Neuroblastoma - Childhood: Diagnosis

Approved by the Cancer.Net Editorial Board, 09/2023

ON THIS PAGE: You will find a list of the common tests, procedures, and scans that doctors can use to find out what’s wrong and identify the cause of the problem. Use the menu to see other pages.

Doctors use many tests to find, or diagnose, a tumor. They also do tests to learn if cancer has spread to another part of the body from where it started. If the cancer has spread, it is called metastasis. Doctors may also do tests to learn which treatments could work best.

For most tumors, a biopsy is the only sure way for the doctor to know if an area of the body has cancer. In a biopsy, the doctor takes a small sample of tissue for testing in a laboratory. If a biopsy is not possible, the doctor may suggest other tests that will help make a diagnosis.

How neuroblastoma is diagnosed

There are different tests used for diagnosing neuroblastoma. Your child’s doctor may consider these factors when choosing a diagnostic test:

  • The type of cancer suspected

  • Your child’s signs and symptoms

  • Your child’s age and general health

  • The results of earlier medical tests

According to international criteria developed by an International Neuroblastoma Risk Group task force, a diagnosis of neuroblastoma can be made if:

  • Neuroblastoma cells are detected in the bone marrow and there are higher-than-normal levels of catecholamine, one of the main chemicals produced by the nervous system, present in the urine

  • Results of a tumor biopsy show neuroblastoma cells

In addition to a physical examination, the following tests may be used. Not all tests described here will be used for every child. Talk with your child's doctor about the tests your child may have.

  • Blood tests and urine tests.

    • Complete blood counts (CBC) are tests to find out if the child has signs of anemia, which is having low levels of red blood cells in the blood. Additional blood tests will be done to check liver and kidney function. In addition, blood clotting tests may also be recommended.

    • Urine is collected to test for tumor markers produced by a neuroblastoma tumor. 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.

      Urinary catecholamine metabolites are found in more than 85% of people with neuroblastoma. Catecholamines are organic compounds that include the hormones epinephrine (adrenaline), norepinephrine (noradrenaline), and dopamine. Release of the hormones epinephrine and norepinephrine from the adrenal medulla of the adrenal glands is part of the body's natural "fight-or-flight" response to a harmful situation, preparing itself to either quickly leave the area or stay to fight. Eventually, the body breaks down the catecholamine molecules into smaller pieces, called metabolites, which are then passed out of the body in the urine. The 2 catecholamine metabolites most often measured are homovanillic acid (HVA) or vanillylmandelic acid (VMA).

  • Biopsy. A biopsy is the only way to make a definite diagnosis, even if other tests can suggest that cancer is present. During biopsy, a small amount of tissue is removed for examination under a microscope. A pathologist analyzes the sample(s). A pathologist is 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 surgeon determines that the entire tumor can be removed, the whole tumor is commonly removed instead of doing a separate biopsy.

  • Bone marrow aspiration and biopsy. These 2 procedures are done to examine the bone marrow. Bone marrow has both a solid and a liquid part. A bone marrow aspiration removes a sample of the fluid with a needle. A bone marrow biopsy is the removal of a small amount of solid tissue using a needle. These procedures are often done at the same time and may be called a bone marrow examination.

    A pathologist then analyzes the samples. A common site for a bone marrow aspiration and biopsy is the pelvic bone, which is located in the lower back by the hip. In many centers, children are sedated before this procedure using a medication that a doctor will give called anesthesia to numb the area. Anesthesia is a medication that blocks the awareness of pain. Stronger types of anesthesia can also be used to lessen the pain.

  • Biomarker testing of the tumor/genetic tests. Your child's doctor may recommend running laboratory tests on the tumor sample to identify specific genes, proteins, and other factors unique to the tumor. Tests of neuroblastoma cell DNA are used to find a change in the oncogene MYCN, a gene responsible for cell growth. Having more than 10 copies of the gene, called amplification, is associated with a tumor that grows and spreads quickly. Approximately 20% of patients have tumors with MYCN amplification. The status of MYCN is used for risk grouping (see Stages and Risk Groups).

    Additional tests may be done to find out if the tumor has changes in the numbers of the whole chromosome or parts of chromosomes. A series of studies have shown that segmental chromosomal irregularities are associated with more aggressive disease, while whole chromosome gains are seen in tumors with more favorable outcomes. DNA sequencing tests to find out if there are mutations of the ALK gene are also commonly done. Sequencing studies have shown that a small subset of neuroblastoma tumors have gene mutations at the time of diagnosis, and some of these mutations, like ALK, can be targeted with new drugs. Studies have shown that tumors that come back, called recurrent tumors, often have increased gene mutation frequency.

    For people with a family history of neuroblastoma (see Risk Factors), genetic tests to determine whether the person has germline mutations in the PHOX2B or ALK genes are commonly done.

  • 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. A special dye called a contrast medium is usually given before the scan to provide better detail on the image. This dye is injected into a patient’s vein or given as a pill or liquid to swallow.

  • Magnetic resonance imaging (MRI). An MRI produces detailed images of the brain and spinal column using magnetic fields, not x-rays. MRI can be used to measure the tumor’s size. A special dye called a contrast medium 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. An MRI is better at showing neuroblastoma around the spine, and it is essential to look at a tumor that is near where nerves leave the spinal column, which can press on the spinal cord.

  • Meta-iodobenzylguanidine (MIBG) scan. MIBG is a protein that neuroblastoma cells absorb. When the protein 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) or PET-CT scan. A PET scan creates pictures of organs and tissues inside the body. A PET scan is usually combined with a CT scan (see above), called a PET-CT scan. However, you may hear your child's doctor refer to this procedure just as a PET scan. 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. However, the amount of radiation in the substance is too low to be harmful. A scanner then detects this substance to produce images of the inside of the body. This test is usually performed when a patient's tumor does not absorb MIBG (see above).

After diagnostic tests are done, your child’s doctor will review the results with you. If the diagnosis is neuroblastoma, these results also help the doctor describe the cancer. This is called staging and risk grouping.

The next section in this guide is Stages and Risk Groups. It explains the system doctors use to describe the extent of the disease. Use the menu to choose a different section to read in this guide.