Neuroblastoma is a cancer that starts in cells called neuroblasts. Neuroblasts are immature nerve cells. They are found in several areas of the body.

Neuroblastoma most often starts in the neuroblasts in the adrenal glands. The adrenal glands are located on top of each kidney. The glands make hormones that control important functions in the body. Other cancers and tumors can happen in the adrenal glands, such as pheochromocytomas. These are different from neuroblastomas but may cause similar symptoms.

Neuroblastoma can happen in other parts of the body that have neuroblasts, such as in the spine, belly, chest and neck. It also can affect other places in the body if it spreads. When the cancer spreads, it's called metastatic neuroblastoma.

Neuroblastoma mostly affects children age 5 or younger. Symptoms vary, depending on where it occurs in the body.

Some forms of neuroblastoma may go away on their own. Other forms of neuroblastoma need treatment. Treatments include surgery, chemotherapy, radiation therapy and bone marrow transplant. Your child's healthcare team will select the neuroblastoma treatments that are best for your child.

Neuroblastoma is different from other cancers that have similar names, such as glioblastoma and nephroblastoma, also called Wilms tumor. All of these names contain the term "blastoma," which means a cancer or tumor that's made up of blasts. Blasts are cells that haven't fully developed yet. Neuroblastoma starts in nerve cells that are in the blast stage, called neuroblasts.

Symptoms

Signs and symptoms of neuroblastoma may vary depending on what part of the body is affected. This cancer starts in immature nerve cells called neuroblasts. Neuroblasts are found in several areas of the body.

When the cancer is only in the place where it starts, called localized neuroblastoma, it doesn't always cause symptoms. Symptoms are more likely to occur when the cancer grows to involve nearby areas, called regional neuroblastoma, or spreads to distant parts of the body, called metastatic neuroblastoma.

Neuroblastoma in the adrenal glands and belly may cause symptoms such as:

• Belly pain.
• A lump under the skin that typically isn't tender when touched.
• Diarrhea or constipation.

Neuroblastoma in the chest and neck may cause symptoms such as:

• Wheezing.
• Difficulty breathing.
• Changes to the eyes, including drooping eyelids and pupils that are different sizes.

Neuroblastoma near the spine may cause symptoms such as:

• Back pain.
• Trouble urinating or passing a bowel movement.
• Weakness in the legs.

Metastatic neuroblastoma may cause symptoms such as:

• Bone pain, which might cause young children to limp when walking.
• Dark, bruiselike circles around the eyes, which are said to look like racoon eyes.
• Fever.
• Fussiness.
• Lumps of tissue under the skin that typically don't hurt.
• Not growing or gaining weight as expected.

When to see a doctor

Contact your child's healthcare professional if your child has any symptoms that worry you. Mention any changes in your child's behavior, habits or appearance.

Causes

It's not clear what causes neuroblastoma. This cancer starts in immature nerve cells called neuroblasts. Neuroblasts are found in several areas of the body.

Neuroblastoma starts when neuroblasts develop changes in their DNA. A cell's DNA holds the instructions that tell the cell what to do. In healthy cells, the DNA gives instructions to grow and multiply at a set rate. The instructions tell the cells to die at a set time. In cancer cells, the DNA changes give different instructions. The changes tell the cancer cells to grow and multiply quickly. Cancer cells can keep living when healthy cells would die. This causes too many cells.

The cancer cells might form a mass called a tumor. The tumor can grow to invade and destroy healthy body tissue. In time, cancer cells can break away and spread to other parts of the body. When cancer spreads, it's called metastatic cancer.

Risk factors

Risk factors for neuroblastoma include:

• Young age. The risk of neuroblastoma is higher in children. This cancer happens mostly in children age 5 and younger.
• Genetic syndromes. Some DNA changes that run in families can raise the risk of neuroblastoma. Genetic syndromes thought to raise the risk include Turner syndrome, Costello syndrome and familial neuroblastoma. Yet, healthcare professionals think only a small number of neuroblastomas are inherited.

There are no known ways to prevent neuroblastoma.

