Christopher R. Graber, MD Salina Women’s Clinic 08 March 2011

Overview Endometrial (Uterine) Cancer Vulvar Cancer Ovarian Cancer Typical Presentation and Differential Risk Factors Different Types and Staging Screening Treatment

Endometrial (Uterine) Cancer A 58 yo obese woman presents with postmenopausal bleeding 10 years without menses, now has had 4 months with “irregular periods.” No cramping. A 47 yo long-distance runner presents with heavier menses x 1y Typical menses: 3-5d, min flow. Now: 5-7d, heavy. 2.6% of US women, 0.5% lifetime mortality Typical: 50-65yo; 5% younger than 40

Differential - Endometrial Cancer Perimenopause Uterine fibroids Adenomyosis Uterine or cervical polyp Postmenopausal endometrial atrophy Endometrial hyperplasia Simple and complex With and without atypia

Endometrial CA risk factors Increased risk Unopposed estrogen Menopause >52yo Obesity (3x 50) Nulliparity DM PCOS Decreased risk Ovulation Progestin therapy OCPs Menopause <49yo Normal weight Nulliparity

Uterine CA – Types Endometrioid adenocarcinoma Clear cell carcinoma Papillary serous carcinoma Secretory carcinoma Mucinous carcinoma Squamous carcinoma

Uterine CA – Staging (surgical) IA – confined, < ½ myometrial invasion IB – confined, > ½ myometrial invasion II – cervical stromal invasion IIIA – invasion of serosa or adnexa IIIB – vaginal or parametrial involvement IIIC 1&2 – positive lymph nodes IVA – invasion of bladder or bowel IVB – distant metastases

Uterine CA – Screening Always have a high index of suspicion EMB for any woman >35yo with suspected anovulatory bleeding EMB for any other woman with long(er) history of anovulatory bleeding and other risk factors Consider D&C if not able to obtain EMB

Uterine CA -- Screening If postmenopausal and EMB shows atrophy Consider sono – endometrial stripe that measures less than or equal to 4mm is reassuring Chances of CA if EMB shows Simple hyperplasia1% Complex hyperplasia5% Simple with atypia10% Complex with atypia25%

Uterine CA – Treatment Treatment for CA is surgery Hysterectomy plus staging procedure By Gyn Oncology Hysterectomy alone often done if Grade I or II No evidence of spread Type other than clear cell or papillary serous Consider progestin therapy for hyperplasia

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Overview Endometrial (Uterine) Cancer Vulvar Cancer Ovarian Cancer Typical Presentation and Differential Risk Factors Different Types and Staging Screening Treatment

Vulvar CA A 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 heal 10y history of LS, usually well controlled 4% of cancer in genital tract Common age 60-79yo; 15% under 40

Vulvar CA – Differential Hypertrophic vulvar dystrophy Lichen sclerosus Benign skin lesions: mole, wart, freckle Trauma STI – HSV, syphilis, chancroid Hidradenitis suppurativa

Vulvar CA – Risk Factors HPV Vulvar dystrophy Lichen sclerosus – lifetime risk 3-5% Cervical or vaginal CA

Vulvar CA – Types Squamous cell carcinoma (90%) Melanoma Bartholin’s gland Basal cell carcinoma Metastatic

Vulvar CA – Staging (surgical) IA – confined to vulva, ≤ 2cm, ≤1mm invasion IB – same as IA but >1mm invasion II – confined to vulva, > 2cm III – 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 LN IVB – distant metastases including pelvic LN

Vulvar CA – Screening Always have a high index of suspicion Biopsy any suspicious lesion Close follow-up for lichen sclerosus Q 3-6 months Keyes punch biopsy

Vulvar CA – Treatment Surgical removal Wide local excision (IA) Hemivulvectomy Radical vulvectomy with bilateral inguinal –femoral node dissection

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To be continued…

Overview Endometrial (Uterine) Cancer Vulvar Cancer Ovarian Cancer Typical Presentation and Differential Risk Factors Different Types and Staging Screening Treatment BRCA overview

Ovarian Cancer 58 yo female complains of abdominal pain for several months; has not seen a doctor for several years Moderate nausea, weight loss 18 yo female complains of subacute abdominal pain and urinary frequency; pelvic mass felt on exam Sono shows 9cm solid and cystic adnexal mass 5 th most common cancer in women in US Highest fatality-to-case ratio of all GYN CA

Ovarian CA – Differential Anything that causes… Bloating Pelvic or abdominal pain Back/leg pain Diarrhea, gas, nausea, constipation, indigestion Difficulty eating or feeling full quickly Pain during sex Abnormal vaginal bleeding Trouble breathing

Ovarian CA – Risk Factors Increased risk Protective Age Infertility Endometriosis Nulliparity Genetics BRCA, HNPCC Early menarche/late menopause ?Milk consumption ?Vitamin D deficiency Combined OCPs 10y  60% reduction Tubal ligation Multiparity Young pregnancy, <25yo

Ovarian CA – Types Epithelial Serous Mucinous Endometrioid Clear cell Brenner Undifferentiated Germ cell Dysgerminoma Yolk sac tumor Teratoma Mature and immature Sex cord-stromal Granulosa cell Thecoma/Fibroma Sertoli-Leydig Metatstatic

Ovarian CA – Staging Stage I –limited to ovaries IA – one ovary, confinedIB – both ovaries, confined IC – IA or IB, not confined Stage II – pelvic extension IIA – uterus and/or tubesIIB – other pelvic tissues IIC – IIA or IIB, not confined Stage III – peritoneal involvement IIIA – microscopicIIIB – macroscopic, <2cm IIIC – 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 exam Pelvic ultrasound CA-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 debulking Chemotherapy and/or radiation Paclitaxel, cisplatin, carboplatin Exceptions: young patient, germ cell tumor, confined to 1 ovary

BRCA Overview BRCA is responsible for approx. 10% of ovarian cancer and 3-5% of breast cancer cases Tumor suppressor genes that help repair DNA Defective allele inherited, second copy becomes damaged “two-hit hypothesis” BRCA1 on chromosome 17, 1,200 different mutations BRCA2 on chromosome 13, 1,300 different mutations Incidence: 1 in 300 to 1 in 800 (1 in 40 Ashkenazi Jews)

BRCA Overview BRCA1 – 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 Transvaginal sono and CA-125 Consider prophylacitc bilateral salpingo-oophorectomy at age 40 or after childbearing is done Reduces ovarian cancer risk by 85-90% Reduces breast cancer risk by 40-70% if premenopausal Better results for BRCA2 +

BRCA + – For Breast Consider annual mammo and breast MRI at age 25 For BRCA 2 – consider tamoxifen Reduces breast cancer risk by 60% Consider prohylacitc bilateral mastectomy Reduces breast cancer risk by 90-95%

Breast CA sugery 1800’s

Points to Remember You won’t find it if you don’t look for it Postmenopausal bleeding is cancer until proven otherwise If you’re not sure what it is, biopsy it Ask about family history of breast/ovarian cancer No screening for uterine CA Annual exams are screening for vulvar CA Always look, at least briefly, before a speculum exam No 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.