Diagnosis of neuroblastoma

Diagnosis is the process of finding out the cause of a health problem. Diagnosing neuroblastoma usually begins with a visit to your child's doctor. The doctor will ask about any symptoms your child has and do a physical exam. Based on this information, the doctor may refer your child to a specialist or order tests to check for neuroblastoma or other health problems.

The process of diagnosis may seem long and frustrating. It's normal to worry, but try to remember that other health conditions can cause similar symptoms as neuroblastoma. It's important for the healthcare team to rule out other reasons for a health problem before making a diagnosis of neuroblastoma. If the doctor thinks your child has neuroblastoma, your child's care will be managed by a healthcare team that specializes in caring for children with cancer.

The following tests are commonly used to rule out or diagnose neuroblastoma. Many of the same tests used to diagnose cancer are also used to determine the stage, which is how far the cancer has spread. The doctor may also order other tests to check your child's general health and to help plan treatment.

Your child's health history is a record of symptoms, risks and all of their medical events and problems. The doctor will ask questions about your child's personal or family history of certain genetic conditions that are very rare, but can be associated with neuroblastoma.

A physical exam allows the doctor to look for any signs of neuroblastoma. During a physical exam, the doctor may:

• check if any lymph nodes are larger than normal (enlarged)

• check for any mass or swelling

• feel the abdomen to see if the liver is larger than normal

• check the skin for bluish movable lumps under the skin

• check if the eyeballs are bulging (called proptosis) or if there is bruising around the eyes (called periorbital ecchymosis

A neurological exam allows the doctor to check how well the brain, spinal cord and nerves are working. It usually involves a series of questions and tests to measure mental status, coordination, movement and how well the muscles, senses and reflexes are working.

Find out more about physical exams.

A urine test (urinalysis), is done to see if certain chemicals are in the urine. Some neuroblastoma cells make chemical substances called catecholamines. When these chemicals break down, they form homovanillic acid (HVA) and vanillylmandelic acid (VMA). Higher than normal levels of these acids in the urine may be a sign of neuroblastoma. Doctors also use HVA and VMA levels to check how well the neuroblastoma responds to treatment. A urinalysis may also be done to check how well the kidneys are working.

Find out more about urinalysis.

Blood chemistry tests measure certain chemicals in the blood. They show how well certain organs are working and can help find abnormalities. Blood chemistry tests may also be used in staging neuroblastoma. Doctors can also use blood chemistry tests as a baseline to check against during treatment. Blood tests may be done to check how well the liver and kidneys are working.

Find out more about blood chemistry tests.

A complete blood count (CBC) measures the number and quality of white blood cells, red blood cells and platelets. A CBC is done to check for anemia (low red blood cell count) and the ability of blood to clot (platelet count). Doctors use the results of a CBC as a baseline that they can check against during treatment.

Find out more about complete blood count (CBC)..

Blood levels of certain substances may be helpful in predicting prognosis and treating neuroblastoma.

Ferritin is a way the body stores iron. Neuroblastoma cells release ferritin. Children with high ferritin levels tend to have a poorer prognosis. But ferritin levels can also be elevated from other conditions, such as anemia.

Lactate dehydrogenase (LDH) is an enzyme found in cells. LDH levels can be higher if a neuroblastoma is present. LDH levels may reflect the overall amount of tumour present in the child and whether it is actively growing.

An ultrasound uses high-frequency sound waves to make images of parts of the body. An ultrasound can be used to examine the abdomen to look for a tumour or find out what is causing swelling. It can also be used to examine organs that may be affected by neuroblastoma, such as the kidneys, spleen or liver.

Find out more about ultrasounds.

Magnetic resonance imaging (MRI) uses powerful magnetic forces and radiofrequency waves to make cross-sectional images of organs, tissues, bones and blood vessels. A computer turns the images into 3D pictures.

An MRI may be used to find the tumour and determine its size. This can help doctors decide whether or not it can be removed with surgery. An MRI may also be used to see if tumours near the spinal cord are pressing on nerves.

Find out more about MRIs.

A computed tomography (CT) scan uses special x-ray equipment to make 3D and cross-sectional images of organs, tissues, bones and blood vessels inside the body. A computer turns the images into detailed pictures.

A CT scan of the primary tumour may be done to show the size of the tumour and if it is touching or next to vital structures. This can help doctors decide whether or not it can be removed with surgery. A CT scan may also be used to see if the cancer has spread to any organs or tissues.

Find out more about CT scans.

