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 Citations (Scopus)

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 - 2016
Externally publishedYes

Fingerprint

Isocitrate Dehydrogenase
Astrocytoma
Glioma
Mutation
Mitosis
Axons
Ganglioglioma
Clonal Evolution
Central Nervous System Neoplasms
Neoplasms
Microdissection
Temporal Lobe
Point Mutation
Headache
Seizures
Necrosis
Magnetic Resonance Imaging

Keywords

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

ASJC Scopus subject areas

  • Anatomy
  • Pathology and Forensic Medicine
  • Surgery

Cite this

Combined infiltrating astrocytoma/pleomorphic xanthoastrocytoma harboring IDH1 R132H and BRAF V600E mutations. / Yamada, Seiji; Kipp, Benjamin R.; Voss, Jesse S.; Giannini, Caterina; Raghunathan, Aditya.

In: American Journal of Surgical Pathology, Vol. 40, No. 2, 2016, p. 279-284.

Research output: Contribution to journalArticle

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