Complications

Complications of neuroblastoma may include:

• Spread of the cancer. With time, the cancer cells may spread to other parts of the body. When it spreads, it's called metastatic neuroblastoma. Neuroblastoma most often spreads to the lymph nodes, bone marrow, liver, skin and bones.
• Pressure on the spinal cord. A neuroblastoma may grow and press on the spinal cord, causing spinal cord compression. Spinal cord compression may cause pain and paralysis.
• Symptoms caused by cancer secretions. Neuroblastoma cells may secrete chemicals that irritate other tissues. The irritated tissues can cause symptoms called paraneoplastic syndromes. Symptoms of paraneoplastic syndromes may include rapid eye movements and difficulty with coordination. Other symptoms include abdominal swelling and diarrhea.

Diagnosis

A neuroblastoma diagnosis might start with a physical exam. Urine and blood tests can give clues about what might be causing your child's symptoms. Imaging tests can look for signs of a growth that could be a neuroblastoma.

To be certain of the diagnosis, the healthcare team removes some of the growth for testing. If that test finds neuroblastoma, your child may have tests to look for signs that the cancer has spread. These might include other imaging tests and a procedure to remove some bone marrow for testing.

Physical exam

A healthcare professional may examine your child to check for signs of neuroblastoma. The healthcare professional may ask you questions about your child's symptoms and health history.

Urine and blood tests

A healthcare professional might test your child's urine and blood. The results can help the healthcare professional better understand your child's condition. Urine tests might look for high levels of chemicals made by neuroblastoma cells. For example, neuroblastoma can produce chemicals called catecholamines. As the body breaks these down, they can be detected in the urine.

Ultrasound

Ultrasound is an imaging test that uses sound waves to make pictures of the body. It's usually the first test used to check out symptoms in the belly area in children. Ultrasound isn't the best imaging test to diagnose neuroblastoma, but it gives the healthcare professional clues about what test to do next.

CT scan

A computerized tomography (CT) scan is an imaging test that uses X-ray techniques to create detailed images of the body. It then uses a computer to create cross-sectional images, also called slices, of the bones, blood vessels and soft tissues inside the body.

Healthcare professionals might use CT to show the size of a neuroblastoma in the belly or chest. It also can show cancer that spreads to the lymph nodes, bones, liver or skin.

CT is widely available and results come back quickly. A healthcare professional might choose this test based on your child's symptoms and the location of the neuroblastoma. CT might be the best choice if results are needed quickly.

MRI

Magnetic resonance imaging (MRI) is an imaging test that uses a magnetic field and radio waves to create pictures of the inside of the body. Healthcare professionals use MRI to show the size and location of neuroblastoma in the belly or chest. It's particularly good at showing neuroblastoma in and around the spine. MRI also can show cancer that spreads to the lymph nodes, bones, liver or skin.

Biopsy

A biopsy is a procedure to remove a sample of tissue for testing in a lab. To get the sample, a healthcare professional might put a hollow needle through the skin and into the cancer. The health professional uses the needle to draw out some cells for testing. Sometimes a surgeon removes the tissue sample during surgery.

In the lab, tests can check the tissue for signs of cancer. Other tests might look for changes in the DNA inside the cancer cells. Results from these tests may help your child's healthcare team make a treatment plan.

MIBG scan

Metaiodobenzylguanidine (MIBG) scans use nuclear imaging to make pictures. Nuclear imaging involves using medicines that have tiny amounts of radioactive substances. These medicines are called radiopharmaceuticals. When they're used for imaging, they also might be called radiotracers.

The MIBG scan uses a radiotracer to find neuroblastoma cells. A healthcare professional puts the tracer into a vein. The tracer goes through the body and attaches to the neuroblastoma cells. A camera in the scanner detects the radiation that the tracer gives off. A computer takes the information from the camera and makes pictures that show where neuroblastoma cells are in the body.

Healthcare professionals use MIBG scans to look for signs that neuroblastoma has spread. This test can find neuroblastoma cells anywhere in the body. The healthcare team might recommend this scan after other tests have confirmed the diagnosis of neuroblastoma. MIBG scans might be repeated during and after treatment to see how well treatment is working.

