The Diagnostic Accuracy of Ex Vivo Confocal Laser Scanning Microscopy for Squamous Cell Carcinoma: A Systematic Review and Meta-Analysis

Background/Objectives: Complete excision of squamous cell carcinoma (SCC) while preserving healthy tissue relies on accurate diagnosis and assessment of tumor margins. Ex vivo confocal laser scanning microscopy (EVCM) allows rapid, high-resolution visualization of freshly excised tissue. This study was conducted to comprehensively assess the diagnostic accuracy of EVCM for SCC diagnosis in tissue specimens and margin assessment in margin-controlled (micrographic) surgery using conventional histopathology as the reference standard. Methods: A systematic literature search of MEDLINE and Embase was conducted on 1 January 2026, in accordance with PRISMA guidelines. Pooled sensitivity and specificity were estimated using bivariate random-effects models. The QUADAS-2 and GRADE frameworks were applied to assess risk of bias and certainty of evidence. Results: Six studies comprising a total of 288 specimens were included. For SCC diagnosis in tissue specimens, the pooled sensitivity was 85.1% (95% confidence interval [CI]: 71.6–92.8) and the pooled specificity was 95.5% (95% CI: 90.9–97.8), with low between-study heterogeneity and moderate certainty of evidence. For margin assessment, pooled sensitivity and specificity were 89.9% (95% CI: 51.6–98.7) and 96.1% (95% CI: 85.8–99.0), respectively, with low heterogeneity but also low certainty of evidence owing mainly to the limited number of included studies and specimens. Conclusions: EVCM demonstrates moderate sensitivity and high specificity for the diagnosis of SCC in tissue specimens and may be used selectively as an adjunct to conventional histology, for example as a rapid confirmatory diagnostic tool capitalizing on its high specificity. Current evidence for margin assessment, although promising, remains limited.