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

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) we re those with focal or diffuse, large, round neoplastic cells with prominen t nucleoli. "Anaplastic" MBs (A MBs) were those with nuclei that were also large but markedly atypical with coarse chromatin and irregular shapes. Twe nty-one cases were identified in the combined LC/A MB group, comprising abo ut 4% of all MBs. Survival curves and Kaplan-Meier estimates of survival pr obabilities were examined separately for the LC/A MB and control groups. Th e logrank test for detecting poorer survival in the 21 cases was significan t (p < 0.0001). Fluorescence in situ hybridization for c-myc showed amplifi cation 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. Com parative genomic hybridization confirmed c-myc amplification and found evid ence for isochromosome 17q in 3 of 4 LC/A cases studied successfully. One a dditional tumor showed high level gain restricted to 2p13 consistent with n -myc amplification. Monosomy 22, common in atypical teratoid/rhabdoid tumor s, 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. Th e study thus confirms original observations about the LC MB in regard to hi stological features, immunohistochemical findings, c-myc amplification, cyt ogenetic findings, and poor prognosis.