'Large cell/anaplastic' medulloblastomas: A Pediatric Oncology Group study

Henry G. Brown, James L. Kepner, Elizabeth J. Perlman, Henry S. Friedman, Douglas R. Strother, Patricia K. Duffner, Larry E. Kun, Patricia T. Goldthwaite, Peter C. Burger

Research output: Contribution to journalArticlepeer-review

170 Scopus citations


495 medulloblastomas (MBs) from 6 Pediatric Oncology Group (POG) protocols were reviewed to assess the incidence and prognostic significance of 'large cell' and 'anaplastic' variants. 'Large cell' medulloblastomas (LC MBs) were those with focal or diffuse, large, round neoplastic cells with prominent nucleoli. 'Anaplastic' MBs (A MBs) were those with nuclei that were also large but markedly atypical with coarse chromatin and irregular shapes. Twenty-one cases were identified in the combined LC/A MB group, comprising about 4% of all MBs. Survival curves and Kaplan-Meier estimates of survival probabilities were examined separately for the LC/A MB and control groups. The logrank test for detecting poorer survival in the 21 cases was significant (p < 0.0001). Fluorescence in situ hybridization for c-myc showed amplification in 4 of 11 cases of the LC/A phenotype and 1 additional case of high level gain at 8q24 was disclosed by comparative genomic hybridization. Comparative genomic hybridization confirmed c-myc amplification and found evidence for isochromosome 17q in 3 of 4 LC/A cases studied successfully. One additional tumor showed high level gain restricted to 2p13 consistent with n-myc amplification. Monosomy 22, common in atypical teratoid/rhabdoid tumors, was not found. These results suggest that LC/A MB phenotype could be, at least in part, a correlate of c-myc, and possibly n-myc, amplification. The study thus confirms original observations about the LC MB in regard to histological features, immunohistochemical findings, c-myc amplification, cytogenetic findings, and poor prognosis.

Original languageEnglish (US)
Pages (from-to)857-865
Number of pages9
JournalJournal of neuropathology and experimental neurology
Issue number10
StatePublished - 2000


  • Amplification
  • Brain tumor
  • Children
  • Large cell
  • Medulloblastoma
  • c-myc
  • n-myc

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Neurology
  • Clinical Neurology
  • Cellular and Molecular Neuroscience


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