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.