Endometrial Cancer Diagnosis

  • Diagnosis

    Endometrial cancer, also known as uterine cancer, most commonly occurs in older women. Fortunately, it is usually caught in its early stages when it is highly curable Figure 01. Endometrial cancer involves abnormal cellular growth of the endometrium, the tissue that lines a woman’s uterus and is normally shed each month during menstruation. Although accounting for only 6% of all cancers among women, it is the fourth most common cancer after breast, colorectal, and lung cancers.

    Endometrial cancer is predominantly a disease of postmenopausal women: 95% of cases occur in women 40 years of age or older. Surgical removal of the uterus (hysterectomy), often combined with radiation, usually cures endometrial cancer. Chemotherapy is used in advanced cases.

    Click to enlarge: Female reproductive anatomy

    Figure 01. Female reproductive anatomy

    Endometrial cancer can result from excess amounts of the female hormone estrogen. Excess, or “unopposed” estrogen can result from a number of causes. Endometrial cancer can develop over time when estrogen is not counterbalanced by sufficient progesterone, another female hormone. This situation is referred to as “unopposed” estrogen. The cancerous cells grow from glandular cells in the lining of the uterus, and are called adenocarcinomas. Most endometrial cancers are of this “endometrioid” type, otherwise called “type I” endometrial cancer, and tend to arise when there is unopposed estrogen.

    Obesity is associated with excess estrogen. This is because the hormones that can become estrogen in the body are converted to active estrogen in the body fat. Therefore, the more body fat, the higher the estrogen levels in the bloodstream and the greater the chance of getting endometrial cancer.

    In addition, women with polycystic ovarian syndrome can develop type I endometrial cancers. Polycystic ovary syndrome is a condition that results in very irregular periods and many cycles during which patients do not successfully ovulate.

    Another uncommon cause of unopposed estrogen is estrogen-secreting tumors, such as ovarian tumors.

    There is another type of endometrial cancer that is not associated with excess or unopposed estrogen. Cancer of other cell types of the endometrium also occur, such as “serous” carcinomas, called “type II” endometrial cancer. This type of cancer tends to have a poorer prognosis than type I adenocarcinomas, and behaves like most ovarian cancers.

    Endometrial cancer tends to spread first by invading the muscular wall of the uterus, and then the other pelvic organs before spreading through lymph vessels to lymph nodes. The tumor may invade deep into the muscular wall of the uterus, as well as into surrounding structures such as the vagina, bladder, or rectum. Cancerous cells can also break off from the tumor and travel (metastasize) into the vagina or through the blood or lymphatic systems to the lymph nodes, lungs, liver, bones, or brain.

    Abnormal bleeding occurs in 98% of cases of endometrial cancer. Endometrial cancer almost always causes vaginal bleeding. In women who are definitely postmenopausal, any vaginal bleeding is considered abnormal until proven otherwise. So if you have stopped having your periods and are in menopause, but you experience vaginal bleeding, you should see your doctor promptly.

    Women who are taking postmenopausal hormone replacement therapy (HRT) may have vaginal bleeding, depending on the schedule and type of hormones prescribed. If a women is experiencing bleeding on HRT, she should discuss this with her doctor.

    Women who are still menstruating may experience:

    • bleeding between periods
    • overly-frequent periods (less than 21 days apart)
    • prolonged, heavy periods

    Bleeding may be excessive or may appear as mere spotting or as a blood-tinged discharge. Some women have abnormal vaginal discharge that is not bloody.

    Symptoms in advanced cancer may include pelvic pain, a mass in the pelvis, or weight loss.

    Endometrial cancer is mostly a disease of postmenopausal women. Most cases of endometrial cancer in the U.S. happen in women between the ages of 50 and 70 years of age. Fewer than 5% of cases occur in women younger than 40.

    Obesity and diabetes are two important risk factors Figure 02. Studies have shown that the risk of endometrial cancer increases two-to-tenfold in obese women, with the greatest risk for the most overweight women.

    Although diabetic women tend to be overweight, diabetes also appears to be an independent risk factor. Women with diabetes who are not overweight also develop endometrial cancer in greater numbers, and heavy women with diabetes are at higher risk than women of the same weight who do not have diabetes.

    Click to enlarge: Body mass index (BMI) calculator

    Figure 02. Body mass index (BMI) calculator

    Taking estrogen without the counteracting hormone, progesterone, increases the risk of endometrial cancer. Tamoxifen (Nolvadex), a drug used to treat breast cancer, that acts like estrogen in the uterus, also increases the risk. When estrogen replacement therapy was first offered to women to help alleviate symptoms of menopause and enhance other aspects of health, rates of endometrial cancer increased significantly nationwide. Doctors now realize that progesterone, the female hormone that counteracts the effects of estrogen, must also be given as part of hormone replacement therapy for women who have not had a hysterectomy.

    Tamoxifen is classified as an “anti-estrogen” drug, and is used to treat women with breast cancer as well as endometrial cancer in some cases. It does, however, act as a weak estrogen in the endometrium, and carries a 1 in 500 risk of causing endometrial cancer, which is about twice the rate of cancer in women who do not take tamoxifen. Because most of the endometrial cancers that develop as a result of tamoxifen are type I cancers and are stage I (see below), they have an excellent prognosis. Indeed, there is no increase in mortality from endometrial cancer that arises in these women.

    Thus, for women who have had breast cancer, the benefits of taking tamoxifen to prevent a recurrence clearly outweigh the relatively lower risk of developing endometrial cancer. Healthy women who have a strong family history of breast cancer also may consider taking tamoxifen, but must more carefully assess the potential risks and benefits.

