Neuroblastoma: What is It, Stages, Causes, Symptoms and Treatment

Neuroblastoma is a type of pediatric cancer that develops in the nervous system of babies and young children. Neuroblastoma grows in immature nerve tissue (neuroblasts).

It usually affects neuroblasts in the adrenal glands (small organs that sit on top of the kidneys). The adrenal glands make hormones that control automatic body functions, such as digestion, blood pressure, breathing and heart rate. Neuroblastoma can also develop in nerve tissue in the spinal cord, abdomen, chest or neck. It can spread to other parts of the body.

The outlook for kids with neuroblastoma depends on the tumor’s location, the child’s age and the cancer stage. The stage describes how advanced the disease is.

Neuroblastoma

How common is neuroblastoma?

Neuroblastoma is rare, but it’s the most common cancer in babies. Every year in the United States, about 800 children are diagnosed with neuroblastoma.

Neuroblastoma almost always develops before age 5. It can occur in babies before they are born. Neuroblastoma is very rare in children over age 10.

What are the stages of neuroblastoma?

Healthcare providers classify neuroblastoma in children based on how advanced the cancer is and how fast it’s growing. They also consider whether it has spread (metastasized) to other parts of the body.

Using this information, providers determine the cancer’s risk level. Then they choose the most appropriate treatments. The stage of neuroblastoma used to be determined by how much neuroblastoma was found in the body after surgery. Now, the International Neuroblastoma Risk Group Staging System (INRGSS) is used. The stage of neuroblastoma is determined by how much tumor spread is seen on initial imaging studies (such as CT scan or MRI, as discussed below), called “image-defined risk factors.” The INRG stages of neuroblastoma are:

• Stage L1: This is the stage with the lowest risk. L1 tumors are confined to one body compartment and have not spread. Also, the tumor does not involve vital structures of the body (no image-defined risk factors are present).
• Stage L2: In this stage, the tumor is confined to one body compartment, but cancer cells can spread to regional lymph nodes, for instance. Also, there ++is++ involvement of vital structures of the body, such as tumor wrapping around large blood vessels (i.e., at least one image-defined risk factor is present).
• Stage M: In this stage, the cancer cells have spread to more than one body compartment – called “distant metastatic disease.” This stage carries the highest risk.
• Stage MS: This is a “special” category of neuroblastoma, affecting children younger than 18 months of age. In this stage, the cancer cells have spread (or metastasized) to either the skin, liver or bone marrow only. Children with stage MS neuroblastoma generally have an excellent prognosis. Stage MS neuroblastoma is usually considered low-risk disease.

What causes neuroblastoma?

Neuroblastoma happens when immature nerve tissues (neuroblasts) grow out of control. The cells become abnormal and continue growing and dividing, forming a tumor. A genetic mutation (a change in the neuroblast’s genes) causes the cells to grow and divide uncontrollably. Healthcare providers aren’t sure what causes the genetic mutation.

Children with a family history of neuroblastoma are more likely to develop this type of cancer. But about 98% to 99% of the time, neuroblastoma is not inherited (or, passed down in families). Children born with other congenital anomalies (birth defects) may have a higher risk of developing neuroblastoma.

What are the symptoms of neuroblastoma?

Neuroblastoma symptoms range from mild to severe. They vary depending on the tumor’s location and the stage of the disease. Most often, cancer has spread to other parts of the body by the time signs appear. Symptoms include:

• Bump or lump in the neck, chest, pelvis or abdomen (belly), or several lumps just under the skin that may appear blue or purple (in infants).
• Bulging eyes or dark circles under eyes (it may look like the child has a black eye).
• Diarrhea, constipation, upset stomach or loss of appetite.
• Fatigue, cough and fever.
• Pale skin, which is a sign of anemia (low red blood cells).
• Painful, bloated belly.
• Trouble breathing (usually in young babies).

• Weakness, movement problems or paralysis in the legs and feet.

  Other symptoms of neuroblastoma may appear later as the disease progresses. They include:

• High blood pressure and a fast heartbeat.

• Horner’s syndrome, which causes droopy eyelid, small pupil and sweating on only one side of the face.
• Pain in the bones, back or legs.
• Problems with balance, coordination and movement.
• Shortness of breath.
• Uncontrollable eye movements or eyes that dart around quickly.

