RESUMO
CONTEXT.: Distinguishing metastatic carcinomas from mesotheliomas or reactive mesothelial cells in pleural, peritoneal, and pericardial effusions is a common diagnostic problem cytopathologists encounter. OBJECTIVE.: To perform the first meta-analysis on the pooled diagnostic accuracy of claudin-4 immunochemistry in serous effusion cytopathology. DESIGN.: 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. RESULTS.: 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). CONCLUSIONS.: 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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The Paris System (TPS) for Reporting Urinary Cytology is a standardized, evidence-based reporting system, comprising seven diagnostic categories: nondiagnostic, negative for high-grade urothelial carcinoma (NHGUC), atypical urothelial cells (AUC), suspicious for high-grade urothelial carcinoma (SHGUC), HGUC, low-grade urothelial neoplasm (LGUN), and other malignancies. This study aimed to calculate the pooled risk of high-grade malignancy (ROHM) of each category and demonstrate the diagnostic accuracy of urine cytology reported with TPS. Four databases (PubMed, Embase, Scopus, Web of Science) were searched. Specific inclusion and exclusion criteria were applied, while data were extracted and analyzed both qualitatively and quantitatively. The pooled ROHM was 17.70% for the nondiagnostic category (95% CI, 0.0650; 0.3997), 13.04% for the NHGUC (95% CI, 0.0932; 0.1796), 38.65% for the AUC (95% CI, 0.3042; 0.4759), 12.45% for the LGUN (95% CI, 0.0431; 0.3101), 76.89 for the SHGUC (95% CI, 0.7063; 0.8216), and 91.79% for the HGUC and other malignancies (95% CI, 0.8722; 0.9482). A summary ROC curve was created and the Area Under the Curve (AUC) was 0.849, while the pooled sensitivity was 0.669 (95% CI, 0.589; 0.741) and false-positive rate was 0.101 (95% CI, 0.063; 0.158). In addition, the pooled DOR of the included studies was 21.258 (95% CI, 14.336; 31.522). TPS assigns each sample into a diagnostic category linked with a specific ROHM, guiding clinical management.
