Neuroblastoma

Neuroblastoma is a type of cancer that forms in neuroblasts (immature nerve tissue) in the adrenal glands, neck, chest, or spinal cord.

Neuroblastoma often begins in the nerve tissue of the adrenal glands. There are two adrenal glands, one on top of each kidney in the back of the upper abdomen. The adrenal glands make important hormones that help control heart rate, blood pressure, blood sugar, and the way the body reacts to stress.

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Neuroblastoma may be found in the adrenal glands and paraspinal nerve tissue from the neck to the pelvis.

Neuroblastoma most often begins in infancy. It is usually diagnosed between the first month of life and age 5 years. The tumor is found when it begins to grow and cause signs or symptoms. Sometimes it forms before birth and is found during an ultrasound of the baby.

By the time cancer is diagnosed, it has usually metastasized (spread). Neuroblastoma spreads most often to the lymph nodes, bones, bone marrow, liver, and skin in infants and children. Adolescents may also have metastasis to the lungs and brain.

Certain genetic conditions affect the risk of having neuroblastoma.

Neuroblastoma is caused by certain changes to the way neuroblast cells function, especially how they grow and divide into new cells. There are many risk factors for neuroblastoma, but many do not directly cause cancer. Instead, they increase the chance of DNA damage in cells that may lead to neuroblastoma. Learn more about how cancer develops at What Is Cancer?

A risk factor is anything that increases the chance of getting a disease. Some risk factors can be changed. Risk factors also include things people cannot change, like family history. It's important to learn about risk factors for neuroblastoma because it can help you make choices about screening for cancer.

Possible risk factors for neuroblastoma include:

• having certain changes in genes (ALK or PHOX2B)
• having certain genetic conditions, such as:
  • Costello syndrome
  • Noonan syndrome
  • neurofibromatosis type 1
  • Li-Fraumeni syndrome
  • Beckwith-Wiedemann syndrome
  • pheochromocytoma/paraganglioma syndromes
  • ROHHAD syndromes (rapid-onset obesity, hypothalamic dysfunction, hypoventilation, and autonomic dysfunction)
• having a strong family history of neuroblastoma

Genetic testing can determine whether a child has an inherited form of neuroblastoma.

Gene mutations that increase the risk of neuroblastoma are sometimes inherited (passed from the parent to the child). In children with a gene mutation, neuroblastoma usually occurs at a younger age, and more than one tumor may form in the adrenal glands or in the nerve tissue in the neck, chest, abdomen, or pelvis.

It is not always clear from the family medical history whether a condition is inherited. Certain families may benefit from genetic counseling and genetic testing. Genetic counselors and other specially trained health professionals can discuss a child's diagnosis and the family's medical history to understand:

• the options for ALK or PHOX2B gene testing
• the risk of neuroblastoma for your child and your child's siblings
• the risks and benefits of learning genetic information

Genetic counselors can also help parents cope with their child's genetic testing results, including how to discuss the results with family members.

Once it is known that your child has an inherited form of neuroblastoma, other family members can be screened for the ALK or PHOX2B mutation.

Learn more about genetic testing at Genetic Testing for Inherited Cancer Risk.

Sometimes children with certain gene mutations should be checked for signs of neuroblastoma.

Children with certain gene mutations or hereditary (inherited) syndromes should be checked for signs of neuroblastoma until they are 10 years old. The following tests may be used:

• Abdominal ultrasound: A test in which high-energy sound waves (ultrasound) are bounced off the abdomen and make echoes. The echoes form a picture of the abdomen called a sonogram.
• Urine catecholamine studies: A test in which a urine sample is checked to measure the amounts of certain substances, vanillylmandelic acid (VMA) and homovanillic acid (HVA), that are made when catecholamines break down and are released into the urine. A higher-than-normal amount of VMA or HVA can be a sign of neuroblastoma.
• Chest x-ray: An x-ray of the organs and bones inside the chest. An x-ray is a type of energy beam that can go through the body and onto film, making a picture of areas inside the body.

Talk to your child's doctor about how often these tests need to be done.

Signs and symptoms of neuroblastoma include bone pain or a lump in the abdomen, neck, or chest.

The most common signs and symptoms of neuroblastoma are caused by the tumor pressing on nearby tissues as it grows or by cancer spreading to the bone.

