Epidemiology and Risk Factors
Neuroblastoma is the third most common solid tumor in children, developing outside the central nervous system. It occurs slightly less frequently in females than in males, though females tend to have a more favorable prognosis.
The etiology is rooted in a hereditary predisposition, hypothesized to involve germline mutations that render cells susceptible to secondary somatic mutations.
Risk Factors and Associations:
- Increased incidence in twins and siblings.
- Association with genetic disorders: Beckwith–Wiedemann syndrome and neurofibromatosis.
Gross Pathology
The tumor forms a mass of varying size, which on cross-section appears as soft, grayish tissue resembling brain parenchyma. Large masses frequently undergo secondary changes that create a heterogeneous structure, including foci of necrosis, hemorrhage, and calcification.
Relationship to Surrounding Tissues:
- The tumor may be well-demarcated with a thin capsule.
- Pronounced infiltrative growth is common, with rapid invasion into adjacent structures: kidneys, renal and inferior vena cava, and aorta.
Microscopic Structure and Differentiation
The histological appearance of neuroblastoma directly depends on its degree of maturity. The tumor is prone to heterogeneity; a single mass may contain areas of varying differentiation.
- Poorly differentiated neuroblastoma (constitutes the majority of cases). Composed of small, lymphocyte-like cells with dark (hyperchromatic) nuclei and scanty cytoplasm. Cells form solid, contiguous sheets.
- More differentiated tumors. Cells acquire eosinophilic neurofibrillar processes and are arranged within an increasing volume of fibrillary stroma. The appearance of Homer Wright pseudorosettes is characteristic—structures where cells form a ring around central eosinophilic clusters of neurofibrils.
- Ganglioneuroma. Represents a terminally differentiated tumor. Composed of large, mature ganglion cells (with broad eosinophilic cytoplasm, large vesicular nuclei, and distinct nucleoli). The cells are surrounded by bundles of connective tissue, nerve fibers, and Schwann cells (lemmocytes).
Transmission electron microscopy reveals specific markers in neuroblastoma cells: neurosecretory granules and processes containing microtubules.
International Staging System
Staging is performed based on the pathological examination of surgically resected material:
- Stage 1: Tumor confined to the organ of origin; complete gross excision, with or without microscopic residual disease; representative ipsilateral lymph nodes negative for tumor.
- Stage 2A: Tumor is unilateral with incomplete gross resection; representative ipsilateral non-adherent lymph nodes are negative for tumor.
- Stage 2B: Unilateral tumor with complete or incomplete gross resection; with positive ipsilateral regional lymph nodes. Enlarged contralateral lymph nodes must be negative.
- Stage 3: Unilateral tumor with infiltration across the midline with or without regional lymph node involvement; OR midline tumor with bilateral infiltration; OR single contralateral tumor with regional lymph node involvement.
- Stage 4: Any primary tumor with dissemination to distant lymph nodes, bone, bone marrow, liver, skin, and/or other organs.
- Stage 4S: Localized primary tumor (corresponding to Stage 1 or 2), with dissemination limited to skin, liver, and/or minimal bone marrow involvement (restricted to infants under 1 year of age).