Neuroblastoma

What is neuroblastoma in children?

Neuroblastoma is cancer that starts when immature nerve cells in the nervous system grow out of control. These cells are called neuroblasts. Over time, the out-of-control cells form a tumor. Neuroblastoma is the most common solid tumor cancer in babies under age 1. Most neuroblastomas are found in children younger than 5 years. It’s rare in children older than age 10. 

Neuroblastoma affects:

• Nerve fibers along the spinal cord

• Clusters of nerve cells (called ganglia) along the nerve fibers

• Nerve-like cells in the adrenal glands

In most cases, neuroblastoma starts in the adrenal glands. These glands are on the top of both kidneys. They make hormones that help control things like heart rate, blood pressure, and the body's stress response.

Neuroblastomas can also form on the nerve fibers in the abdomen and near the spine in the chest, neck, or lower belly (pelvis). 

In most cases, the cancer cells have spread to the bones, lymph nodes, or both by the time neuroblastoma is diagnosed.

What causes neuroblastoma in a child?

Cancer is caused by changes (mutations) in the DNA of the cells. In most children, this happens by chance. A very small number of children inherit the changed genes from their parents.

What are the symptoms of neuroblastoma in a child?

Symptoms of neuroblastoma depend on the size of the tumor, where it is, if the cancer has spread, and if the neuroblastoma cells make hormones. They tend to be different in each child.       

Symptoms of a tumor in the belly (abdomen) can include:

• A lump you can see or feel

• Swelling in the abdomen

• Loss of appetite

• Weight loss

• Swelling of the legs

• Swelling of the scrotum

• Feeling full

• Pain

• Constipation

• Trouble passing urine

Symptoms of a tumor in the chest can include:

• A lump you can see or feel

• Swelling in the face, neck, arms, or chest (change in skin color to bluish-red)

• Headache

• Dizziness

• A change in mental state

• Coughing or trouble breathing

• Trouble swallowing

• Drooping eyelids and other eye changes

• Changes in feeling or movement of the arms or legs

Symptoms of a neuroblastoma that has spread to other parts of the body can include:

• Enlarged lymph nodes

• Bone pain or limping 

• Weakness, numbness, or inability to move arms or legs

• Bruising around the eyes

• Bulging eyes

• Enlarged liver

• Bluish bumps on the skin

• Lumps on the head

• Feeling tired or weak

• Frequent infections

• Easy bruising or bleeding

A neuroblastoma may release hormones. This is called paraneoplastic syndrome. It can cause symptoms, such as:

• Constant watery diarrhea

• Fever

• High blood pressure

• Fast heart rate

• Flushing or redness of skin

• Sweating

A neuroblastoma can also cause opsoclonus-myoclonus-ataxia syndrome. This can lead to symptoms, such as:

• Quick eye movements

• Muscle twitching or spasms

• Trouble with coordination

• Trouble speaking

Many of these symptoms can be caused by other health problems. Still, it's important to take your child to a healthcare provider if you notice these symptoms. Only a healthcare provider can tell if your child has cancer.

How is neuroblastoma diagnosed in a child?

You may take your child to a healthcare provider because of a lump, swelling, or other change you've noticed. Your child's healthcare provider will ask about your child's medical history and symptoms. A physical exam will be done. Your child may be referred to a specialist in diagnosing and treating cancer in children (called pediatric oncologist).

If a neuroblastoma is suspected, tests will be needed to learn more:

• Blood and urine tests.  Blood tests check for certain substances that could be signs of disease and to check your child's overall health and organ function. Your child may also have urine and blood tests to check for hormones released by the tumor. These hormones are called catecholamines (such as epinephrine and norepinephrine). Catecholamine metabolites (substances made when catecholamines break down) are usually found in the urine of children with neuroblastoma.

• Ultrasound exam (US).  Sound waves and a computer are used to create images of the inside of the body. An ultrasound may be done to check your child's belly (abdomen) or kidneys.

• X-ray.  X-rays may be done to check your child's chest or bones.

• CT scan. X-rays taken from different angles and a computer are used to make 3-D images of the inside of your child's body. Scans of the belly (abdomen), lower belly (pelvis), or chest may be done. A contrast medium may be given before the scan to get clearer pictures.

• MRI scan. An MRI uses large, powerful magnets, radio waves, and a computer to make detailed pictures of the inside of the body. This test is used to check for tumors in the brain and spinal cord. A contrast medium may be given before the scan to get clearer pictures.

• PET (positron emission tomography) scan.  For this test, a radioactive sugar is put right into the bloodstream. Cancer cells use the sugar faster than normal cells, so the sugar collects in cancer cells. A special camera is then used to see where the radioactive sugar is in the body. A PET scan can sometimes spot cancer cells in different parts of the body, even when they can’t be seen with other tests. This test is often used in combination with a CT scan. This is called a PET/CT scan.

