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.