Neuroblastoma

Intro & Patho - Tiny Tumour Terror

⭐ Most common extracranial solid tumor in children; originates from neural crest cells of the sympathetic nervous system.

• Origin: Derived from primitive neural crest cells (sympathogonia) of sympathetic ganglia or adrenal medulla.
• Epidemiology:
  • Median age at diagnosis: 18-24 months; 90% diagnosed by age 5.
  • Accounts for 7-10% of all childhood cancers.
• Pathology: "Small, round, blue cell" tumor.
  • Homer-Wright pseudorosettes (tumor cells around neuropil).
  • Neurosecretory granules on electron microscopy.
• Key Molecular Markers:
  • MYCN oncogene amplification (critical poor prognostic factor).
  • ALK gene mutations/amplifications.
  • Chromosome 1p deletion (unfavorable).
  • Ploidy: Hyperdiploidy (favorable, especially in infants <18 months).
• 📌 Mnemonic: Neural crest, MYCN, Young child, Catecholamines, Neuronal markers.

Clinical Picture - Symptom Spotlight

• General: Fever, weight loss, irritability. Presentation varies by site.
• Primary Tumor Sites & Signs:
  • Abdomen (most common): Palpable mass (firm, irregular, crosses midline), pain.
  • Thorax: Respiratory distress, cough. Horner syndrome (ptosis, miosis, anhydrosis).
  • Neck/Cervical: Mass, Horner syndrome.
• Metastatic Manifestations:
  • Bone Marrow: Pancytopenia (pallor, bleeding, infection), bone pain.
  • Bone: Proptosis, periorbital ecchymoses ("raccoon eyes").
  • Skin: Subcutaneous nodules ("blueberry muffin" rash - infants).
• Systemic/Paraneoplastic:
  • Hypertension (catecholamines).
  • Watery diarrhea (VIPoma - rare).

  ⭐ Opsoclonus-myoclonus-ataxia syndrome ('dancing eyes, dancing feet') is a highly characteristic paraneoplastic syndrome.

Diagnosis & Staging - Detective Work

• Biochemical Markers:
  • ↑ Urine VMA & HVA (Vanillylmandelic & Homovanillic acid).
  • ↑ Serum Neuron-Specific Enolase (NSE), LDH.
• Imaging:
  • CT/MRI of primary site.
  • MIBG Scintigraphy: >90% uptake; for staging & response.
• Histopathology & Molecular:
  • Biopsy: Small, round, blue cells; Homer-Wright pseudorosettes.
  • Bone Marrow Aspiration/Biopsy: For metastasis.
  • N-MYC amplification: Key prognostic factor.
• Staging (INRGSS - Pre-treatment):
  • L1: Localized, no IDRFs (Image-Defined Risk Factors).
  • L2: Localized, with IDRFs.
  • M: Metastatic.
  • MS: Special metastatic (<18 months): skin, liver, marrow.

⭐ Elevated urinary catecholamine metabolites (VMA, HVA) and MIBG scintigraphy are crucial for diagnosis; histology shows small, round, blue cells and Homer-Wright rosettes.

Treatment & Prognosis - Battle Plan & Outlook

Risk stratification (COG/SIOPEN) dictates therapy intensity.

• Low Risk: Surgery ± observation. Excellent prognosis (>95% survival).
• Intermediate Risk: Surgery + moderate-intensity chemotherapy. Good prognosis (80-90% survival).
• High Risk: Intensive multimodal: induction chemo, surgery, consolidation (myeloablative chemo + ASCT), RT, maintenance (immunotherapy: anti-GD2 Dinutuximab + Isotretinoin). Guarded prognosis (~50% survival).

⭐ MYCN amplification is the single most important adverse prognostic factor, dictating aggressive therapy.

Other Key Prognostic Factors: Age at diagnosis (<18 months favorable), INRGSS Stage (L1/L2/M/MS), Histopathology (favorable/unfavorable), Ploidy (hyperdiploid favorable in infants).

High‑Yield Points - ⚡ Biggest Takeaways

• Most common extracranial solid tumor in childhood, from neural crest cells (sympathetic nervous system).
• Median age ~18-24 months; adrenal medulla is the most common primary site.
• Presents with abdominal mass, opsoclonus-myoclonus syndrome, Horner's syndrome, or blueberry muffin rash.
• Key labs: ↑ urinary VMA/HVA, ↑ serum NSE, ↑ ferritin.
• N-myc amplification is a major poor prognostic indicator.
• Histology: small, round, blue cells; Homer-Wright pseudorosettes.
• Spontaneous regression can occur, especially in infants (<1 year) or Stage 4S disease.