The Role of Vimentin, Synaptophysin, and Histone H3 Lysine 27 Methylation (H3K27me) as Surrogate Markers in the Diagnosis and Classification of Oligodendrogliomas and Diffuse Midline Gliomas: A Comprehensive Review.

Oligodendrogliomas and diffuse midline gliomas (DMGs) are distinct subtypes of central nervous system (CNS) tumors with differing prognoses and treatment responses. Accurate differentiation between these tumors is critical yet often challenging, particularly when comprehensive molecular testing is unavailable. This review explores the diagnostic value of immunohistochemical surrogate markers, vimentin, synaptophysin, and histone H3 lysine 27 methylation (H3K27me), in distinguishing these tumor types. A narrative review methodology was employed following the Scale for the Assessment of Narrative Review Articles (SANRA) guidelines. Relevant peer-reviewed studies were identified through comprehensive database searches of PubMed, Embase, Scopus, Web of Science (WoS), and Google Scholar using targeted keywords and Medical Subject Headings (MeSH) terms. Articles were included based on their focus on the immunohistochemical and molecular characterization of oligodendrogliomas and DMGs. Vimentin, typically associated with mesenchymal transition, is highly expressed in DMGs and high-grade gliomas, reflecting aggressive behavior and invasiveness. In contrast, oligodendrogliomas usually lack vimentin expression. Synaptophysin, a neuronal differentiation marker, is frequently expressed in oligodendrogliomas but largely absent in DMGs, offering discriminatory value. The loss of H3K27 trimethylation (H3K27me3) expression is a defining feature of H3K27M-mutant DMGs and serves as a highly specific diagnostic marker. Together, these markers improve diagnostic precision, particularly in resource-limited settings or where molecular assays are not readily available. Vimentin, synaptophysin, and H3K27me expression patterns offer practical, cost-effective surrogate tools to enhance diagnostic accuracy in glioma classification. Their integration into routine neuropathological assessment can support timely and appropriate therapeutic decision-making, especially in settings lacking full molecular testing capabilities. Further research is needed to explore their potential roles in guiding targeted therapies and prognostication.