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Neuroblastoma, an aggressive cancerous tumor affecting infants and young children, begins in the sympathetic nerve tissues, or the nerves responsible for the body's emergency "fight or flight" response. In the United States, about 600 children are diagnosed with neuroblastoma each year. It is the most common tumor found in children younger than 1 year of age.

Although these tumors may be present at birth, they often aren't detected until they've grown and compressed surrounding organs or have spread to lymph nodes, bones, the central nervous system or bone marrow. In rare cases, neuroblastoma can be detected before birth by a fetal ultrasound.

The tumor usually begins in the tissues of the adrenal glands, which are located in the abdomen on top of the kidneys. These glands secrete hormones and other important substances that are required for normal functions in the body such as the nervous system. The tumor also may begin in nerve tissue next to the spine in the neck, chest or pelvis.

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Signs & symptoms

The most common symptoms of neuroblastoma are caused by pressure from the tumor or bone pain from cancer that has spread to the bone and bone marrow. Symptoms may include:

  • Protruding eyes and dark circles around the eyes caused by cancer that has spread to the area behind the eye
  • Paralaysis from neuroblastoma that compresses the spinal cord
  • Fever, anemia and high blood pressure are occasionally experienced

Other less common symptoms include:

  • Severe diarrhea
  • Uncoordinated or jerky muscle movements
  • Uncontrollable eye movement

Symptoms also may include:

  • A firm mass in the abdomen
  • Difficulty breathing
  • Weight loss
  • Fever
  • Bone pain
  • Difficulty swallowing


If a child has symptoms of neuroblastoma, blood and urine tests, tissue samples, and imaging studies will be needed. These tests are important because many of the symptoms and signs of neuroblastoma also can be caused by other cancers or by non-cancerous diseases.

Blood and Urine Tests

Normal nerve cells release chemicals called neurotransmitters that control nerve activity. Catecholamines are the main group of neurotransmitters produced by cells of the sympathetic nervous system. The body breaks down the catecholamine molecules into metabolites, or smaller pieces, and they are passed out of the body in the urine.

In about 90 percent of cases, neuroblastoma causes elevated levels of catecholamines or neurotransmitters, which are detected by blood or urine tests. Some of the symptoms associated with neuroblastoma — such as high blood pressure, rapid heartbeat or diarrhea — are caused by increased catecholamines.

Your child's doctor may order other blood tests to check liver and kidney function and salt balance. A urinalysis will be conducted to further check kidney function.

Imaging Tests

Imaging tests include diagnostic X-rays and other procedures that produce images or pictures of the body's interior. Two or more of these tests are generally used to identify tumors in areas where neuroblastomas tend to spread. These tests may include:

  • Computed Tomography (CT or CAT) Scan — This is a diagnostic imaging procedure that uses a combination of X-rays and computer technology to produce cross-sectional images, both horizontally and vertically, of the body. A CT scan shows detailed images of the body, including the bones, muscles, fat and organs. CT scans are more detailed than general X-rays. To produce the image, it often is necessary to use a contrast dye administered either intravenously or consumed orally.
  • Magnetic Resonance Imaging (MRI) — This scan uses magnets, rather than X-rays, to produce detailed images of the body. The MRI machine sends radio waves into the body and then measures the response with a computer. The computer makes an image or picture of the interior of the body. MRIs are used for certain types and locations of tumors because they can produce a better image than X-rays.
  • Ultrasound — An ultrasound exam or sonogram uses high frequency sound waves to create images of organs in the body. There is no radiation used in this test. Sound waves bounce off tissues using the same principles as sonar. The echoes that return to the transducter are used to draw the images on the screen.
  • MIBG — An MIBG scan uses a chemical called metaiodobenzylguanidine that is slightly radioactive to identify areas where the neuroblastoma has spread. It is a very sensitive method of detecting the spread of cancer in bone and soft tissues. MIBG is injected intravenously. A scan, which takes about an hour, is performed 24 hours later.
  • Positron Emission Tomography (PET) Scan A PET scan is a nuclear medicine test in which a radioactive glucose compound is injected and shows the areas of tumor in the body. It's used in about 10 percent of the cases where the MIBG scan is negative.
  • Biopsies — Signs and symptoms, blood and urine tests and imaging studies may indicate that a neuroblastoma is probably present, but a conclusive diagnosis can be made only by biopsy — when neuroblastoma cells in tissue samples are seen under a microscope.

