Anti-dimethyl Histone H3 (Lys14) monoclonal antibody, clone SN276

BACKGROUND AND PURPOSE: Diffuse midline gliomas with histone H3 K27M mutation are biologically aggressive tumors with poor prognosis defined as a new diagnostic entity in the 2016 World Health Organization Classification of Tumors of the Central Nervous System. There are no qualitative imaging differences (enhancement, border, or central necrosis) between histone H3 wildtype and H3 K27M-mutant diffuse midline gliomas. Herein, we evaluated the utility of diffusion-weighted imaging to distinguish H3 K27M-mutant from histone H3 wildtype diffuse midline gliomas. MATERIALS AND METHODS: We identified 31 pediatric patients (younger than 21 years of age) with diffuse gliomas centered in midline structures that had undergone assessment for histone H3 K27M mutation. We measured ADC within these tumors using a voxel-based 3D whole-tumor measurement method. RESULTS: Our cohort included 18 infratentorial and 13 supratentorial diffuse gliomas centered in midline structures. Twenty-three (74%) tumors carried H3-K27M mutations. There was no difference in ADC histogram parameters (mean, median, minimum, maximum, percentiles) between mutant and wild-type tumors. Subgroup analysis based on tumor location also did not identify a difference in histogram descriptive statistics. Patients who survived <1 year after diagnosis had lower median ADC (1.10 ? 10(?3)mm(2)/s; 95% CI, 0.90?1.30) compared with patients who survived >1 year (1.46 ? 10(?3)mm(2)/s; 95% CI, 1.19?1.67; P < .06). Average ADC values for diffuse midline gliomas were 1.28 ? 10(?3)mm(2)/s (95% CI, 1.21?1.34) and 0.86 ? 10(?3)mm(2)/s (95% CI, 0.69?1.01) for hemispheric glioblastomas with P < .05. CONCLUSIONS: Although no statistically significant difference in diffusion characteristics was found between H3-K27M mutant and H3 wildtype diffuse midline gliomas, lower diffusivity corresponds to a lower survival rate at 1 year after diagnosis. These findings can have an impact on the anticipated clinical course for this patient population and offer providers and families guidance on clinical outcomes.

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.