Gynecologic Cancer: Uterine, Vulvar , and Ovarian

Christopher R. Graber, MDSalina Women’s Clinic

08 March 2011

OverviewEndometrial (Uterine) CancerVulvar CancerOvarian Cancer

Typical Presentation and DifferentialRisk Factors Different Types and StagingScreeningTreatment

Endometrial (Uterine) CancerA 58 yo obese woman presents with postmenopausal

bleeding10 years without menses, now has had 4 months with

“irregular periods.” No cramping.A 47 yo long-distance runner presents with heavier

menses x 1yTypical menses: 3-5d, min flow. Now: 5-7d, heavy.

2.6% of US women, 0.5% lifetime mortalityTypical: 50-65yo; 5% younger than 40

Differential - Endometrial CancerPerimenopauseUterine fibroidsAdenomyosisUterine or cervical polypPostmenopausal endometrial atrophyEndometrial hyperplasia

Simple and complexWith and without atypia

Endometrial CA risk factorsIncreased risk

Unopposed estrogenMenopause >52yoObesity (3x<50, 10x>50)NulliparityDMPCOS

Decreased risk

OvulationProgestin therapyOCPsMenopause <49yoNormal weightNulliparity

Uterine CA – TypesEndometrioid adenocarcinomaClear cell carcinomaPapillary serous carcinomaSecretory carcinomaMucinous carcinomaSquamous carcinoma

Uterine CA – Staging (surgical)IA – confined, < ½ myometrial invasionIB – confined, > ½ myometrial invasionII – cervical stromal invasionIIIA – invasion of serosa or adnexaIIIB – vaginal or parametrial involvementIIIC 1&2 – positive lymph nodesIVA – invasion of bladder or bowelIVB – distant metastases

Uterine CA – ScreeningAlways have a high index of suspicionEMB for any woman >35yo with suspected anovulatory

bleedingEMB for any other woman with long(er) history of

anovulatory bleeding and other risk factorsConsider D&C if not able to obtain EMB

Uterine CA -- ScreeningIf postmenopausal and EMB shows atrophy

Consider sono – endometrial stripe that measures less than or equal to 4mm is reassuring

Chances of CA if EMB showsSimple hyperplasia 1%Complex hyperplasia 5%Simple with atypia 10%Complex with atypia 25%

Uterine CA – Treatment Treatment for CA is surgery

Hysterectomy plus staging procedureBy Gyn Oncology

Hysterectomy alone often done ifGrade I or IINo evidence of spreadType other than clear cell or papillary serous

Consider progestin therapy for hyperplasia

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OverviewEndometrial (Uterine) CancerVulvar CancerOvarian Cancer

Typical Presentation and DifferentialRisk Factors Different Types and StagingScreeningTreatment

Vulvar CAA 63yo woman with daily itching and occasional bleeding

“down there”Duration: several years

A 45yo woman with history of lichen sclerosus reports she has a sore that won’t heal10y history of LS, usually well controlled

4% of cancer in genital tractCommon age 60-79yo; 15% under 40

Vulvar CA – DifferentialHypertrophic vulvar dystrophyLichen sclerosusBenign skin lesions: mole, wart, freckleTraumaSTI – HSV, syphilis, chancroidHidradenitis suppurativa

Vulvar CA – Risk FactorsHPVVulvar dystrophy

Lichen sclerosus – lifetime risk 3-5%Cervical or vaginal CA

Vulvar CA – Types Squamous cell carcinoma (90%)MelanomaBartholin’s glandBasal cell carcinomaMetastatic

Vulvar CA – Staging (surgical)IA – confined to vulva, ≤ 2cm, ≤1mm invasionIB – same as IA but >1mm invasionII – confined to vulva, > 2cmIII – adjacent spread to lower urethra, vagina, anus,

and/or unilateral lymph nodes (regional)IVA – invasion of upper urethra, bladder/rectal mucosa,

pelvic bone and/or bilateral LNIVB – distant metastases including pelvic LN

Vulvar CA – ScreeningAlways have a high index of suspicionBiopsy any suspicious lesionClose follow-up for lichen sclerosus

Q 3-6 months Keyes punch biopsy

Vulvar CA – Treatment Surgical removal

Wide local excision (IA)HemivulvectomyRadical vulvectomy with bilateral inguinal –femoral node

dissection

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To be continued…

OverviewEndometrial (Uterine) CancerVulvar CancerOvarian Cancer

Typical Presentation and DifferentialRisk Factors Different Types and StagingScreeningTreatmentBRCA overview

