Tumor-type-specific expression of TTF-1 in primary central nervous system tumors classified by the 2021 WHO criteria.
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Thyroid transcription factor-1 (TTF-1) is a widely used immunohistochemical marker for tumors of thyroid and pulmonary origin; however, its expression profile and diagnostic relevance in primary central nervous system (CNS) tumors remain incompletely characterized, particularly following the revisions in the 2021 WHO Classification of CNS Tumors. We systematically evaluated TTF-1 expression in a cohort of 214 primary CNS tumors diagnosed between 2021 and 2024 at The First Affiliated Hospital of China Medical University and classified according to current WHO criteria. Immunohistochemistry for TTF-1 was performed, and expression patterns were correlated with histological tumor type, molecular classification, and WHO grade. Statistical analyses were conducted to compare expression frequencies across tumor subtypes. TTF-1 showed tumor-specific expression patterns. It was highly sensitive in central neurocytomas (89.47%) and fully specific for subependymal giant cell astrocytoma (SEGA) among circumscribed gliomas. Focal TTF-1 positivity was sporadically detected in high-grade diffuse gliomas, without significant links to molecular alterations, anatomical sites, or other common immunohistochemical indicators. TTF-1 was consistently negative in multiple newly classified and rare CNS tumors, whereas partial intracranial mesenchymal tumors with FET-CREB fusions presented TTF-1 positivity. In conclusion, TTF-1 serves as a reliable sensitive marker for central neurocytomas and a highly specific marker for SEGA. Given its occasional positivity in high-grade gliomas and certain intracranial mesenchymal tumors, pathologists should interpret TTF-1 results prudently to avoid misdiagnosing primary CNS lesions as metastatic tumors. TTF-1 is therefore a valuable auxiliary biomarker for difficult differential diagnosis of CNS tumors.