    Women who take tamoxifen must be informed about the symptoms of endometrial cancer, and seek help if abnormal bleeding develops.

    All women are naturally exposed to estrogen throughout their lives. However, some have relatively higher levels and are more at risk. Women who do not ovulate regularly (release an egg at midcycle) are more likely to develop a precancerous condition of the endometrium called endometrial hyperplasia. This condition results from abnormal regulation of the hormones associated with the menstrual cycle, and an excess of circulating estrogen for longer intervals during a woman's menstrual cycle. Women at risk for endometrial hyperplasia include those with polycystic ovarian syndrome, for example.

    In addition, women who have more periods during their lives—those who start menstruation at an early age, go through late menopause, or have no children—are more likely to develop endometrial cancer.

    Women who do not ovulate because ovulation is suppressed by birth control pills actually have a lower risk of endometrial cancer. Therefore, it is not the lack of ovulation that is the problem; it is the lack of proper regulation of ovulation, which also produces abnormal hormonal levels of estrogen and progesterone during the menstrual cycle.

    Women who have had breast cancer, ovarian cancer, or certain colon cancers are at higher risk. Another inherited condition that is associated with a high rate of inherited colon and uterine cancer, called hereditary nonpolyposis colon cancer (Lynch II syndrome), is also associated with a high risk of endometrial cancer.

    Women with postmenopausal or abnormal vaginal bleeding are usually referred to a gynecologist for diagnostic tests.

    A woman will undergo an endometrial biopsy (EMB) if she has significant postmenopausal bleeding or unexplained irregular vaginal bleeding. This office biopsy allows endometrial cells to be examined under the microscope. To perform an endometrial biopsy, a speculum is inserted into the vagina, and a small flexible plastic tube is inserted through the cervix and into the uterus. A small amount of endometrium can be suctioned through the tube so the cells can be examined in a laboratory.

    This sample will show whether cells are cancerous, and if so, what the grade of the cells is. Grade is assessed by how closely the cells resemble normal endometrial cells. A lower grade indicates more normal cells, and is associated with a better prognosis. Cancer cells can also be tested for progesterone receptors, which, if present in high numbers, indicate a better prognosis.

    An endometrial biopsy is performed in a gynecologist’s office as an outpatient procedure. The discomfort is similar to brief but moderate-to-severe menstrual cramps.

    A woman may undergo a procedure called dilation and curettage (D&C) if an endometrial biopsy cannot be performed in the office, or if she is strongly suspected to have cancer but had uncertain EMB results. A D&C is not necessary if the EMB already shows cancer. A D&C involves a thorough sampling of the endometrium, and thus is the most accurate test for endometrial cancer. The gynecologist dilates the cervix, and then scrapes the endometrium with a special instrument. A pathologist examines the tissue under a microscope. The gynecologist may also view the endometrium with a fiber-optic scope, a procedure called hysteroscopy.

    A D&C takes about one half-hour, is done on an outpatient basis, and usually requires either general anesthesia or sedation.

    Although it can’t provide a conclusive diagnosis for endometrial cancer, a transvaginal ultrasound may provide clues about whether or not cancer is present. A transvaginal ultrasound is a test that is easily performed in the doctor’s office and allows the uterus to be seen. A special wand that uses ultrasound to create a picture is inserted into the vagina. A saline solution may be introduced through the vagina to enable the doctor to see the outline of the endometrium more clearly. The doctor can determine if the endometrium is abnormally thickened, and detect other abnormalities in the uterine wall.

    After a diagnosis of endometrial cancer, other tests may be performed to get more information before surgery. Other tests may include:

    • Chest x- ray for evidence of metastases to the lungs
    • Pelvic and abdominal CT scan to check for metastases
    • A blood test for CA-125 in women with possible advanced- stage endometrial cancer. CA-125 is a substance that is often found in gynecological cancers. The test may be used to monitor treatment progress, and may enable doctors to determine if cancer has recurred after treatment before symptoms arise

    Regular pelvic examinations and Pap smears are important for womens’ health, but do not usually detect endometrial cancer. Most doctors recommend that every woman over the age of 18 have an annual pelvic examination, which includes palpation of the uterus and ovaries by the doctor. A Pap smear is usually taken at the same time, which is an important test for early detection of cancer of the cervix. Pap smears are required annually unless otherwise specified by the doctor.

    In some cases, cells from the endometrium are discovered during a Pap smear, and endometrial cancer can be detected on this basis. However, a Pap smear is not regarded to be an adequate screening or diagnostic test for endometrial cancer, and any woman who has abnormal bleeding, whether or not she has had a recent gynecological exam, should be checked by her doctor.

    Using oral contraceptives significantly reduces the risk of endometrial cancer. Losing weight if you are overweight can help lower the risk of uterine cancer.

    No general screening test is available for endometrial cancer.

  • Prevention and Screening

    Regular pelvic examinations and Pap smears are important for womens’ health, but do not usually detect endometrial cancer. Most doctors recommend that every woman over the age of 18 have an annual pelvic examination, which includes palpation of the uterus and ovaries by the doctor. A Pap smear is usually taken at the same time, which is an important test for early detection of cancer of the cervix. Pap smears are required annually unless otherwise specified by the doctor.

    In some cases, cells from the endometrium are discovered during a Pap smear, and endometrial cancer can be detected on this basis. However, a Pap smear is not regarded to be an adequate screening or diagnostic test for endometrial cancer, and any woman who has abnormal bleeding, whether or not she has had a recent gynecological exam, should be checked by her doctor.

    Using oral contraceptives significantly reduces the risk of endometrial cancer. Losing weight if you are overweight can help lower the risk of uterine cancer.

    No general screening test is available for endometrial cancer.

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