The great imitator: clinical, surgical, and molecular insights into diffuse midline gliomas, H3 K27-altered. Illustrative cases.

backgroundH3 K27-altered diffuse midline gliomas (DMGs) are a rare form of primary CNS tumors. In this retrospective single-center case study, DMGs were reviewed for clinical and imaging findings, surgical approaches and challenges, and molecular diagnosis. OBSERVATIONS: Four cases of adult DMG, H3 K27-altered, located among midline structures of the thalamus, brainstem, and spinal cord are presented here. All tumors exhibited heterogeneous presentations on imaging. Symptoms ranged from unspecific back pain and vertigo to focal neurological deficits. Surgery was complicated by high vascularization, infiltrative growth, and proximity to eloquent areas. Diagnostic accuracy was increased by epigenetic DNA methylation-based classification. Three cases were rapidly progressive and resulted in death within 1 year of diagnosis. One case had an exceptionally long overall survival of > 5 years, which was associated with a FGFR1 p.N546K hotspot mutation. LESSONS: DMGs are rare but imitate other pathologies due to variable clinical and radiological characteristics. Surgery is complicated by location and high vascularization. Although DMGs are rare, they should be considered as a differential diagnosis in intracranial and spinal masses in adults. As the FGFR1 p.N546K hotspot mutation is associated with prolonged survival, it may justify more radical surgery in eloquent regions. https://thejns.org/doi/10.3171/CASE25357.