Metastatic Neuroblastoma

Definition

A malignant embryonal tumour of neural crest cells arising from the adrenal medulla or sympathetic chain. Bone and marrow are its common metastatic sites in children.

Epidemiology

  • Most common extracranial solid tumour of childhood
  • Median age at diagnosis about 18 months, with 90% under 5 years
  • About half have metastases at presentation, mostly to bone and marrow

Pathology

  • Small round blue cell tumour with Homer Wright rosettes
  • MYCN amplification predicts aggressive disease
  • ALK mutations in familial cases and some sporadic tumours

Classification

  • INRG stage L1, localised without image defined risk factors
  • INRG stage L2, localised with image defined risk factors
  • INRG stage M, distant metastases
  • INRG stage MS, metastases confined to skin, liver or marrow under 18 months

Clinical Features

  • Bone pain, limp or refusal to walk, mimicking infection or arthritis
  • Fever, weight loss, irritability and pallor
  • Periorbital ecchymosis, the raccoon eyes sign, from orbital deposits
  • Abdominal mass crossing the midline
  • Spinal cord compression from dumbbell extension through the foramina
  • Opsoclonus myoclonus ataxia syndrome as a paraneoplastic feature

Investigations

  • Raised urinary catecholamine metabolites, VMA and HVA
  • Radiographs show permeative metaphyseal lysis, periosteal reaction and lucent metaphyseal bands
  • MIBG scintigraphy for skeletal and marrow staging
  • Bilateral bone marrow aspirate and trephine
  • Tumour biopsy for histology and MYCN status

Differential Diagnosis

Management

  • Multimodal therapy. Induction chemotherapy, surgery and myeloablative chemotherapy with stem cell rescue for high risk disease
  • Immunotherapy. Anti-GD2 antibody with isotretinoin for minimal residual disease
  • Orthopaedic care. Pathological fracture and cord compression are managed with the oncology team

Prognosis

  • Five year survival about 50% for high risk disease
  • Stage MS can regress spontaneously

References

  1. Matthay KK, Maris JM, Schleiermacher G, Nakagawara A, Mackall CL, Diller L, Weiss WA. Neuroblastoma. Nat Rev Dis Primers. 2016, 2, 16078. PubMed
  2. Monclair T, Brodeur GM, Ambros PF, Brisse HJ, Cecchetto G, Holmes K, Kaneko M, London WB, Matthay KK, Nuchtern JG, von Schweinitz D, Simon T, Cohn SL, Pearson AD, INRG Task Force. The International Neuroblastoma Risk Group (INRG) staging system. An INRG Task Force report. J Clin Oncol. 2009, 27(2), 298-303. PubMed

Reviewed by Professor Phong Tran, Head of Orthopaedic Surgery, Western Health. Last updated 19 October 2026.