Ovarian Cancer58 yo female complains of abdominal pain for several

months; has not seen a doctor for several yearsModerate nausea, weight loss

18 yo female complains of subacute abdominal pain and urinary frequency; pelvic mass felt on examSono shows 9cm solid and cystic adnexal mass

5th most common cancer in women in USHighest fatality-to-case ratio of all GYN CA

Ovarian CA – Differential Anything that causes…

BloatingPelvic or abdominal painBack/leg painDiarrhea, gas, nausea,

constipation, indigestion

Difficulty eating or feeling full quickly

Pain during sexAbnormal vaginal bleedingTrouble breathing

Ovarian CA – Risk FactorsIncreased risk ProtectiveAgeInfertilityEndometriosisNulliparityGenetics

BRCA, HNPCCEarly menarche/late menopause?Milk consumption?Vitamin D deficiency

Combined OCPs10y 60% reduction

Tubal ligationMultiparityYoung pregnancy, <25yo

Ovarian CA – Types Epithelial

SerousMucinousEndometrioidClear cellBrennerUndifferentiated

Germ cellDysgerminomaYolk sac tumorTeratoma

Mature and immatureSex cord-stromal

Granulosa cellThecoma/FibromaSertoli-Leydig

Metatstatic

Ovarian CA – Staging Stage I –limited to ovaries

IA – one ovary, confined IB – both ovaries, confinedIC – IA or IB, not confined

Stage II – pelvic extensionIIA – uterus and/or tubes IIB – other pelvic tissuesIIC – IIA or IIB, not confined

Stage III – peritoneal involvementIIIA – microscopic IIIB – macroscopic, <2cmIIIC – macroscopic >2cm, positive lymph nodes

Stage IV – distant mets including liver parenchma

Ovarian CA – Screening Routine screening is not recommended

No trial has shown improved M/M with screening

Annual examPelvic ultrasoundCA-125 Other tumor markers

LDH, AFP, hCG, Estradiol, Testosterone, Alk Phos

Ovarian CA – Treatment Surgery

Removal of affected ovary(s)Staging procedure: free fluid or washings, peritoneal

biopsies, pap smear of diaphragm, infracolic omentectomy, retroperitoneal and paraaortic lymph nodes

Typically also uterus and cervix, overall debulkingChemotherapy and/or radiation

Paclitaxel, cisplatin, carboplatinExceptions: young patient, germ cell tumor, confined to 1

ovary

BRCA OverviewBRCA is responsible for approx. 10% of ovarian cancer

and 3-5% of breast cancer casesTumor suppressor genes that help repair DNADefective allele inherited, second copy becomes damaged

“two-hit hypothesis”

BRCA1 on chromosome 17, 1,200 different mutationsBRCA2 on chromosome 13, 1,300 different mutationsIncidence: 1 in 300 to 1 in 800 (1 in 40 Ashkenazi Jews)

BRCA OverviewBRCA1 – risk of ovarian cancer is 39-46%BRCA 2 – risk of ovarian cancer is 12-20%

Baseline risk 1.5%

BRCA1&2 – risk of breast cancer is 65-74%Baseline risk 12.5% (1 in 8)

Consider referral to a Genetic Counselor

BRCA – Who to Test

BRCA + – For Ovary Consider ovarian cancer screening at age 30-35

Transvaginal sono and CA-125Consider prophylacitc bilateral salpingo-oophorectomy at

age 40 or after childbearing is doneReduces ovarian cancer risk by 85-90%Reduces breast cancer risk by 40-70% if premenopausal

Better results for BRCA2 +

BRCA + – For BreastConsider annual mammo and breast MRI at age 25For BRCA 2 – consider tamoxifen

Reduces breast cancer risk by 60%Consider prohylacitc bilateral mastectomy

Reduces breast cancer risk by 90-95%

Breast CA sugery1800’s

Points to RememberYou won’t find it if you don’t look for it

Postmenopausal bleeding is cancer until proven otherwiseIf you’re not sure what it is, biopsy itAsk about family history of breast/ovarian cancer

No screening for uterine CAAnnual exams are screening for vulvar CA

Always look, at least briefly, before a speculum examNo screening for ovarian CA

I don’t care what popular magazines say … No, I won’t order a CA-125 just because you want me to.