Neuroblastoma

Intro & Pathophysiology - Neural Crest Chaos

• Most common extracranial solid tumor of childhood.
• Arises from primitive neural crest cells (neuroblasts) of the sympathetic nervous system.
  • Represents a failure of normal differentiation and migration.
  • Can occur anywhere along the sympathetic chain.
• Locations: Adrenal medulla (~65%), abdomen, thorax, neck, pelvis.
• Genetics: N-myc/MYCN gene amplification is the most important prognostic factor (→ poor prognosis).
• 💡 Unique feature: High rate of spontaneous regression, especially in infants < 1 year old.

⭐ Opsoclonus-myoclonus syndrome ("dancing eyes, dancing feet") is a classic paraneoplastic presentation.

Clinical Features - The Great Masquerader

• Primary Site Dependent

  • Abdomen (65%): Most common site. Firm, irregular, non-tender mass that crosses the midline.
  • Thoracic: Posterior mediastinal mass; may cause cord compression or respiratory distress.
  • Cervical: Palpable neck mass, may present with Horner's syndrome (ptosis, miosis, anhidrosis).

• Metastatic Disease

  • Orbital: Periorbital ecchymoses (“Raccoon eyes”) & proptosis.
  • Skin: Bluish, non-tender subcutaneous nodules (“Blueberry muffin baby”).
  • Bone Marrow: Anemia, bone pain, pathological fractures.

• Paraneoplastic Syndromes

  • Opsoclonus-Myoclonus-Ataxia (OMA): "Dancing eyes, dancing feet".
  • Kerner-Morrison Syndrome: VIP-secreting tumor → Watery Diarrhea, Hypokalemia, Achlorhydria (WDHA).

⭐ 💡 Pearl: OMA syndrome, while rare, is highly specific. Patients with OMA tend to have a better prognosis as the tumor is often less aggressive.

Diagnosis & Staging - Finding the Foe

• Definitive Diagnosis: Tissue biopsy showing small, round, blue cells.
  • Histopathology: Homer-Wright pseudorosettes are characteristic.
• Biochemical Markers: ↑ 24-hr urinary catecholamines.
  • Vanillylmandelic acid (VMA)
  • Homovanillic acid (HVA)
• Imaging for Staging:
  • ¹²³I-MIBG Scan: Gold standard for detecting bony & soft tissue metastasis. Neuroblastoma is MIBG-avid.
  • CT/MRI of chest/abdomen/pelvis to define primary tumor & spread.

• Staging (INSS - International Neuroblastoma Staging System):
  • Stage 1/2: Localized tumor.
  • Stage 3: Unresectable tumor crossing the midline.
  • Stage 4: Metastatic disease.
  • Stage 4S (Special): Age <1 year, localized primary with mets limited to skin, liver, and/or bone marrow.

⭐ Opsoclonus-myoclonus-ataxia syndrome ("dancing eyes, dancing feet"), a paraneoplastic finding, is paradoxically associated with a better prognosis.

Prognosis & Management - Taming the Tumor

• Prognostic Factors: Key determinants of outcome.
  • Age: Better if diagnosed < 18 months.
  • Stage: Lower INSS stage (1, 2, 4S) has better prognosis.
  • Genetics: MYCN amplification is the most powerful adverse factor. Hyperdiploidy is favorable.

⭐ High-Yield Fact: High-risk neuroblastoma treatment now includes anti-GD2 immunotherapy (e.g., Dinutuximab) post-transplant, significantly improving survival.

• Most common extracranial solid tumor of childhood, arising from neural crest cells.
• Typically presents as an abdominal mass crossing the midline, most commonly from the adrenal medulla.
• Look for opsoclonus-myoclonus syndrome (dancing eyes, dancing feet).
• Diagnosis is supported by elevated urinary VMA and HVA.
• Biopsy classic finding: Homer-Wright pseudorosettes.
• N-myc amplification is the single most important poor prognostic factor.
• Spontaneous regression is common in infants < 1 year.