Check with your child's doctor if your child has:

• a lump in the abdomen, neck, or chest
• bone pain
• a swollen stomach and trouble breathing (in infants)
• bulging eyes
• dark circles around the eyes ("black eyes")
• painless, bluish lumps under the skin (in infants)
• weakness or paralysis (loss of ability to move a body part)

Less common signs and symptoms of neuroblastoma include:

• fever
• shortness of breath
• feeling tired
• easy bruising or bleeding
• petechiae (flat, pinpoint spots under the skin caused by bleeding)
• high blood pressure
• severe watery diarrhea
• Horner syndrome (droopy eyelid, smaller pupil, and less sweating on one side of the face)
• jerky muscle movements
• uncontrolled eye movements

These and other signs and symptoms may be caused by neuroblastoma or by other conditions. The only way to know is to see your child's doctor.

Tests that examine many different body tissues and fluids are used to diagnose neuroblastoma.

If your child has symptoms that suggest neuroblastoma, the doctor will need to find out if these are due to cancer or another condition. The doctor will ask when the symptoms started and how often your child has been having them. They will also ask about your child's personal and family medical history and do a physical exam.

Depending on your child's symptoms and medical history and the results of their physical and neurological exam, the doctor may recommend more tests to find out if your child has neuroblastoma, and if so, its extent (stage). If neuroblastoma is diagnosed, the results of these tests and procedures will help you and your child's doctor make decisions about treatment.

The following tests and procedures may be used:

• Urine catecholamine studies: A test in which a urine sample is checked to measure the amounts of certain substances, vanillylmandelic acid (VMA) and homovanillic acid (HVA), that are made when catecholamines break down and are released into the urine. A higher-than-normal amount of VMA or HVA can be a sign of neuroblastoma.
• Blood chemistry studies: A test in which a blood sample is checked to measure the amounts of certain substances released into the blood by organs and tissues in the body. A higher-than-normal amount of lactate dehydrogenase (LDH) can be a sign of disease.
• Ferritin level: A test in which a blood sample is checked to measure the amount of ferritin (a protein that stores iron in cells). A higher-than-normal amount may be a sign of disease.
• MIBG scan: A procedure used to find neuroendocrine tumors, such as neuroblastoma. A very small amount of a substance called radioactive MIBG is injected into a vein and travels through the bloodstream. Neuroendocrine tumor cells take up the radioactive MIBG and are detected by a scanner. Scans may be taken over 1–3 days. An iodine solution may be given before or during the test to keep the thyroid gland from absorbing too much of the MIBG. This test is also used to find out how well the tumor is responding to treatment. MIBG is also used in high doses to treat neuroblastoma.
• CT scan (CAT scan): A procedure that makes a series of detailed pictures of areas inside the body, taken from different angles. The pictures are made by a computer linked to an x-ray machine. A dye may be injected into a vein or swallowed to help the organs or tissues show up more clearly. This procedure is also called computed tomography, computerized tomography, or computerized axial tomography. Learn more about Computed Tomography (CT) Scans and Cancer.
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  Computed tomography (CT) scan. The child lies on a table that slides through the CT scanner, which takes a series of detailed x-ray pictures of areas inside the body.
  

• MRI (magnetic resonance imaging) with gadolinium: A procedure that uses a magnet, radio waves, and a computer to make a series of detailed pictures of areas inside the body. A substance called gadolinium is injected into a vein. The gadolinium collects around the cancer cells so they show up brighter in the picture. This procedure is also called nuclear magnetic resonance imaging (NMRI).
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  Magnetic resonance imaging (MRI) scan. The child lies on a table that slides into the MRI machine, which takes a series of detailed pictures of areas inside the body. The positioning of the child on the table depends on the part of the body being imaged.
  

• PET scan (positron emission tomography scan): A procedure to find malignant tumor cells in the body. A small amount of radioactive glucose (sugar) is injected into a vein. The PET scanner rotates around the body and makes a picture of where glucose is being used in the body. Malignant tumor cells show up brighter in the picture because they are more active and take up more glucose than normal cells do. This test will usually only be done if the tumor does not take up MIBG.
• X-ray of the chest or bone: An x-ray is a type of energy beam that can go through the body and onto film, making a picture of areas inside the body.
• Ultrasound exam: A procedure in which high-energy sound waves (ultrasound) are bounced off internal tissues or organs and make echoes. The echoes form a picture of body tissues called a sonogram. An ultrasound exam is not done if a CT/MRI has been done.
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  Abdominal ultrasound. An ultrasound transducer connected to a computer is pressed against the skin of the abdomen. The transducer bounces sound waves off internal organs and tissues to make echoes that form a sonogram (computer picture).
  

