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Background  Diffuse midline gliomas with the H3K27M mutation are now recognized as separate entities due to their unique molecular signature, clinical features, and adverse outcome.  Objective  To determine the morphological spectrum and survival rate of diffuse midline gliomas with H3K27M mutation.  Material and methods  This retrospective study was conducted between January 2015 and January 2021 at Shaukat Khanum Memorial Cancer Hospital and Research Centre. Medical records of 28 cases of H3K27M-mutated midline gliomas were retrieved. Case slides were reviewed and the pertinent histological spectrum was evaluated.  Results  The mean age of patients was 24.36 ± 14.06 years. There were 21 (75%) males and 7 (25%) females. Biopsy was performed in 22 (78.6%), total resection in 1 (3.6%) while subtotal resection was done in 5 (17.9%) cases. Histologically, a spectrum of morphologies was noted with pilocytic astrocytoma (WHO grade 1) at one end and glioblastoma (WHO grade IV) at the other end. Immunohistochemically, all 28 cases were positive for Histone 3 immunohistochemistry. ATRX was performed in 7 (25.0%) cases with loss of ATRX expression in 3 (10.7%) and retained expression in 4 (14.3%) cases. Ki67 was <5% in 6 (21.4%), 5-10% in 1 (3.6%), 11-15% in 1 (3.6%), 16-20% in 3 (10.7%), 21-25% in 4 (14.3%), and 26-30% in 2 (7.1%) cases. The mean survival was 8.00 ± 9.39 months. Out of 28 patients, 15 (62.5%) patients died of disease.  Conclusion  Diffuse midline gliomas with H3K27M mutation is an aggressive entity with a broad morphological spectrum.

Morphological Spectrum and Survival Analysis of Diffuse Midline Glioma With H3K27M Mutation