Neuroblastoma

Neuroblastoma is an embryonal malignancy of the sympathetic nervous system and is the most common extracranial solid tumor of childhood. It arises from neural crest cells, which normally give rise to the sympathetic ganglia and the adrenal medulla. The tumor most frequently originates in the adrenal glands but can also develop anywhere along the sympathetic nervous chain, including the neck, chest, abdomen, and pelvis. Neuroblastoma is highly heterogeneous in its clinical behavior, ranging from spontaneous regression (particularly in infants) to aggressive, treatment-resistant metastatic disease. Common symptoms depend on tumor location and stage but may include an abdominal mass, bone pain, periorbital ecchymosis (raccoon eyes), proptosis, weight loss, fever, fatigue, and in some cases opsoclonus-myoclonus syndrome. Metastatic disease frequently involves bone, bone marrow, liver, and skin. Amplification of the MYCN oncogene is a well-established marker of aggressive disease and poor prognosis. The majority of neuroblastoma cases are sporadic, though approximately 1-2% of cases are familial. Germline mutations in the ALK (anaplastic lymphoma kinase) gene and, less commonly, in the PHOX2B gene have been identified in hereditary neuroblastoma. Common somatic genetic alterations include MYCN amplification, segmental chromosomal aberrations (such as 1p deletion, 11q deletion, and 17q gain), and ALK mutations. Diagnosis involves imaging studies, urinary catecholamine metabolites (vanillylmandelic acid and homovanillic acid), histopathological examination, and assessment of biological markers including MYCN status. Treatment is risk-stratified based on age at diagnosis, tumor stage (International Neuroblastoma Staging System or INRGSS), histology, MYCN amplification status, and tumor ploidy. Low-risk patients may require observation alone or minimal surgery, as some tumors spontaneously regress. Intermediate-risk patients typically receive moderate chemotherapy and surgery. High-risk neuroblastoma requires intensive multimodal therapy including induction chemotherapy, surgical resection, high-dose chemotherapy with autologous stem cell rescue, radiation therapy, and maintenance therapy with anti-GD2 immunotherapy (such as dinutuximab) combined with isotretinoin (13-cis-retinoic acid) and cytokines. Despite aggressive treatment, high-risk neuroblastoma carries a significant relapse rate, and ongoing clinical trials continue to explore novel targeted therapies, including ALK inhibitors and other immunotherapeutic approaches.

Data sourced from FDA regulatory filings and ClinicalTrials.gov. Updated periodically.

Common questions about Neuroblastoma