An MIBG scan is a nuclear imaging test. It involves injecting a special medicine called metaiodobenzylguanidine (MIBG) that contains a small amount of radioactive material. MIBG is absorbed by specialized cells called neuroendocrine cells. This allows doctors to find the tumour and to see if the disease has spread to other tissues or bones. Doctors can also use MIBG scans to see if the tumour is responding to treatment.

About 10% of children with neuroblastoma have tumours that don't take up MIBG, which means they can't be found with an MIBG scan. These tumours are called MIBG negative and in this case a PET scan may be used instead to look for disease that may have spread.

MIBG scans may not be available at all centres. Find out more about MIBG scan.

A positron emission tomography (PET) scan uses radioactive materials called radiopharmaceuticals to look for changes in the metabolic activity of body tissues. A computer analyzes the radioactive patterns and makes 3D colour images of the area being scanned.

A PET scan may be used to look for neuroblastoma that does not take up MIBG. It is typically combined with a CT scan (called a PET-CT scan) for a more complete picture and 3D assessment of the neuroblastoma.

Find out more about PET scan.

A bone scan uses bone-seeking radioactive materials called radiopharmaceuticals and a computer to create a picture of the bones. It is used to see if neuroblastoma has spread to the bones (called bone metastasis), but increasingly MIBG or PET scans are being used instead of bone scans to determine metastatic spread for neuroblastoma. A bone scan may be done if a child has bone pain or if blood tests suggest a problem with the bones.

Find out more about bone scans.

An x-ray uses small doses of radiation to make an image of parts of the body on film. A chest or abdominal x-ray may be used to check for a mass in the chest or abdomen.

Find out more about x-rays.

During a biopsy, the doctor removes tissues or cells from the body so they can be tested in a lab. A report from a pathologist will show whether or not cancer cells are found in the sample.

The type of biopsy done depends on where the neuroblastoma is in the body.

Incisional biopsy is a type of surgical biopsy. It may be done to remove part of the tumour through an incision (cut).

Core needle biopsy may be used to remove part of the tumour using a needle. The doctor may use a CT scan or ultrasound to guide the needle during the biopsy.

Find out more about surgical biopsies and core needle biopsies.

During a bone marrow aspiration and biopsy, the doctor removes tissues or cells from the bone marrow so they can be tested in a lab. A bone marrow aspiration and biopsy may be used to see if neuroblastoma has spread to the bone marrow. Usually the bone marrow tests are performed from both sides.

Find out more about bone marrow aspiration and biopsy.

Doctors usually examine and take biopsy samples of enlarged lymph nodes. They will use a CT scan to get a 3D image of lymph nodes that they can't feel. This helps doctors decide whether or not to biopsy the lymph nodes.

A lymph node biopsy may be done if an enlarged lymph node is the only possible area where the tumour has spread or if it would be difficult or risky to biopsy the primary tumour.

Core needle biopsy may be used to remove tissue from a lymph node. The doctor uses a needle to collect a sample from the lymph node.

Incisional biopsy is a type of surgical biopsy. It may be used to remove part of a lymph node so it can be examined.

Excisional biopsy is another type of surgical biopsy. It may be done to remove the entire lymph node so it can be examined. This is the most common type of biopsy used to check lymph nodes for neuroblastoma. It can be done at the time of surgery to remove or biopsy the main tumour.

Find out more about core needle biopsy, and surgical biopsy.

Molecular genetic methods are used in combination with cell and tissue studies. They look at abnormalities in chromosomes (the part of a cell that contains genetic information) or the DNA of cells and tissue. Doctors use these methods to identify changes to the chromosomes and genes, such as duplications, translocations, mutations and deletions.

For neuroblastoma, molecular studies can be very important in helping doctors to predict outcomes and to determine what treatment is needed. One of the most important studies determines if the neuroblastoma cells have amplification (many copies) of the MYCN gene, which is an oncogene (a gene that can cause cancer). Molecular studies can also show DNA ploidy (the amount of DNA content), and look at the pattern of changes across all of the chromosomes in the neuroblastoma cells. These changes can be losses or gains (fewer or more copies) of whole chromosomes (called numerical chromosomal aberrations) or losses or gains of just parts of individual chromosomes (called segmental chromosomal aberrations). The neuroblastoma cells may also be tested for mutations in specific genes. One example is the ALK gene, since neuroblastomas that have mutations in this gene may respond to specific medicines called ALK inhibitors.

Find out more about molecular genetic methods in cell and tissue studies.

To make the decisions that are right for your child, ask your healthcare team questions about diagnosis.