Uterine Neoplasms

Introduction

The uterus consists of both the cervix and the body (or ‘corpus’) of the uterus. For many reasons, including their causative factors and their treatment, tumours arising from the corpus and the cervix are usually regarded as originating from two separate organs. This chapter will consider cancers arising from the uterine body; cancers arising from the cervix are discussed in Chapter 14.

The majority of malignancies arising from the uterine body arise from the endometrium. The endometrium consists of both glandular and supporting (or ‘stromal’) elements; it is possible for either to undergo malignant change. The majority of uterine malignancies are adenocarcinomas arising from the endometrial glands ( Figs 13.1 and 13.2 A). Sarcomas of the muscle of the uterus, the myometrium or the stromal tissues of the endometrium are rare (see Fig. 13.2 B).

Incidence

In the United Kingdom, the incidence of endometrial cancer has been increasing. It is now the fourth most common cancer in women after breast, bowel and lung cancers. Each year, there are around 9000 cases diagnosed annually in the United Kingdom.

Approximately 90% of cases will be diagnosed after menopause whereas only around 1% of endometrial carcinomas will develop in women under the age of 40 years. The incidence is rising in high-resource settings.

Aetiology

The majority of endometrial cancers are associated with conditions in which there are prolonged, high levels of estrogen. Therefore, it is postulated that estrogen has a role in the development of the disease ( Box 13.1 ).

High levels of estrogen may be physiological, as observed in the presence of obesity (due to the aromatisation in body fat of peripheral androgens to estrogens), or with conditions such as polycystic ovary syndrome (due to chronic anovulation) and late menopause. Around one-third of cases are related to obesity.

Non-physiological causes of increased estrogen include unopposed (without progesterone to protect the endometrium) estrogen hormone replacement therapy (HRT), which increases the risk four-fold. This risk is reduced to a relative risk of <1.0 with opposed HRT (i.e., with the addition of progestogen for at least 10 days per cycle). Tamoxifen, which is commonly used in the treatment of breast cancer, increases the risk of endometrial cancer. Rarely occurring estrogen-secreting tumours also increase the risk of endometrial carcinoma.

Endometrial cancer is diagnosed less frequently in women who have used the combined oral contraceptive pill, probably because it induces regular withdrawal bleeding. Women who smoke, and are thereby likely to reach an earlier menopause, also have a lower than expected incidence of the disease.

The more common estrogen-dependent type of endometrial cancer is called ‘type I cancer’ and is diagnosed in women around the time of menopause. It is generally diagnosed at an earlier stage and, as a result, can have a better prognosis. There may be a premalignant phase (see Endometrial Hyperplasia section, later in this chapter) and the tumour cells of type I disease usually have estrogen and progesterone receptors.

Type II endometrial cancers are not generally related to estrogen production. They are diagnosed in older women, can progress more rapidly, and are not associated with a premalignant phase. The likelihood of surviving 5 years after being diagnosed with this type of cancer are lower than for type I disease.

Endometrial cancer is inherited in 2% to 5% of cases. Lynch syndrome is caused by an autosomal-dominant inherited mutation in DNA mismatch repair genes. In addition to colorectal cancer, Lynch syndrome is associated with an increased risk of endometrial cancer (both types I and II) with a 30% to 60% lifetime risk of developing the disease.

Clinical Features and Diagnosis