If a child has symptoms of neuroblastoma, blood and urine tests, tissue samples, and imaging studies will be needed. These tests are important because many of the symptoms and signs of neuroblastoma also can be caused by other cancers or by non-cancerous diseases.

Blood and Urine Tests

Normal nerve cells release chemicals called neurotransmitters that control nerve activity. Catecholamines are the main group of neurotransmitters produced by cells of the sympathetic nervous system. The body breaks down the catecholamine molecules into metabolites, or smaller pieces, and they are passed out of the body in the urine.

In about 90 percent of cases, neuroblastoma causes elevated levels of catecholamines or neurotransmitters, which are detected by blood or urine tests. Some of the symptoms associated with neuroblastoma — such as high blood pressure, rapid heartbeat or diarrhea — are caused by increased catecholamines.

Your child's doctor may order other blood tests to check liver and kidney function and salt balance. A urinalysis will be conducted to further check kidney function.

Imaging Tests

Imaging tests include diagnostic X-rays and other procedures that produce images or pictures of the body's interior. Two or more of these tests are generally used to identify tumors in areas where neuroblastomas tend to spread. These tests may include:

• Computed Tomography (CT or CAT) Scan — This is a diagnostic imaging procedure that uses a combination of X-rays and computer technology to produce cross-sectional images, both horizontally and vertically, of the body. A CT scan shows detailed images of the body, including the bones, muscles, fat and organs. CT scans are more detailed than general X-rays. To produce the image, it often is necessary to use a contrast dye administered either intravenously or consumed orally.



• Magnetic Resonance Imaging (MRI) — This scan uses magnets, rather than X-rays, to produce detailed images of the body. The MRI machine sends radio waves into the body and then measures the response with a computer. The computer makes an image or picture of the interior of the body. MRIs are used for certain types and locations of tumors because they can produce a better image than X-rays.



• Ultrasound — An ultrasound exam or sonogram uses high frequency sound waves to create images of organs in the body. There is no radiation used in this test. Sound waves bounce off tissues using the same principles as sonar. The echoes that return to the transducter are used to draw the images on the screen.



• MIBG — An MIBG scan uses a chemical called metaiodobenzylguanidine that is slightly radioactive to identify areas where the neuroblastoma has spread. It is a very sensitive method of detecting the spread of cancer in bone and soft tissues. MIBG is injected intravenously. A scan, which takes about an hour, is performed 24 hours later.



• Positron Emission Tomography (PET) Scan — A PET scan is a nuclear medicine test in which a radioactive glucose compound is injected and shows the areas of tumor in the body. It's used in about 10 percent of the cases where the MIBG scan is negative.



• Biopsies — Signs and symptoms, blood and urine tests and imaging studies may indicate that a neuroblastoma is probably present, but a conclusive diagnosis can be made only by biopsy — when neuroblastoma cells in tissue samples are seen under a microscope.

If blood or urine levels of catecholamines or their metabolites are elevated, then finding cancer cells in a bone marrow biopsy is sufficient evidence for a diagnosis of neuroblastoma. The disease spreads to bone marrow in about a quarter of patients.

Bone marrow can be sampled in two ways, and both are generally done at the same time. A bone marrow biopsy uses a large needle to remove a cylindrical piece of the bone about 1/2 inch long and 1/16 inch across. A bone marrow aspiration uses a thinner needle and a syringe to extract cells from the marrow, the soft tissue inside bone cavities.

Alternatively, tissue samples can be taken from the primary tumor. If examination under the microscope shows certain features typical of neuroblastoma, a definite diagnosis can be made, even if catecholamine levels are not elevated. Some cases of neuroblastoma are easily recognized under a microscope when examined by doctors experienced in testing children's tumor samples.

Other cases of neuroblastoma have features easily confused with other types of children's cancers. In these cases, special tests of the tissue samples must be done. For example, immunohistochemistry uses special laboratory antibodies that specifically recognize chemicals found in neuroblastoma cells and other antibodies that recognize chemicals of other cancer cells. Electron microscopy uses a special microscope hundreds of times more powerful than usual laboratory microscopes, and can recognize tiny packages of catecholamines inside neuroblastoma cells and other abnormalities.

Categories of Neuroblastoma

When neuroblastoma is diagnosed, your child's doctor may use the following categories or terms to describe the cancer:

• Localized Resectable — The cancer is confined to the site of origin, there is no evidence of spread, and the cancer can be surgically removed.



• Localized Unresectable — The cancer is confined to the site of origin, but the cancer cannot be completely removed surgically.



• Regional — The cancer has extended beyond the site of origin to regional lymph nodes and/or surrounding organs or tissues, but has not spread to distant parts of the body.



• Disseminated — The cancer has spread from the site of origin to distant lymph nodes, bone, liver, skin, bone marrow, and/or other organs (except as defined for stage 4S).



• Stage 4S — This also is called "special" neuroblastoma because it is treated differently. The cancer is localized, with dissemination or spreading limited to liver, skin and to a very limited extent to bone marrow.



• Recurrent — This means the cancer has come back or continues to spread after treatment. It may come back in the original site or in another part of the body.

Reviewed by health care specialists at UCSF Benioff Children's Hospital.