• MIBG (meta-iodobenzylguanidine) scan.  Neuroblastoma cells absorb MIBG (a protein). A small amount of radioactive iodine is linked to MIBG and is injected into a vein. It travels through the blood and attaches to cancer cells. Scans may be taken over a few days to see where it collects. Regular iodine is taken by mouth for several days before the scan. This is done to protect your child's thyroid gland from absorbing the radioactive iodine in MIBG.

• Bone marrow aspiration or biopsy.  Bone marrow is found in the center of some bones. It’s where blood cells are made. A small amount of bone marrow fluid may be taken out with a needle. This is called aspiration. Or solid bone marrow tissue may be taken with a bigger needle. This is called a core biopsy. Bone marrow is usually taken from the back of the pelvic bone. This test may be done to see if cancer cells have reached the bone marrow.

• Tumor biopsy. This is when a small piece (called a sample) of the tumor is taken out for testing. It may be taken out with a needle or by making a surgical cut (incision). The removed sample is tested for cancer cells. A biopsy is needed to diagnose neuroblastoma. An imaging test, like an ultrasound or CT scan may be used to guide the needle during a biopsy.

Staging neuroblastoma

Once neuroblastoma has been diagnosed, a stage is assigned. The stage is how much cancer there is and if and where it has spread. Staging is used to guide treatment options. Your child's healthcare provider will use one of these two staging systems:

• International Neuroblastoma Staging System (INSS)

• International Neuroblastoma Risk Group Staging System (INRGSS)

The INSS system divides tumors into stages 1 through 4. It’s assigned after surgery has been done to remove the tumor.

• Stage 1 is early cancer. It's only in the place where it first started and only on one side of the body. This means the tumor can be fully seen and completely removed by surgery. Lymph nodes near the tumor do not have cancer. Lymph nodes attached to the tumor after surgery may or may not have cancer.

• Stage 2:

  • Stage 2A. The cancer has not spread to nearby lymph nodes. It's only located in the area where it started on one side of the body. All of the tumor that can be seen can't be completely removed during surgery.

  • Stage 2B. The cancer has spread to nearby lymph nodes. It's only located in the area where it started on one side of the body and may or may not be completely removed during surgery.

• Stage 3: The cancer has not spread to distant parts of the body. One of the following is true:

  • The cancer can't be fully removed with surgery. It has spread to the other side of the body and may have spread to nearby lymph nodes.

  • The cancer is on one side of the body and has spread to lymph nodes on the other side.

  • The cancer is in the middle of the body and has spread to tissues or lymph nodes on both sides of the body. The cancer can't be fully removed with surgery.

• Stage 4 means cancer cells from the tumor have spread to other parts of the body far from the primary (first) tumor. They may be in distant lymph nodes, the bone marrow, skin, liver, or bones.

• Stage 4S is only used in infants under age 1. The cancer may have spread to lymph nodes, the liver, skin, or bone marrow, but it's only on one side of the body. There's no cancer in the bones and no more than 10% of the bone marrow cells are cancer.

The INRGSS system divides tumors into 4 stages labeled L1, L2, M, and MS. Surgery does not need to be done before assigning one of these stages. They're based on how the tumor looks on imaging scans and biopsies. These stages are used to predict how much of the tumor can be taken out with surgery.

• The L groups means the cancer is only in one part of the body and has not spread far from where it first started. Stage L1 has no IDRFs (image-defined risk factors) found on imaging scans. Stage L2 does have IDRFs found on imaging scans (such as a CT scan).

• The M group means it has spread beyond where it first started to distant organs.

• MS is used in children younger than 18 months with cancer that has spread to the skin, liver, less than 10% of the bone marrow, or all three. There's no sign of cancer in the bones.

The healthcare team also looks at prognostic factors to get an idea of how your child’s neuroblastoma will likely respond to treatment. These factors include:

• Where the main tumor is

• Gene and chromosome changes in the tumor cells

• The amount of DNA in the tumor cells (called the DNA index)

• Tumor histology, which is how different the cancer cells look compared to normal cells and tissues

• The presence and amount of certain receptors on the cancer cells (called neurotrophin receptors)

• The age of your child

• Lab test results that measure the levels of certain substances in your child's blood (like ferritin, neuron-specific enolase, and lactate dehydrogenase)

Your child’s healthcare team will tell you more about the stage of your child’s cancer and what the prognostic factors mean. The stages of neuroblastoma are very complex. Be sure to ask the healthcare provider to explain the details of your child's cancer to you in a way you can understand. Also be sure to ask the healthcare provider if you have any questions.

How is neuroblastoma treated in a child?

Treatment will depend on the stage and other factors. Neuroblastomas can be treated with any of these:

• Surgery. Surgery is often done to remove as much of the tumor as possible (called resection). It may not be an option if the cancer has spread.

• Chemotherapy. These are strong drugs that kill cancer cells or stop them from growing. They may be given into the vein (IV), injected as a shot, or taken by mouth. Chemo might be used before or after surgery. Or it may be the main treatment if surgery can't be done.

• Radiation therapy.  High-energy X-rays or other types of energy are used to kill cancer cells or stop them from growing. Radiation beams are aimed at the tumor from a large machine. This is called external beam radiation.

