A 58-year-old postmenopausal woman on estrogen replacement complains of recent onset of spotting. A bimanual pelvic examination is unremarkable. Most likely diagnosis?

Any postmenopausal woman who has been on unopposed estrogen and who is now experiencing vaginal bleeding is suspect for either endometrial hyperplasia or endometrial cancer. Endometrial hyperplasia is the end result of prolonged estrogenic stimulation of the endometrial mucosa. Morphologic forms of hyperplasia include cystic, adenomatous, and atypical hyperplasia. In cystic hyperplasia (simple hyperplasia), there are large, dilated glands lined by actively mitosing epithelial cells. Adenomatous hyperplasia refers to branching of the glands with papillary infolding or outpouchings (sometimes referred to as complex hyperplasia). Atypical hyperplasia has more glandular crowding and nuclear atypia than the latter condition and has the highest risk for progressing into carcinoma in situ and endometrial carcinoma. Endometrial carcinoma is the most common invasive cancer of the female genital tract. As with endometrial hyperplasia, the risk factors for endometrial cancer primarily relate to hyperestrinism and include obesity, nulliparity, diabetes, hypeension, infeility, breast cancer, low fiber/high fat diet, early menarche or late menopause, and tamoxifen. The most common clinical presentation is vaginal bleeding (90%) in a postmenopausal woman.