Neuroblastoma

What is neuroblastoma?

Neuroblastoma is a cancerous tumor that begins in nerve tissue of infants and very young children. The abnormal cells are often found in the nerve tissue that is present in the unborn baby and later develops into a detectable tumor. Neuroblastoma is rare in children older than 10 years of age, however, it does occur occasionally in adults.

The tumor usually begins in the tissues of the adrenal gland found in the abdomen, but may also begin in nerve tissue in the neck, chest or pelvis. The adrenal glands are positioned on top of the kidneys. These glands secrete hormones and other important substances that are required for normal functions in the body such as the nervous system.

Most children affected by neuroblastoma have been diagnosed before the age of 5. It is often present at birth, but not detected until the tumor begins to grow and compress the surrounding organs. In rare cases, neuroblastoma can be detected before birth by a fetal ultrasound.

In the US, approximately 500 children are diagnosed with neuroblastoma each year. It is the most common tumor found in children younger than 1 year of age. For unknown reasons, it occurs slightly more often in males than in females.

Neuroblastoma cancer cells can spread (metastasize) quickly to other areas of the body (i.e., lymph nodes, liver, lungs, bones, central nervous system and bone marrow). Approximately 70 percent of all children diagnosed with neuroblastoma will have some metastatic disease.

What causes neuroblastoma?

Most neuroblastoma cells have genetic abnormalities involving chromosome #1, where a deletion or rearrangement is found on the short arm of this chromosome. The chromosome abnormality, in turn, causes amplification of an oncogene called n-myc, even though this gene is not located on chromosome #1. The amplification of n-myc causes uncontrolled cell growth. A variety of other chromosome abnormalities may also be present in neuroblastoma.

It is estimated that as many as 20 percent of neuroblastoma cases result from an inherited mutation, followed by a second mutation occurring after birth, which together initiate uncontrolled cell growth. The remainder of the cases occur from two acquired mutations after birth. Because the tumor occurs very early in childhood, it is doubtful that any environmental exposures the child has incurred could be linked to the development of the tumor.

Neuroblastoma is more common in children born with fetal hydantoin syndrome, neurofibromatosis and Beckwith-Wiedemann syndrome. The exact relationship between these conditions and the disease are not known.

The chance for neuroblastoma to be present in a future sibling of the patient is about 1 percent. If more than one child has neuroblastoma, the chance for reoccurrence increases.

Research is being conducted to determine if maternal exposure to any toxic substances, environmental pollutions, or radiation during pregnancy could have any link to the child developing neuroblastoma.

What are the symptoms of neuroblastoma?

The following are the most common symptoms of neuroblastoma. However, each child may experience symptoms differently. The symptoms of neuroblastoma vary greatly depending on size, location and spread of the tumor. Symptoms may include:

• Abdominal mass, either felt during an examination or seen as swollen abdomen.
• Tumors in the face or head can cause swelling and bruising of the area around the eyes and uncontrolled eye movement.
• Compression of kidney or bladder by the tumor may cause changes in urination.
• Bone marrow involvement may present as pain, limping, paralysis, or weakness.
• Diarrhea may be present; diarrhea is caused by a substance produced by the tumor (vasoactive intestinal peptide or VIP).
• Fever.
• High blood pressure and increased heart rate may occur depending on location of tumor and the organs the tumor compresses.

The symptoms of neuroblastoma may resemble other conditions or medical problems. Always consult your child's physician for a diagnosis.

How is neuroblastoma diagnosed?

In addition to a complete medical and physical examination, diagnostic procedures for neuroblastoma may include the following:

