Neuroblastoma is a rare cancerous tumor that grows from immature nerve cells usually in the abdominal area. It is most common in infants and children, but can also occur in adults. This cancer usually grows in cells of the nervous system but also may grow in the cells of the adrenal glands, which produce and release adrenaline and cortisone. Neuroblastoma may be present at birth but also may be detected later, usually before the age of 5 and very rarely after age 10.

Immature nerve cells called neuroblasts vary in their development. Neuroblasts that do not develop into functioning nerve cells may die with no trace, develop into a benign tumor or become a malignant tumor. The cause for most neuroblastomas is unknown, although a tiny percentage run in families.

Most neuroblastomas do not produce symptoms early in their development. Consequently, they are not diagnosed until they have spread (metastasized) and begin to produce symptoms. Signs and symptoms of neuroblastoma can be related to the site of the metastasis, such as an abdominal mass, bone pain or difficulty moving or paralysis. Neuroblastomas in the adrenal glands can cause the release of hormones from the cancer cells and produce high blood pressure and a rapid heart beat.

A neuroblastoma mass is often discovered during a routine physical examination or in an x-ray taken to diagnose an unrelated condition. Cells from the tumor are analyzed by a pathologist and the cancer is staged, which will determine the severity and spread of the cancer. The information is combined with the age of the child, DNA factors, cell type, rate of growth and spread to determine the patient’s treatment and prognosis.

There is no known prevention method for neuroblastoma, and usually detection before symptoms appear is not possible.

Neuroblastoma is a rare cancer that grows from immature nerve cells. It is usually found in infants and children before the age of 10, but may also occur in adults. Cancer in children is much rarer than cancer in adults. According to the American Cancer Society (ACS), children’s cancers account for 1 percent of all cancers. While rare in general, neuroblastoma is the most common type of cancer in infants by far, and the third most common cancer in children, after leukemia and brain tumors. About 650 new cases occur each year, according to the ACS.

Neuroblastomas develop from immature nerve cells called neuroblasts. Neuroblasts are cells remaining from embryonic and fetal nerve tissue that normally mature into cells of the adrenal glands, the brain and the spinal cord. The cells that do not mature can grow into:

• Mature nerve cells at a later time or disappear, thereby resolving naturally.
  
  
• Ganglioneuroma. A benign tumor that develops when neuroblasts mature into masses called ganglion cells and then stop multiplying.
  
  
• Ganglioneuroblastoma. A tumor containing malignant and benign cells. This form of tumor contains cells that are similar to ganglioneuroma cells. It also contains malignant neuroblasts.
  
  
• Neuroblastomas. A tumor composed entirely of malignant cells.

Neuroblastomas most often affect the sympathetic nervous system, which controls vital life functions such as heart rate, blood pressure, digestion and production of some hormones. They may also affect the tissues of the adrenal glands, which produce and release adrenaline and cortisone. 

Because of their origin in the sympathetic nervous system or adrenal glands, neuroblastomas can affect vital involuntary body functions such as heart rate, blood pressure, digestion, blood sugar, stress response and specific emergency hormone production. The cells grow rapidly and expand into a mass that compresses the organs around it, affecting their functioning.

According to the ACS, the tumors originate in adrenal gland tissue in approximately one-third of neuroblastoma cases. The adrenal glands produce and release adrenaline and cortisone.  Catecholamines are hormones secreted by the adrenal glands and are found in high amounts in children with neuroblastoma. This can lead to problems such as high blood pressure. Neuroblastomas may also be located elsewhere, such as the neck, chest, brain or spinal cord, and can spread to the liver, the lymph nodes, lungs, bones and bone marrow. At the time of diagnosis, 7 out of 10 cases have metastasized.

More than 90 percent of patients diagnosed with neuroblastoma that is localized or concentrated in one area can be cured, according to the National Cancer Institute (NCI). However, even in the advanced stages, children can respond favorably to treatment. When neuroblastoma has metastasized the prognosis is significantly less favorable. Factors included in prognosis (recovery outcome) are:

• Patient’s age at diagnosis. The younger the patient, the better the outcome. About 40 percent of patients are diagnosed before their first birthday.
  
  
• Stage of the disease.  Higher stage cancer indicates the disease has spread to other areas of the body, which relates to a poorer prognosis.
  
  
• Regional lymph node metastasis after one year of age.

According to the ACS, children are diagnosed with the condition before the age of five in 90 percent of cases, and rarely after 10 years (about 2 percent).

The causes of most neuroblastomas are unknown. In the fetus, cells called neuroblasts normally develop into nerve cells and tissues. However, if these cells do not become mature and instead continue to grow rapidly as immature cells, they can potentially become cancerous.

