Diffuse Midline Gliomas with Histone H3‐K27M Mutation: A Series of 47 Cases Assessing the Spectrum of Morphologic Variation and Associated Genetic Alterations |
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| Authors: | David A. Solomon Matthew D. Wood Tarik Tihan Andrew W. Bollen Nalin Gupta Joanna J. J. Phillips Arie Perry |
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| Affiliation: | 1. Division of Neuropathology, Department of Pathology, University of California, San Francisco, CA;2. Department of Neurological Surgery University of California;3. Department of PediatricsUniversity of California |
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| Abstract: | Somatic mutations of the H3F3A and HIST1H3B genes encoding the histone H3 variants, H3.3 and H3.1, were recently identified in high‐grade gliomas arising in the thalamus, pons and spinal cord of children and young adults. However, the complete range of patients and locations in which these tumors arise, as well as the morphologic spectrum and associated genetic alterations remain undefined. Here, we describe a series of 47 diffuse midline gliomas with histone H3‐K27M mutation. The 25 male and 22 female patients ranged in age from 2 to 65 years (median = 14). Tumors were centered not only in the pons, thalamus, and spinal cord, but also in the third ventricle, hypothalamus, pineal region and cerebellum. Patients with pontine tumors were younger (median = 7 years) than those with thalamic (median = 24 years) or spinal (median = 25 years) tumors. A wide morphologic spectrum was encountered including gliomas with giant cells, epithelioid and rhabdoid cells, primitive neuroectodermal tumor (PNET)‐like foci, neuropil‐like islands, pilomyxoid features, ependymal‐like areas, sarcomatous transformation, ganglionic differentiation and pleomorphic xanthoastrocytoma (PXA)‐like areas. In this series, histone H3‐K27M mutation was mutually exclusive with IDH1 mutation and EGFR amplification, rarely co‐occurred with BRAF‐V600E mutation, and was commonly associated with p53 overexpression, ATRX loss (except in pontine gliomas), and monosomy 10. |
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| Keywords: | astrocytoma diffuse midline glioma diffuse intrinsic pontine glioma DIPG glioblastoma histone H3.1 histone H3.3 H3F3A HIST1H3B K27M mutation |
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