• Blood tests - including a complete blood count, blood chemistries, kidney and liver function tests and a urinalysis.
• Multiple imaging studies - to evaluate primary tumor and determine extent/location of any metastases, including:
  • Computed tomography scan (Also called a CT or CAT scan) - a diagnostic imaging procedure that uses a combination of x-rays and computer technology to produce cross-sectional images (often called slices), both horizontally and vertically, of the body. A CT scan shows detailed images of any part of the body, including the bones, muscles, fat and organs. CT scans are more detailed than general x-rays.
  • Magnetic resonance imaging (MRI) - a diagnostic procedure that uses a combination of large magnets, radiofrequencies, and a computer to produce detailed images of organs and structures within the body.
    ◦X-ray - a diagnostic test which uses invisible electromagnetic energy beams to produce images of internal tissues, bones and organs onto film.
  • Ultrasound (Also called sonography) - a diagnostic imaging technique which uses high-frequency sound waves and a computer to create images of blood vessels, tissues and organs. Ultrasounds are used to view internal organs as they function and to assess blood flow through various vessels.
  • Bone scans - pictures or x-rays taken of the bone after a dye has been injected that is absorbed by bone tissue. These are used to detect tumors and bone abnormalities.
• Bone marrow biopsy and/or aspiration - a procedure that involves a small amount of bone marrow fluid and tissue to be taken, usually from part of the hip bones, to further examine the number, size and maturity of blood cells and abnormal cells.
• Spinal tap/lumbar puncture - a special needle is placed into the lower back, into the spinal canal. This is the area around the spinal cord. The pressure in the spinal canal and brain can then be measured. A small amount of cerebral spinal fluid (CSF) can be removed and sent for testing to determine if there is an infection or other problems. CSF is the fluid that bathes your child's brain and spinal cord.
• Biopsy of primary tumor and metastatic lesions.

Diagnosing neuroblastoma also involves staging and classifying the disease which determines treatment options and prognosis. Staging is the process of determining whether cancer has spread and, if so, how far. There are various staging systems that can be used for neuroblastoma. Always consult your child's physician for information on staging. One method of staging neuroblastoma is the following:

• Stage 1 - involves a tumor that does not cross the midline of the body, is completely resectable and has not spread to other areas of the body. The lymph nodes on the same side of the body as the tumor do not have cancer cells present.
• Stage 2A - involves a tumor that does not cross the midline of the body, but is not completely resectable. This stage of tumor has not spread to other areas of the body and lymph nodes on the same side as the tumor do not have tumor cells present.
• Stage 2B - involves a tumor that may or may not be completely resectable, has not spread to other areas of the body, but lymph nodes on the same side of the tumor have tumor cells present. Lymph nodes on the opposite side of the tumor must be negative for tumor cells in this stage of disease.
• Stage 3 - involves a tumor that crosses the midline of the body, is not completely resectable, and lymph nodes are positive for tumor cells. This stage also includes a tumor that does not cross the midline, but the lymph nodes on the opposite side also contain tumor cells.
• Stage 4 - involves a tumor that has metastasized to distant lymph nodes, bone marrow, liver, skin and other organs (except as defined in stage 4S).
• Stage 4S - involves a tumor that has metastasized (spread) to liver, skin or bone marrow (includes minimal bone marrow involvement; more extensive bone marrow involvement should be classified as stage 4).

Treatment for neuroblastoma

Specific treatment for neuroblastoma will be determined by your child's physician based on:

• Your child's age, overall health and medical history.
• Extent of the disease.
• Your child's tolerance for specific medications, procedures or therapies.
• Expectations for the course of the disease.
• Your opinion or preference.

Treatment may include (alone or in combination):

• Surgery (for tumor and metastatic resection and removal of lymph nodes involved).
• Chemotherapy.
• Radiation therapy.
• Bone marrow transplant.
• Supportive care (for the side effects of treatment).
• Antibiotics (to prevent/treat infections).
• Continuous follow-up care (to determine response to treatment, recurrent disease and late effects of treatment).

Treatment options should be discussed with your child's physician.

Long-term outlook for a child with neuroblastoma

Prognosis greatly depends on:

• The extent of the disease.
• The size and location of the tumor.
• A presence or absence of metastasis.
• The tumor's response to therapy.
• The age and overall health of your child.
• Your child's tolerance of specific medications, procedures or therapies.
• New developments in treatment.

As with any cancer, prognosis and long-term survival can vary greatly from individual to individual. Prompt medical attention and aggressive therapy are important for the best prognosis. Continuous follow-up care is essential for a child diagnosed with neuroblastoma. Side effects of radiation and chemotherapy, as well as recurrence of the disease, can occur in survivors of neuroblastoma. New methods are continually being discovered to improve treatment and to decrease side effects.