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Atypical endometrial hyperplasia

What is atypical endometrial hyperplasia?

Atypical endometrial hyperplasia is a pre-cancerous condition associated with an abnormally thick tissue on the inside of the endometrium. It is considered a pre-cancerous condition because it can turn into a type of cancer called endometrioid carcinoma if left untreated. Another name for atypical endometrial hyperplasia is endometrioid intraepithelial neoplasia.

The uterus and endometrium

The uterus is a pear-shaped hollow organ found in the female pelvis between the rectum (the last part of the large bowel) and the urinary bladder. The upper part of the uterus (fundus) is attached to the fallopian tubes while the lower part is connected to the vagina through the uterine cervix.​

The walls of the uterus are made up of three layers: ​

  • Endometrium – The endometrium forms the inner lining of the uterus. The endometrium is made up of specialized epithelial cells that connect together to form round structures called glands. The glands are surrounded by a type of connective tissue called the stroma.
  • Myometrium – The myometrium is the middle layer and is made up of smooth muscle which allows the uterus to change size and contract.
  • Perimetrium – The perimetrium is a thin layer of tissue that surrounds the outside of the uterus.
Changes during the menstrual cycle

During the menstrual cycle, the endometrium cycles through a proliferative phase (growth phase) and secretory phase in response to hormones (estrogen and progesterone) made and released by the ovaries.

Normal endometrium

In a normal menstrual cycle, the endometrium grows thicker under the influence of estrogen during the proliferative phase. This is followed by ovulation where a mature egg is released from the ovary, pushed down the fallopian tube, and is made available to be fertilized.

After ovulation, the endometrium enters the secretory phase under the influence of progesterone. If fertilization does not occur, the endometrium breaks down, which leads to the discharge of blood and endometrial tissue through the vagina (menstruation, menstrual period, menstrual flow).

Abnormal growth of the endometrium

Some women experience an imbalance in the hormones that control the growth of the endometrium, resulting in high levels of estrogen and low levels of progesterone. When there is too much estrogen and not enough progesterone, the endometrium continues to grow and becomes abnormally thick.

When viewed under the microscope, the abnormally thick endometrium can show a variety of changes that include both non-cancerous conditions and pre-cancerous conditions that can lead to cancer over time. Atypical endometrial hyperplasia is a non-cancerous change associated with excess estrogen.

What causes increased estrogen?

Some common situations that can result in increased or prolonged estrogen exposure include polycystic ovary syndrome, obesity, estrogen-only birth control pills, and tamoxifen treatment. Women nearing menopause (perimenopause) may also experience prolonged estrogen exposure.

Symptoms of atypical endometrial hyperplasia

Symptoms of atypical endometrial hyperplasia include abnormal uterine bleeding, such as heavy menstrual bleeding, bleeding between menstrual periods, or postmenopausal bleeding.

How do pathologists make this diagnosis?

In patients with abnormal uterine bleeding, the endometrium is sampled by endometrial biopsy or endometrial (uterine) curetting (scrapings of the endometrium with a spoon-shaped instrument). The tissue sample is then examined by your pathologist under the microscope.

Atypical endometrial hyperplasia

In cases of atypical endometrial hyperplasia, your pathologist will see crowded endometrial glands that are irregular in size and shape. The epithelial cells that line the inside of the glands will look abnormal compared to the cells that are usually found inside the endometrial glands. Pathologists use the word atypical to describe these abnormal cells.

Treatment options for atypical endometrial hyperplasia

High levels of estrogen and atypical endometrial hyperplasia are associated with an increased risk of cancer called endometrioid carcinoma. As a result, women with atypical endometrial hyperplasia are offered treatment.

Options for treatment include a surgical procedure to remove the uterus (hysterectomy) typically with both fallopian tubes and ovaries or an intrauterine device (IUD) for women who are still considering having children in the future.

by Emily Goebel, MD FRCPC (updated June 24, 2021)
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