Combined "Infiltrating Astrocytoma/Pleomorphic Xanthoastrocytoma" Harboring IDH1 R132H and BRAF V600E Mutations

• Published in: The American journal of surgical pathology Vol. 40; no. 2; p. 279
• Main Authors: Yamada, Seiji, Kipp, Benjamin R, Voss, Jesse S, Giannini, Caterina, Raghunathan, Aditya
• Format: Journal Article
• Language: English
• Published: United States 01.02.2016
• Subjects: Astrocytoma - enzymology; Astrocytoma - genetics; Astrocytoma - pathology; Astrocytoma - surgery; Biomarkers, Tumor - analysis; Biomarkers, Tumor - genetics; Brain Neoplasms - enzymology; Brain Neoplasms - genetics; Brain Neoplasms - pathology; Brain Neoplasms - surgery; DNA Mutational Analysis; Genetic Predisposition to Disease; Humans; Immunohistochemistry; Isocitrate Dehydrogenase - genetics; Magnetic Resonance Imaging; Male; Middle Aged; Mutation; Neoplasm Invasiveness; Neoplasms, Complex and Mixed - enzymology; Neoplasms, Complex and Mixed - genetics; Neoplasms, Complex and Mixed - pathology; Neoplasms, Complex and Mixed - surgery; Phenotype; Proto-Oncogene Proteins B-raf - genetics; Xanthomatosis - enzymology; Xanthomatosis - genetics; Xanthomatosis - pathology; Xanthomatosis - surgery
• ISSN: 1532-0979
• DOI: 10.1097/pas.0000000000000515

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 high-power 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 neurofilament 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.