PET scan

Positron emission tomography (PET) scans are nuclear imaging tests that use radioactive tracers to highlight areas of disease. The tracer contains a substance that helps it stick to fast-growing cells, such as cancer cells. The PET images show the places where the tracer builds up.

PET scans aren't often used for neuroblastoma. A PET scan might be used if MIBG scans don't show the neuroblastoma. MIBG scans don't work for about 1 out of every 10 neuroblastomas.

Bone marrow aspiration and biopsy

Bone marrow aspiration and biopsy are procedures that involve collecting cells from the bone marrow. The cells are sent for testing. These procedures are used to check if neuroblastoma has spread to the bone marrow.

Bone marrow is the soft matter inside bones where blood cells are made. Bone marrow has a solid part and a liquid part. In a bone marrow aspiration, a needle is used to draw a sample of the fluid. In a bone marrow biopsy, a needle is used to collect a small amount of the solid tissue. The samples are typically taken from the hip bone.

Treatment

Treatments for neuroblastoma include surgery, radiation therapy and medicines, such as chemotherapy, and others. Healthcare teams consider many things when creating a treatment plan. These include the child's age, the stage of the cancer and the risk group.

Surgery

During surgery for neuroblastoma, surgeons use cutting tools to remove the cancer cells. In children with low-risk neuroblastoma, surgery to remove the cancer may be the only treatment needed.

Whether the cancer can be removed completely depends on its location and size. Cancers that are attached to nearby vital organs may be too risky to remove.

In intermediate-risk and high-risk neuroblastoma, treatment usually starts with chemotherapy to shrink the cancer. Surgeons may try to remove as much of the cancer as possible.

Chemotherapy

Chemotherapy treats cancer with strong medicines. Many chemotherapy medicines exist. Most chemotherapy medicines are given through a vein. Some come in pill form.

Children with intermediate-risk neuroblastoma often receive a combination of chemotherapy medicines before surgery. This improves the chances that the entire cancer can be removed.

Children with high-risk neuroblastoma often receive high doses of chemotherapy medicines to shrink the cancer. Chemotherapy also helps kill any cancer cells that have spread to other parts in the body. Chemotherapy often is used before surgery and before bone marrow transplant.

Bone marrow transplant

A bone marrow transplant, also called a bone marrow stem cell transplant, involves putting healthy bone marrow stem cells into the body. These cells replace cells hurt by chemotherapy and other treatments.

A bone marrow transplant might be an option for children with high-risk neuroblastoma. A bone marrow transplant for neuroblastoma uses the child's own blood stem cells. This kind of transplant is called an autologous stem cell transplant.

Before the transplant, a procedure is done to filter and collect blood stem cells from the child's blood. The stem cells are stored for later use. Next, the child receives high doses of chemotherapy to kill any remaining cancer cells. Then the blood stem cells are put back into the child's body. The transplanted cells can form new, healthy blood cells.

Radiation therapy

Radiation therapy treats cancer with powerful energy beams. The energy can come from X-rays, protons or other sources.

Children with high-risk neuroblastoma may receive radiation therapy after chemotherapy and surgery. The radiation can help lower the risk that the cancer will come back.

Proton therapy

Proton therapy is a type of radiation therapy that uses energy from protons. Proton beams can be more carefully targeted to the cancer cells. Proton therapy may be less likely to hurt healthy tissue near the cancer. This is a newer form of radiation therapy. It's not available at all medical centers.

For neuroblastoma, proton therapy may be an option for children with high-risk neuroblastoma. Like other forms of radiation therapy, it's typically used after chemotherapy and surgery.

Immunotherapy

Immunotherapy is a treatment with medicine that helps the body's immune system kill cancer cells. The immune system fights off diseases by attacking germs and other cells that shouldn't be in the body. Cancer cells survive by hiding from the immune system. Immunotherapy helps the immune system cells find and kill the cancer cells.

Immunotherapy medicines for neuroblastoma target a substance called glycolipid GD2 on the surface of neuroblastoma cells. Medicines that work in this way are called anti-GD2 immunotherapies. The medicine is given through a vein. It travels through the body and attaches to the cancer cells. This causes the immune system cells to attack the cancer.