• High-dose chemotherapy/radiation with a stem cell transplant.  Young blood cells (stem cells) are taken from the child or from a donor. This is followed by high doses of chemotherapy, radiation, or both. This damages the bone marrow. Your child will then get the stem cells to rebuild the bone marrow.

• Immunotherapy. This treatment helps the body's immune system attack cancer cells. A substance called GD2 may be present in large amounts on neuroblastoma cells. Anti-GD2 monoclonal antibodies might be used if there's a high risk of cancer returning.

• Retinoid therapy.  Retinoid medicine may be used for 6 months after stem cell transplant if there's a high risk of cancer returning. It can help reduce the chance of the cancer coming back.

• Supportive care.  Treatment can cause side effects. Medicines and other treatments can be used for pain, fever, infection, and nausea and vomiting.

• Clinical trials. Ask your child's healthcare provider if there are any treatments being tested that may work well for your child. Clinical trials allow your child to get the best treatment available now, and maybe new treatments that are expected to be better. Most children with cancer are treated as part of a clinical trial.

With any cancer, how well a child is expected to recover (prognosis) varies. Keep in mind:    

• Getting medical treatment right away is important for the best outcome. 

• Ongoing follow-up care during and after treatment is needed.

• New treatments are being tested to improve outcome and to reduce side effects.

What are possible complications of neuroblastoma in a child?

A child may have complications from the tumor or from treatment. These can include:

• Easy bruising, bleeding, or both

• Higher risk of infection

• Hair loss

• Mouth sores

• Nausea and vomiting

• Diarrhea

• Feeling tired (fatigue)

• Skin changes

• Problems with growth and development

• Heart and lung problems

• Infusion reactions

• Eye and vision problems

• Changes in sexual development (delayed puberty)

• Problems with the ability to have children (fertility) in the future

• Memory, learning problems, or both

• Return of the cancer

• Higher risk of other cancers later in life

Talk with your child's healthcare provider about side effects linked with their treatment. Tell them about any changes you notice. There are often ways to manage side effects. There may be things your child can do and medicines they can take to help prevent or control many treatment side effects.

Most side effects get better and go away over time after treatment ends. But some can last the rest of your child's life. Talk to your child's treatment team about what you can expect.

How can I help my child live with a neuroblastoma?

A child with a neuroblastoma needs ongoing care. Your child will be seen by oncologists and other healthcare providers to treat any late effects of treatment and to watch for signs or symptoms of the tumor returning. Imaging scans and other tests will be done.

Your child may need therapy to help with movement and muscle strength. This may be done by physical and occupational therapists.                                                     

You can help your child manage treatment in many ways. For instance:

• Your child may have trouble eating. A dietitian may be able to help.

• Your child may be very tired. They will need to balance rest and activity. Encourage your child to be active. This is good for overall health. And it may help to reduce tiredness. Ask your child's healthcare provider what exercises are safe for your child.

• Get emotional support for your child. Find a counselor, psychologist, or child support group that can help.

• Make sure your child attends all follow-up appointments.

When should I call my child’s healthcare provider?

Your child's healthcare provider will talk with you about when to call. You may be told to call if your child has:

• Symptoms that get worse

• New symptoms

• Signs of an infection, such as fever

• Side effects from treatment that affect your child's daily routine or don't get better with treatment

Ask your child's provider what signs to watch for and when to call. Know how to get help after office hours and on weekends and holidays.

Key points about neuroblastoma in children

• Neuroblastoma is a cancerous (malignant) tumor that starts in nerve tissue of infants and very young children. 

• The symptoms of neuroblastoma vary a lot depending on the size of the tumor, where it is, and whether it has spread. Common symptoms are a lump or swelling.

• Neuroblastoma is diagnosed with blood and urine tests, imaging tests, and biopsy.

• Treatment of neuroblastoma may include surgery, chemotherapy, radiation therapy, high-dose chemotherapy/radiation with stem cell transplant, immunotherapy, and other medicines.

• Continuous follow-up care during and after treatment is needed

Next steps

Tips to help you get the most from a visit to your child’s healthcare provider:

• Know the reason for the visit and what you want to happen.

• Before your visit, write down questions you want answered.

• At the visit, write down the name of a new diagnosis, and any new medicines, treatments, or tests. Also write down any new instructions your provider gives you for your child.

• Know why a new medicine or treatment is prescribed and how it will help your child. Also know what the side effects are.

• Ask if your child’s condition can be treated in other ways.

• Know why a test or procedure is recommended and what the results could mean.

• Know what to expect if your child does not take the medicine or have the test or procedure.

• If your child has a follow-up appointment, write down the date, time, and purpose for that visit.

• Know how you can contact your child’s healthcare provider after office hours. This is important if your child becomes ill and you have questions or need advice.

Online Medical Reviewers:

• Jessica Gotwals RN BSN MPH
• Liora C Adler MD
• Susan K. Dempsey-Walls RN