• Tumor biopsy: Cells and tissues are removed during a biopsy so they can be viewed under a microscope by a pathologist to check for signs of cancer. The way the biopsy is done depends on where the tumor is in the body. Sometimes the whole tumor is removed at the same time the biopsy is done. The doctor who reviews the tumor biopsy will determine if the tumor appears to have more favorable or unfavorable features. These features may affect treatment and survival.

  Children up to age 6 months may not need a biopsy or surgery to remove the tumor because the tumor may disappear without treatment.

• Bone marrow aspiration and biopsy: The removal of bone marrow, blood, and a small piece of bone by inserting a hollow needle into the hipbone or breastbone. A pathologist views the bone marrow, blood, and bone under a microscope to look for signs of cancer. This test is also used to stage the tumor.
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  Bone marrow aspiration and biopsy. After a small area of skin is numbed, a bone marrow needle is inserted into the child’s hip bone. Samples of blood, bone, and bone marrow are removed for examination under a microscope.
  

• Lymph node biopsy: The removal of all or part of a lymph node. A pathologist views the lymph node tissue under a microscope to check for cancer cells. This test is used to diagnose and stage the tumor. One of the following types of biopsies may be done:
  • Excisional biopsy: The removal of an entire lymph node.
  • Incisional biopsy: The removal of part of a lymph node.
  • Core biopsy: The removal of tissue from a lymph node using a wide needle.
  • Fine-needle aspiration (FNA) biopsy: The removal of tissue or fluid from a lymph node using a thin needle.
• Light microscopy: A laboratory test in which cells in a sample of tissue are viewed under regular and high-powered microscopes to look for certain changes in the cells.
• Immunohistochemistry: A laboratory test that uses antibodies to check for certain antigens (markers) in a sample of a patient’s tissue. The antibodies are usually linked to an enzyme or a fluorescent dye. After the antibodies bind to a specific antigen in the tissue sample, the enzyme or dye is activated, and the antigen can then be seen under a microscope. This type of test is used to help diagnose cancer and to help tell one type of cancer from another type of cancer.
• Molecular testing: A molecular test checks for certain genes, proteins, or other molecules in a sample of tissue, blood, or bone marrow. Molecular tests also check for certain changes in a gene or chromosome that may cause or affect the chance of developing neuroblastoma. A molecular test may be used to help plan treatment, find out how well treatment is working, or make a prognosis.

  Children with newly diagnosed high-risk neuroblastoma may be eligible for molecular testing through the Molecular Characterization Initiative.

  The Molecular Characterization Initiative offers free molecular testing to children, adolescents, and young adults with certain types of newly diagnosed cancer. The program is offered through NCI's Childhood Cancer Data Initiative. To learn more, visit About the Molecular Characterization Initiative.

• Biomarker testing: Biomarker testing is a way to look for genes, proteins, and other substances (called biomarkers or tumor markers) that can provide information about cancer. Some biomarkers affect how certain cancers behave and how certain treatments work. Biomarker testing may help your doctor choose a cancer treatment.

  To check for these biomarkers, samples of tissue containing neuroblastoma cells are removed during a biopsy or surgery and tested in a laboratory.

  Neuroblastoma biomarker testing includes:

  • MYCN amplification study: A laboratory study in which cells in a sample of tumor or bone marrow are checked to see how many copies of the MYCN gene are in the tumor DNA. MYCN is important for cell growth. Having more than 10 copies of the gene is called MYCN amplification. Neuroblastoma with MYCN amplification is more likely to spread in the body and more likely to show rapid growth.
  • ALK: The tumor cells may be checked in the laboratory for mutations or amplification (checking the number) of the ALK gene. These changes may increase the growth of cancer cells. Finding changes in the ALK gene in tumor tissue may lead to changes in the cancer treatment plan.
  • Cytogenetic analysis: A laboratory test in which the number and structure of chromosomes of cells in a sample of tissue are counted and checked for any changes, such as broken, missing, rearranged, or extra chromosomes. Changes in certain chromosomes may be a sign of cancer. Cytogenetic analysis is used to help diagnose cancer, plan treatment, or find out how well treatment is working.
• ALK or PHOX2B genetic tests: A laboratory test in which a sample of blood or tissue is tested for a change in the ALK gene or PHOX2B gene in normal cells.

Getting a second opinion.