Immunotherapy is sometimes used for high-risk neuroblastoma. It's typically used after other treatments. Immunotherapy medicines are usually combined with other medicines, such as chemotherapy and isotretinoin, which used to be sold under the brand name Accutane.

Treatment to prevent relapse

Children with high-risk neuroblastoma sometimes receive extra treatment to reduce the risk that the cancer will start growing again. It's generally used after other treatments have controlled the cancer.

Eflornithine (Iwilfin) comes as a pill that's taken twice a day. It can be taken for as long as two years. This medicine also is called difluoromethylornithine (DFMO).

The medicine reduces the risk of relapse. Relapsed neuroblastoma happens when the cancer starts to get worse after a period of getting better.

Treatment for recurrence or relapse

Other treatments might be needed if the cancer comes back, called recurrence, or if it relapses. Other treatments also might be used if the cancer doesn't respond to the usual treatments, called refractory cancer.

Most neuroblastoma relapses and recurrences happen in the first two years after treatment. Rarely, the cancer can come back many years later.

Treatment usually starts with medicines that may have helped before, such as chemotherapy and immunotherapy. If these are no longer helping, other options might include:

• Radiopharmaceutical therapy. Radiopharmaceutical therapy uses a medicine that contains a radioactive substance. The medicine goes through the body, attaches to target cells and releases the radiation. One neuroblastoma medicine that works in this way is I-131 MIBG, also called MIBG therapy. It's being studied in clinical trials. Researchers are studying other radiopharmaceutical therapies for neuroblastoma, including lutetium Lu-177 dotatate.
• Targeted therapy. Targeted therapy for cancer is a treatment that uses medicines that attack specific chemicals in the cancer cells. By blocking these chemicals, targeted treatments can cause cancer cells to die. Clinical trials are studying targeted therapy medicines for neuroblastoma.
• CAR-T cell therapy. CAR-T stands for chimeric antigen receptor (CAR)-T cell therapy. It's a cancer treatment that takes cells from the body and changes them so that they can fight cancer. It's most often used to treat cancers that affect blood cells, such lymphoma. Clinical trials are studying CAR-T cell therapy for neuroblastoma.

Coping and support

When your child is diagnosed with cancer, it's common to feel a range of emotions. Some parents say they had feelings such as shock, disbelief, guilt and anger. At the time you might be feeling these strong feelings, you also may need to make decisions about your child's treatment. This can feel overwhelming. Here are some ideas to help with coping.

Gather all the information you need

Find out enough about neuroblastoma to feel comfortable making decisions about your child's care. Talk with your child's healthcare team. Keep a list of questions to ask at the next appointment. Ask your child's healthcare team to recommend good sources of information. In the United States, the National Cancer Institute and the American Cancer Society are good organizations to go to for more information.

Organize a support network

Friends and family can provide both emotional and practical support as your child goes through treatment. Your friends and family will likely ask you what they can do to help. Take them up on their offers. Loved ones can go with your child to healthcare visits or sit by your child's bedside in the hospital when you can't be there. When you're with your child, your friends and family can help out by spending time with your other children or helping around your home.

Take advantage of resources for children with cancer

Seek out special resources for families of kids with cancer. Ask your clinic's social workers about what's available. Support groups for parents and siblings put you in touch with people who understand what you're feeling. Your family may be eligible for summer camps, temporary housing and other support.

Maintain your usual routines as much as possible

Small children can't understand what's happening to them as they undergo cancer treatment. To help your child cope, try to keep your usual routines as much as possible. Try to arrange appointments so that your child can have a set nap time each day. Have routine mealtimes. Allow time for play when your child feels up to it. If your child must spend time in the hospital, bring items from home that help your child feel more comfortable.

Ask your healthcare team about other ways to comfort your child through treatment. Some hospitals have recreation therapists or child life workers who can give you more-specific ways to help your child cope.

Preparing for an appointment

Make an appointment with your family healthcare professional if your child has any symptoms that worry you.

