Subtypes of Melanomas Associated with Different Degrees of Actinic Elastosis in Conventional Histology, Irrespective of Age and Body Site, Suggesting Chronic Ultraviolet Light Exposure as Driver for Lentigo Maligna Melanoma and Nodular Melanoma

Simple Summary Increased sun exposure and sunburns lead to higher numbers of moles as well as melanomas and non-melanoma skin cancers. Scientists are unsure whether there is a difference between being in the sun very often (chronic sun damage) and being in the sun for too long at certain times (intermittent exposure) in terms of the individual melanoma risk. In this study, we used light microscopy to look at typical connective tissue changes in the skin that occur with long-term sun exposure. We analyzed whether these changes are correlated with different subtypes of melanomas and whether they are associated with sun-exposed body sites (chronic exposure) and shaded body sites (intermittent exposure). Our results show that tissue changes near moles and melanomas as well as subtypes of melanomas vary, regardless of patient age and tumor site. This finding is important because it sheds light on the biological effects of sunlight on pigment cells, which are the source of moles and melanomas. Moreover, it emphasizes the need to more clearly differentiate among the subtypes of melanomas.Abstract (1) Background: Ultraviolet (UV) radiation and sunburns are associated with an increased incidence of acquired nevi and melanomas. However, the data are controversial as to whether chronic UV exposure or high intermittent UV exposure is the major carcinogenic factor in melanocytic tumors. In this study, we compared the degree of actinic elastosis (AE) as a surrogate for lifetime UV exposure in nevi and different clinical melanoma subtypes (i.e., superficial spreading melanoma (SSM), nodular malignant melanoma (NMM), acral lentiginous melanoma (ALM), and lentigo maligna melanoma (LMM)) with respect to clinical variables (age, sex, and body site). (2) Methods: We defined a semi-quantitative score for the degree of AE ranging from 0 = none to 3 = total loss of elastic fibers (basophilic degeneration) and multiplied it by the perilesional vertical extent (depth), measured histometrically (tumor-associated elastosis grade (TEG)). We matched the TEG of n = 595 melanocytic lesions from 559 patients with their clinical variables. (3) Results: The TEG was correlated with age and UV-exposed body sites. Furthermore, the TEG was significantly higher in LMM than in all other types of melanomas and the TEG in NMM was higher than in SSM, irrespective of patient age and tumor site. (4) Conclusions: High cumulative UV exposure is more strongly associated with LMM and NMM than with other melanoma subtypes.