Causes

Beginning or ending of reproductive life.

Dysfunction of hypothalamic-pituitary axis.
Excess estrogen as a result of adrenal disease, pituitary tumors, granulosa cell tumor, polycystic ovarian disease,
obesity, or malnutrition

Endometrial Hyperplasia
Cause: Endometrial hyperplasia (or endometrial intraepithelial neoplasia) results from increased estrogen levels
from failure of ovulation, exogenous estrogen, or estrogen-secreting conditions such as polycystic ovaries or
granulosa cell tumor.

Risk factors: Any condition that increases lifetime estrogen exposure increases the risk of endometrial hyperplasia.
In general, risk factors are the same as for endometrial cancer (see below).

Complications of endometrial hyperplasia: Hyperplasia leads to dysplasia, which leads to carcinoma.

Endometrial hyperplasia is a premalignant condition.

Mutation: Inactivation of PTEN (phosphatase and tensin homologue). Without PTEN, endometrial cells are more
sensitive to estrogen stimulation.

Gross morphology of endometrial hyperplasia: Thickening of the endometrium.

Microscopic morphology of endometrial hyperplasia (Figure 17-12 A and B)

Simple hyperplasia: Cystic hyperplasia; very uncommonly progresses to carcinoma.

Complex hyperplasia: Crowded, back-to-back glands (> 50% of tissue is glands).
Complex hyperplasia with atypia: Crowded back-to-back glands with nuclear pleomorphism and mitotic figures. It
can be difficult to separate complex hyperplasia with atypia from invasive carcinoma.

Figure 17-12.
Endometrial hyperplasia. A, Simple hyperplasia, cystic glands in the endometrium. B, Complex hyperplasia with
atypia (back-to-back glands, with dysplastic features such as pleomorphism, hypercellularity, and nuclear
hyperchromasia). Hematoxylin and eosin, A, 40×; B, 400×.

Clinical presentation of endometrial hyperplasia

Symptoms: Vaginal bleeding, especially in a postmenopausal woman.

Signs: Widened endometrial stripe on transvaginal ultrasound and endometrial or atypical glandular cells on PAP
smear. Endometrial biopsy is diagnostic.

Tumors of the Uterus

Overview: Although there are many different tumors of the uterus, the most common endometrial carcinoma is
endometrial adenocarcinoma. Leiomyomas are the most common tumor overall of the uterus. Their malignant
counterpart, the leiomyosarcoma, is not common, however. In addition to these three neoplasms, endometrial
stromal sarcomas and combination tumors will be discussed briefly in this section.

Endometrial Adenocarcinoma (Figure 17-13 A and B)

Epidemiology: Many occur about age 55 years or older.

Figure 17-13.