Application of The International System for Serous Fluid Cytopathology to cerebrospinal fluid and adjunct flow cytometry analysis improves diagnostic accuracy

BACKGROUND: Cerebrospinal fluid (CSF) is an important diagnostic tool for detecting leptomeningeal involvement by malignancy or other etiologies. Currently, there is no standardized reporting system for CSF cytology. This study aims to assess the application of The International System for Serous Fluid Cytopathology (TIS) in categorizing CSF diagnoses and the role of flow cytometry in improving diagnostic performances. METHODS: CSF cases at our institution between January 1, 2023, and December 31, 2023, were reviewed and selected slides were examined. Based on the retrospective review of cytomorphologic findings and flow cytometry results, cases were reclassified into five diagnostic categories according to TIS: nondiagnostic (ND), negative for malignancy (NFM), atypia of uncertain significance (AUS), suspicious for malignancy (SFM), and malignant (MAL). RESULTS: The study cohort included 854 CSF cases from 439 patients. Flow cytometry was performed in 185 (21.7%) cases with a positive result in 23 cases. After applying TIS, final cytological diagnoses included NFM (87.2%), AUS (7.1%), SFM (0.6%), and MAL (5.0%). The calculated risk of malignancy was 0.3% for NFM, 4.5% for AUS, 66.7% for SFM, and 100% for MAL. The diagnostic performance metrics were 95% sensitivity, 100% specificity, and 99% diagnostic accuracy. CONCLUSIONS: The application of TIS to CSF specimens helps standardize reporting terminology, improves diagnostic accuracy, and offers predictive risk stratification. The conjunction with flow cytometry to CSF cytology helps reduce indeterminate diagnosis, especially for those with an uncertain etiology or prior history of hematological malignancy.