How is neuroblastoma diagnosed?

Most children with neuroblastoma receive a diagnosis before age 5. In fact, neuroblastoma is the most common cancer in infants. Sometimes, providers diagnose neuroblastoma in unborn babies during a prenatal ultrasound.

To diagnose neuroblastoma, your child’s provider will do a physical and neurological examination. A neurological exam checks your child’s nerve function, reflexes and coordination. Your child’s provider may order several tests to confirm a diagnosis and see if the cancer has spread. These tests include:

• Blood and urine tests: To check for anemia and abnormalities in the blood, your child’s provider will order a complete blood count (CBC). Blood chemistry tests measure hormone levels and detect substances in the blood that may be a sign of cancer. A urine test measures the levels of chemicals in your child’s body.
• Biopsy: During a biopsy, your child’s provider removes a tissue sample and sends it to a laboratory. The laboratory will look at the tumor tissue under a microscope, and perform various tests on the biopsy sample to confirm the diagnosis of neuroblastoma. Specialized tests of the biopsy sample will check for specific chromosomal alterations of the tumor cells themselves – this can help determine your child’s risk category and treatment plan.
• Bone marrow biopsy: A bone marrow biopsy tests bone, bone marrow and blood for signs of cancer. Bone marrow is the sponge-like tissue at the center of large bones. Blood cells form in bone marrow.
• CT scan: During a CT scan, your provider injects a special dye into your child’s vein and then performs a series of X-rays. The dye makes it easier for the provider to see tissues and tumors.
• MRI scan: An MRI scan uses a magnet and radio waves to produce images of soft tissues.
• Methyliodobenzylguanine (MIBG) scan: This imaging test uses a safe radioactive chemical called 123-iodinated MIBG radiotracer. Your child’s provider injects radiotracer into a vein, and the next day, uses a special type of scanner to take pictures of your child’s organs. The 123-iodinated MIBG compound is very specific for neuroblastoma cells, so the radiotracer will go to any areas of the body where neuroblastoma is located. This specialized nuclear medicine scan helps your doctor determine whether or not the neuroblastoma has spread to other areas of the body. However, about 10% of patients will have neuroblastoma tumors that do ++not++ take up the MIBG compound. In this situation, another type of nuclear medicine scan called a PET scan can be done to find all areas of active neuroblastoma cells in the body.
• Ultrasound: An ultrasound test uses high-frequency sound waves to create images of soft tissues.
• X-ray: A chest X-ray or abdominal X-ray can help your child’s provider see the location of the tumor and how it’s affecting other tissues in the body. An X-ray is an easy screening test to determine a less detailed picture of how the cancer is affecting the body.

How is neuroblastoma treated?

Treatment for neuroblastoma depends on your child’s age and the disease stage, risk category and tumor location. Your child’s team of providers will work with you to determine the most appropriate treatment plan based on the risk category.

The risk categories for neuroblastoma are:

Low-risk neuroblastoma
Children in the low-risk category may not need treatment right away. For children younger than 6 months old, some tumors go away without treatment. Other children with low-risk neuroblastoma may need surgery to remove the tumor, chemotherapy or a combination of both. Your child’s provider will monitor your child’s health carefully.

Intermediate-risk neuroblastoma

Children with intermediate-risk neuroblastoma usually have surgery to remove the tumor. Surgeons also remove any cancer cells that have spread to the lymph nodes. After surgery, children receive chemotherapy treatments. Sometimes chemotherapy is started prior to surgery, to shrink the tumor and make surgery more successful. The number of cycles of chemotherapy depends on certain risk factors, and on how the tumor responds to treatment.

High-risk neuroblastoma

Healthcare providers often treat high-risk neuroblastoma with a combination of chemotherapy, surgery, high-dose chemotherapy with stem cell rescue (also known as autologous stem cell transplantation), radiation and immunotherapy. Children with high-risk neuroblastoma may need to take medications (such as 13-cis-retinoic acid) for several months after treatment.

Children with extra copies of a gene called MYCN will receive treatment for high-risk neuroblastoma no matter what stage of the disease they have. Providers use the most aggressive treatment when a child has more of this gene. The MYCN gene drives abnormal cell growth. It can cause tumors to grow faster and spread throughout the body.

What are the treatments for neuroblastoma?

