Strong OLIG2 expression in supratentorial ependymoma, ZFTA fusion-positive: A potential diagnostic pitfall

Ependymomas (EPN) are central nervous system neoplasms that exhibit an ependymal phenotype. In particular, supratentorial EPN (ST-EPN) must be differentiated from more aggressive entities such as glioblastoma, IDH-wildtype. This task is frequently addressed with the use of immunohistochemistry coupled with clinical presentation and morphological features. Here we describe the case of a young adult presenting with migraine-like symptoms and a temporoinsular-based expansile mass that was first diagnosed as a GBM, mostly based on strong and diffuse oligodendrocyte transcription factor 2 (OLIG2) expression. Molecular characterization revealed a ZFTA::RELA fusion, supporting the diagnosis of ST-EPN, ZFTA fusion-positive. OLIG2 expression is rarely reported in tumors other than GBM and oligodendrocyte-lineage committed neoplasms. The patient was treated with radiotherapy and temozolomide after surgery and was alive and well at follow-up. This report illustrates the need to assess immunostains within a broader clinical, morphological and molecular context to avoid premature exclusion of important differential diagnoses.