Because appointments can be brief it's a good idea to be prepared. Here's some information to help you get ready, and what to expect.

What you can do

• Be aware of any restrictions before your appointment. At the time you make the appointment, be sure to ask if there's anything you need to do in advance, such as change your child's diet.
• Write down any symptoms your child is experiencing, including any that may seem unrelated to the reason for which you scheduled the appointment.
• Write down key personal information, including any major stresses or recent life changes.
• Make a list of all medicines, vitamins or supplements your child is taking and the doses.
• Consider taking a family member or friend along. Sometimes it can be hard to remember all the information provided during an appointment. Someone who comes with you may remember something that you missed or forgot.
• Write down questions to ask your child's healthcare team.

Your time with your child's healthcare team may be limited, so preparing a list of questions can help you make the most of your time together. List your questions from most important to least important in case time runs out. For neuroblastoma, some basic questions to ask include:

• What may be causing my child's symptoms or condition?
• What kinds of tests does my child need?
• What is the best course of action?
• What are the alternatives to the approach that you're suggesting?
• My child has these other health conditions. How can they best be managed together?
• Are there any restrictions that my child needs to follow?
• Should my child see a specialist?
• Where can I find more information?

In addition to the questions that you've prepared, don't hesitate to ask other questions during your appointment.

What to expect from your child's doctor

Your child's healthcare team is likely to ask you questions, such as:

• When did your child begin experiencing symptoms?
• How have your child's symptoms changed over time?
• What, if anything, seems to improve your child's symptoms?
• What, if anything, appears to worsen your child's symptoms?

Once the healthcare team diagnoses neuroblastoma, the next step may be to give the cancer a stage. The stage tells the healthcare team about how big the cancer is, whether it involves important structures such as nerves and blood vessels, and whether it has spread to other parts of the body. The stage is one piece of information that's needed to decide on a treatment plan.

The stages of neuroblastoma have changed over the years. The stages currently follow a system called the International Neuroblastoma Risk Group Staging System. The current staging system uses imaging tests to decide on the stage. An older staging system required results from surgery. As most children with neuroblastoma start treatment with chemotherapy and many may not have surgery, the older staging system isn't used as much.

The stages of neuroblastoma are L1, L2, M and MS.

• Stage L1 means the neuroblastoma is growing in one area. Healthcare professionals sometimes call this localized neuroblastoma. The cancer doesn't involve any structures that would make it hard to remove the cancer completely with surgery. In an older staging system, this was called stage 1.
• Stage L2 means the neuroblastoma is growing in one area. However, the cancer involves structures that might make it hard to remove all the cancer with surgery. Healthcare professionals sometimes call this regional neuroblastoma. In an older staging system, this was called stage 2 and stage 3.
• Stage M means the neuroblastoma has spread to other parts of the body. Healthcare professionals sometimes call this metastatic neuroblastoma. In an older staging system, stage M was called stage 4.
• Stage MS applies to children younger than 18 months. It means the neuroblastoma has spread to the skin, liver or bone marrow. In an older staging system, stage MS was called stage 4S.

The stage is one thing healthcare professionals consider when thinking about what treatments to use for neuroblastoma. Staging can tell where the cancer is and how far it has spread. But it doesn't tell the healthcare team about how aggressive the cancer is or whether it's likely to respond to treatment. That's where risk groups can help.

Neuroblastoma risk groups consider many other factors in order to decide whether a cancer is low risk, intermediate risk or high risk. The risk group helps the healthcare team understand whether there is a low, intermediate or high risk that the cancer will grow quickly and whether it might come back after treatment.

To choose the risk group, the healthcare team uses:

• Cancer stage. Stage M neuroblastoma, formerly called stage 4, has spread to other parts of the body. It has the greatest risk of coming back after treatment.
• The child's age. In general, children younger than 18 months tend to have a better prognosis than older children.
• Histology. Histology means how the cancer cells look and behave when viewed with a microscope. If healthcare professionals in the lab find concerning results, they might say the neuroblastoma has "unfavorable histology." This increases the risk that the cancer may come back after treatment.
• MYCN gene. Tests in the lab also can show if the cancer cells have an extra copy of a gene called MYCN that tends to make the cancer grow more quickly. Neuroblastomas with extra copies of MYCN have a higher risk of coming back after treatment.

