A common parenchymal tumor in children that originates primarily in the adrenal gland, but can also originate in other parts of the sympathetic nerve outside the adrenal gland, including the retroperitoneum or thorax. Approximately 75% of patients with neuroblastoma are under 5 years of age. Some patients have a familial predisposition. Approximately 65% of tumors originate in the abdomen, 15% to 20% in the chest, and the remaining 15% in various locations such as the neck, pelvis, etc. Neuroblastoma originating in the central nervous system is rare. Many neuroblastomas produce catecholamines, and elevated concentrations of catecholamine breakdown products can be measured in the urine of children with neuroblastoma. Ganglioneuroma generally occurs in adults and is a well-differentiated, benign tumor that is distinct from neuroblastoma. Signs, symptoms and diagnosis Signs and symptoms depend on the location and stage of the tumor, such as an abdominal mass, or dyspnea due to a tumor in the chest. Occasionally, signs and symptoms are caused by tumor metastases, such as liver enlargement due to liver metastases; bone pain due to bone metastases; or pallor (anemia), skin bleeding spots (thrombocytopenia), and leukopenia due to bone marrow metastases. Intra-tumor hemorrhage or necrosis may occur, and abdominal tumors may extend beyond the midline. Other rare sites of metastasis are the skin and brain. Occasionally, children may exhibit neoplastic-like syndromes such as strabismus-nystagmus-myoclonus, watery diarrhea, or hypertension. Localized neurological deficits may also be seen due to direct infiltration of the spinal cord by the tumor. Diagnostic tests include ultrasound and CT to investigate the nature and extent of the primary tumor. The following tests are used to evaluate metastatic lesions: bone marrow aspiration from multiple sites, skeletal exploration, bone scan, CT, and sometimes 131I metal iodobenzylguanidine scan. Urinary vanillo-mandelic acid (VMA) is elevated in >65% of patients; concomitant elevation of hypervanillic acid is seen in more than 90% of cases. Although a single urine test is usually sufficient, there is value in collecting 24-hour urine. When the tumor is removed, a portion of the tumor should be taken for DNA indexing (quantitative determination of chromosome content) and MYCN proto-oncogene amplification analysis. The differential diagnosis includes Wilms’ tumor, renal mass, rhabdomyosarcoma, hepatocellular tumor, leukemia, and tumors originating in the genital system. Prognosis and treatment Surgical resection of a localized primary tumor offers the best chance of cure. The prognosis is better in children under 1 year of age, in early stages of disease and in the absence of amplification of the MYCN proto-oncogene. Chemotherapy is often required in older children (e.g., >1 year of age) and in children with advanced disease. Chemotherapeutic agents (e.g., vincristine, cyclophosphamide, adriamycin, and cisplatin) and radiation therapy are required in advanced disease.