Diagnostic Pitfalls of Oligodendroglioma-like Morphology: Integrated Reappraisal of 23 Non-Oligodendroglial Central Nervous System Tumors

Background/Objectives: Oligodendroglioma-like morphology may generate diagnostic uncertainty in central nervous system tumors, although oligodendroglioma is defined by the integrated presence of IDH mutation and whole-arm 1p/19q codeletion. This study aimed to evaluate the diagnostic pitfalls of oligodendroglioma-like morphology by comparing initial microscopic impressions with final integrated diagnoses. Methods: We retrospectively reviewed 23 non-oligodendroglial central nervous system tumors showing focal or predominant oligodendroglioma-like morphology but not fulfilling the integrated diagnostic criteria for oligodendroglioma. Clinical, radiological, histopathological, immunohistochemical, molecular/cytogenetic, initial microscopic impression, final integrated diagnosis, and follow-up data were analyzed descriptively. Results: Initial microscopic impressions included low-grade glial tumor, high-grade glial tumor, dysembryoplastic neuroepithelial tumor, ependymoma, astroblastoma, oligodendroglioma, dysplasia, central neurocytoma, metastatic epithelial tumor, and pilocytic astrocytoma/low-grade glial tumor. Final integrated diagnoses were astrocytoma, IDH-mutant, CNS WHO grade 2–4 (n = 9); dysembryoplastic neuroepithelial tumor (n = 3); central neurocytoma (n = 3); metastatic renal cell carcinoma (n = 2); low-grade glioneuronal tumor (n = 2); and PLNTY, glioblastoma IDH-wildtype, supratentorial ependymoma, and pilocytic astrocytoma (n = 1 each). Conclusions: Oligodendroglioma-like morphology should be interpreted as a diagnostic pitfall pattern rather than a specific diagnosis. Structured integrated reappraisal using targeted immunohistochemical and molecular/cytogenetic testing helps refine differential diagnosis in routine neuropathology practice.