# 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.