| Summary: | Actinic cheilitis (AC) is one of the most frequent pathologies to affect the lips. Studies show that the most commonplace oral malignancy, squamous cell carcinoma (SCC), often emerges from AC lesions. Invasive diagnostic techniques performed on the lips carry a high risk of complications, but reflectance confocal microscopy (RCM), a non-invasive skin imaging technique, may change the current diagnostic pathway. This retrospective study was aimed at consolidating the RCM diagnostic criteria for AC and lip SCC. The study was conducted in two tertiary care centers in Bucharest, Romania. We included adults with histopathologically confirmed AC and SCC who also underwent RCM examination. Of the twelve lesions included in the study, four were AC and eight were SCC. An atypical honeycomb pattern and the presence of target cells in the epidermis were RCM features associated with AC. SCC was typified by the presence of complete disruption of the epidermal architecture and dermal inflammatory infiltrates. The mean blood vessel diameter in SCC was 18.55 µm larger than that in AC (<i>p</i> = 0.006) and there was no significant difference (<i>p</i> = 0.64) in blood vessel density, as measured by RCM, between SCC and AC. These data confirm that RCM can be useful for the <i>in vivo</i> distinction between AC and lip SCC.
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