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Diagnosis of Neuroendocrine Cancer

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Frequently, neuroendocrine cancer is found unexpectedly during a medical procedure done for reasons unrelated to suspected cancer. The following are some of the tests used to diagnose a suspected neuroendocrine cancerous tumor:

  • Biopsy. A biopsy is the removal of a small amount of tissue for examination under a microscope and is required to make a diagnosis of neuroendocrine cancer.  A pathologist (a doctor who specializes in interpreting laboratory tests and evaluating cells, tissues, and organs to diagnose disease) analyzes the sample(s) removed during the biopsy. 

  • Blood/urine tests. Blood and urine samples may be used to check for abnormal levels of hormones and other substances. Tests of urine or blood (plasma) check the amount of 5-hydroxyindoleacetic acid (5-HIAA), a breakdown product of serotonin which is made by some neuroendocrine cancer. Measurements of blood serotonin levels may also be taken; however, these are less reliable due to fluctuations.  Chromogranin A is a protein produced by tumor cells; since it is not a hormone so is not part of diagnostic testing.  A blood test to measure Chromogranin A is sometimes performed after diagnosis.

  • Biomarker: Biomarkers are used to identify specific genes, proteins, and other factors unique to the tumor. This may also be called molecular testing of the tumor. Results of these tests can sometimes help determine treatment options. This testing is considered less meaningful in neuroendocrine cancers than in other cancers.

  • Endoscopy: An endoscopy provides a view of the inside the body with a thin, lighted, flexible tube called an endoscope. There are many different types of endoscopy, including upper endoscopy to examine the esophagus and stomach and colonoscopy to examine the rectum and colon. The patient may be sedated as the tube is gently inserted into the body. 

  • Ultrasound: An ultrasound uses sound waves to create a picture of the internal organs. Tumors generate different echoes of the sound waves than normal tissue. This means that when the waves are bounced back to a computer, creating images, the doctor can locate a mass inside the body. There are different types of ultrasounds used to examine different parts of the body. In some cases, a biopsy may be done during the procedure.

  • X-ray: An x-ray is a way to create a picture of the structures inside the body using a small amount of radiation. Sometimes, neuroendocrine cancer does not display in an x-ray because of its size or location.  If gastrointestinal (GI) tract neuroendocrine cancer is suspected, a barium x-ray may be done. In this case, the patient swallows a liquid containing barium that coats the lining of the esophagus, stomach, and intestines. Then a series of x-rays is taken.

  • Computed tomography (CT or CAT) scan: A CT scan takes pictures of the inside of the body using x-rays taken from different angles. A computer combines these pictures into a detailed, 3-dimensional image that shows any abnormalities or tumors. A CT scan can be used to measure the tumor’s size. Additionally, a CT scan is used to see if a tumor has spread to the liver. Sometimes, a special dye called a contrast medium is given before the scan to provide better detail on the image. This dye can be injected into a patient’s vein or given as a pill or liquid to swallow.

  • Magnetic resonance imaging (MRI): An MRI uses magnetic fields, not x-rays, to produce detailed images of the body. MRIs can be used to measure the tumor’s size. A special dye called gadolinium is given before the scan to create a clearer picture. This dye can be injected into a patient’s vein or given as a pill or liquid to swallow.

  • Nuclear medicine imaging: During this test, a small amount of a radioactive drug, called a tracer, is injected into a patient’s vein. The body is then scanned to show where the radioactivity has built up in the body. However, the amount of radiation in the substance is too low to be harmful. PET-CT scans are the type of nuclear imaging used for neuroendocrine cancer.  There are three types of tracers used in a PET scan: gallium-68 (68Ga) DOTATATE, copper-64 (64Cu) DOTATATE, and (18F) fluorodeoxyglucose (FDG).

    • 68Ga DOTATATE PET and 64Cu DOTATATE PET are forms of somatostatin receptor imaging and are primarily used to look at slow-growing neuroendocrine tumors such as grades 1 and 2 and well differentiated grade 3.) Somatostatin receptors are proteins present on the surface of a neuroendocrine cancerous cell that serve as a target for these imaging agents. When the 68Ga or 64Cu attaches to the somatostatin receptor and a picture is taken, cancer spots glow like light bulbs. For neuroendocrine cancer patients, the 68Ga DOTATATE PET scan has replaced a different method of nuclear imaging called OctreoScan. In the United States, the 64Cu DOTATATE PET scan is the latest tracer to be made available to locate neuroendocrine cancer.

    • 18F FDG PET scan is another type of PET scan, but it does not use the somatostatin receptor. It is sometimes used to identify faster-growing neuroendocrine tumors, such as grade 3.

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