Endometrial cancer

Endometrial cancer refers to several types of malignancy which arise from the endometrium, or lining of the uterus. Endometrial cancers are the most common gynecologic cancers in the United States, with over 35,000 women diagnosed each year in the U.S. The most common subtype, endometrioid adenocarcinoma, typically occurs within a few decades of menopause, is associated with excessive estrogen exposure, often develops in the setting of endometrial hyperplasia, and presents most often with vaginal bleeding. Because symptoms usually bring the disease to medical attention early in its course, endometrial cancer is only the third most common cause of gynecologic cancer death (behind ovarian and cervical cancer). A hysterectomy (surgical removal of the uterus) is the most common therapeutic approach.

 Endometrial cancer may sometimes be referred to as uterine cancer. However, different cancers may develop from other tissues of the uterus, including cervical cancer, sarcoma of the myometrium, and trophoblastic disease.

 Classification

 Most endometrial cancers are carcinomas (usually adenocarcinomas), meaning that they originate from the single layer of epithelial cells which line the endometrium and form the endometrial glands. There are many microscopic subtypes of endometrial carcinoma, including the common endometrioid type, in which the cancer cells grow in patterns reminiscent of normal endometrium, and the far more aggressive papillary serous and clear cell endometrial carcinomas. Some authorities have proposed that endometrial carcinomas be classified into two pathogenetic groups:

     * Type I: These cancers occur most commonly in pre- and peri-menopausal women, often with a history of unopposed estrogen exposure and/or endometrial hyperplasia. They are often minimally invasive into the underlying uterine wall, are of the low-grade endometrioid type, and carry a good prognosis.

     * Type II: These cancers occur in older, post-menopausal women, are more common in African-Americans, and are not associated with increased exposure to estrogen. They are typically of the high-grade endometrioid, papillary serous or clear cell types, and carry a generally poor prognosis

 In contrast to endometrial carcinomas, the uncommon endometrial stromal sarcomas are cancers which originate in the non-glandular connective tissue of the endometrium. Malignant mixed müllerian tumor is a rare endometrial cancer which contains cancerous cells of both glandular and connective tissue appearance - in this case, the cell of origin is unknown.

 Signs and Symptoms

     * Abnormal uterine bleeding, abnormal menstrual periods

    * Bleeding between normal periods in premenopausal women

    * Vaginal bleeding and/or spotting in postmenopausal women

 in women older than 40: extremely long, heavy, or frequent episodes of bleeding (may indicate premalignant changes)

     * Anemia, caused by chronic loss of blood. (This may occur if the woman has ignored symptoms of prolonged or frequent abnormal menstrual bleeding.)

    * Lower abdominal pain or pelvic cramping

    * Thin white or clear vaginal discharge in postmenopausal women.

Causes

 Most women with endometrial cancer have a history of unopposed and increased levels of estrogen. One of estrogen's normal functions is to stimulate the buildup of the endometrial lining of the uterus. Excess estrogen activity, especially in the setting of insufficient progesterone, may produce endometrial hyperplasia, which can be a precursor for cancer.

Increased estrogen may be due to:

     * obesity (> 30 lb or 14 kg overweight)

    * exogenous (medication)

The incidence of endometrial cancer in women in the U.S. is 1 % to 2 %. The incidence peaks between the ages of 60 and 70 years, but 2 % to 5 % of cases may occur before the age of 40 years. Increased risk of developing endometrial cancer has been noted in women with increased levels of natural estrogen.

Associated conditions include the following:

     * obesity

    * hypertension

    * polycystic ovary syndrome

Increased risk is also associated with the following:

     * nulliparity (never having carried a pregnancy)

    * infertility (inability to become pregnant)

    * early menarche (onset of menstruation)

    * late menopause (cessation of menstruation)

Women who have a history of endometrial polyps or other benign growths of the uterine lining, postmenopausal women who use estrogen-replacement therapy (specifically if not given in conjunction with periodic progestin) and those with diabetes are also at increased risk.

 Tamoxifen, a drug used to treat breast cancer, can also increase the risk of developing endometrial cancer.

 The same risk factors predisposes women to endometrial hyperplasia, which is a precursor lesion for endometrial carcinoma. An atypical complex hyperplasia carries a 30% risk of developing endometrial carcinoma, while a typical simple hyperplasia only carries a 2-3% risk.

 Diagnosis

 Clinical evaluation

 Routine screening of asymptomatic women is not indicated, since the disease is highly curable in its early stages. Results from a pelvic examination are frequently normal, especially in the early stages of disease. Changes in the size, shape or consistency of the uterus and/or its surrounding, supporting structures may exist when the disease is more advanced.

     * A Pap smear may be either normal or show abnormal cellular changes.

    * Endometrial curettage is the traditional diagnostic method. Both endometrial and endocervical material should be sampled.

    * If endometrial curettage does not yield sufficient diagnostic material, a dilation and curettage (D&C) is necessary for diagnosing the cancer.

    * Endometrial biopsy or aspiration may assist the diagnosis.

    * Transvaginal ultrasound to evaluate the endometrial thickness in women with postmenopausal bleeding is increasingly being used to evaluate