Neuroblastoma is a cancer arising in the adrenal gland or less often from the extra-adrenal sympathetic chain, including the retroperitoneum, chest, and neck. Diagnosis is based on biopsy. Treatment may include surgical resection, chemotherapy, radiation therapy, and high-dose chemotherapy with stem cell transplantation.

Neuroblastoma is the most common cancer among infants. Almost 90% of neuroblastomas occur in children < 5 yr. Neuroblastoma can result from numerous different cytogenetic abnormalities on several chromosomes; in 1 to 2%, abnormalities appear to be inherited. Some markers (eg, N-myc oncogene, hyperdiploidy, histopathology) correlate with progression and prognosis.

Neuroblastomas may begin in the abdomen (about 65%), thorax (15 to 20%), neck, pelvis, or other sites. Neuroblastoma occurs very rarely as a primary CNS cancer.

Most neuroblastomas produce catecholamines, which can be detected as elevated levels of urinary catecholamine breakdown products. Ganglioneuroma is a fully differentiated, benign variant of neuroblastoma.

About 40 to 50% of children have localized or regional disease at diagnosis; 50 to 60% have metastases at diagnosis. Neuroblastoma may metastasize to bone marrow, bone, liver, lymph nodes, or, less commonly, skin or brain.

Symptoms and Signs

Symptoms and signs depend on the site of the primary cancer and pattern of disease spread. The most common symptoms are abdominal pain, discomfort, and a sense of fullness due to an abdominal mass.

Certain symptoms may result from metastases. These include bone pain due to widespread bone metastases, periorbital ecchymosis and proptosis due to retrobulbar metastasis, and abdominal distention and respiratory problems due to liver metastases, especially in infants. Occasionally, pallor due to anemia and petechiae due to thrombocytopenia occur in children with bone marrow metastases.

Children occasionally present with focal neurologic deficits or paralysis due to direct extension of the cancer into the spinal canal. They may also present with paraneoplastic syndromes (see Overview of Cancer: Paraneoplastic Syndromes), such as cerebellar ataxia, opsoclonus-myoclonus, watery diarrhea, or hypertension.

Diagnosis

• CT
• Biopsy
• Sometimes bone marrow aspirate or core biopsy plus measurement of urinary catecholamine intermediates

Routine prenatal ultrasonography occasionally detects neuroblastoma. Patients presenting with abdominal symptoms or a mass require CT. Diagnosis is then confirmed by biopsy of any identified mass. Alternatively, diagnosis can be confirmed by finding characteristic cancer cells in a bone marrow aspirate or core biopsy plus elevated urinary catecholamine intermediates. Urinary vanillylmandelic acid (VMA), homovanillic acid (HVA), or both are elevated in ≥ 90% of patients. A 24-h urine collection can be used, although a spot urine test is usually sufficient. Neuroblastomas must be differentiated from Wilms' tumor, other renal masses, rhabdomyosarcoma, hepatoblastoma, lymphoma, and tumors of genital origin.

The following should be done to evaluate for metastases:

• Bone marrow aspirates and core biopsies from multiple sites (typically, both iliac crests)
• Skeletal survey
• Bone scan or ¹³¹I-metaiodobenzylguanidine (MBIG) scan
• Abdominal, pelvis, and chest CT or MRI

Cranial imaging with CT or MRI is indicated if symptoms or signs suggest brain metastases.

When the cancer is resected, a portion should be analyzed for DNA index (a quantitative measure of chromosome content) and amplification of the N-myc oncogene to determine prognosis and intensity of therapy. Risk categorization is complex, but generally classified as

• Low: Age < 1 yr, no amplification of the N-myc oncogene, and lower-stage (localized) disease
• Intermediate: Regional spread but no amplification of the N-myc oncogene
• High: Age ≥ 1 yr plus metastatic disease, amplification of the N-myc oncogene, or both

Prognosis

Prognosis is better for children with low-risk disease.

Treatment

• Surgical resection
• Chemotherapy
• Sometimes stem cell transplantation
• Sometimes radiation therapy

Surgical resection is important for low-risk and intermediate-risk disease. Chemotherapy (typical drugs include vincristineSome Trade Names
ONCOVIN
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, cyclophosphamideSome Trade Names
CYTOXAN
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, doxorubicinSome Trade Names
ADRIAMYCIN
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, cisplatinSome Trade Names
PLATINOL
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, carboplatinSome Trade Names
PARAPLATIN
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, ifosfamideSome Trade Names
IFEX
MITOXANA
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, and etoposideSome Trade Names
ETOPOPHOS
VEPESID
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) is usually necessary for children with intermediate-risk disease. High-dose chemotherapy with stem cell transplantation and cis-retinoic acid are frequently used for children with high-risk disease. Radiation therapy is sometimes needed for children with intermediate-risk or high-risk disease or for inoperable tumors.

Last full review/revision January 2009 by David N. Korones, MD

Content last modified February 2012