## Neuroblastoma: Sites of Metastasis **Key Point:** Bone and bone marrow are the most common sites of metastasis in neuroblastoma at diagnosis, occurring in approximately 55% of metastatic cases. ### Frequency of Metastatic Sites in Neuroblastoma | Site | Frequency | Clinical Features | |---|---|---| | **Bone and bone marrow** | ~55% | Most common; bone pain, pathological fractures | | Liver | ~30% | Hepatomegaly, can cause Pepper syndrome | | Lymph nodes | ~25% | Regional and distant nodal involvement | | Lung | ~10% | Less common than bone | | Brain | ~5% | Rare; poor prognostic indicator | | Orbit | ~5% | "Raccoon eyes" (periorbital ecchymosis) | **High-Yield:** The INSS (International Neuroblastoma Staging System) stage 4 disease (metastatic) is the most common presentation at diagnosis in children >18 months old. Bone metastases are the hallmark of advanced neuroblastoma. ### Clinical Presentation of Bone Metastases - Bone pain and limping - Pathological fractures - Elevated alkaline phosphatase and lactate dehydrogenase (LDH) - MIBG (metaiodobenzylguanidine) scan shows characteristic uptake in bone lesions **Mnemonic:** **BONE-LIVER-NODES** — the three most common metastatic sites in neuroblastoma, with bone being the most frequent. **Clinical Pearl:** Neuroblastoma has a unique propensity for bone marrow infiltration, which can be detected by bone marrow aspiration and biopsy. This is part of the staging workup and affects prognosis. [cite:Robbins 10e Ch 8] 
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