Neuroblastoma is a cancer that originates in the tissues that form the sympathetic nervous system. The normal function of these nerves is to regulate the automatic and non-voluntary body functions such as heart rate, blood pressure, breathing, and digestion.
Neuroblastoma typically begins in the nerve tissues of the adrenal glands but may also begin in the nerves that are located anywhere along the spinal cord, including the neck, chest, or abdomen. The cancer can metastasize (spread) rapidly to other organs (ie, liver), lymph nodes, bones, and bone marrow.
This cancer is rare, affecting only about 1 in 100,000 people. It often develops at birth or soon after, and is most commonly diagnosed in children younger than 5 years of age.
What causes a neural tumor?
Its cause is unknown, but it is believed to form during normal development of the sympathetic nervous system. Gene abnormalities in persons with the tumor are typical. The gene associated with this tumor is named n-myc. This gene is normally functional for a brief period in the first trimester of fetal life and then is silenced throughout the rest of gestation as well as throughout life. If this gene is activated, the result can be development of a neuroblastoma.
What are the signs and symptoms of neuroblastoma?
The specific symptoms will depend on the site of the tumor. In many circumstances, the tumor will cause the child to have abdominal pain or non-specific tiredness. If the tumor has invaded the bone marrow, as it often does by the time it is diagnosed, the child may look pale due to anemia. A lump may be felt in the abdomen, neck, or chest. Common symptoms are dark circles around the eyes, an enlarged abdomen (particularly if the cancer has spread to the liver), difficulty breathing, bone pain or tenderness (if the cancer has spread to the bones), and weakness or loss of movement (paralysis) of the hips, legs, or feet.
Some less common signs are shortness of breath, severe diarrhea, uncontrolled eye movements, and uncoordinated movement. The syndrome of "dancing eyes – dancing feet" or opsoclonus-myoclonus, should quickly make the doctor think of neuroblastoma. Some children with neuroblastoma may also have problems with balance, also known as ataxia. Both opsoclonus-myoclonus and ataxia are known as a paraneoplastic syndrome and are associated with neuroblastoma.
How is neuroblastoma diagnosed?
A physical examination of the body is performed to feel for lumps. In this way, the abdomen may be felt (palpated) for a mass. An enlarged liver indicates that the cancer has spread to the liver. Tumors of the adrenal glands often cause high blood pressure and a fast heart rate.
Several tests may be done to look for the origin of the tumor and sites of metastases:
- A urine test may be performed to check for catecholamine metabolites called homovanillic acid (HVA) and vanillylmandelic acid (VMA), which appear in higher-than-normal amounts in people with neuroblastoma.
- A blood test, including a complete blood count (CBC), which is a test on the blood to look for anemia or other abnormalities.
- A blood chemistry test may be performed to detect elevated amounts of the sympathetic hormones dopamine and norepinephrine.
- A chest X-ray or abdominal X-ray may be helpful if positive.
- An abdominal ultrasound may be diagnostic if the tumor is located in the abdomen.
- A computed tomography (CT) scan, an imaging procedure in which a dye may be injected into a vein and is then taken up by organs and tissues, allowing any abnormalities to be seen more clearly on an X-ray.
- Magnetic resonance imaging (MRI), which uses a large magnet, radio waves, and a computer to produce images of various tissues of the body. If a contrast agent is used, it is injected into a vein; any lesions will "light up" after receiving the injection.
- A biopsy, a procedure in which cells or tissue are removed and then examined by a pathologist to detect cancer.
- A cytogenetic analysis, in which cells obtained from a tissue sample are examined for changes in the chromosomes and for the presence of n-myc.
- Bone marrow aspiration (removing a small amount of the liquid portion of bone marrow through a needle) and a bone marrow biopsy (removing a small sample of bone marrow tissue through a needle) allow a pathologist to examine the bone, bone marrow, and blood for cancer.
Some of these tests may also be performed after the diagnosis is made to determine the extent of cancer and whether it has spread (metastasized). Once these tests have been performed, the cancer is given a stage, 1 through 4, depending on how extensive it is:
- Stage 1 is the least invasive stage and carries the lowest risk. The tumor in stage 1 is confined to one area.
- Stage 2 is divided into stage 2A and stage 2B. In stage 2A, the primary tumor is confined to one area but cannot be removed completely by surgery. In stage 2B, the primary tumor is confined to one area and may or may not be removed completely by surgery, but cancer cells are found in nearby lymph nodes.
