Neuroblastoma

Key points

• The most common solid extracranial malignancy in the paediatric population (still rare: ~1–3 per 100,000 per year).
• Part of the Neuroblastic tumour spectrum (neural crest–derived small round blue cell tumor of the sympathetic nervous system).
  • Can arise anywhere along the sympathetic chain (cervical to pelvis).
  • Most commonly involves:
    • Adrenal medulla
    • Retroperitoneum
    • Posterior mediastinum
• Onset commonly < 2 years old (younger than Wilms tumour which peaks around 3 years).
• Buzzword patho: Homer Write rosettes (circular orientation of neuroblastoma cells around neuropil)

Imaging features

• Large heterogeneous mass (“big fucking mass”).
• Heterogeneous due to internal haemorrhage, necrosis, and calcification.
• Internal mottled / coarse calcification (much more common than in Wilms).
• MRI: hyperintense T2, hypointense T1, heterogeneous enhancement.
• Tends to encase / engulf vascular structures (aorta, IVC, renal vessels) rather than true intraluminal tumour thrombus as in Wilms tumour.
  • Vascular invasion / tumour thrombus is rare.
• Frequently invades paraspinal muscles and the neural foramina, especially at thoracolumbar levels → dumbbell-shaped tumour (best seen on MRI).
• May cause spinal cord compression when there is significant intraspinal extension.

Staging systems (INSS vs INRG)

• INSS (International Neuroblastoma Staging System)

  • Post-surgical staging (depends on extent of resection, operative findings, nodal status).
  • Classic special stage: 4S (infants <12 months, limited metastases to liver/skin/marrow).

• INRG / INRGSS (International Neuroblastoma Risk Group Staging System)

  • Pre-treatment, imaging-based staging.
  • Uses IDRFs (Image Defined Risk Factors) to define local stage and surgical risk.
  • Stages:
    • L1 – Localised tumour, no IDRFs.
    • L2 – Locoregional tumour, one or more IDRFs.
    • M – Distant metastases.
    • MS – “4S-like” special infant stage (<18 months, mets limited to liver/skin/limited marrow).

Distant metastasis evaluation

At the time of diagnosis, neuroblastoma frequently already metastasises to bone/bone marrow (50%), lymph nodes, and liver. Since most tumors are MIBG-avid, MIBG is the first choice and mandatory imaging for metastasis evaluation at the time of evaluation in most guidelines.

Bone metastasis

MIBG scintigraphy/SPECT/CT

• Main functional imaging due to best accuracy/reliability (and cheaper than other choices in most settings).
• Also use for monitoring treatment response and follow up.
• Any uptake in bone = metastasis since normal bone do not physiologically uptake any MIBG (very useful in paediatric population since they are skeletally immature).

FDG18-PET/CT

• Useful for locating primary lesion and soft tissue metastasis in non-MIBG avid cases.
• Limit evaluation in area adjacent to organ with high physiologic uptake e.g. skull base (brain).

Whole body MRI

• Coronal whole body STIR is very sensitive to detected marrow change but may be less specific compared with MIBG imaging.

Skeletal survey and bone scan are no longer standard of practice.

Dedicated radiograph or CT at the area with equivocal MIBG lesions may be helpful. Classic findings include:

• Moth-eaten lytic diffuse lesion involves metadiaphysis.
• Aggressive periosteal reaction seen as multiple perpendicular spike with soft tissue formation.

Other metastatic sites

Liver

Mainly observed in infants along with subcutaneous metastasis (Blueberry muffin baby).
Two forms of manifestation:

• Focal masses
• Diffuse infiltration (can be missed at CT since it can be subtle and just looks like big liver).

Lung and pleura

Overall, no specific pattern.

• Rarely observed, more common among MYCN-amplified tumours.
• CT is the best method to identify small lung nodules.

CNS

Brain parenchyma and meningeal metastatic disease are very rare (unlike spinal involvement).

Special stages

These stages are associated with favourable prognosis (spontaneous regression) seen in younger patients.

• INSS 4S

  • Age <12 months.
  • Localised primary (stage 1 or 2).
  • Metastases limited to liver, skin, and/or bone marrow

• INRG MS

  • Age <18 months.
  • Primary tumour can be L1 or L2.
  • Metastases again confined to liver, skin, and/or bone marrow

Both MS and 4S require BM involvement less than 10% of total nucleated cells, and no cortical bone involvement.

Special entities

• Pepper syndrome
  • Clinical pattern of massive liver metastases in an infant with neuroblastoma.
  • Marked hepatomegaly → respiratory compromise ± abdominal compartment issues.
  • Usually falls within the 4S/MS group, but Pepper = phenotype, not a separate stage.

• Blueberry muffin baby
  • In 4S / MS neuroblastoma, metastases can involve the skin, appearing as multiple blue-purple papules/nodules (dermal/subcutaneous deposits).
  • Clinically this can mimic “blueberry muffin” baby, but remember this pattern is not specific – TORCH infections, extramedullary haematopoiesis (due to marrow infiltration or haemolytic anemia), congenital leukaemia and LCH can look similar.

Tumour genetics

Certain tumour genetics in neuroblastoma have prognostic implications.

Associated conditions

• Neurofibromatosis type 1
• Beckwith-Wiedemann syndrome
• Hirschsprung disease
• Congenital central hypoventilation syndrome
• Turner syndrome

However, most cases are otherwise normal without associated abnormalities.