Fig. 5.

Examples of histone H3 mutant gliomas. a Post-contrast T1-weighted imaging of an enhancing pontine mass occurring in a 33-year-old woman. Biopsy showed a markedly pleomorphic astrocytoma with frequent mitotic figures and prominent perivascular inflammation (b). Tumor cell nuclei were positive for histone H3 K27M mutant protein (c), while inflammatory cells were negative for this marker (white arrowhead). Immunohistochemistry for trimethylated histone H3 is negative in tumor nuclei (d), and appropriately stains inflammatory cells. e Post-contrast T1-weighted imaging of a left thalamic tumor occurring in a 31-year-old man who presented with headaches. Sections showed an astrocytic neoplasm with mitotic activity (black arrows) (f). ATRX was absent in tumor cell nuclei, and stained a background population of macrophages and microglial cells (g). An immunostain for H3 K27M was positive in tumor nuclei (h), supporting the diagnosis of diffuse midline glioma, H3 K27M-mutant, WHO grade IV. (i) T2-weighted imaging of a right frontal cerebral hemispheric tumor in a 35-year-old man who presented with headaches. Sections showed a tumor with brisk mitotic activity, frequent apoptotic cells, high nuclear to cytoplasmic ratios, and nuclear molding (j). ATRX was negative in tumor cell nuclei (k), with preserved staining in the endothelial cells (white arrowhead). GFAP showed only focal staining (l), and OLIG2 was completely negative (m). p53 (not pictured) was strongly positive. Sequencing of this tumor showed wildtype IDH1 and IDH2, and a further sequencing study revealed an H3F3A G34R mutation