ENDOMETRIAL HYPERPLASIA & CARCINOMA
ESSENTIALS OF DIAGNOSIS
Abnormal uterine bleeding: premenopausal (menstrual history, intermenstrual bleeding, and/or irregular bleeding patterns) versus postmenopausal
Risk factors: hyperestrogenism—long-term exposure to unopposed estrogens (polycystic ovarian syndrome, chronic anovulation, late menopause, and exogenous estrogens); metabolic syndrome including diabetes, hypertension, and obesity; nulliparity; increasing age; history of breast cancer; genetic predisposition (hereditary nonpolyposis colon cancer syndrome/Lynch and Cowden’s syndromes)
Diagnosis: endometrial sampling, ultrasonography
Endometrial cancer is the most common gynecologic malignancy in developed counties and the second most common in developing countries. The American Cancer Society estimates that over 61,000 new cases will be diagnosed in 2017, and over 10,900 women will die from cancers of the uterine body. In the United States, white women have a lifetime risk of endometrial carcinoma of 2.4% compared with 1.3% for black women; however, survival for white women is about 8% greater at each stage of diagnosis compared to black women. For women up to age 74 years, the incidence is 14.7 per 100,000. The peak incidence of onset is in the seventh decade, but 25% of cancers occur in premenopausal women, and the disease has even been reported in women age 20–30 years. The mortality rate is 2.3 per 100,000.
Most endometrial carcinomas arise on the background of endometrial hyperplasia and are well-differentiated tumors. There are 2 major types of endometrial cancer. Type I tumors are more common (85%) and tend to occur in younger women. These are associated with either endogenous or exogenous unopposed estrogen exposure and usually consist of a low-grade or well-differentiated tumor with a favorable prognosis. Type II tumors grow independent of estrogen, are associated with endometrial atrophy, and occur in an older population. Poorly differentiated endometrioid or nonendometrioid, such as papillary serous and clear cell, histologies are included in type II tumors and confer a high risk of relapse with poor prognosis. Gene expression profiles have also been shown to be different between type I and II tumors, with PTEN, KRAS, ARID1A, PIK3CA, CTNNB1, and microsatellite instability mutations more common in type I tumors. PTEN inactivation appears to play an early role in carcinogenesis and is detectable in premalignant lesions. For type II tumors, p53 overexpression is more commonly identified.
Estrogens and progesterone are the 2 main hormones that influence the metabolic and proliferative state of the endometrium. In general, estrogens stimulate the endometrium, unlike progesterone, which has an antiproliferative effect. Long-term exposure to estrogens can lead to endometrial hyperplasia and, subsequently, to hormone-driven atypical endometrial hyperplasia and endometrial cancer. Clinical circumstances with chronically high levels of estrogenic stimulation include nulliparity, early menarche, late menopause, obesity, metabolic syndrome, polycystic ovary syndrome, exogenous and unopposed estrogen replacement therapy, chronic anovulation in the premenopausal women, and estrogen-producing tumors. Granulosa cell tumors of the ovary can produce high levels of estrogens and can be associated with endometrial hyperplasia or cancer. The selective estrogen receptor modulator (SERM) ...