Introduction: Ex vivo confocal microscopy (EVCM) enables rapid intraoperative margin assessment of cutaneous tumors in Mohs and slow-Mohs surgery. Objectives: To systematically review the diagnostic accuracy of EVCM in margin-controlled surgery across device types, imaging modalities, surgical techniques, and reader expertise. Methods & Materials: Following PRISMA guidelines, PubMed and Scopus were searched to January 2025 for English-language studies evaluating EVCM against histopathology. A bivariate random-effects model pooled sensitivity and specificity. Summary ROC curves, likelihood ratios, diagnostic odds ratios, heterogeneity, and QUADAS-2 risk of bias were evaluated. Results: Fourteen studies (2009–2024; 1,178 patients, 2,811 margins) met inclusion criteria, with 11 contributing 13 datasets to the quantitative meta-analysis. Devices included VivaScope 2000/2500 and Histolog Scanner using reflectance, fluorescence, or digital staining. Pooled sensitivity was 0.91 (95% CI: 0.84–0.95) and specificity was 0.93 (95% CI: 0.84–0.97). The HSROC curve showed an AUC of 0.96. Pooled positive and negative likelihood ratios were approximately 13 and 0.10, respectively. Deeks' test showed no funnel-plot asymmetry (P = 0.33). Conclusion: EVCM shows high diagnostic accuracy for intraoperative margin assessment. However, substantial clinical and methodological heterogeneity warrants cautious interpretation. Standardized protocols, structured training, and multicenter prospective studies are needed to define its clinical role.
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