Uterus and endometrium

Atypical endometrial hyperplasia

This article was last reviewed by Emily Goebel, MD FRCPC on December 10, 2018

Quick facts:

  • Atypical endometrial hyperplasia is a pre-cancerous condition caused by increased growth of the tissue that lines that inside of the uterus.
  • It is considered a pre-cancerous condition because it can turn into cancer called endometrioid carcinoma if left untreated.

The normal 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 composed of endometrial glands lined by one layer of columnar epithelial cells and surrounded by endometrial 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.

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 spectrum of changes that include both non-cancerous conditions and pre-cancerous conditions that can lead to cancer over time.

What is atypical endometrial hyperplasia?

Atypical endometrial hyperplasia is a pre-cancerous condition associated with an abnormally thick endometrium. Symptoms of atypical endometrial hyperplasia include abnormal uterine bleeding, such as heavy menstrual bleeding, bleeding between menstrual periods, or postmenopausal bleeding.

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.

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.

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

Why is this important? High levels of estrogen and atypical endometrial hyperplasia are associated with an increased risk of a 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.

Some pathology reports refer to atypical endometrial hyperplasia as endometrioid intraepithelial neoplasia.

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