- Stage 3, a stage in which the cancer has spread more extensively than in stage 2, often to areas on the opposite side of the body.
- Stage 4 is the most invasive (highest risk) stage and means that the cancer has spread to distant lymph nodes or other parts of the body. A substage of stage 4 is stage 4S, which consists of a neuroblastoma in a child younger than 1 year in whom the cancer has spread to other parts of the body, the primary tumor is confined to one area and may or may not be removed completely by surgery, and cancer cells may be found in nearby lymph nodes.
Any stage tumor with a genetic characteristic called the n-myc amplification is considered to be high risk (n-myc is a gene that turns on cell growth).
How is neuroblastoma treated?
Neuroblastomas, usually those that are staged as "4S," may go away spontaneously or regress to the point that they can be removed entirely by surgery. Other neuroblastomas spread rapidly.
Treatment depends on the cancer's stage, the primary tumor's location, the characteristics of the tumor, and the patient's age. Several modalities (ie, surgery, chemotherapy, radiation, immunotherapy) may be used in a patient to treat the cancer, especially with high-risk tumors, which are the most difficult to treat. Cure is much more likely with the lowest-stage neuroblastomas. Unfortunately, about half of neuroblastomas aren't discovered until they've already spread to the bone and bone marrow, meaning that treatment becomes more complicated.
Treatment may include:
- Surgery. In most cases, surgery is needed to remove the primary tumor, often after several cycles of chemotherapy to shrink the tumor. Stage-1 tumors are most able to be removed entirely by surgery.
- Chemotherapy. Chemotherapy refers to the use of any of a group of drugs whose main effect is either to kill or slow the reproduction of rapidly multiplying cells. Cancer cells absorb chemotherapy drugs faster than normal cells do (but all cells are exposed to the chemotherapy drug). For the treatment of neuroblastoma, chemotherapy drugs are given intravenously (injected through a vein). Five or more cycles of chemotherapy are usually needed to shrink the tumor sufficiently so that surgery can be performed.
- Radiation. Radiation therapy is a form of cancer treatment that uses high levels of radiation to kill cancer cells or to keep them from growing and dividing. Radiation may be used following surgery to reduce the risk of the cancer relapsing (recurring), and it may be used together with chemotherapy at sites where the cancer has spread. Targeted forms of radiotherapy may be used to minimize the risk of radiation damage to tissues or organs that surround the tumor.
- Immunotherapy. Usually used after surgery, immunotherapy aims to train the body's immune system to attack neuroblastoma cells that remain after chemotherapy or radiation. The treatment uses a monoclonal antibody that is injected into the bloodstream, which searches for neuroblastoma cells and once identified signals the body's immune system to attack them.
- Stem cell transplant. Stem cell transplant allows high doses of chemotherapy and radiation to be used to treat neuroblastoma. Stem cells are removed and stored prior to the treatments and then reinfused to replace bone marrow cells destroyed by chemotherapy and radiation.
- Specialized treatments. Isotretinoin is a drug used in patients treated with immunotherapy who are in remission. It stops immature neuroblastoma cells from growing and dividing, thus reducing the risk of a relapse. An anti-angiogenesis drug, which restricts the growth of blood vessels that feed the tumor, may be tried in patients who don't respond to standard treatments.
What if the cancer relapses?
Relapse is usually caused by neuroblastoma cells that survive treatment and are too small or spread too diffusely throughout the body to be detected. Relapses in the central nervous system (such as the brain) are more difficult to cure and may be treated with monoclonal antibodies to deliver liquid radiation directly to the neuroblastoma cells at the site of relapse. Remission may be extended by using monoclonal antibodies with other forms of treatment.
Treatment for relapses outside the central nervous system depends on previous treatments but usually requires multiple modalities.
- National Cancer Institute. General Information About Neuroblastoma Accessed 12/13/2013.
- American Cancer Society. What is neuroblastoma? Accessed 12/13/2013.
- American Society of Clinical Oncology. Neuroblastoma-Childhood Accessed 12/13/2013.
- Graham DK, Quinones RR, Keating AK, Maloney K, Foreman NK, Giller RH, Greffe BS. Chapter 31. Neoplastic Disease. In: Hay, Jr. WW, Levin MJ, Deterding RR, Ross JJ, Sondheimer JM, eds. CURRENT Diagnosis & Treatment: Pediatrics. 21st ed. New York: McGraw-Hill; 2012. library.ccf.org Accessed 12/13/2013.
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