SOX10 Distinguishes Oligodendrogliomas from Low-Grade Glioneuronal Tumors/low-Grade Gliomas with Oligodendrocyte-Like Features

Oligodendrogliomas exhibit significant morphological overlap with low-grade glioneuronal tumors/low-grade gliomas with oligodendrocyte-like features, posing challenges in histopathological diagnosis. SOX10, a transcription factor critical for oligodendrocyte maturation and central nervous system myelination, may serve as a diagnostic marker. We evaluated the diagnostic utility of SOX10 immunohistochemical expression in 300 oligodendrogliomas versus 52 low-grade glioneuronal tumors/low-grade gliomas with oligodendrocyte-like features. Notably, SOX10 was negative in 251/300 (83.7%) oligodendrogliomas but diffusely positive in 47/52 (90.4%) low-grade glioneuronal tumors/low-grade gliomas with oligodendrocyte-like features (except polymorphous low-grade neuroepithelial tumors of the young, PLNTY). SOX10 expression was significantly higher in the latter group (p < 0.001) and showed a WHO grade dependent up-regulation in oligodendrogliomas (p < 0.001). The diagnostic utility of SOX10 was evident in IDH1-immunonegative cases, yielding 72% sensitivity, 90.4% specificity, and a 78.3% positive predictive value for oligodendroglioma. Combining H3K27me3 loss with SOX10 negativity markedly improved diagnostic sensitivity for oligodendroglioma to 88.5%, substantially surpassing the 35% sensitivity achieved with H3K27me3 loss alone. Additionally, an immunohistochemical panel comprising SOX10, Olig2, and IDH1 aided in discriminating non-neoplastic oligodendrocyte hyperplasia from oligodendroglioma and evaluating the presence of peritumoral tumor residue, particularly in IDH1-immunonegative oligodendroglioma. In conclusion, SOX10 negativity effectively excludes low-grade glioneuronal tumors/low-grade gliomas with oligodendrocyte-like features (except PLNTY) and non-neoplastic oligodendrocyte hyperplasia from oligodendrogliomas. SOX10 serves as a specific diagnostic marker, enhancing pathological diagnostic accuracy.