The failure of cells to mature and stop growing is caused by DNA mutations (changes). In most cases of neuroblastoma, these mutations occur due to some factor or combination of factors that have not yet been identified. However, there is a familial or inherited form of neuroblastoma that may affect more than one child in a family. 

Usually, neuroblastomas start in a single site. In inherited neuroblastomas, the original tumors are located in several different places in addition to the areas to which they have spread. Inherited neuroblastomas spread more aggressively and affect 1 to 2 percent of all patients, according to the American Cancer Society (ACS).

Research continues to focus on the factors that may influence risks of non-inherited neuroblastoma. Geographic or environmental factors such as pollution or toxins in the environment have not been linked to neuroblastoma, although one study linked codeine use in pregnant or nursing mothers to increased risk. Gestational diabetes has also been linked to neuroblastoma.

Neuroblastomas release hormones that cause changes in a child’s body called paraneoplastic syndrome (symptoms that develop when cancer cells release certain chemicals). In some children, such symptoms are the first indicators of the condition. Paraneoplastic symptoms include rapid, dancing eye movements; rhythmic jerking, protruding abdomen and diarrhea. At times, tumors are identified by x-rays that are taken for an unrelated condition.  

Neuroblastoma symptoms may also vary with the location of the tumors. If the tumor is compressing a certain part of the brain or spinal cord, it may affect the functions controlled by that part of the nervous system. Also, hormones released from the cancer cells can affect specific functions (e.g., tumors in the adrenal glands can affect blood pressure). The most common symptoms of neuroblastoma include:

• Pressure from the growing tumor
  
  
• Abdominal mass that may or may not cause pain (possibly due to spread to the liver)
  
  
• Constipation or compression of the bowel
  
  
• Weight loss or failure to thrive
  
  
• Difficulty swallowing or walking
  
  
• Bone pain from cancer that has spread
  
  
• Protruding eyes or dark circles if the cancer is behind the eye
  
  
• Compression of the spinal cord causing pain or paralysis
  
  
• Pale skin or skin lesions (when the disease has spread)
  
  
• Chronic fatigue and tiredness
  
  
• Irritability and poor temper control
  
  
• Difficulty breathing

Infrequent symptoms include:

• Fever
• Anemia (low number of red blood cells)
• High blood pressure or rapid pulse (from adrenal gland activity)
• Profuse sweating and flushing skin

Rare symptoms include:

• Severe diarrhea
• Opsoclonus (rotary eye movements)
• Myoclonus (jerky muscle movements)

In rare cases, neuroblastoma can be detected prior to birth, however it is usually found later. About 40 percent of the cases are diagnosed in the first year. If the patient is older than a year and the cells are growing rapidly, they are usually malignant and have spread to other areas such as the lymph nodes, liver, lungs and bones. The older the patient is, the more aggressive the cancer and the poorer the outcome. For this reason, early detection is important.

Diagnosing neuroblastoma usually begins by obtaining a medical history, including family history of disease. The physician will perform a physical examination of the patient’s body with focus on signs of disease, including tumor masses and lumps. Tests that may be performed when neuroblastoma is suspected include:

• Blood tests. Laboratory tests performed on a sample of blood to detect chemical or hormonal imbalances and genetic predispositions for cancer. They may include:
  
• • Catecholamine test. A blood test that measures levels of these hormones secreted by the adrenal glands. High levels of catecholamines may indicate neuroblastoma.
    
    
  • Complete blood count (CBC). A blood test that provides information about all blood cells (red, white and platelets). Low levels of red blood cells (anemia) may be present in neuroblastoma.
    
    
  • Genetic testing. DNA can be checked for the presence of oncogenes and deletions of tumor suppressor genes. Genetic alterations such as these can indicate a genetic predisposition for cancer as well as potential prognosis for survival. Also, there are tests for inherited attributes related to neuroblastoma. Recent research has identified a gene called caspase 8 that may suppress the spread of neuroblastoma. This gene is missing in 70 percent of aggressive neuroblastomas.

Diagnostic imaging tests may be performed to locate primary tumors or possible metastasis. Location makes finding some primary tumors difficult. Imaging tests may be difficult to perform on infants because they must remain motionless for extended periods of time. Some imaging tests that may be used include:

• X-rays. A chest x-ray is taken to show if there are masses in the organs and bones in the chest cavity. If an x-ray locates a tumor, a CAT scan or MRI will be performed.
  
  
• CAT scan (computed axial tomography). A computerized x-ray that takes three-dimensional images of the body to locate tumors. The CAT scan is much more accurate than standard x-rays. The chest, abdomen and pelvis are scanned. Tumors in the brain, spinal column and other areas appear in the images.
  