The risk groups for neuroblastoma are low, intermediate and high.

• Low-risk neuroblastoma has a low risk of coming back after treatment. It often can be removed completely with surgery. Sometimes it doesn't need treatment, for example, for babies with cancer that affects only the adrenal gland.
• Intermediate-risk neuroblastoma needs stronger treatment to keep it from coming back. Treatment usually involves chemotherapy to help shrink the cancer. This may make it more likely that the cancer can be removed completely.
• High-risk neuroblastoma has the greatest risk of coming back, so it needs the strongest treatments. Treatments often involve chemotherapy, surgery, bone marrow transplant, radiation therapy, immunotherapy and other medicines.

If your child has been diagnosed with neuroblastoma, one of the first things you might wonder about is the survival rate for this type of cancer. Survival rates come from following a large group of people with the same diagnosis for a set amount of time.

Neuroblastoma survival rates can give you an idea of the life expectancy and prognosis for children in the same situation as your child. But survival rates can't say whether your child will be cured.

For the clearest and most complete picture of your child's outlook, talk about it with your child's healthcare team. The care team understands your child's overall health and can give a more personalized prognosis. Still, many parents want to know the survival rates to help them get a sense of what to expect.

Neuroblastoma survival rates

Neuroblastoma survival rates are given by risk category. This is different from other cancers that might give survival rates by cancer stage.

The healthcare team determines the risk category using the stage, the results of lab tests on the cancer cells and the child's age. The risk category tells the healthcare team whether the cancer has a low, intermediate or high risk of coming back after treatment.

Survival rates vary by risk category.

• Low-risk neuroblastoma has a five-year overall survival rate of about 98%. This means that for every 100 children diagnosed with low-risk neuroblastoma, about 98 can be expected to be living five years after their diagnosis. Most neuroblastomas in this category are localized, which means the cancer affects one area of the body.
• Intermediate-risk neuroblastoma has a five-year overall survival rate of about 96%. This category includes regional neuroblastoma, which means the cancer has grown beyond the place it started. Some cancers that spread, called metastatic neuroblastomas, also might be in this category.
• High-risk neuroblastoma has a five-year overall survival rate of about 63%. Most metastatic neuroblastomas, also called stage M, are in this category. Stage M neuroblastoma used to be called stage 4.

Studies of cancer survival rates may not include people who had the latest treatments. The studies include people who were diagnosed more than five years ago. Neuroblastoma treatment is quickly advancing to include new treatments and new ways of using existing treatments.

What you can do

Ask your child's healthcare team about things you can do to support your child's health during treatment. There is much about neuroblastoma you can't control. But you can help improve your child's sense of well-being during treatment by helping your child:

• Avoid infections. Cancer treatments can lower the number of disease-fighting cells in the body. This increases the risk of serious infections. Lower the risk by washing your hands frequently. Wash toys and surfaces your child often touches.
• Be active. Physical activity may improve mood and help with fatigue. For young children, being physically active often involves playing and dancing. Ask your healthcare team about any restrictions on activity. A physical therapist can help if your child has difficulty being active during cancer treatment.
• Feel rested. Cancer treatment often causes fatigue. Help your child manage this symptom by sticking to a regular bedtime as much as possible. Allow for extra rest when your child needs it. Physical activity helps too.
• Feel supported. Help support your child in this stressful time by being with your child as much as possible. When you can't, have someone familiar provide care. Try to maintain your usual routines as much as possible, such as allowing for playtime and having a usual bedtime.
• Get enough to eat. Cancer treatments and side effects can make it hard to eat. Buy food you know your child likes. Have snacks that are always ready in case your child feels hungry. Focus on frequent snacks rather than larger meals. Talk with your healthcare team about other ways to make sure your child gets enough nutrition.

Your child's healthcare team can connect you with healthcare professionals who can help you make sure your child feels as well as possible during cancer treatment.