DESCRIPTION

• Neuroblastoma is an embryonic, neural crest cell–derived small round blue cell tumor of childhood.
• 75% of neuroblastomas arise in the adrenal gland, but primary tumors can occur anywhere along the sympathetic chain. The clinical behavior of neuroblastoma is diverse and can vary from spontaneous regression to rapid progression and patient death despite highly intensive multimodal therapy.
• About half of patients have widely metastatic disease at presentation.

EPIDEMIOLOGY

• Median age at diagnosis is 18 months, with 90% of cases diagnosed before 5 years of age, including 5% diagnosed perinatally. <5% of patients are diagnosed after 10 years of age.
• The male-to-female ratio is 1.1:1.
• Approximately 800 new cases per year in the United States
• Neuroblastoma accounts for 8–10% of all childhood cancer.
  • Most common cancer diagnosed during infancy and most common extracranial solid tumor of childhood
  • Accounts for a disproportionately high percentage (15%) of pediatric cancer deaths

RISK FACTORS

• Most cases arise spontaneously, with no known specific risk factors.
• 1% are familial (autosomal dominant) and are usually associated with ALK genetic mutations.

PATHOPHYSIOLOGY

Molecular features of neuroblastoma, including segmental chromosomal aberrations (e.g., MYCN amplification) and aberrations in ALK, ATRX, and PTPN11, are thought to be oncogenic drivers that lead to dysregulation of normal autonomic neurodevelopmental pathways.

COMMONLY ASSOCIATED CONDITIONS

Some cases of familial neuroblastoma are associated with a loss of function mutation in the PHOX2B gene, which may also result in central congenital hypoventilation syndrome and Hirschsprung disease.