BRAF V600E, TERT, and IDH2 Mutations in Pleomorphic Xanthoastrocytoma: Observations from a Large Case-Series Study.

Background: Anaplastic pleomorphic xanthoastrocytoma (PXA) was added to grade III glial tumors as a distinct entity in the 2016 World Health Organization (WHO) classification of tumors of the central nervous system. We retrospectively reviewed and analyzed 55 pathologically confirmed PXA cases according to the newest WHO classification to better clarify the clinical, molecular, and prognostic features of this rare neoplasm.

Methods: In total, 55 pathologically confirmed PXA cases according to the newest WHO classification were retrospectively reviewed and analyzed. After sequencing for BRAF, TERT, IDH1/2, and H3F3A, survival analysis was performed to determine the factors affecting survival.

Results: The patients with BRAF V600E mutations were generally younger than those without it, although not statistically significant (27.9 ± 15.4 years and 37.1 ± 17.0 years, respectively, P = 0.054). TERT promoter mutation frequency in PXA was lower than in patients with anaplastic PXA although not statistically significant (4.4% and 28.6%, P = 0.083). One instance of PXA with IDH2 mutation, and no IDH1 and H3F3A mutations were found. In terms of prognosis, patients with anaplastic PXA had shorter overall survival and progression-free survival compared with patients with PXA. The subgroup with gross total resection had a longer median OS (not reached vs. 60.0 months, P = 0.0221) and PFS (not reached vs. 60.0 months, P = 0.0232) compared with patients with PXA with subtotal resection.

Conclusions: The identification of BRAF V600E, TERT, and IDH2 mutations in PXA expands our molecular understanding of PXA. Patients with PXA with gross total resection achieve good outcomes.