How is Endometrial Cancer Diagnosed?

If your doctor suspects you may have endometrial cancer, usually because of abnormal uterine bleeding, there are several tests and procedures that can confirm a diagnosis. Diagnosis relies on a combination of your symptoms, a physical examination, imaging, and a tissue sample examined under a microscope.

Some tests are used to confirm an endometrial cancer diagnosis. Others are used to learn more about the cancer, such as its extent and genetic features, and help guide treatment. You may not have all of the tests on this list.

Physical examination

Your doctor will begin with a thorough medical history and a physical examination, including a pelvic exam. During the pelvic exam, the doctor checks the uterus, ovaries, and vagina for any abnormalities. An enlarged uterus or pelvic mass may suggest endometrial cancer or another uterine condition.

Transvaginal ultrasound

A transvaginal ultrasound uses a small probe placed in the vagina to create images of the uterus. It measures the thickness of the endometrium. A thickened endometrium that is greater than 4-5 mm after menopause raises concern for endometrial cancer or abnormal cell growth and warrants further evaluation.

Endometrial biopsy

An endometrial biopsy is the most common and important test for diagnosing endometrial cancer. A thin, flexible tube is inserted through the cervix into the uterus, and a small sample of the endometrial lining is removed. The procedure can usually be done in the office without general anesthesia. A pathologist then examines the tissue under a microscope.

Dilation and curettage (D&C)

If the endometrial biopsy does not provide a clear diagnosis, or if the doctor cannot obtain enough tissue, a D&C may be performed. Under anesthesia, the cervix is dilated and a larger instrument is used to scrape and remove tissue from the lining of the uterus. This is done in an operating room.

Hysteroscopy

A thin, lighted telescope (hysteroscope) is inserted through the cervix into the uterus to directly visualize the inside of the uterus. Biopsies can be taken through the hysteroscope. This allows the doctor to see the exact location of any abnormal area.

Imaging tests to diagnose and stage endometrial cancer

• Computed tomography (CT). A CT scan of the abdomen and pelvis is commonly used to look for lymph node involvement and spread of cancer to other organs.

• Magnetic resonance imaging (MRI). MRI is particularly useful for evaluating the depth of invasion into the uterine wall and spread to nearby structures. It is often used to help plan surgery.

• PET-CT (positron emission tomography). Combines a metabolic scan with a CT scan to find areas of high cancer cell activity. Most useful in high-grade or advanced disease.

• Chest X-ray or CT chest. Used to check whether cancer has spread to the lungs.

Molecular and biomarker testing

Molecular testing of the tumor tissue is now a standard and essential part of endometrial cancer evaluation. Results guide both prognosis and treatment decisions:

• Mismatch repair (MMR)/microsatellite instability (MSI) testing. All endometrial cancers should be tested for mismatch repair deficiency (dMMR) or microsatellite instability (MSI). This test identifies cancers that are likely to respond to a type of immunotherapy called checkpoint inhibitors. It also helps identify patients who may have Lynch syndrome.

• POLE mutation testing. Tumors with POLE mutations have an excellent prognosis regardless of grade. POLE testing is increasingly part of routine molecular profiling.

• TP53 testing. Mutations in TP53 indicate a high-risk tumor, similar to serous carcinoma.

• HER2 testing. Serous carcinomas are tested for HER2 expression, as HER2-positive serous carcinomas may respond to trastuzumab (Herceptin).

• Estrogen receptor (ER) and progesterone receptor (PR) testing. May help guide hormonal therapy decisions for recurrent disease.

Blood tests

Blood tests are not used to diagnose endometrial cancer directly, but they help evaluate overall health. In some cases, the tumor marker CA-125 is checked, as elevated levels can indicate advanced or high-grade disease, though it is not specific for endometrial cancer.

Genetic counseling and testing

Because of the strong association between endometrial cancer and Lynch syndrome, guidelines recommend that all women diagnosed with endometrial cancer be evaluated for Lynch syndrome through tumor testing and, when appropriate, germline genetic testing. This is important not only for the patient but for family members who may also be at risk.