Combined infiltrating astrocytoma/pleomorphic xanthoastrocytoma harboring IDH1 R132H and BRAF V600E mutations

Seiji Yamada, Benjamin R. Kipp, Jesse S. Voss, Caterina Giannini, Aditya Raghunathan

Research output: Contribution to journalArticle

15 Scopus citations

Abstract

Pleomorphic xanthoastrocytoma (PXA) has rarely been reported in combination with infiltrating glioma, historically interpreted as a collision tumor. Isocitrate dehydrogenase 1 (IDH1) and BRAF V600E mutations are usually not concurrent. The former is typical of adult infiltrating gliomas, and the latter is identified in a variety of primary central nervous system neoplasms, including PXA, ganglioglioma, pilocytic astrocytoma, and rarely infiltrating gliomas. We report the case of a 56-year-old man presenting with seizures and headaches. Magnetic resonance imaging revealed a large right temporal lobe mass with low T1 and high T2/FLAIR signal and a discrete contrast-enhancing focus. Histologically, the tumor showed 2 distinct components: an infiltrating astrocytoma harboring 5 mitoses/10 high-power fields and a relatively circumscribed focus, resembling PXA with, at most, 2 mitoses/10 highpower fields. No microvascular proliferation or necrosis was present in either component. The infiltrating astrocytoma component contained numerous axons, whereas the PXA-like component had sparse axons, as demonstrated by the neuro-filament immunostain. Both components were positive for the mutant IDH1 R132H and showed loss of ATRX expression, whereas BRAF V600E was restricted to the PXA-like component. On sequencing of the 2 components separately after microdissection, both showed identical IDH1 R132H and TP53 R273C point mutations, whereas the BRAF V600E mutation was limited to the PXA-like component. These findings are consistent with clonal expansion of a morphologically distinct focus, harboring a private BRAF V600E mutation within an IDH1-mutant glioma. Intratumoral heterogeneity and clonal evolution, as seems to have occurred here, suggest reevaluation of collision tumors as a concept.

Original languageEnglish (US)
Pages (from-to)279-284
Number of pages6
JournalAmerican Journal of Surgical Pathology
Volume40
Issue number2
DOIs
StatePublished - Jan 1 2016

Keywords

  • Astrocytoma
  • BRAF V600E
  • Collision tumor
  • IDH1 mutation
  • Pleomorphic xanthoastrocytoma

ASJC Scopus subject areas

  • Anatomy
  • Surgery
  • Pathology and Forensic Medicine

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