Neuroblastoma (NB) is the MC extracranial solid tumour of childhood. It is an embryonal neuroendocrine tumour arising from neural crest–derived sympathetic progenitor cells, and can occur anywhere along the sympathetic chain, most commonly in the adrenal glands. Clinical presentation is highly variable, ranging from an asymptomatic abdominal mass to severe illness due to metastatic disease. Despite improved overall survival, outcomes remain poor in high-risk disease, highlighting the need for targeted therapeutic approaches

Pathophysiology/genesis

Genesis (cell of origin)

• Arises from neural crest–derived sympathetic progenitor cells
• Develops along the sympathetic nervous system (most commonly adrenal medulla)

Genetic drivers

• ALK, PHOX2B (germline) → familial neuroblastoma (rare, AD)
• MYCN amplification (~25%) → rapid progression, poor prognosis
• 1p loss, 11q loss, 17q gain → aggressive behaviour
• BARD1, LIN28B polymorphisms → sporadic disease susceptibility
• High telomerase, ↑LDH, ↑ferritin, ↑NSE → poor prognosis
• Hyperdiploidy (DNA index >1) → better chemo response

Biochemical hallmark

• Catecholamine production → ↑ urinary VMA & HVA (>90%)
• Risk Factors

Clinical Presentation

Primary mass effects

• Abd mass/distension (adrenal)
• Neck/thoracic mass (infants)
• Pain, abdominal girth increase

Neurologic

• Spinal cord compression → weakness/paralysis
• Horner syndrome (ptosis, miosis, anhidrosis)

Metastatic disease (common at dx )

• Bone marrow → anaemia, cytopenias
• Bone → pain, limp, fractures
• Lymph nodes, liver (infants

Paraneoplastic

• Opsoclonus–myoclonus (good prognosis)
• Secretory diarrhoea (VIP secretion)

Systemic

• Fever, weight loss, fatigue

• Hypertension (rare; renal artery compression)

  

Diagnosis

Labs

• ↑ Urinary VMA/HVA
• CBC, renal/liver function
• ↑ LDH, ferritin, NSE (prognostic)

Histology

• Small round blue cells

• Homer-Wright pseudorosettes

  

• Genetics / biology

Imaging

• MRI → local extent, surgical planning

• mIBG scan → metastatic mapping

  

• CT chest/abdomen → calcifications, spread

• Bone marrow biopsy → staging

  

Management

Low risk

• Observation ± surgery
• ↑chance of spontaneous regression (infants)

Intermediate risk

• Chemotherapy ± surgery

High risk

• Induction chemotherapy
• Surgical resection
• Myeloablative therapy + stem cell transplant
• Maintenance immunotherapy (anti-GD2: dinutuximab)

Surgery

• Curative in localised disease
• Diagnostic or debulking role after chemotherapy