You may want to get a second opinion to confirm their child's neuroblastoma diagnosis and treatment plan. If you seek a second opinion, you will need to get medical test results and reports from the first doctor to share with the second doctor. The second doctor will review the genetic test results, pathology report, slides, and scans. This doctor may agree with the first doctor, suggest changes to the treatment plan, or provide more information about your child's cancer.

To learn more about choosing a doctor and getting a second opinion, see Finding Cancer Care. You can contact NCI's Cancer Information Service via chat, email, or phone (both in English and Spanish) for help finding a doctor or hospital that can provide a second opinion. For questions you might want to ask at your child's appointments, see Questions to Ask Your Doctor About Cancer.

Certain factors affect prognosis (chance of recovery) and treatment options.

If your child has been diagnosed with neuroblastoma, you may have questions about how serious the cancer is and your child's chances of survival. The likely outcome or course of a disease is called prognosis.

The prognosis and treatment options depend on:

• age at the time of diagnosis
• the child's risk group
• whether there are certain changes in the MYCN or ALK genes
• whether the tumor is diploid or hyperdiploid
• whether there are changes to the tumor chromosomes
• the type of tumor neurotrophin receptor
• where in the body the tumor started (abdomen, chest, neck, or spine)
• the stage of the cancer
• levels of LDH and ferritin
• how the tumor responds to treatment
• how much time passed between diagnosis and when the cancer recurred (for recurrent cancer)

Prognosis and treatment options for neuroblastoma are also affected by tumor histology, which includes:

• the patterns of the tumor cells
• how different the tumor cells are from normal cells
• how fast the tumor cells are growing

The tumor histology is said to be favorable or unfavorable, depending on these factors. A child with favorable tumor histology has a better chance of recovery.

In some children up to age 6 months, neuroblastoma may disappear without treatment. This is called spontaneous regression. The child is closely watched for signs or symptoms of neuroblastoma. If signs or symptoms occur, treatment may be needed.

After neuroblastoma has been diagnosed, tests are done to find out if cancer has spread from where it started to other parts of the body.

The process used to find out the extent or spread of cancer is called staging. The information gathered from the staging process helps determine the stage of the disease. For neuroblastoma, the stage of disease affects whether the cancer is low risk, intermediate risk, or high risk. It also affects the treatment plan. The results of some tests and procedures used to diagnose neuroblastoma may be used for staging. See the General Information section for a description of these tests and procedures.

The International Neuroblastoma Risk Group Staging System (INRGSS) is used to determine the stage of neuroblastoma.

Treatment of neuroblastoma is based on risk groups.

For many types of cancer, stages are used to plan treatment. For neuroblastoma, treatment depends on the patient's risk group. The risk group is determined by the following factors:

• the stage of the cancer
• the child's age at diagnosis
• the International Neuroblastoma Pathologic Classification (INPC) (tumor histology)
• whether the tumors are diploid or hyperdiploid (DNA index)
• whether the cancer gene MYCN is found in the tumor cells
• how much of the cancer could be removed by surgery

There are three risk groups: low risk, intermediate risk, and high risk.

• Low-risk and intermediate-risk neuroblastoma have a good chance of being cured.
• High-risk neuroblastoma may be hard to cure.

For more information on the risk group classification, see the Revised International Neuroblastoma Response Criteria (INRC) section in Neuroblastoma Treatment (Health Professional Version).

Sometimes neuroblastoma does not respond to treatment or comes back after treatment.

Refractory neuroblastoma is a tumor that does not respond to treatment.

Recurrent neuroblastoma is cancer that has recurred (come back) after it has been treated. The tumor may come back in the site where it began or in the central nervous system.

There are different types of treatment for children with neuroblastoma.

There are different types of treatment for children and adolescents with neuroblastoma. You and your child's cancer team will work together to decide treatment. Many factors will be considered, such as your child's overall health and whether the cancer is newly diagnosed or has come back.

Children with neuroblastoma should have their treatment planned by a team of doctors who are experts in treating childhood cancer, especially neuroblastoma.

A pediatric oncologist, a doctor who specializes in treating children with cancer, will oversee treatment. The pediatric oncologist works with other pediatric health care professionals who are experts in treating children with cancer and who specialize in certain areas of medicine. These may include the following specialists and others:

• pediatric surgeon
• pediatric radiation oncologist
• endocrinologist
• neurologist
• pediatric neuropathologist
• neuroradiologist
• pediatrician
• pediatric nurse specialist
• social worker
• child life professional
• psychologist

Your child's treatment plan will include information about the cancer, the goals of treatment, treatment options, and the possible side effects. It will be helpful to talk with your child's cancer care team before treatment begins about what to expect. For help every step of the way, see our downloadable booklet, Children with Cancer: A Guide for Parents.