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  MRI (magnetic resonance imaging). Magnetic and radio waves are used to create detailed images of internal organs to locate tumors.
  
  
• PET scan (positron emission tomography).  A radioactive tracer substance is injected into a patient’s bloodstream. Cancer cells attract the substance and create “hot spots” that appear on the image. PET scan is commonly used to detect cancer that has spread in the body.
  
  
• Bone scan. Radioactive material injected into the bloodstream collects in the bones and images are taken by scanner.  A bone scan can detect cancer cells in the bones, which is a common location for neuroblastoma to spread.
  

If tumors are located, the physician may order the following:

• Biopsy. Samples of tissues from the suspected tumor are obtained for analysis by a pathologist who determines the presence of cancer.
  
  
• Bone marrow biopsy. Samples of bone marrow (spongy tissue inside large bones where blood cells are produced) tissue can be taken to view cells under a microscope.

Treatment is determined according to the stage of the tumor, its location and the patient’s general health. Standard treatment and clinical trial options are available and should be discussed with the cancer care team.

Of the children diagnosed with neuroblastoma, about 70 percent have metastasis (spreading) of the disease. The extent of the spread of the cancer is determined by staging of the cancer, which is critical to planning treatment.

Treatment methods for neuroblastoma may include:

• Surgery. Removal of a part or complete area of cancerous cell growth. Optimally, all of the tumor should be removed but this may not be possible if there is metastasis. Risks include bleeding, blood vessel damage and damage to organs or nerves. This is the primary treatment for low-risk tumors.
  
  
• Chemotherapy. The use of powerful drugs for killing cancer cells. It is typically administered before surgery to shrink the tumor, when the whole tumor cannot be excised or when there is metastasis. Childhood cancers tend to respond well to chemotherapy.
  
  
• Radiation. Use of high-energy x-rays to destroy cancer cells. Internal radiation involves placing the substance directly in the area of the cancer. External radiation involves the use of a machine outside the body to direct the precise beams of radiation to the cancer site. This type of therapy is usually reserved for tumors that cannot be removed surgically and do not respond to chemotherapy.
  
  
• Retinoid therapy. Medications related to vitamin A. These substances are known to mature the cells into normal cells. Use of 13-cis-retinoic acid for six months is generally considered for neuroblastoma.
  
  
• Bone marrow transplant. A surgical procedure used to replace cancerous bone marrow with healthy bone marrow. The bone marrow may come from the patient for a matched donor, although neuroblastoma is confined to transplant from the patient.  For children with high-risk neuroblastoma and a poor prognosis, bone marrow transplant and/or retinoid medication have successfully induced remission.

One or more of these treatments may be used for neuroblastoma, depending on the stage and assessed risk for the child. Both chemotherapy and radiation have been shown to have a risk of long-term side effects for childhood cancer patients and may increase the risk of developing another cancer later in life. Research is continuing into the potential use of biological therapy drugs such as monoclonal antibodies or vaccines for neuroblastoma. These agents have shown promise for treating recurrent neuroblastoma.

Several factors are considered when determining treatment of the recurrence, including initial treatment and new growth factors. Surgery, chemotherapy, high-dose chemotherapy and/or  biological agents may be used as treatment.

There is no known way to prevent neuroblastoma. Because genetic factors can be associated with the disease, people with a family history of cancers, especially childhood cancers, should discuss genetic testing with their children’s physician.

Researchers have conducted tests to determine if large amounts of catecholamines in the urine of infants could help in early detection of neuroblastoma. However, the test results revealed too large a number of positive growths. The large number may be due to neuroblast cells that release high levels of catecholamines, which regress and die independently. For this reason, urine tests have not been useful for early detection, prevention or treatment of neuroblastoma.

Preparing questions in advance can help patients have more meaningful discussions with their physicians regarding their conditions. Patients may wish to ask their doctor the following questions about neuroblastoma:

1. How can I tell if my child has neuroblastoma?
   
   
2. Is there anything in my family history that indicates a greater risk for neuroblastoma in my children?
   
   
3. What tests will be used to diagnose the condition in my child?
   
   
4. What stage is the neuroblastoma?
   
   
5. What are the treatment options for my child’s cancer?
   
   
6. What are the chances of a recurrence?
   
   
7. What is the prognosis for this cancer?
   
   
8. If one child has neuroblastoma, are my other children at risk?
   
   
9. Is there any genetic testing that I should receive before my next pregnancy?
   
   
10. What are the potential long-term side effects of chemotherapy or radiation?
    
    
11. Is my child at risk for other cancers?