Neuroblastoma

Neuroblastoma is a cancerous tumor that begins in nerve tissue of infants and very young children. Neuroblastoma is rare in children older than 10-years-old. However, it does occasionally occur 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 and/or pelvis. The adrenal glands are positioned one on top of each 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 5-years-old. In rare cases, neuroblastoma can be detected before birth by a fetal ultrasound.

In the U.S., approximately 500 children are diagnosed with neuroblastoma each year. It is the most common tumor found in children younger 1-year-old. 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 (e.g. lymph nodes, liver, lungs, bones, central nervous system and bone marrow). Approximately 70% of all children diagnosed with neuroblastoma will have some metastatic disease.

What Causes Neuroblastoma?

A variety of chromosome abnormalities may present in 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 MYCN. The amplification of MYCN causes uncontrolled cell growth. A variety of other chromosome abnormalities may also be present in neuroblastoma.

It is estimated that many 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.

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 a patient is about 1%. 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 a swollen abdomen
• Tumors in the face or head can cause swelling and bruising of the area around the eyes, uncontrolled eye movement, unsteadiness
• 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.

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.

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.

MIBG scans

Similar to a bone scan except that a special dye is injected that may be absorbed by neuroblastoma tissue throughout the body.

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 look for the presence of tumor cells.

Biopsy of primary tumor and/or metastatic lesions

Diagnosing neuroblastoma also involves staging and classifying the disease which determines treatment options and prognosis. Staging is the process of determining whether a 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/or other organs (except as defined in stage 4S).
• Stage 4S — A special stage used only in children under one-year-old. It involves a small tumor that has metastasized (spread) to liver, skin and/or bone marrow (includes minimal bone marrow involvement [less than 10%]; more extensive bone marrow involvement should be classified as stage 4).

How Is Neuroblastoma Treated?

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 (location and size of the tumor)
• Biologic and genetic studies of tumor tissue
• 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/or metastatic resection, and removal of lymph nodes involved)
• Chemotherapy
• Radiation therapy
• Bone marrow transplant and peripheral blood stem cell transplantation
• 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.

What Are the Long-term Effects of Neuroblastoma?

Prognosis greatly depends on:

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

As with any cancer, prognosis and long-term survival can vary greatly from child to child. Prompt medical attention and aggressive therapy are important for the best prognosis.