Application of the International System for Serous Fluid Cytopathology in cerebrospinal fluid cytology: Overall survival analysis associated with diagnostic categories

BACKGROUND: Cerebrospinal fluid (CSF) cytopathology lacks standardized reporting, leading to diagnostic variability and inconsistent clinical management. Although the International System for Reporting Serous Fluid Cytopathology (TIS) has been established for effusions, its utility in CSF remains underexplored. For this study, the authors applied TIS categories to CSF specimens from three academic centers across two continents and evaluated their association with overall survival (OS). METHODS: A retrospective review of pathology databases (2019-2022) across three institutions was performed. Data included demographics, cytologic diagnosis, and OS. Diagnoses were reclassified using TIS criteria. OS was analyzed using Kaplan-Meier curves and Cox proportional hazards models, and multivariable analysis was used for predictors of mortality. RESULTS: In total, 1137 patients underwent CSF cytologic evaluation. Diagnostic distribution was as follows: 3.2% nondiagnostic, 67.1% negative for malignancy, 6.2% atypia of undetermined significance, 2.7% suspicious for malignancy, and 20.8% malignant. Among 579 patients with follow-up, OS differed across categories (p < .001). Mean survival was longest in patients who were diagnosed as negative for malignancy (53.9 months), followed by atypia of undetermined significance (48.4 months), and suspicious for malignancy (40.3 months), and it was shortest in patients who were diagnosed with malignancy (18.7 months). CONCLUSIONS: Leveraging a large, multi-institutional cohort with up to 5 years of follow-up, this study demonstrated that TIS categories effectively stratify CSF specimens into distinct prognostic groups. The authors identified a significant correlation between diagnostic classification and OS, with a clear decline in patient outcomes from those who had diagnoses of negative for malignancy/atypia of undetermined significance to those who had diagnoses of suspicious for malignancy and malignancy. These findings support the TIS system as a standardized, evidence-based framework that enhances risk stratification and clinical decision-making in CSF cytopathology.