Histologic Correlates of Molecular Group 4 Pediatric Medulloblastoma: A Retrospective Canadian Review

Pediatr Dev Pathol. 2021 Jul-Aug;24(4):309-317. doi: 10.1177/10935266211001986. Epub 2021 Mar 22.


Introduction: The World Health Organization currently classifies medulloblastoma (MB) into four molecular groups (WNT, SHH, Group 3 and Group 4) and four histologic subtypes (classic, desmoplastic nodular, MB with extensive nodularity, and large cell/anaplastic). "Classic" MB is the most frequent histology, but unfortunately it does not predict molecular group or patient outcome. While MB may exhibit additional histologic features outside of the traditional WHO subtypes, the clinical significance of such features, in a molecular context, is unclear.

Methods: The clinicopathologic features of 120 pediatric MB were reviewed in the context of NanoString molecular grouping. Each case was evaluated for five ancillary histologic features, including: nodularity without desmoplasia (i.e., "biphasic", B-MB), rhythmic palisades, and focal anaplasia. Molecular and histological features were statistically correlated to clinical outcome using Chi-square, log-rank, and multivariate Cox regression analysis.

Results: While B-MB (N = 32) and rhythmic palisades (N = 12) were enriched amongst non-WNT/SHH MB (especially Group 4), they were not statistically associated with outcome. In contrast, focal anaplasia (N = 12) was not associated with any molecular group, but did predict unfavorable outcome.

Conclusion: These data nominate B-MB as a surrogate marker of Groups 3 and particularly 4 MB, which may earmark a clinically significant subset of cases.

Keywords: NanoString; biphasic; histology; molecular subtypes; nodules; pediatric medulloblastoma.

MeSH terms

  • Biomarkers, Tumor / metabolism*
  • Canada
  • Cerebellar Neoplasms / diagnosis
  • Cerebellar Neoplasms / metabolism
  • Cerebellar Neoplasms / mortality
  • Cerebellar Neoplasms / pathology*
  • Child
  • Child, Preschool
  • Female
  • Follow-Up Studies
  • Hedgehog Proteins / metabolism*
  • Humans
  • Kaplan-Meier Estimate
  • Male
  • Medulloblastoma / diagnosis
  • Medulloblastoma / metabolism
  • Medulloblastoma / mortality
  • Medulloblastoma / pathology*
  • Prognosis
  • Retrospective Studies
  • Sensitivity and Specificity
  • Tissue Array Analysis
  • Wnt Proteins / metabolism*


  • Biomarkers, Tumor
  • Hedgehog Proteins
  • SHH protein, human
  • Wnt Proteins