Description

Neuroblastomas arise from neural crest tissue and function similarly to paragangliomas and pheochromocytomas. Clinical activity varies from benign tumors that spontaneously regress to aggressive metastatic disease.

• Primary tumor location (1):
  • Adrenal medulla—40%
  • Sympathetic ganglia:
    • Abdominal—25%
    • Thoracic—15%
    • Cervical—5%
    • Pelvic—5%
  • Other—10%
• Sites of metastasis: bone—specifically to sphenoid bone and retrobulbar tissue, bone marrow, regional/disseminated lymph nodes, liver, subcutaneous tissue producing blue subcutaneous nodules

Epidemiology

• Third most common pediatric malignancy
• Most common tumor in infants <1 year of age
• Accounts for 6% of all childhood cancers (2)
• Most common solid neoplasm outside of the CNS
• Predominant age at diagnosis
  • Within 2 years of life: 50%
  • Within first 5 years of life: 90%
  • Median age 17.3 months
• Older children are at higher risk for metastatic disease and have a poorer prognosis.
• Screening has no impact on mortality.

Incidence

• 800 new cases of neuroblastoma each year in United States (1)
• From birth to age 1 year in the United States: 52.1 cases per million children per year (1)
• From age 1 to 4 years in the United States: 19.1 cases per million children per year
• First 15 years of life in the United States: 9.8 cases per million children per year

Etiology and Pathophysiology

Genetics

• 80% of tumors have genetic abnormalities.
• Autosomal dominant inheritance pattern
• Mutations in anaplastic lymphoma kinase (ALK) oncogene and PHOX2B account for the majority of hereditary neuroblastoma (2,3).
• MYCN oncogene amplification and mutations at chromosome 11q are used as markers for prognostication and treatment stratification (3).
• Other genetic mutations associated with increased susceptibility for disease (3):
  • FLJ22536
  • BARD1
  • NBPF23
• DNA ploidy: Hyperdiploidy in infants <1 year of age is associated with excellent long-term survival; diploidy is associated with treatment failure.

Risk Factors

• Maternal phenytoin or opiates
• Folate deficiency
• Opsoclonus–myoclonus syndrome
  • 50% have neuroblastoma.
• Beckwith-Wiedemann syndrome
• Pancreatic islet cell dysplasia
• Fetal alcohol syndrome
• Hirschsprung disease
• Family history of neuroblastoma
• Neurofibromatosis type 1
• Congenital central hypoventilation syndrome
• Gestational diabetes mellitus