Neuroblastoma

Symptoms and signs of neuroblastoma depend on the site of the primary cancer and pattern of disease spread. The most common symptoms are abdominal pain, discomfort, irritability, decreased appetite, 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. Children with anemia may have pallor, and those with thrombocytopenia may have petechiae.

Children occasionally present with focal neurologic deficits or paralysis due to direct extension of the cancer into the spinal canal. Tumors in the neck or upper chest may cause Horner syndrome Horner Syndrome Horner syndrome is ptosis, miosis, and anhidrosis due to dysfunction of cervical sympathetic output. (See also Overview of the Autonomic Nervous System.) Horner syndrome results when the cervical... read more (ptosis, miosis, anhidrosis). They may also present with paraneoplastic syndromes Paraneoplastic Syndromes Paraneoplastic syndromes are symptoms that occur at sites distant from a tumor or its metastasis. Although the pathogenesis remains unclear, these symptoms may be secondary to substances secreted... read more , such as cerebellar ataxia, opsoclonus-myoclonus, watery diarrhea, or hypertension.

Rare diseases that are associated with neural crest tumors (eg, neuroblastoma, ganglioneuroblastoma, ganglioneuroma) include ROHHADNET (rapid-onset obesity with hypothalamic dysfunction, hypoventilation, autonomic dysregulation, and neuroendocrine tumors) and congenital central hypoventilation syndrome.

Routine prenatal ultrasonography occasionally detects neuroblastoma. Patients presenting with abdominal symptoms or a mass require CT or MRI. Diagnosis of neuroblastoma is then confirmed by biopsy of any identified mass.

Alternatively, diagnosis can be established without biopsy or surgery of the primary tumor by finding characteristic cancer cells in a bone marrow aspirate or core biopsy plus elevated urinary catecholamine intermediates. These methods of diagnosis are not commonly done but can be useful in situations where biopsy and/or surgery is considered high risk because of patient or tumor characteristics.

Urinary vanillylmandelic acid (VMA), homovanillic acid (HVA), or both are elevated in ≥ 90% of patients. A 24-hour urine collection can be used, but a spot urine test is usually sufficient. If the primary site of the neuroblastoma is adrenal, it must be differentiated from Wilms tumor Wilms Tumor Wilms tumor is an embryonal cancer of the kidney composed of blastemal, stromal, and epithelial elements. Genetic abnormalities have been implicated in the pathogenesis, but familial inheritance... read more and other renal masses. It may also need to be differentiated from rhabdomyosarcoma Rhabdomyosarcoma Rhabdomyosarcoma is a cancer arising from embryonal mesenchymal cells that have potential to differentiate into skeletal muscle cells. It can arise from almost any type of muscle tissue in any... read more , hepatoblastoma Hepatoblastoma Primary liver cancer is usually hepatocellular carcinoma (HCC). The first manifestations of liver cancer are usually nonspecific, delaying the diagnosis. When diagnosed at advanced stages, prognosis... read more , lymphoma Overview of Lymphoma Lymphomas are a heterogeneous group of tumors arising in the reticuloendothelial and lymphatic systems. The major types are Hodgkin lymphoma Non-Hodgkin lymphoma See table Comparison of Hodgkin... read more , and tumors of genital origin.

Treatment of neuroblastoma is based on the risk category (see also the National Cancer Institute's Neuroblastoma Treatment—Health Professional Version).

Surgical resection is important for low-risk and intermediate-risk disease. It is often delayed until adjuvant chemotherapy is given to improve the chance of adequate surgical resection.

Chemotherapy (typical drugs include vincristine, cyclophosphamide, doxorubicin, cisplatin, carboplatin, ifosfamide, and etoposide) is usually necessary for children with intermediate-risk or high-risk disease. In addition, high-dose chemotherapy with stem cell transplantation and cis-retinoic acid are also frequently used for children with high-risk disease.

Radiation therapy is sometimes needed for children with intermediate-risk disease or for children with inoperable tumors and is a standard part of treatment for local control of high-risk disease.

Immunotherapy using monoclonal antibodies against neuroblastoma antigens (GD2) combined with cytokines is used as maintenance therapy in high-risk disease. In a recent study of relapsed/refractory neuroblastoma, a combination of immunotherapy with chemotherapy led to impressive clinical responses (1 Treatment reference Neuroblastoma is a cancer arising in the adrenal gland or less often from the extra-adrenal sympathetic chain, including in the retroperitoneum, chest, and neck. Diagnosis is confirmed by biopsy... read more ).

Prognosis for neuroblastoma depends on age at diagnosis, stage, and biologic factors (eg, histopathology, tumor cell ploidy in younger patients, MYCN amplification). Younger children with localized disease have the best outcome.

Survival rates for low-risk and intermediate-risk disease are about 90 to 95%. Historically, the survival rate for high-risk disease was about 15%. This rate has improved to > 50% with use of more intensified therapy. And a recent randomized study showed intensive therapy combined with immunotherapy resulted in a 2-year event-free survival rate of 66% (1 Prognosis reference Neuroblastoma is a cancer arising in the adrenal gland or less often from the extra-adrenal sympathetic chain, including in the retroperitoneum, chest, and neck. Diagnosis is confirmed by biopsy... read more ).

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