Obstetrics and Gynecology/Endometrial Neoplasia

Epidemiology Endometrial cancer is the most common gynecological cancer in Canada Endometrial cancer has the best cure rate of all endometrial cancers due to early diagnosis Diagnosed at a median age of 58 Most patients present with Stage I disease Etiology and Risk Factors Postmenopausal Bleeding The most common cause of postmenopausal bleeding is atrophic endometritis, followed by side effects of exogenous estrogens, endometrial cancer, and other etiologies. Endometrial Hyperplasia Arises from unopposed estrogen (of at least 6 mo) causing hyperplasia of glandular and stromal tissues in the endometrium Endometrial hyperplasia may lead to estrogen sensitive endometrial cancer Endometrial Adenocarcinoma Lack of progesterone Anovulation Obesity: aromatization of androstenedione to estrogen in peripheral fat cells. During menopause, fat cells continue to produce estrogen in the absence of progesterone. Therefore, endometrial adenocarcinoma has an increased incidence. SERM use (i.e. Tamoxifen for breast cancer -> 2-3X increased risk) Hormone replacement therapy without progesterone use. Gallbladder disease, diabetes, and/or hypertension History of breast, colorectal, or ovarian cancer (family history of lynch syndrome) Nulliparity Late menopause Clinical Presentation and Diagnostic Approach Endometrial Cancer Postmenopausal vaginal bleeding. In any postmenopausal woman, vaginal bleeding is endometrial cancer until proven otherwise. Abnormal premenopausal bleeding Rule out pregnancy. If the woman is anovulatory, they are more likely to have a malignant etiology. Metastatic disease and signs of advanced cancer Hematometrium Endometrial cells on pap smear Enlarged uterus Recurrent endometrial cancer typically presents in the vagina, lymph nodes, and lungs. Diagnostic Approach to Abnormal Uterine Bleeding First, a pap smear should be done, with relevant follow up for pap smear abnormalities (if abnormal) Second, an endometrial biopsy should be performed Finally, transvaginal ultrasound should be requested, with the following parameters qualified Endometrial thickness (<5mm if hypoestrogenic, and >10mm if pathological) Dilation and curettage may be ultimately performed for diagnosis of cancer. For women on tamoxifen, estrogen hormone replacement therapy, and anovulatory women not taking progesterone, perform yearly endometrial biopsies. Pathology, Histology, and Staging Endometrial Hyperplasia Simple-cystic Complex Adenomatous Atypical Adenomatous Atypical adenomatous endometrial hyperplasia has a 20-30% chance of malignant transformation. Endometrial Cancer Adenocarcinoma (75% of endometrial cancer) Serous papillary: staging should be done as ovarian cancer Small cell neuroendocrine (oat cell) Clear cell carcinoma Sarcoma Leiomyosarcoma Staging Stage I (~85% survival at 5yr) IA: Tumor confined to the uterus with less than 1/2 myometrial invasion IB: Tumor confined to the uterus with more than 1/2 myometrial invasion Stage II (~65% survival at 5yr) II: Cervical extension, with persistent uterine confinement Stage III (~45% survival at 5yr) IIIA: Invasion of serosa/adenexa IIIB: Vaginal/parametrial invasion IIIC1: Pelvic node invasion IIIC2: Para-aortic node invasion Stage IV (~16% survival at 5yr) IVA: Tumor invasion of bladder/bowel IVB: Distant metastases (includes inguinal lymph nodes) Management Endometrial Hyperplasia Hysterectomy for atypical adenomatous. Endometrial Cancer Serous papillary: chemotherapy (carbo/taxol) even if confined to uterus. Small cell neuroendocrine (cisplatin/etoposide) Surgery (total abdominal hysterectomy and bilateral salpingo-oophorectomy with or without lymph node dissection) and postoperative radio- and chemo-therapy. Chemotherapy is reserved for high risk patients with positive nodes, metastatic disease. Chemo- and radio-therapy alone are reserved for inoperable patients. Radiation for vaginal recurrence. High dose progesterone for hormone-sensitive recurrent cancer.