Endometrial Cancer – most common gynecological cancer; 97% of uterine carcinomas are of endometrial glands

• Nomenclature for Hyperplasia: simple – simple architecture (no crowding of glands), cells normal;1-4% become malignant
• complex – complex architecture (crowding), cells are normal; 1-4% become malignant
• atypical – atypical cells (enlarged nuclei, hyprochromatic nucleoli), stratification, dyspolarity; 20% become malignant
• Risk Factors: almost all associated with excessive estrogen (estrogen normally causes endometrial hyperplasia)
• obesity: peripheral conversion of androstenedione to estrone in adipose (10x relative risk if 50 lbs overweight)
• nulliparity: progesterone of pregnancy interrupts estrogen stimulation of the endometrium (2x risk vs. one child)
• late menopause: prolonged estrogen stimulation
• exogenous unopposed estrogen: tamoxifen (agonist in uterus), sequential oral contraceptives (old type)
• other risk factors: radiation (8x increased risk); diabetes (2.8x increased risk); fat consumption; HTN
• not risk factors: history of endometriosis, breast feeding, number of sexual partners,
• ß risk: combination oral contraceptives(1/2 risk,protective effect of progesterone); smoking(hydroxylates estrogen)
• Classification: type I (but not type II) is caused by estrogen
• Type I – superficial invasion; low metastasis rate; sensitive to progesterone; long duration of symptoms; good prognosis
• Type II – invasive; high metastasis rate; low progesterone sensitivity; short duration of symptoms; poor prognosis
• Diagnosis: myometrial invasion leads to bleeding Þ early detection (usually in stage I)
• Grading: based on % of tumor with non-squamous or non-morular growth pattern; grade 1 (< 5%), 2 (5-50%), 3 (>50%)
• notable nuclear atypia Ý grade one level (if grade 1 or 2); grade and depth of invasion associated with frequency of nodal metastasis
• Histology: majority of tumors are adenocarcinoma (60%) or adenocanthomas (22%)

• 1% of all uterine cancers, but 15% of all uterine cancer deaths
• 2% of uterine cancers arise from endometrial stroma (endometrial stromal sarcoma) Þ nodal/intraabdominal spread
• 1% from myometrium (leiomyosarcoma; rarely malig. transformation of leiomyoma)Þ hematogenous spread to lungs
• Signs and Symptoms: irregular vaginal bleeding most common – 94% of endometrial sarcomas, 58% of leiomyosarcomas
• less common: pelvic/abdominal pain, enlarged uterus, pelvic/abdominal mass, vaginal discharge
• Pathology: may be pure or mixed; may be homologous (contain only uterine tissues) or heterologous (foreign tissues)

Ovarian Cancer – 2^nd most common gynecological cancer but most lethal (no symptoms = late diagnosis)

• Risk Factors: a huge number of factors are possible, but break down into three general categories:
• (1) Environmental and Industrial Exposure – Ý incidence in developed countries (except Japan)
• ascent of carcinogens (asbestos, talc) into genital tract; evidence: hysterectomy and tubal ligation ß risk
• incidence related to per capita fat consumption; galactose in yogurt or ß galactose transferase could cause O₂ toxicity
• possible association with viral infections such as measles and mumps
• (2) Ovulation and Reproductive Function–normal ovulatation followed by repair of ovary Þ hyperplasia Þ mutation
• oral contraceptives and pregnancy ß risk; early menarche,late menopause,regular periods Ý risk; age=biggest risk factor
• (3) Family History: most significant risk factor after age – relative risk Ý 3.6x if one relative affected, 7x if two affected
• BRCA1: long arm of chromosome 17; associated with Ý risk of breast and ovarian cancer (68% incidence by age 60)
• Tumor Types: epithelial (85%); germ cell (5%); sex cord/mesenchymal (5%); secondary tumors (5%)
• secondary tumors: metastasis from other sites (usu. breast or GI) – breast metastasis to ovary 10% clinically, 80% at autopsy
• Krukenberg tumor: signet-ring carcinoma metastatic to the ovary
• Symptoms: rapidly growing abdominal mass, pain, abdominal distension, hemoperitoneum, vaginal bleeding
• Pathophysiology: ascites (Ý interstitial oncotic pressure due to tumor protein; ß plasma osmotic pressure from malnutrition); intestinal obstruction; metastatic effects (pleural effusion, lung or brain metastasis)

Cervical Carcinoma – cervical intraepithelial neoplasia (CIN); 3^rd most lethal gynecologic malignancy in US

• Pap smear introduction has reduced mortality, but still 8^th leading female cancer, 10^th leading cause of female death
• Risk Factors: young age at first intercourse (possible introduction of carcinogen during squamous metaplasia of puberty)
• # of sexual partners and # of partner’s partners; smoking, low economic status, STD (HSV, HPV), immune compromise
• Diagnosis: Pap smear is screening test; biopsy makes diagnosis; median age of diagnosis is 45-50 yrs
• grade determines progression to invasive cancer: (CIN1Þ 16%; CIN2 Þ 30%; CIN3 Þ 75%)
• Staging: clinical, by physical exam, biopsy, sigmoidoscopy, cystoscopy, XR, etc
• Clinical Presentation: exophytic – cervix is enlarged, tissue may be protruding; endophytic – outside of cervix appears normal, inside is enlarged and may be barrel-shaped; ulcerative – normal cervix is destroyed by the tumor
• Pathophysiology – pre-invasive state is assymptomatic; presenting symptom is usu. vaginal bleeding (post-coital bleeding (trauma) is pathognomonic); malodorous discharge from tumor outgrowing blood supply and necrosing
• local or metastatic invasion Þ pelvic/sciatic pain, renal colic, leg pain, ureter obstruction Þ incontinence
• distant metastasis Þ pulmonary symptoms, left supra-clavicular swelling (Virchow’s node) is early sign of dissemination

Vulvar Cancer – relatively rare (4000 per year, US); 3% of genital cancers

Vaginal Cancer – 1-2% of gynecological cancers; associated with CIN; most are squamous cell; mean age 60-65

Gestational Trophoblastic Disease – genetic; most lethal but most curable gynecologic malignancy