Objective To explore the clinicopathological features, immunophenotype, molecular genetics, differential diagnosis and prognosis of diffuse midline glioma, H3 K27M mutant. Methods and Results A 21-year-old male patient suffered from polydipsia and polyuria. Physical examination showed that the visual sensitivity on both sides was weakened, the visual field was complete, and other signs were negative. Brain MRI showed that T1WI iso-low signal and T2WI iso-high signal occupied the suprasellar space, and enhanced unevenly. The patient underwent surgical treatment, with a greyish-red colour, soft texture and abundant blood supply. The tumor was partially resection. Histological findings showed the tumor was mainly composed of spindle shaped and ellipsoidal cells with occasionally typical mitotic activity, which were arranged in fascicularis, swirly or perivascular pseudorosettes patterns, with the moderate-to high-density. Small focal areas of necrosis and proliferation of microvessel also could be seen. Immunohistochemical staining showed the nuclei of tumor cells was diffusely positive for histone H3 K27M mutant protein (H3 K27M), oligodendrocytes transcription factor-2 (Olig-2) and P53, cytoplasm was positive for glial fibrillary acidic protein (GFAP), vimentin (Vim), microtubule-associated protein-2 (MAP-2), synaptophysin (Syn) and nestin (Nes), cytoplasm and nuclei were positive for S-100 protein (S-100). Ki-67 labeling index was 10%-20%. Whole genome sequencing (WGS) revealed the presence of H3 K27M and BRAF V600E gene mutations. Integrational diagnosis was diffuse midline glioma, H3 K27M mutant (WHO Ⅳ) lied in saddle area. The patient died 11 months after surgery. Conclusions Diffuse midline glioma, H3 K27M mutant is a group of primary brain neoplasm of recent acquisition in the 2016 WHO classification of central nervous system tumors, with the diverse histological appearance (WHOⅡ-Ⅳgrade), which was misdiagnosed easily. The most important clues for diagnosis were age (mostly in child), location (midline of the brain), diffusely growth pattern, and harbored histone H3 K27M mutation.
