubes StageStage IC:IC: OneOne oror bbothoth tubestubes and:and: – Involvement of tubal serosa – Malignant ascites – (+) washings from the abdomen/pelvis StageStage IIII ConfiConfinneded toto PPeelvislvis StageStage IIIIA:A: InvolveInvolvemementnt ofof uterusuterus oror oovaries,varies, oror both.both. StageStage IIBIIB:: OtheOtherr pelvicpelvic tissuetissue – bladder, sigmoid colon, or the rectum. StageStage IICIIC:: IIIIAA oror IIIBIB withwith ((++)) wwashings,ashings, mamalignantlignant aasscitescites StageStage IIIIII ExtraExtrappelvicelvic DDiisseaseease StageStage IIIIIA:IA: MiMiccroscopicroscopic diseasdiseasee ofof uuppperper abdabdoomenmen StageStage IIIIIB:IB: UppeUpperr abdabdoominalminal involveinvolvemement,nt, butbut lessless thanthan 22 ccmm inin sizesize StageStage IIIIIC:IC: – Lymph node involvement, inguinal included. – Upper abdominal disease ≥ 2 cm StageStage IVIV DistantDistant SpreSpreadad StageStage IVIV:: DistantDistant memetastasttasisasis – Liver parenchyma – Lung parenchyma – Malignant pleural fluid – Other distant organs located outside of the peritoneal cavity SurgerySurgery anandd TreatmentTreatment FallopianFallopian TubeTube CCaancerncer RoleRole SurgeSurgerryy SSimimilailarr toto ovarianovarian cancercancer ProperProper stagingstaging forfor earearllyy disediseaasese – Adjuvant therapy CytoreductionCytoreduction ofof advancedadvanced diseasedisease – Optimal ≤ 1cm ReasseReassessmssmenentt laplapaarotrotomomyy SecondarySecondary debulkingdebulking GGOOGG SurgicalSurgical ProceduresProcedures ManualManual AdequateAdequate abdabdomominalinal incisionincision EstEstimimaattee volvolumumee ooff peritonealperitoneal fluid.fluid. IfIf nono fluid,fluid, obtainobtain washwashiingsngs frfroomm pelvispelvis aanndd abdabdoomenmen ifif suspesuspecctedted stagestage II oror IIII InspectInspect allall ppeeritonealritoneal surfacessurfaces InfraInfra--coliccolic omomenentetectctomomyy – At minimum, a biopsy must be obtained GGOOGG SurgicalSurgical ProceduresProcedures ManualManual If possible, extrafascial TAH with BSO. Unilateral SO if patient desires fertility and cancer appears stage I Resect all remaining gross disease in abdomen pelvis Selective pelvic and para-aortic lymph node sampling – Not required if stage IIIc or IV, except for cytoreduction If no gross disease, perform peritoneal biopsies – Cul-de-sac – Vesical peritoneum – Right and left pelvic sidewalls – Right and left paracolic gutters – Right hemidiaphragm TreatmentTreatment SurgicalSurgical stagingstaging aass forfor ovarianovarian canccancerer DataData lliimmitedited onon feferrtilitytility--sparingsparing surgsurgeeryry – Potential for bilaterality FourFour studiesstudies showshow nono benefitbenefit toto adjuadjuvvantant therapytherapy inin earearllyy sstatagege diseasedisease – Under staging? – 50-60% survival for stage I/II PlatinPlatinumum--basedbased ccomombinationbination chcheemmoottherapyherapy 55--YearYear SuSurrvivalvival I II III IV Overall Podratz 64 60 81 25 41 Pfeiffer 64 40 6 37 Peters 61 29 17 Muntz 100 63 - Frigerio 48 48 25 41 FIGO 84 52 36 OverallOverall SuSurvrvivalival 1 year 2 year 3 year 4 year 5 year 87.8% 69% 60% 56% 56% FIGO Report, J Epidemiol Biostat 3:99, 1998 N=83 ConclusionConclusionss 1. Very rare gynecologic malignancy 2. Serous histology most common 3. Lymphatic and peritoneal spread 4. Staging and treatment similar to ovarian cancer 5. Optimal cytoreduction 6. Survival is similar to ovarian cancer ReviewReview QuQueestionsstions Review Questions GenGeneess andand CCananccerer 1. NNameame thethe ththrreeee mamainin typestypes ofof cancanccerer protectionprotection genes.genes. 2. GiveGive anan eexamxamplplee ofof eacheach typtypee.. Review Questions GenGeneess andand CCananccerer 1. Name the three main types of cancer protection genes. 2. Give an example of each type. Tumor suppressor genes . RB (13q), p53 (17p), APC (5q21), BRCA1 (17q), BRCA2 (13q) . Oncogenes . Heregulin receptor (her-2/neu, erb-b), k-ras, h-ras, abl and src, EGF, PDGF, c-myc, cyclins . mismatch repair genes . MSH2, MLH1, MSH6, PMS1, PMS2 Review Questions PrePre--invinvaasivesive DiDisseeaasese ofof thethe VaginaVagina aanndd VulvaVulva 1. WhatWhat iiss thethe nnaameme ofof thisthis conditconditiioon?n? 2. WhatWhat araree thethe rrelatelateedd clinicalclinical conconccernernss?? Review Questions PrePre--invinvaasivesive DiDisseeaasese ofof thethe VaginaVagina aanndd VulvaVulva 1. WhatWhat iiss thethe nnaameme ofof thisthis conditconditiioon?n? . Paget’s disease of the vulva 2. WhatWhat araree thethe rrelatelateedd clinicalclinical conconccernernss?? . Synchronous or metachronous adenocarcinomas of the breast and GI tract Review Questions EndometrialEndometrial HyperHyperpplaslasiiaa aandnd HormHormoonene TTheherapyrapy 1. Based on the WHI, estrogen-alone replacement therapy increases the risk of the following: (True or False) . Breast cancer . Endometrial hyperplasia and cancer . Stroke . Improved cognition . Fracture . Thrombosis . Death Review Questions EndometrialEndometrial HyperHyperpplaslasiiaa aandnd HormHormoonene TTheherapyrapy 1. Based on the WHI, estrogen replacement therapy alone increases the risk of the following (True of False) : . Breast cancer No . Endometrial hyperplasia Yes (implied) . Stroke Yes . Improved cognition Yes . Fracture No . Thrombosis Yes . Death No! Review Questions AdenAdenoocacarrcicinonomama ofof thethe UterusUterus 1. WhatWhat araree thethe toptop threethree causecausess ofof posposttmenopausalmenopausal bblleedineedingg?? 2. ForFor typetype 22 endendomeometrialtrial ccanceancerr,, discudiscusss:s: . Typical body habitus . Common cell types and clinical course . Precursor lesion Review Questions AdenAdenoocacarrcicinonomama ofof thethe UterusUterus 1. What are the top three causes of postmenopausal bleeding? . ERT, atrophy, CA (Mayo → polyps then CA 2. For type 2 endometrial