If blood or urine levels of catecholamines or their metabolites are elevated, then finding cancer cells in a bone marrow biopsy is sufficient evidence for a diagnosis of neuroblastoma. The disease spreads to bone marrow in about a quarter of patients.

Bone marrow can be sampled in two ways, and both are generally done at the same time. A bone marrow biopsy uses a large needle to remove a cylindrical piece of the bone about 1/2 inch long and 1/16 inch across. A bone marrow aspiration uses a thinner needle and a syringe to extract cells from the marrow, the soft tissue inside bone cavities.

Alternatively, tissue samples can be taken from the primary tumor. If examination under the microscope shows certain features typical of neuroblastoma, a definite diagnosis can be made, even if catecholamine levels are not elevated. Some cases of neuroblastoma are easily recognized under a microscope when examined by doctors experienced in testing children's tumor samples.

Other cases of neuroblastoma have features easily confused with other types of children's cancers. In these cases, special tests of the tissue samples must be done. For example, immunohistochemistry uses special laboratory antibodies that specifically recognize chemicals found in neuroblastoma cells and other antibodies that recognize chemicals of other cancer cells. Electron microscopy uses a special microscope hundreds of times more powerful than usual laboratory microscopes, and can recognize tiny packages of catecholamines inside neuroblastoma cells and other abnormalities.

Categories of Neuroblastoma

When neuroblastoma is diagnosed, your child's doctor may use the following categories or terms to describe the cancer:

  • Localized Resectable — The cancer is confined to the site of origin, there is no evidence of spread, and the cancer can be surgically removed.
  • Localized Unresectable — The cancer is confined to the site of origin, but the cancer cannot be completely removed surgically.
  • Regional — The cancer has extended beyond the site of origin to regional lymph nodes and/or surrounding organs or tissues, but has not spread to distant parts of the body.
  • Disseminated — The cancer has spread from the site of origin to distant lymph nodes, bone, liver, skin, bone marrow, and/or other organs (except as defined for stage 4S).
  • Stage 4S — This also is called "special" neuroblastoma because it is treated differently. The cancer is localized, with dissemination or spreading limited to liver, skin and to a very limited extent to bone marrow.
  • Recurrent — This means the cancer has come back or continues to spread after treatment. It may come back in the original site or in another part of the body.


Treatment options are related to the age of your child, tumor location, stage of disease, regional lymph node involvement and tumor biology. More than one method of treatment may be used, depending on your child's needs.


Surgery is used when possible to remove as much of the cancer as possible. If the cancer can't be removed, surgery may be limited to a biopsy.

Radiation Therapy

Radiation therapy uses high-energy rays to damage or kill cancer cells and shrink tumors. Radiation usually comes from a machine outside the body called external beam radiation therapy.


Chemotherapy is the use of drugs to kill cancer cells and shrink tumors. Chemotherapy drugs may be taken orally or injected into a vein or a muscle. Chemotherapy is called a systemic treatment because the drug enters the bloodstream, travels through the body and can kill cancer cells throughout the body. Chemotherapy may be given after the tumor has been surgically removed to kill any remaining cancer cells. This is called adjuvant chemotherapy. Chemotherapy also can be used to shrink the tumor before surgery. This is called neoadjuvant chemotherapy.

Bone Marrow Transplant

Bone marrow transplantation is a procedure in which healthy bone marrow is given to replace bone marrow destroyed by anti-cancer drugs or radiation. At UCSF Benioff Children's Hospital, the Bone & Marrow Transplant Program offers autologous bone marrow stem cell transplants to treat children with high-risk neuroblastoma. In this type of transplant, high-dose chemotherapy is given to kill the tumor. Bone marrow function is restored by infusing the patient's own bone marrow cells, which were previously removed and stored.

MIBG Therapy


UCSF Benioff Children's Hospital is one of the few centers in the country to offer MIBG therapy for high-risk neuroblastomas that have not responded to chemotherapy, or have recurred after treatment. MIBG is a chemical that mimics certain natural compounds in the body that are concentrated in selective tissues, including neuroblastoma cells. MIBG can be attached to radioactive forms of iodine and given as an IV treatment.

Doctors at UCSF led a clinical trial of MIBG treatment for patients with resistant neuroblastoma. This treatment led to decreases in tumor size or number of tumor spots in approximately one-third of patients, making MIBG one of the most active drugs for these patients. In some patients, all of the tumor spots went away for a time.