Depending on several factors, your child’s team of providers may recommend surgery, chemotherapy, radiation or other cancer treatments. Neuroblastoma treatments include:

• Chemotherapy: Chemo stops cancer cells from multiplying. Healthcare providers inject chemotherapy drugs through a vein. It usually requires treatments over several weeks or months. The type of chemotherapy regimen and length of treatment depends on which risk category of neuroblastoma your child has.
• Surgery: Surgeons remove the tumor through an incision, but it may not be possible to remove the entire tumor. Some children receive chemotherapy before or after surgery to shrink a tumor or destroy remaining cancer cells.
• Radiation: This treatment kills cancer cells or stops them from multiplying. Radiation therapy uses high levels of radiation to target cancer cells. Radiation oncologists often use radiation to prevent cancer from coming back after treatment. Radiation is most often used in high-risk neuroblastoma patients. Low and intermediate-risk patients usually do not require radiation therapy.
• Immunotherapy: Sometimes, cancer cells remain after chemotherapy and radiation. Providers may use immunotherapy to train the body to attack abnormal cells. Your child’s provider injects antibodies (cells that fight infection) through a vein. The currently used immunotherapy medications target a protein called GD2, which sits on the outside of the neuroblastoma cell. The antibodies find GD2 proteins on neuroblastoma cells and attach to them, which signals the body’s immune system to destroy them.
• Iodine 131-MIBG therapy: This treatment uses radiation to target tumor cells. Your child’s provider injects radioactive iodine into the bloodstream through a vein. The radioactive iodine kills tumor cells with radiation. This treatment has been used in children whose neuroblastoma has come back or when it won’t go away (relapsed or refractory disease), and is being studied when given as part of frontline therapy in high-risk neuroblastoma.
• Medications: Your child’s provider may recommend drugs to destroy cancer cells, stop them from multiplying or restrict blood flow to the tumor. Some of these drugs work after treatment to keep the cancer from coming back (such as retinoid therapy with a drug called 13-cis-retinoic acid). Other drugs target tumors that haven’t gone away after standard treatments. There are also newer drugs being studied in clinical trials which are promising, such as DFMO (or, difluoromethylornithine). This drug has been the first drug tried as a “maintenance therapy” regimen in high-risk or relapsed neuroblastoma, and has shown promising results so far – but is still being studied in clinical trials.
• Stem cell transplant: In a stem cell transplant, providers remove a child’s stem cells from the bloodstream (which come from the bone marrow) and store them in a freezer during the initial cycles of chemotherapy. Then, after giving high-dose chemotherapy, they inject the stem cells back into the child’s bloodstream, which will then travel to the bone marrow to replace the stem cells destroyed during treatment. Your child’s body uses the new cells to rebuild the immune system.

Can I prevent neuroblastoma?

It isn’t possible to prevent neuroblastoma. If you or your partner had neuroblastoma as a child or have a family history of the disease, talk to your provider. All children diagnosed with neuroblastoma should receive genetic counseling to see if genetic testing is needed. Genetic testing can tell you if your child has the gene markers for familial (inherited) neuroblastoma. However, it is important to remember that the inherited form of neuroblastoma is very rare – only 1% to 2% of cases. Additionally, some gene mutations that increase the risk of getting neuroblastoma are passed down through families – for instance, patients with Li Fraumeni syndrome (or a mutation in the p53 gene, which forms a tumor suppressor protein) are at increased risk for many types of cancers, including neuroblastoma.

What is the outlook for people with neuroblastoma?

The outlook for children with neuroblastoma varies. Cancer specialists measure cancer outlook by the five-year survival rate. Younger children with low- or intermediate-risk neuroblastoma have a good prognosis and a 90% to 95% survival rate. Older kids and those with high-risk neuroblastoma live cancer-free around 60% of the time. Healthcare providers and researchers continue to search for better treatments for this group of patients, and there are promising treatments on the horizon.

The prognosis depends on several factors, including:

• How old the child was at the time of diagnosis.
• The biological makeup of the tumor.
• If the tumor has spread to lymph nodes or other parts of the body.

When should I see my healthcare provider about neuroblastoma?

If your child has any signs or symptoms of neuroblastoma, see your provider right away. Early diagnosis and treatment can affect your child’s prognosis.