Introduction: The International System for Reporting Serous Fluid Cytopathology (ISRSFC) has recently been announced. Pericardial effusion (PE) is a clinical manifestation of a large variety of both neoplastic and non-neoplastic conditions. Herein, we have applied the ISRSFC on reporting PE cytopathology and report our experience in a large academic institution. Method and Materials: After the Institutional Research Board approval, the electronic pathology database of a large academic institution was queried for PEs collected from January 2014 to January 2019. The diagnosis, patient demographics, and specimen volume were recorded for each case. The ISRSFC was applied and the cases were divided into 5 categories: nondiagnostic (ND), negative for malignancy (NFM), atypia of uncertain significance (AUS), suspicious for malignancy (SFM), and malignant (MAL). Each category was evaluated separately. Results: A total of 299 cases were identified, 162 females and 137 males. The age of the subjects ranged from less than a year to 89 years (average 51.25 years). The volume ranged from 3 to 1,700 mL (average 298 mL). There were 252 NFM (84.3%), 13 AUS (4.3%), 4 SFM (1.3%), and 30 MAL (10%) cases. Metastatic lung cancer followed by metastatic breast cancer were the most common malignancies involving pericardial fluid (PF). No cases were diagnosed as ND. However, no mesothelial cells were seen in 97 specimens (38% of the negative cases). None of these patients developed malignant PE in at least 6 months of follow-up. Conclusion: The ISRSFC is a user-friendly reporting system which is easily applicable on serous fluid including PF. The vast majority of PEs was benign (84.3%). Our study shows that the presence of mesothelial cells is not necessary for specimen adequacy in serous effusions as no mesothelial cells were identified in 38% of the negative cases. Metastatic lung carcinoma was the most common diagnosis of malignant effusions.

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