MIBG therapy is only offered by entering a study or clinical trial because it is not yet FDA approved; UCSF conducts several MIBG therapy studies for the treatment of neuroblastoma and pheochromocytoma. The study a child enters will depend upon a number of factors, including open studies and their prior treatment.

One of the major side effects of MIBG treatment is low blood counts, or bone marrow suppression. Giving a dose of the patient's own stem cells can help to improve blood counts after MIBG treatment.

Sometimes MIBG is combined with chemotherapy or other medications. This may make neuroblastoma cells more sensitive to MIBG treatment. Your doctor will decide whether your child should be treated with MIBG alone or in combination with other medications. To learn more about MIGB therapy, go to

Intraoperative Radiation Therapy (IORT)

Radiation oncologists at UCSF have been pioneering the use of intraoperative radiation therapy (IORT) for some of the most difficult cases of neuroblastoma. UCSF is one of the few medical centers nationwide at the forefront of advancing this mode of treatment.

IORT delivers a concentrated beam of radiation to cancerous tumors while they are exposed during surgery. This allows high doses of radiation to be administered to tumors without exposing nearby healthy organs to radiation, lessening the risk that healthy tissue will be damaged.

Another advantage of IORT is that patients do not have to return for successive rounds of therapy after surgery. Those who receive the most common standard alternative, external beam radiation therapy (EBRT), typically receive treatment five days a week for several weeks. A single dose of IORT may have as much effect on the tumor as 10 to 20 daily radiation treatments.

Prior to IORT, oncologists treated the most aggressive cases of neuroblastoma with surgery, high doses of chemotherapy and some form of radiation. These high-dose treatments kill tumor cells more effectively. But the treatments also result in toxicities in many normal tissues, such as the death of bone marrow cells that make blood and immune cells. Thanks to these high-dose combinations of radiotherapy and chemotherapy, survival among neuroblastoma patients has improved greatly over the past two decades. Even so, among the 45 percent with high-risk tumors, the worst prognosis, only about one in three lives free of cancer regrowth for three years or more.

Treatment by Category

As described in the diagnosis section, neuroblastoma is categorized as localized resected, localized unresected, regional, disseminated and special.

Localized Resectable Neuroblastoma

Your child's treatment may be one of the following:

  • Surgery to remove the cancer
  • Surgery plus adjuvant chemotherapy
  • Surgery plus radiation therapy

Localized Unresectable Neuroblastoma

Initial treatment generally consists of surgery to remove as much of the cancer as possible, followed by chemotherapy. A second surgery may be performed to remove any cancer that remains. Radiation therapy also may be prescribed.

Regional Neuroblastoma

Treatment depends on your child's age. If your child is younger than 1 year of age, treatment may include the following:

  • Surgery to remove the cancer
  • Chemotherapy

If your child is older than 1 year of age, treatment may be one of the following:

  • Surgery to remove the cancer
  • Surgery followed by chemotherapy
  • Chemotherapy with or without radiation therapy to reduce the tumor, followed by surgery
  • Multi-drug chemotherapy
  • Radiation therapy
  • New methods of treatment in a clinical trial or study

Disseminated Neuroblastoma

Your child's treatment may be one of the following:

  • Multi-drug chemotherapy with or without surgery and/or radiation therapy
  • Chemotherapy followed by peripheral stem cell transplantation and 13-cis retinoic acid
  • New methods of treatment in a clinical trial or study

Stage 4S Neuroblastoma

Children with this special type of neuroblastoma may not require therapy. You may want to have your child take part in a clinical trial that provides new methods of treatment.

Recurrent Neuroblastoma

The selection of treatment for recurrent or progressive neuroblastoma depends on the location and extent of the recurrence and previous therapy as well as individual circumstances. A clinical trial may be appropriate. UCSF Benioff Children's Hospital has available national and local studies for recurrent neuroblastoma, including new therapies with targeted radiation (I-131-MIBG), Phase I trials of the New Approaches to Neuroblastoma Therapy (NANT) consortium and Phase I and II trials of the Children's Oncology Group.

UCSF Benioff Children's Hospitals medical specialists have reviewed this information. It is for educational purposes only and is not intended to replace the advice of your child's doctor or other health care provider. We encourage you to discuss any questions or concerns you may have with your child's provider.

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