Neuroblastoma

What is Neuroblastoma?

Neuroblastoma is a type of cancer that grows from immature nerve cells called neuroblasts. It is the most common solid tumor that occurs outside the brain in children.

Neuroblastoma can occur anywhere along the sympathetic nervous system (SNS). Neuroblastoma most often occurs in the abdomen and frequently develops in nerve tissue of the adrenal glands which are located on top of the kidneys. It can also occur in nerve tissue in the neck, chest, or pelvis.

Neuroblastoma is usually diagnosed in young children under 5 years of age. It is the most common tumor in infants. Neuroblastoma accounts for 50% of cancers in infants and 7-10% of all childhood cancers. About 650 children are diagnosed with neuroblastoma in the United States each year.

Symptoms of neuroblastoma depend on the location of the tumor but may include a lump or mass, pain in the abdomen, loss of appetite, and irritability. Often, neuroblastoma has spread to other parts of the body by the time it is diagnosed.

Treatment for neuroblastoma depends on the stage of disease (how much cancer has spread from the main tumor). Some children can be treated with surgery alone. Patients with more severe disease require intense treatment including surgery, chemotherapy, radiation therapy, and/or immunotherapy.

Risk Factors and Causes of Neuroblastoma

Certain factors may increase risk for neuroblastoma. Neuroblastoma is most often seen in young children and occurs slightly more often in males compared to females.

A small number of patients (1-2%) have hereditary neuroblastoma. This type of neuroblastoma can be passed down in families. Hereditary neuroblastoma is most commonly caused by a change, or mutation, in the ALK or PHOX2B gene. Children with hereditary neuroblastoma have a 50% chance of passing the disease on to their children.

Learn More About Hereditary Neuroblastoma

Signs and Symptoms of Neuroblastoma

Signs and symptoms of neuroblastoma depend on where the tumor is located and the age of the child. These may include:

• Lump in the neck, chest, or abdomen
• Bulging eyes or dark circles around the eyes
• Stomach pain
• Irritability
• Decreased appetite
• Constipation
• Leg weakness

Other symptoms of neuroblastoma may include chronic diarrhea, change in eye movement, high blood pressure, headache, cough, difficulty breathing, fever, bruising, or Horner syndrome.

Diagnosis of Neuroblastoma

Several types of procedures and tests are used to diagnose neuroblastoma. These include:

• A health history and physical exam to learn about symptoms, general health, past illnesses, family history, and other risk factors.
• Lab studies to look at substances in blood and urine. These may include a complete blood count and measures of kidney and liver function.

• A neurological exam to measure different aspects of brain and nerve function including memory, vision, hearing, muscle strength, balance, coordination, and reflexes.
• Imaging tests to look for tumors and help determine other tests and treatment.
  • X-ray uses electromagnetic energy to take pictures of different areas of the body such as the chest and abdomen.
  • Ultrasound or ultrasonography uses sound waves to create an image of body tissues.
  • Computed tomography (CT or CAT scan) uses X-rays to create cross-sectional images of the organs and tissues inside the body. The machine takes many pictures to make a very detailed image. The images are taken as a series of “slices” of the body and are put together by a computer. These slices or sections can allow very small tumors to be seen.
  • Magnetic resonance imaging (MRI) makes detailed pictures of the body using radio waves and magnets. The images can help doctors get a better view of the tumor and plan treatment.
  • Full body imaging including a bone scan, PET scan, or MIBG scan is used to look for disease in other areas of the body.

• Bone marrow aspiration and biopsy to see if there are cancer cells in the bone marrow. Doctors will obtain bone marrow samples by inserting a thin, hollow needle into the hipbone. A pathologist views the sample under a microscope.
• A biopsy of the tumor is often needed to make a correct diagnosis. In a biopsy, the doctor removes a small amount of tissue from the tumor. The cells are then examined with a microscope to look for signs of cancer. An incisional biopsy or core needle biopsy may be used depending on tumor location.

The tumor will be studied to look for features that are important to the diagnosis and treatment of neuroblastoma. Some neuroblastoma tumors are more aggressive and require more intense therapy. Doctors can predict how the tumor might respond to treatment by how the cells look and whether there are certain gene changes in the tumor.

Staging of Neuroblastoma

In neuroblastoma, there are several ways the disease can be classified.

The International Neuroblastoma Staging System (INSS) stages neuroblastoma based on tumor location, spread of disease, and result of surgery. 

The International Neuroblastoma Risk Group Staging System (INRGSS) stages cancer without using the results of surgery. This system is based on tumor location and spread of disease. Imaging tests are used to determine the stage based on image defined risk factors (a prediction of how risky it would be to remove the tumor).

Neuroblastoma risk groups

Doctors also use risk groups to classify neuroblastoma and plan treatments. High risk means the tumor is more likely to come back. Patients with high risk neuroblastoma need more intense therapy.

Factors that determine risk group include:

• Age of the patient
• Stage of disease
• Characteristics of the tumor

Learn more about Risk of Relapse Groups from the Children’s Oncology Group.

Prognosis for Neuroblastoma

The chance of recovery from neuroblastoma depends on several factors:

• Child’s age at diagnosis (younger age is associated with better outcomes)
• Features of the tumor including histology, gene changes, and how fast the cells grow 
• Risk group: Low, Intermediate, or High
• Location of the tumor
• Whether the cancer has spread to lymph nodes or other parts of the body (metastatic)
• The ability of surgery to completely remove the tumor
• How the tumor responds to treatment
• If the cancer is recurrent (has come back) and how much time has passed before recurrence

Treatment of Neuroblastoma

Treatment for neuroblastoma depends on the child’s age, location of the tumor, features of the tumor (gene changes and histology), and stage of disease. These factors help determine neuroblastoma risk group (low, intermediate, or high) and treatment plans.

Treatment options for neuroblastoma include:

• Observation
• Surgery
• Chemotherapy
• High-dose chemotherapy with stem cell rescue
• Immunotherapy
• Radiation therapy

Very young, low risk patients may be followed with observation instead of active treatment. In certain cases, neuroblastoma may go away on its own (regression). However, this is rare, and patients will be monitored very closely to watch for tumor progression.

Children may be offered treatment for neuroblastoma as part of a clinical trial.

Neuroblastoma treatments are planned according to risk groups:

Life After Neuroblastoma

Monitoring for recurrence

Patients with high risk disease are at greater risk for relapse. In patients with low-risk disease, chance of recurrence is 5-15%. However, for high-risk patients, risk of relapse is as high as 50%. Recurrence in neuroblastoma is most common within the first 2 years after treatment ends. Relapse is rare when there is no evidence of cancer after 5 years of completing treatment. 

Patients will receive frequent follow-up care to screen for recurrence after treatment ends. The medical team will make specific recommendations for frequency and types of tests needed.

Health after cancer 

Survivors treated with systemic chemotherapy or radiation should be monitored for acute and late effects of therapy. Potential problems due to treatment may include hearing loss, heart problems, and kidney damage. 

Serious chronic health conditions are present 25 years after diagnosis in approximately 25% of survivors, according to the Childhood Cancer Survivor Study. These conditions include second cancers (increased risk following exposure to radiation), congestive heart failure, infertility or complications during pregnancy, and end-stage renal disease or renal failure.

Regular physical checkups by a primary care physician are important to watch for health problems that can develop years after therapy.