Neuroblastoma is a malignant, embryonal neuroendocrine neoplasm of the sympathetic nervous system that originates from neural crest cells, potentially secretes catecholamines, and is usually found in the adrenal glands or sympathetic ganglia.

Epidemiology

• Most common malignancy of the adrenal medulla in infants
• Mean age at diagnosis: 1–2 years

Etiology

• Amplification and overexpression of oncogene MYCN (N-myc)

Pathophysiology

• Homer Wright rosettes: Halo-like clusters of neuroblast cells surrounding a central pale area containing neuropil (associated with tumors of neuronal origin such as neuroblastoma, medulloblastoma, primitive neuroectodermal tumors, and pineoblastoma)
• Bombesin and NSE positive

  • A tumor marker for neuroblastoma, small cell carcinoma of the lung, pancreatic cancer, and gastric cancer.

Clinical features

General symptoms

• Failure to thrive or weight loss
• Fever
• Nausea, vomiting, loss of appetite

Localized symptoms

Primary Tumor Locations and Symptoms

• Abdomen (in > 60% of cases)
  • In adults, pheochromocytoma is the most common tumor of the adrenal medulla, while in children it is neuroblastoma.
  • Palpable, firm, irregular abdominal mass that may cross the midline (in contrast to nephroblastoma, which is smooth and usually does not cross the midline)
• Chest (in ∼ 20% of cases): particularly paravertebral ganglia
  • Spinal cord compression → back pain, weakness, numbness, ataxia, loss of bowel or bladder control
  • Scoliosis
  • Dyspnea, cough
  • Inspiratory stridor
• Neck
  • Horner syndrome

Metastases Locations and Symptoms

• Orbit of the eye

  • Periorbital ecchymoses ("raccoon eyes")
  • Proptosis

• Bones

  • Bone pain
  • Anemia (bone marrow suppression)

• Skin

  • Subcutaneous nodules

Paraneoplastic syndromes

• Chronic diarrhea → electrolyte imbalances
• Opsoclonus-myoclonus-ataxia: a paraneoplastic syndrome of unclear etiology characterized by rapid and multi-directional eye movements, rhythmic jerks of the limbs, and ataxia (dancing eyes dancing feet syndrome)
• Possibly hypertension, tachycardia, palpitations, sweating, flushing (hypertension is more commonly seen in pheochromocytoma)

Diagnostics

Laboratory tests

• Urine
  • ↑ Catecholamine metabolites homovanillic acid (HVA) and vanillylmandelic acid (VMA) in 24-hour urine
• Blood
  • ↑ Catecholamine metabolites (HVA/VMA)
  • ↑ Lactate dehydrogenase (LDH), ferritin, neuron-specific enolase (NSE)

Treatment