Spinal low-grade ependymal tumors harboring telomerase reverse transcriptase promoter mutation and chromosome 7 gain with methylation profile of spinal subependymoma

ABSTRACT: Spinal intramedullary tumors comprise a heterogeneous group of entities with diverse histopathological features, making their diagnosis particularly challenging. In this study, we identified three cases of spinal ependymal tumors exhibiting a methylation profile of spinal (SP-) subependymoma (SEPN). One case exhibited histopathological features and a methylation profile typical of SP-SEPN, whereas the other two cases occurred in elderly patients and demonstrated circumscribed growth consistent with low-grade ependymal tumors; however, these tumors did not exhibit the typical histopathological features required for a diagnosis of SEPN in the 2021 WHO classification of CNS tumors, showing indistinct cluster formation, an astrocytic immunohistochemical profile suggested by Olig2 expression, and relatively elevated Ki-67 labeling indices of 4.5% and 3.1%. At the molecular level, both cases harbored telomerase reverse transcriptase promoter (pTERT) mutations and whole chromosome 7 gain. On two-dimensional t-distributed stochastic neighbor embedding analysis, both clustered within the SP-SEPN methylation class at its periphery, with low classifier calibration scores (0.70 and 0.69). According to the current WHO classification, one case in this study fulfills the diagnostic criteria for SP-SEPN, whereas the remaining two are designated as low-grade ependymal tumors (CNS WHO grade 2) with methylation profile of SP-SEPN because they do not meet the essential WHO histopathological criteria. Ependymal tumors exhibiting a methylation profile consistent with SEPN, but discordant histopathological features have been increasingly recognized, and the appropriate classification of such tumors remains a subject of ongoing debate. These cases provide important insights into the histopathological diversity of ependymal tumors and contribute to establishing a more comprehensive and systematic classification of ependymal tumors.

ORGANISM(S): Homo sapiens

PROVIDER: GSE319845 | GEO | 2026/08/26

REPOSITORIES: GEO