Neuroblastoma
Signs and 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. Protruding eyes and dark circles around the eyes are common symptoms caused by cancer that has spread to the area behind the eye. Neuroblastoma also may compress the spinal cord, causing paralysis. Fever, anemia and high blood pressure are occasionally experienced. Other less common symptoms include severe diarrhea, uncoordinated or jerky muscle movements or uncontrollable eye movement.
Diagnosis
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 renal 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 include a computed tomography (CT) scan, bone scan, MIBG (meta-iodobenzylguanidine) scan, magnetic resonance imaging (MRI) and ultrasound.
Computerized Tomography (CT) 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.
Types 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
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 -- 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 -- 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 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.
Treatment by Type
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:
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:
If your child is older than 1 year of age, treatment may be one of the following:
Disseminated Neuroblastoma
Your child's treatment may be one of the following:
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 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.
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