The Troubling Differential Diagnosis of Extracerebellar Pilocytic Astrocytoma with Atypical Features and High-Grade Pediatric Glioma: Clinical, Histopathologic and Molecular Analyses of 16 Cases
Matthew Cykowski, Richard Allen, Kar-Ming Fung, Ethan Stolzenberg, Terence Dunn. University of Oklahoma Health Sciences Center, Oklahoma City, OK
Background: Pilocytic astrocytoma (PA) is the most common glioma of childhood, recognized in classic form by a constellation of radiologic and pathologic findings. Rarely, PAs acquire a spectrum of atypical features (e.g., marked atypia, necrosis, infiltrative growth, elevated mitotic rate) that raises the differential diagnoses of atypical/anaplastic PA versus pediatric glioblastoma multiforme (pGBM). This study examines the histologic, immunohistochemical, and molecular features that might aid in this distinction, particularly considering the recently reported high rate of BRAF missense mutations in extracerebellar PAs.
Design: 10 PAs (9 atypical, 1 anaplastic, 8 extracerebellar, 4 recurrent) and 6 pGBMs were retrieved from institutional archives (1999-2011). Quantitative morphologic parameters (observer-independent Ki-67 and p53 labeling indices (LI), mitotic rate/20 hpfs) were compared using the Kolmogorov-Smirnov test. Qualitative morphologic parameters (presence of marked atypia, endothelial proliferation, atypical mitoses, and extent and pattern of necrosis) were compared using the Chi-square test. Pyrosequencing of BRAF (codon 600), IDH1 (codon 132), and IDH2 (codon 172) and dideoxynucleotide sequencing of TP53 (exons 5-9) was performed following PCR of DNA isolated from representative tissue sections.
Results: Significant differences were seen between PAs and pGBMs in mitotic rate (PA = 4.3, pGBM = 21.2), atypical mitoses, (2/10 PAs, 6/6 pGBM), pseudopalisading necrosis (5/6 pGBMs), and Ki-67 LI (PA = 18.9 %, pGBM = 34.5 %). No other morphologic features met significance criteria, including extent of necrosis and p53 nuclear LI (only 2 pGBMs and 1 anaplastic PA had p53 LIs ≥ 50 % with the latter case demonstrating a TP53 c.841G>A mutation). No IDH1 or IDH2 mutations were detected. BRAF V600E mutation was seen in 1 extracerebellar PA; upon closer examination of deeper sections this tumor was found to harbor rare, non-entrapped ganglion cells.
Conclusions: PAs with atypical/anaplastic features and pGBMs differed in select microscopic parameters, including atypical mitoses and Ki67 LIs (5/6 pGBMs having LIs ≥ 26 %). Although reported in anaplastic PA, pseudopalisading necrosis was specific to pGBM in this series. There was considerable overlap in other histologic and molecular parameters. This case series also indicates that careful histologic review and further phenotypic study of BRAF V600E-mutated PAs is warranted.
Monday, March 19, 2012 9:30 AM
Poster Session I Stowell-Orbison/Surgical Pathology/Autopsy Awards Poster Session # 275, Monday Morning