Introduction: Malignant serous effusions are common in metastatic carcinomas. Although cytomorphology is recognized as the gold standard diagnostic method, it exhibits moderate sensitivity. This study aimed to assess the diagnostic value of immunophenotyping with a single epithelial marker, known as the epithelial cell adhesion molecule (EpCAM, CD326), in discriminating malignant metastatic carcinomas of serous fluids. Methods: This prospective study was conducted on suspicious or confirmed cases of malignant tumors from September 16, 2019, to June 21, 2020. Serous fluid samples were assessed via cytomorphology using the Wright-Papanicolaou method and the anti-EpCAM mouse monoclonal antibody (clone VU-1D9) flow cytometry. The EpCAM(+)/CD45(−) immunophenotype was defined as the metastatic involvement of carcinoma in the serous cavity. Results: A total of 118 samples (90 females and 28 males; mean age, 54.04 ± 16.14 years), collected from peritoneal and pleural fluids, were examined in this study. Five samples (4.24%) were positive in both EpCAM flow cytometry and cytology, while 102 samples (86.44%) were negative for both EpCAM flow cytometry and cytology, yielding an overall agreement of 92%, 84%, and 90.7% for the peritoneal, pleural, and total samples, respectively. Based on the Bayesian latent class model, the EpCAM flow cytometry showed sensitivity and specificity of 58.5% (95% CI: 0.3, 99.7) and 96.2% (95% CI: 47.8, 100), respectively. The corresponding values were 68.7% (95% CI: 0.3, 99.9) and 96.1% (95% CI: 47, 100) for cytology, respectively. Conclusion: The EpCAM flow cytometry and cytology showed comparable performance in detecting metastatic effusions. The EpCAM flow cytometry might have a diagnostic value in decreasing the false-negative rate of cytomorphology, while maintaining excellent specificity.

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