The following types of treatment may be used:

New types of treatment are being tested in clinical trials.

A treatment clinical trial is a research study meant to help improve current treatments or obtain information on new treatments for people with cancer. For some patients, taking part in a clinical trial may be an option. Because cancer in children is rare, taking part in a clinical trial should be considered.

Use our clinical trial search to find NCI-supported cancer clinical trials that are accepting patients. You can search for trials based on the type of cancer, the age of the patient, and where the trials are being done. Some clinical trials are open only to patients who have not started treatment. Clinical trials supported by other organizations can be found on the ClinicalTrials.gov website.

Learn more at Clinical Trials Information for Patients and Caregivers.

Treatment for neuroblastoma causes side effects and late effects.

To learn more about side effects that begin during treatment for cancer, visit Side Effects.

Side effects from cancer treatment that begin after treatment and continue for months or years are called late effects. Late effects of cancer treatment may include:

• physical problems, such as:
  • tooth development
  • intestinal blockage (obstruction)
  • bone and cartilage growth
  • hearing function
  • metabolic syndrome (elevated blood pressure, elevated triglycerides, elevated cholesterol, increased body fat percentage)
• changes in mood, feelings, thinking, learning, or memory
• second cancers (new types of cancer), such as myelodysplastic syndrome, acute myeloid leukemia, thyroid cancer, or kidney cancer

Some late effects may be treated or controlled. It is important to talk with your child's doctors about the effects cancer treatment can have on your child. Learn more about Late Effects of Treatment for Childhood Cancer.

Follow-up care may be needed.

As your child goes through treatment, they will have follow-up tests or check-ups. Some tests that were done to diagnose or stage the cancer may be repeated to see how well the treatment is working. Decisions about whether to continue, change, or stop treatment may be based on the results of these tests.

Some of the tests will continue to be done from time to time after treatment has ended. The results of these tests can show if your child's condition has changed or if the cancer has recurred (come back).

Follow-up care for children with neuroblastoma may include:

• urine catecholamine studies
• MIBG scan

Patients First Treated for Low-Risk Neuroblastoma

Treatment for recurrent neuroblastoma that comes back in the area where the cancer first formed may include:

• surgery followed by observation or chemotherapy
• chemotherapy that may be followed by surgery

Treatment for recurrent neuroblastoma that comes back in other parts of the body or that has not responded to treatment may include:

• observation
• chemotherapy
• surgery followed by chemotherapy
• treatment as for newly diagnosed high-risk neuroblastoma, for children older than 18 months

Patients First Treated for Intermediate-Risk Neuroblastoma

Treatment for recurrent neuroblastoma that comes back in the area where the cancer first formed may include:

• surgery that may be followed by chemotherapy
• radiation therapy for children whose disease has gotten worse after chemotherapy and second-look surgery

Treatment for recurrent neuroblastoma that comes back in other parts of the body may include:

• treatment as for newly diagnosed high-risk neuroblastoma

Patients First Treated for High-Risk Neuroblastoma

There is no standard treatment for recurrent neuroblastoma in patients first treated for high-risk neuroblastoma. Treatment may include:

• Combination chemotherapy with monoclonal antibody therapy (dinutuximab).
• Iodine 131-MIBG therapy to relieve symptoms and improve quality of life. It may be given alone or in combination with chemotherapy, or followed by stem cell rescue.
• Chemotherapy.
• A clinical trial of CAR T-cell therapy.

Because there is no standard treatment, patients first treated for high-risk neuroblastoma may want to consider a clinical trial. Learn more about clinical trials at Clinical Trials Information for Patients and Caregivers.

Patients with Recurrent CNS Neuroblastoma

Treatment for neuroblastoma that recurs (comes back) in the central nervous system (CNS; brain and spinal cord) may include:

• surgery to remove the tumor in the CNS followed by radiation therapy
• chemotherapy, surgery, and radiation therapy

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PDQ® Pediatric Treatment Editorial Board. PDQ Neuroblastoma Treatment. Bethesda, MD: National Cancer Institute. Updated <MM/DD/YYYY>. Available at: https://www.cancer.gov/types/neuroblastoma/patient/neuroblastoma-treatment-pdq. Accessed <MM/DD/YYYY>. [PMID: 26389278]

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