Updates and challenges in serous fluid cytopathology

Serous fluids, encompassing pleural, pericardial, and peritoneal fluids, exhibit a wide spectrum of neoplastic and non-neoplastic conditions. Malignant effusions commonly result from metastasis, particularly from adenocarcinomas, and less frequently from primary malignant mesothelioma. Cytologic assessment of serous effusions remains an invaluable tool, especially with the expanding role of ancillary techniques available to resolve diagnostically challenging cases. The recently introduced International System for Reporting Serous Fluid Cytopathology (TIS) establishes a standardized reporting system with five distinct diagnostic categories: nondiagnostic (ND), negative for malignancy (NFM), atypia of undetermined significance (AUS), suspicious for malignancy (SFM), and malignant (MAL). Understanding the distribution of malignancy in serous fluids by site of origin in effusion cytology is important, especially in patients with an unknown primary. Immunohistochemistry (IHC) combined with clinical and radiologic data plays a crucial role in confirming malignancy, establishing the primary site, determining the stage, predicting prognosis, monitoring recurrence, and influencing medical management. This review aims to provide an overview of TIS reporting system, emphasizing its malignant category. It provides updates on the distribution of malignancies in serous fluids and discusses valuable IHC panels based on differential diagnosis, addressing challenging cases within this context.