Distinguishing metastatic carcinomas from mesotheliomas or reactive mesothelial cells in pleural, peritoneal, and pericardial effusions is a common diagnostic problem cytopathologists encounter.


To perform the first meta-analysis on the pooled diagnostic accuracy of claudin-4 immunochemistry in serous effusion cytopathology.


This report followed the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines for diagnostic test accuracy studies. Three databases (PubMed, Scopus, and the Cochrane Library) were searched until October 9, 2023, followed by study selection using specific inclusion and exclusion criteria and data extraction. The study quality assessment was performed by using the Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2) tool. Statistical analysis was performed by using R to calculate the pooled sensitivity and specificity of claudin-4 immunochemistry. In addition, the diagnostic odds ratio was measured, representing the odds ratio of a positive result indicating a carcinoma rather than a mesothelial process in serous effusion cytology.


Fourteen observational studies, published between 2011 and 2023, fulfilled the selection criteria and were included. All 14 studies used the 3E2C1 clone. Claudin-4 immunochemistry showed a high diagnostic accuracy in serous effusion cytology. The pooled sensitivity and specificity were 98.02% (95% CI, 93.96%–99.37%) and 99.72% (95% CI, 97.36%–99.97%), respectively. Lastly, the pooled diagnostic odds ratio was 1660.5 (95% CI, 760.0–3627.8) and no evidence of statistical heterogeneity between the included studies was found (I2 = 0%, τ2 = 0).


Claudin-4 may be used as a single pan-carcinoma immunochemical biomarker in the differential diagnosis between metastatic carcinomas and mesotheliomas or reactive mesothelial cells in serous effusion cytology.

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Author notes

The authors have no relevant financial interest in the products or companies described in this article.

Supplementary data