Reflectance confocal microscopy detects distinct features of field damage in chronically UV-irradiated SKH1 mouse skin.

UVR drives keratinocyte clonal expansion and cutaneous field damage, yet the assessment of early UV-induced field damage remains subjective and lacks an objective, non-invasive method. Reflectance confocal microscopy provides near-histologic imaging of the epidermis and may enable the detection of subclinical UV-induced changes before overt lesion development. Using SKH1 hairless mice, reflectance confocal microscopy images were analyzed during an early post-UV period at weeks 12 and 14 and a late post-UV period at weeks 16 and 18, corresponding to 6-8 and 2-4 weeks before the first visible tumor emergence, respectively. Five epidermal features significantly differentiated irradiated from control skin. Among the 5 features, atypical honeycombing and keratinocyte pleomorphism showed the strongest discriminatory value. In the early post-UV period, the expert-derived mean positivity for atypical honeycombing was 66.7-100% in irradiated skin versus 0-46.7% in control skin, while that for keratinocyte pleomorphism was 33.3-60% versus 0-13.3%, respectively. In the late post-UV period, atypical honeycombing was 46.7-100% in irradiated skin versus 0-33.3% in control skin, and keratinocyte pleomorphism was 33.3-80% versus 0-33.3%, respectively. Expert readers classified irradiated versus non-irradiated cases with 96.7% sensitivity and 90% specificity early and with 90% sensitivity and 90% specificity late. These findings support reflectance confocal microscopy as a non-invasive tool for detecting subclinical UV-related field damage.