Doctors use many tests to diagnose neuroblastoma and find out if it has metastasized (spread). Some tests may also determine which treatments may be the most effective. For most tumors, a biopsy is the only way to make a definitive diagnosis of cancer. If a biopsy is not possible, the doctor may suggest other tests that will help make a diagnosis. Imaging tests may be used to find out whether the cancer has metastasized. Your child’s doctor may consider these factors when choosing a diagnostic test:
- Medical condition
- Type of cancer suspected
- Previous test results
According to international criteria developed by the International Neuroblastoma Staging System Committee (INSS), diagnosing neuroblastoma depends on two factors:
- Neuroblastoma in the bone marrow and higher than normal levels of one of the main chemicals produced by the nervous system, called catecholamine, in the urine
- A tumor biopsy showing neuroblastoma cells
In addition to a physical examination, the following tests may be used to find out if a child has neuroblastoma:
Blood and urine tests . Complete blood counts (CBC) are tested to find out if the child has signs of anemia. Liver and kidney function are tested, and urine is collected to learn if there are any tumor markers or other substances produced by neuroblastoma. A tumor marker is a substance found in higher than normal amounts in the blood, urine, or body tissues of people with certain kinds of cancer.
Normal nerve cells communicate with each other by releasing certain chemicals called neurotransmitters. Catecholamines are neurotransmitters. Eventually the body breaks down the catecholamine molecules into smaller pieces, called metabolites, which are then passed out of the body in the urine.
About 90% of the time, neuroblastoma cells make enough catecholamines to be found in blood or urine tests. The two catecholamine metabolites most often measured are:
- Homovanillic acid (HVA)
- Vanillylmandelic acid (VMA)
Biopsy . A biopsy is the removal of a small amount of tissue for examination under a microscope. Other tests can suggest that cancer is present, but only a biopsy can make a definite diagnosis. The sample removed from the biopsy is analyzed by a pathologist (a doctor who specializes in interpreting laboratory tests and evaluating cells, tissues, and organs to diagnose disease). The type of biopsy performed depends on the location of the tumor. If the doctor determines that the entire tumor can be removed during the biopsy, the whole tumor will be removed at that time.
Molecular genetic studies. Tests of neuroblastoma cell DNA are used to measure the tumor ploidy (DNA content). Recent studies looking at all of a patient’s chromosomes (whole genome studies) have found that having chromosomes that are missing pieces is linked with more aggressive tumors and worse outcome, while having extra chromosomes is associated with less aggressive tumors and better outcomes. Therefore, additional DNA content, or hyperdiploidy, is associated with less aggressive disease, while diploid DNA content, or having near normal amounts of DNA, is associated with more aggressive tumors.
Other genetic tests are done to find a change in the oncogene MYCN, a gene responsible for cell growth. More than 10 copies of the gene, called amplification, is associated with a tumor that grows and spreads quickly, making it more difficult to treat. A non-amplified MYCN gene is linked to less aggressive tumors, which grow and spread more slowly. Additional tests are done to find out if the tumor has changes in chromosomes 1p, 11q, and 17q. Changes to these chromosomes may be signs of a more aggressive tumor. Research on DNA molecular tests to help determine a patient’s prognosis (chance of recovery) is ongoing.
Bone marrow biopsy and aspiration . These two procedures are similar and often done at the same time to find if any neuroblastoma cells have spread to the bone marrow. Bone marrow has both a solid and a liquid part. A bone marrow biopsy is the removal of a small amount of solid tissue using a needle. An aspiration removes a sample of fluid with a needle. The sample(s) are then analyzed by a pathologist. A common site for a bone marrow biopsy and aspiration is the pelvic bone, which is located in the lower back by the hip. The skin in this area is usually numbed with medication beforehand, and other types of anesthesia (medication to block the awareness of pain) may be used. The tissue sample may also be sent for additional tests to find whether there are very small numbers of neuroblastoma cells.
Computed tomography (CT or CAT) scan . A CT scan creates a three-dimensional picture of the inside of the body with an x-ray machine. A computer then combines these images into a detailed, cross-sectional view that shows any abnormalities or tumors. Sometimes, a contrast medium (a special dye) is injected into a patient’s vein to provide better detail.
Magnetic resonance imaging (MRI) . An MRI uses magnetic fields, not x-rays, to produce detailed images of the brain and spinal column. A contrast medium may be injected into a patient’s vein to create a clearer picture. An MRI is better at showing tumors around the spine, and it is essential to look at a tumor that is near where nerves leave the spinal column, as it can press on the spinal cord.
Bone scan . A bone scan uses a radioactive tracer to look at the inside of the bones. The tracer is injected into a patient’s vein. It collects in areas of the bone and is detected by a special camera. Healthy bone appears gray to the camera, and areas of injury, such as those caused by cancer, appear dark.
MIBG scan. MIBG stands for meta-iodobenzylguanidine. Neuroblastoma cells take up (absorb) this protein, and when it is linked to a small amount of radioactive iodine, it can be used to find neuroblastoma in the bone, bone marrow, and other parts of the body. Because the child’s thyroid gland will also absorb radioactive iodine, regular iodine is taken by mouth for several days before the scan to protect the thyroid.
Positron emission tomography (PET) scan . A PET scan is a way to create pictures of organs and tissues inside the body. A small amount of a radioactive substance is injected into a patient’s body. This substance is absorbed mainly by organs and tissues that use the most energy. Because cancer tends to use energy actively, it absorbs more of the radioactive substance. A scanner then detects this substance to produce images of the inside of the body. This test is usually performed for patients who have a tumor that does not take up (absorb) MIBG (see above).
Find more about what to expect when having common tests, procedures, and scans. 
After these diagnostic tests are done, your child’s doctor will review all of the results with you. If the diagnosis is a tumor, these results also help the doctor describe the tumor; this is called staging and risk grouping . Learn more about the first steps to take after a diagnosis of a tumor .