Real-time assessment of mitotic rate in malignant melanoma by ex vivo confocal microscopy

Abstract Background Malignant melanoma has exhibited a significant increase in incidence over the past decade and remains the most common cause of skin cancer-related deaths. Early diagnosis and treatment are essential, as delays correlate with poorer clinical outcomes. Ex vivo confocal laser scanning microscopy (EVCM) enables intraoperative examination of fresh tissues within minutes and has shown potential for detecting morphological criteria and accurately determining Breslow thickness in melanoma. Objectives The aim of the present pilot study was to evaluate whether EVCM can also reliably assess the mitotic rate, an important prognostic marker influencing the indication for sentinel lymph node biopsy (SLNB). Methods 40 histologically confirmed melanomas from various anatomical sites were examined using the current gold standard of histopathology and EVCM. The confocal mitotic rate (CMR) and the histopathological mitotic rate (HMR) were statistically compared. In this context, two clinically relevant groups (0 mitoses/mm2 and ≥ 1 mitosis/mm2) were defined for analysis, taking into consideration the clinically significant thresholds typically used in histopathological assessment. Results Overall, 95.0% of melanomas were correctly assigned to the respective group. With a sensitivity of 100%, a specificity of 77.8%, a positive predictive value of 93.9% and a negative predictive value of 100%, EVCM demonstrated promising performance for detecting mitotic activity. Conclusions These findings emphasize the potential of EVCM for reliable detection of atypical mitotic figures. Prior to clinical implementation, prospective validation in larger, multicenter cohorts involving multiple EVCM experts is required.