Molecular classification of medulloblastoma

This article focuses on the classification of medulloblastomas. For a general discussion of medulloblastoma refer to the parent article. Individual articles on the subtypes of medulloblastoma are available.

Traditionally four 'common' subtypes with two additional rare types had been described based on histology and morphology in the WHO classification. Recent genomic work has replaced this classical division with one based on tumor transcriptome .

Genomic classification

A classification derived from the tumors' transcriptome divides medulloblastomas into four groups, each with different demographics, biological behavior and prognosis :

  • WNT
    • least common subgroup (11% of all medulloblastomas) 
    • histology: usually classic, rarely large cell
    • genetics: somatic mutations of CTNNB1 encoding b-catenin
    • gene expression: WNT signaling
  • SHH (Sonic hedgehog)
    • histology: desmoplastic/nodular, classic, large cell
    • genetics:
      • Shh receptor PTCH mutation leading to Gorlin syndrome
      • Shh inhibitor SUFU mutations
      • amplifications of GLI1 and GLI2
    • gene expression: Sonic Hedgehog signaling
  • group 3
    • 27% of all medulloblastomas
    • histology: classic, large cell
    • genetics: MYC amplification
    • gene expression: photoreceptor/GABAergic 
  • group 4
    • most common subgroup (34% of all medulloblastomas) 
    • histology: classic, large cell
    • genetics: CDK6 and MYCN amplification
    • gene expression: neuronal/glutamatergic

World Health Organization 2007 (WHO) classification

  • classic
    • dense sheet-like growth of cells
    • hyperchromatic round-to-oval nuclei
    • increased mitotic activity
    • conspicuous apoptosis 
    • neuroblastic or Homer-Wright rosettes (neoplastic cell nuclei disposed in a radial arrangement around fibrillary processes) are common features
    • necrosis is less common
  • desmoplastic
    • more common in adults
    • once termed "circumscribed arachnoidal cerebellar sarcoma"
  • extensively nodular with neuronal differentiation
    • usually in children less than 3 years of age
    • also known as cerebellar neuroblastoma
    • "grapelike" macroscopic nodularity
    • intranodular
      • cellular uniformity
      • fine fibrillary matrix
      • occasional mature ganglion cells
  • large cell / anaplastic
    • rarest histologic subtype
    • high mitotic activity and pleomorphism
    • large round nuclei with variable eosinophilic cytoplasm
    • not distinguishable on imaging from other types
    • hemorrhage and necrosis is common