Neuroblastoma is the most common malignant (cancerous) extracranial solid tumor of childhood. It develops from the tissues that form the sympathetic nervous system, which is the part of the nervous system that regulates involuntary body functions.

The tumor usually begins in the nerve tissues of the adrenal gland (above the kidney), but may also begin in nerve tissues of the neck, chest or pelvis.

Although neuroblastoma often is present at birth, it generally is not detected until the tumor begins to grow and compress the surrounding organs.

Cancer cells can metastasize (spread) quickly to other areas of the body, such as lymph nodes, liver, lungs, bones, the central nervous system and bone marrow. Close to 70 percent of children diagnosed with neuroblastoma will have metastatic disease.

Approximately 650 children in the United States are diagnosed with this tumor each year, and most children affected by the disease are diagnosed before age 5. Neuroblastoma occurs with slightly more frequency in males than in females.

Neuroblastoma Causes

Most neuroblastoma cells have abnormalities involving a particular chromosome (chromosome No. 1), and the more malignant tumors often have multiple copies of the oncogene MYCN in the tumor cells, but a number of other genetic abnormalities may also be present.

The likelihood of the disease being present in a future sibling of a child with neuroblastoma is about 1 percent.

Research is currently underway to determine if maternal exposure during pregnancy to toxic substances, environmental pollutants or radiation could be linked to development of the disease.

Neuroblastoma Symptoms

The symptoms of neuroblastoma vary greatly depending on size, location and spread of the tumor; however, the most common symptoms include:

• An abdominal mass, either felt during an examination or seen as a swollen abdomen
• Uncontrolled eye movement caused by the tumor
• Swelling and bruising of the area around the eyes, caused by metastases (tumor spread)
• Compression of kidney or bladder by the tumor may cause changes in urination
• Pain, limping or weakness may be present from bone involvement
• Anemia or bruising may be present if there is bone marrow involvement
• Paralysis and weakness may be present if there is spinal cord involvement
• Diarrhea caused by a substance produced by the tumor (vasoactive intestinal peptide, or VIP) may be present
• Fever
• High blood pressure and increased heart rate may occur depending on location of tumor and the organs the tumor compresses

Neuroblastoma Diagnosis

In some cases, neuroblastoma can be detected before birth by a fetal ultrasound. For the most part, however, a complete medical and physical examination must be conducted, and a large number of diagnostic tests and procedures must be performed. These may include:

• Blood tests -- These should include a complete blood count, blood chemistries, and kidney and liver function tests.
• Determination of urine and plasma catecholamine excretion levels -- These levels are usually higher than normal due to tumor production.
• Multiple imaging studies -- These are done in order to evaluate the primary tumor and to determine the extent and location of any metastases.
• Ultrasonography -- This imaging technique uses high-frequency sound waves and a computer to create images of blood vessels, tissues and organs. It is used to view internal organs as they function, and to assess blood flow through various vessels. It is often the first test to screen for the presence of an abdominal tumor.
• Computerized tomography scan (also called CT or CAT scan) -- This is a diagnostic imaging procedure that uses a combination of X-rays and computer technology to produce cross-sectional images of the body. A CT scan shows detailed images of any part of the body, including bones, muscles, fat and organs. CT scans are more detailed than standard X-rays.
• Magnetic resonance imaging (MRI) -- This procedure uses a combination of large magnets, radiofrequencies and a computer to produce detailed images of organs and structures within the body.
• Bone scans -- These are X-rays of the bone that are taken after an injected dye is absorbed by bone tissue. Bone scans are used to detect tumors and bone abnormalities.
• MIBG scans -- MIBG is a substance selectively taken up by neuroblastoma cells. The MIBG is tagged with small amounts of radioactive iodine, which then can be localized in a patient's body by a nuclear medicine scan. This scan highlights the location of the tumors in a patient's body.
• Bone marrow biopsy and / or aspiration -- A small amount of bone marrow fluid and tissue is taken, usually from the hip bones, to further examine the number, size and maturity of blood cells and / or abnormal cells.
• Biopsy of primary tumor and / or metastatic lesions

Neuroblastoma Stages

Diagnosing neuroblastoma involves staging and classifying the disease so treatment strategies can be determined and a prognosis can be made. The various stages, as classified by the International Neuroblastoma Staging System (INSS), are described below:

• Stage 1 involves a tumor that does not cross the midline of the body. The tumor is completely resected (removed) 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. Though all visible tumor is removed, tumor removal is incomplete. 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 resected, but has not spread to other areas of the body. Lymph nodes on the same side as the tumor have tumor cells present, while those on the opposite side do not.
• Stage 3 involves a tumor that crosses the midline of the body and is not completely resected. Lymph nodes may or may not have tumor cells present. This stage also includes a tumor that does not cross the midline, but has lymph nodes on the opposite side of the body with 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 involves a tumor that has metastasized to liver, skin and / or bone marrow, but not to the bones. This stage generally occurs in children younger than 1 year of age.

Neuroblastoma Treatment

Decisions pertaining to treatment strategies should be jointly made by parents and the child's physician(s). A number of factors must be considered:

• The child's age, medical history, and overall health
• Extent of the disease
• The child's tolerance for specific medications, procedures, or therapies

Treatment includes a wide range of approaches. Depending on individual circumstances, these approaches are used either alone or in combination:

• Surgery. This is done to remove the primary tumor and stage the patient in order to assess metastases.
• Chemotherapy
• Radiation therapy
• Blood and marrow transplant
• Immunotherapy

Despite the benefits of these treatments, each treatment has certain associated side effects. Close attention is paid to these side effects and to antibiotics to prevent or treat infections. Other supportive care is also given.

Also, new methods are continually being discovered to improve treatment approaches and to decrease side effects.

Neuroblastoma Prognosis

As with any cancer, prognosis and long-term survival can vary greatly. While prompt medical attention and aggressive therapy are of utmost importance, prognosis depends upon a wide range of factors. These include:

• Extent of disease
• Size and location of the tumor
• Presence or absence of metastases
• Type of pathology (favorable or unfavorable)
• Biological factors, such as the number of copies per tumor cell of the N-myc oncogene, which is a tumor-specific protein
• Response of the tumor to therapy
• Child's tolerance of specific medications, procedures, and therapies

Depending on various prognostic factors, children are considered to be in low-, medium- or high-risk categories, and different treatment protocols have been developed for each risk group.

With current therapies, low-risk patients (stages 1 and 2) carry more than a 90 percent long-term survival rate, regardless of age.

In higher-risk patients with more advanced stages of disease, survival rates diminish. Treatment for children in the more advanced stages of neuroblastoma is much more aggressive, including chemotherapy, radiotherapy and blood and marrow transplantation.

Despite treatment, however, the more advanced stages of neuroblastoma have a much less optimistic prognosis.

Follow-Up Care

Continuous follow-up care is absolutely essential for the determination of response to treatment, recurrent disease and late effects of treatment.

Cincinnati Children's is an international referral center for the treatment of children and young adults with high-risk and relapsed neuroblastoma. Our faculty members lead national efforts in the development of new targeted therapies, immunological approaches, and stem cell transplantation.

We have a number of active treatment regimens for relapsed neuroblastoma. Check out our research studies.