Diagnostic Efficacy of the International System for Reporting Serous Fluid Cytopathology Classification in Pleural Effusion Samples to Analyze the Risk of Malignancy Associated with Each Category and Explore the Prognostic Significance of the Systemic Immune-Inflammation Index within These Classifications.

BACKGROUND: Pleural effusion is a common clinical manifestation of both neoplastic and nonneoplastic conditions. Cytological evaluation of serous fluids remains a cost-effective and minimally invasive diagnostic tool. To standardize reporting and improve the diagnostic accuracy, the International Academy of Cytopathology and the American Society of Cytopathology proposed the International System for Reporting Serous Fluid Cytopathology (ISRSFC). The Systemic Immune-Inflammation Index (SII) is a composite measure of systemic inflammatory status, being a novel prognostic biomarker. It has been linked to adverse outcomes in several malignancies. This study aimed to evaluate the diagnostic efficacy of the ISRSFC in categorizing pleural effusion samples, determine the risk of malignancy (ROM) for each diagnostic category, and assess the prognostic significance of SII across ISRSFC categories. MATERIALS AND METHODS: A retrospective cross-sectional study was conducted on 142 pleural effusion cases diagnosed at the All India Institute of Medical Sciences, Rajkot, from January 2023 to April 2025. Cytological samples were classified according to ISRSFC categories and correlated with histopathology, radiology, and clinical data. Complete blood count parameters were retrieved to calculate the SII (neutrophil × platelet/lymphocyte count). Statistical analysis was performed using Statistical Package for the Social Sciences version 23. RESULTS: Of 142 cases, the majority fell into benign categories (2A and 2B, 88%). ROM increased progressively across ISRSFC categories: 0% (Category 1), 14.4% (2A+2B), 25% (3), 66% (4), and 100% (5). Using analysis of variance, neutrophil count and SII were revealed to be significantly higher in malignant categories (P <0.05). High SII values correlated strongly with categories 4 and 5, suggesting poor prognosis. CONCLUSION: The ISRSFC framework effectively stratifies pleural effusion cases with a stepwise increase in ROM, reinforcing its diagnostic reliability. Additionally, the SII provides independent prognostic value, being significantly elevated in malignant categories. Together, the ISRSFC and SII offer a reproducible, low-cost marker for risk assessment and prognosis in pleural effusion patients. Larger multicentric studies are warranted to validate these findings.