2. Malignant & Pre-malignant Diseases of the Endometrium Jose B Moran MD Assistant Professor III Section of Gynecologic Oncology Department of Obstetrics & Gynecology St. Luke’s College of Medicine- William H. Quasha Memorial

3. EPIDEMIOLOGY ∏Most common gynecologic cancer in the developed countries. ∏Accounts for 7% of all cancers in women. ∏Commonly a disease of postmenopausal women (average age 59 years) ۀ 5% before age 40 ۀ 20-25% before onset of menopause

4. EPIDEMIOLOGY ∏Type I: ۀ Obesity ۀ Hyperlipidemia ۀ Hyperestrogenism ∏Type II: ۀ Non-obese ۀ High parity ۀ No background of hyperestrogenism

5. EPIDEMIOLOGY ∏Most common gynecologic cancer in the developed countries. ∏Accounts for 7% of all cancers in women. ∏Commonly a disease of postmenopausal women (average age 59 years) ۀ 5% before age 40 ۀ 20-25% before onset of menopause

6. ETIOLOGY & RISK FACTORS ∏Review of the menstrual cycle: Estrogen Progesterone Menstruation Prolonged bleeding ∏Unopposed Estrogenic stimulation

7. ETIOLOGY & RISK FACTORS ∏Nulliparity or low parity ∏Obesity ∏Hypertension ∏Diabetes ۀ 21-50 lbs overweight --- 4x ۀ >50 lbs overweight --- 10x ۀ Compared with 1 child ---2x ۀ Compared with 5 or more children --- 3x

8. ETIOLOGY & RISK FACTORS ∏Late menopause ∏Exogenous estrogen intake ∏Polycystic Ovarian Disease ∏Estrogen-secreting tumor ∏Tamoxifen administration ۀ Monitoring required? ۀ What is the risk?

9. ETIOLOGY & PROTECTIVE FACTORS ∏Pregnancy ∏Combination OCP use ∏Smoking ۀ 1 year OCP use --- 10 years protection? ۀ 30% reduction in relative risk ۀ + 30% for > 1 pack/day - Lawrence, et.al., 1987

10. DIAGNOSIS ∏Based on the symptoms: ۀ Abnormal uterine bleeding ۀ Postmenopausal bleeding ۀ Menometrorrhagia ∏Pelvic sonogram: ۀ Endometrial thickness after menopause ۀ Screening? ∏Hysteroscopy

11. DIAGNOSIS ∏Tissue diagnosis is essential: ۀ Pap smear? ۀ Office endometrial biopsy ۀ Hysteroscopically-directed biopsy ۀ Endometrial curettage ۀ Fractional curettage?

12. PRECURSOR LESIONS ∏Endometrial hyperplasia: ۀ Simple hyperplasia without atypia ۀ Simple hyperplasia with atypia ۀ Complex hyperplasia without atypia ۀ Complex hyperplasia with atypia ∏Endometrial polyps?

13. MALIGNANT LESIONS ∏Endometrioid adenocarcinoma (87.4%) § Adenocarcinoma with squamous differentiation* ∏Mucinous adenocarcinoma (0.6%) ∏Secretory adenocarcinoma ∏Clear-cell adenocarcinoma (2.2%) ∏Papillary serous carcinoma (2.9%) ∏Squamous cell carcinoma (0.2%) *formerly adenosquamous carcinoma/adenoacanthoma ---- Pecorelli (1998)

14. STAGING: Guidelines ∏Staging is surgico-pathologic: ۀ Peritoneal washing cytology ۀ Thorough pelvo-abdominal exploration ۀ Hysterectomy ۀ Bilateral oophorectomy ۀ Regional lymph node evaluation

15. STAGING: Guidelines ∏Degree of histopathologic differentiation should be classified: ۀ G1: 5% or less of a nonsquamous/nonmorular solid growth pattern ۀ G2: 6-50% of a nonsquamous/nonmorular solid growth pattern ۀ G3: more than 50% of a nonsquamous/nonmorular growth pattern ۀ In serous adenocarcinomas, clear-cell adenocarcinomas, and squamous cell carcinomas, nuclear grading takes precedence. ۀ Adenocarcinomas with squamous differentiation takes the nuclear grade of the glandular component.

16. STAGING: Guidelines ∏Pre-surgical findings are not applicable in determining the stage. ∏In cases where surgery is not the primary treatment, clinical staging based on FIGO 1971 classification shall apply. ∏The width of the myometrium should be measured along with the width of tumor invasion.

18. STAGING ∏Stage I: Ia Ib Ic

19. STAGING ∏Stage II: IIa IIb

20. STAGING ∏Stage III: IIIa IIIb IIIc IIIa

21. TREATMENT ∏Endometrial hyperplasia: ۀ Is curettage adequate? ۀ To treat or not to treat TYPENUMBERREGRESSEDPROGRESSED Simple hyperplasia 93 74 (80%) 1 (11 y) Complex hyperplasia 29 23 (79%) 1 (8 y) Atypical hyperplasia 48 28 (58%) 11 (4 y)

22. TREATMENT ∏Endometrial hyperplasia: ۀ Depends on the degree of hyperplasia ۀ Presence of atypia ۀ Is curettage adequate? ۀ Desires of the patient to preserve fertility § Simple hysterectomy § Progestins - cyclic or continuous - dose

23. TREATMENT ∏Primary staging laparotomy: ۀ Simple hysterectomy ۀ Bilateral Oophorectomy ۀ Peritoneal and abdominal washings ۀ Evaluation of the regional lymph nodes ∏Primary radiation therapy: ۀ Poor surgical risk patients ۀ Selected stage II diseases

24. TREATMENT ∏Adjuvant therapy is indicated: ۀ Radiotherapy: § higher than stage Ib of any grade § higher than Grade 2 of any stage § cervical involvement § poor histologic type of any stage ۀ Chemotherapy: § poor histologic type of any stage § stage III disease

25. TREATMENT ∏Adjuvant therapy is indicated: ۀHormonal therapy § stage III disease § hormone-receptor assay necessary? § consider histologic grade § Progestins- dose, duration

26. PROGNOSTIC FACTORS ∏Histologic type ∏Histologic differentiation ∏Stage of disease ∏Myometrial invasion ۀ Myometrial Invasion & Recurrence Endometrial only ------ 8% Superficial ------------- 12% Deep ------------------- 46%

27. PROGNOSTIC FACTORS ∏Peritoneal cytology ∏Lymph node metastasis ∏Adnexal metastasis

33. ∏26 year old nulligravid with menorhagia. Diagnostic curettage was done. HP: complex hyperplasia w/o atypia Management? Follow-up? ∏Complex hyperplasia with atypia? ∏26 year old G3P3? Case Studies: