松果体のびまん性正中グリオーマ、H3K27M改変型：初のシナプトフィジン陽性例および系統的レビュー

Diffuse midline gliomas (DMGs) with H3K27M alterations are rare, aggressive, World Health Organization (WHO) grade 4 tumors arising in midline central nervous system (CNS) structures, characterized by a lysine-to-methionine substitution at histone H3K27, which disrupts epigenetic regulation via global loss of H3K27 trimethylation. The pineal gland is an exceptionally uncommon site of origin. We report the first case of a synaptophysin-positive, H3K27M-altered DMG in the pineal gland of a 7-year-old female, characterized by hypercellularity, moderate atypia, high mitotic activity, and a Ki-67 index of 30%. Immunohistochemistry confirmed positivity for glial markers: glial fibrillary acidic protein (GFAP), oligodendrocyte transcription factor 2 (Olig2), loss of hypotrimethylation of lysine 27 on histone H3 (H3K27me3), and synaptophysin expression, an unusual feature for DMGs. Methylation profiling established the diagnosis. A systematic review identified seven cases of pineal H3K27M-altered DMG (age ranged from 7 to 65 years, with three pediatric and four adult) revealing notable immunohistochemical heterogeneity, limited molecular data (only our case had available methylation profiling) and a synaptophysin expression limited to our pediatric case. Sparse clinical outcome data precluded robust prognostic comparisons. These findings underscore the biological heterogeneity and diagnostic challenges of pineal DMGs and underscore the necessity of comprehensive molecular and immunohistochemical assessments to optimize diagnosis and guide emerging targeted therapies.