Neuroblastoma is an important malignancy of early childhood.
About 1/7000 children develop neuroblastoma. The mean age at diagnosis is 18 months and some babies may be born with the tumour.
Aetiology and Pathogenesis
About 1-2% of cases are familial due to germline mutations in the ALK gene. The remainder have no known cause.
Neuroblastomas can occur in many body locations in association with sympathetic nerves:
- 40% arise in the adrenal medulla
- 25% arise from abdominal paravertebral ganglia
- 15% arise from mediastinal paravertebral ganglia
- The remainder can arise in the pelvis, neck, or brain
Neuroblastoma can invade locally, spread to regional nodes, and disseminate through the bloodstream, most commonly to the lungs, liver and bone. A significant number of patients develop orbital metastases and this can cause proptosis or periorbital haemorrhage (raccoon eyes). In infants, a number of cases will spontaneously regress despite widespread metastases to the skin and viscera.
Presentation depends on age and aggressiveness. Young children present with an abdominal mass, weight loss, and fevers. Older children often present with symptomatic metastases.
Staging investigations include CT Chest/Addomen/Pelvis and 123Iodine MIBG scan.
- The 123I labelled MIBG is taken up by malignant cells are allows detection of metastatic disease with more accuracy than other methods (90% sensitivity).
Tumours are usually infiltrative and grey to tan in colour. They may contain areas of necrosis or haemorrhage.
Neuroblastoma is a small round blue cell tumour and must be in the differential particularly in children. Cells may be arranged in rosettes (Horner-Wright) around a central deposit of neuropil. Maturing cells are larger, with more abundant cytoplasm and vesicular nuclei. These warrant the diagnosis of ganglioneuroblastoma if present or ganglioblastoma if there is minimal small round blue cell component.
The small round blue cells stain positively for neuron specific enolase (NSE).
Neurosecretory granules may be visible.
Mutation is ALK is common in sporadic cases of neuroblastoma. N-MYC amplification is associated with a poor prognosis and should be evaluated. Tumours containing significantly increased numbers of chromosomes (hyper-diploid or triploid) are associated with a better prognosis. Loss of the short arm of chromosome 1 and gain of the long arm of chromosome 17 are both associated with worse prognosis.
The International Neuroblastoma Staging System is most commonly used (INSS).
- Stage 1 - Localised disease with complete macroscopic clearance and negative regional nodes
- Stage 2A - Localised disease with incomplete macroscopic clearance and negative regional nodes
- Stage 2B - Localised disease with ipsilateral lymph node involvement and/or enlarged contralateral nodes that are not microscopically involved
- Stage 3 - Unresectable primary tumour (eg. extends across midline) or with contralateral nodal involvement
- Stage 4 - Metastatic disease
- Stage 4S - Metastatic disease to skin, liver, bone marrow ONLY in a child under 12 months of age WITH a stage 1/2A/2B tumour
Survival is best for stage 1-2 and 4S patients (90%) but poor in stage 3-4 patients (40%).
- Age: < 18 months is associated with a significantly better prognosis (80% survival if younger, less if older).
- Stage: Stage 1/2 better than stage 3/4
- Histology: Presence of a high mitotic rate or absence of scwhannian stroma/ganglionic differentiation is associated with poorer prognosis
- Genetics: N-MYC amplification, loss of chromosome 1 short arm or gain of chromosome 17 long arm all associated with poorer prognosis