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 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 not 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 does 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 antiangiogenesis 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.
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This information is provided by the Cleveland Clinic and is not intended to replace the medical advice of your doctor or health care provider. Please consult your health care provider for advice about a specific medical condition. This document was last reviewed on: 5/7/2009…#14390
