Pathophysiology
Clinical meaning
Neuroblastoma is the most common extracranial solid tumor in children and the most common cancer diagnosed during infancy, accounting for approximately 8-10% of all childhood cancers. It arises from primitive neural crest cells, which are embryonic precursor cells that normally differentiate into sympathetic ganglia, adrenal medulla chromaffin cells, and other components of the sympathetic nervous system. During embryogenesis, neural crest cells migrate from the neural tube to populate the sympathetic chain ganglia, adrenal medulla, and paraganglia throughout the body. Malignant transformation of these undifferentiated or partially differentiated neural crest cells produces neuroblastoma. The most common primary site is the adrenal medulla (approximately 40% of cases), followed by the retroperitoneal sympathetic ganglia (25%), posterior mediastinum (15%), pelvis (5%), and neck (5%). The tumor produces and secretes catecholamines (dopamine, norepinephrine, and their metabolites), which are metabolized to vanillylmandelic acid (VMA) and homovanillic acid (HVA). These metabolites can be measured in 24-hour urine collections or spot urine samples and serve as tumor markers for diagnosis and treatment monitoring. Elevated urinary VMA and HVA are found in approximately 90% of neuroblastoma cases, making them...