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

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.

Keywords: actinic elastosis; carcinogenesis; histopathology; melanoma; nevogenesis.

Figure 1

Example of histopathological assessment (tumor-associated elastosis grade—TEG) and measurement of AE depth. The depth of elastotic material was measured in the vicinity of the tumor in the absence of the tumoral stroma. The semi-quantitative score was defined as follows: 0 = absent, 1 = low: less elastotic material than regular fibers (collagenous and elastic), 2 = moderate: more elastotic fibers than regular fibers, and 3 = strong: complete or almost complete loss of normal fibers or homogeneous basophilic zone. Scale bars indicate 500 µm. (A) Example of score 0; (B) example of score 1; (C) example of score 2 and exemplified measurement of the depth of AE; and (D) example of score 3.

Figure 2

Mean thickness (depth) of AE and TEG correlated with UV-exposed body sites and age at time of diagnosis in all groups combined (nevi and melanomas). (A) Boxplot diagram of the mean depth of AE, showing differences between UV-exposed and non-UV-exposed body sites (p < 0.001; *** stands for p < 0.001). (B) Boxplot diagram of TEG (depth × semi-quantitative score), showing differences between UV-exposed and non-UV-exposed body sites (p < 0.001; *** stands for p < 0.001). (C) Point scatter plot, showing a significant correlation (p < 0.001) between mean depth of AE and age at time of tumor diagnosis (defined as time of excision). (D) Point scatter plot, showing a significant correlation (p < 0.001) between TEG and age at time of tumor diagnosis (defined as time of excision).

Figure 3

Mean thickness (depth) of AE and TEG, comparing LMM with other melanoma subtypes. (A) Boxplot diagram of the mean depth of AE, showing differences between LMM and other melanoma subtypes (p < 0.001; *** stands for p < 0.001). (B) Boxplot diagram of TEG (depth × semi-quantitative score), showing differences between LMM and other melanoma subtypes (p < 0.001; *** stands for p < 0.001). Abbreviations: AE—actinic elastosis; TEG—tumor elastosis grade.

Figure 4

Comparison of thickness (depth) of AE and TEG between SSM and NMM. (A) Boxplot diagram of depth of AE in SSM and NMM (p < 0.001). (B) Boxplot diagram of TEG in SSM and NMM (p = 0.006). ** stands for p < 0.005, *** stands for p < 0.001. Abbreviations: AE—actinic elastosis; TEG—tumor elastosis grade; SSM—superficial spreading melanoma; NMM—nodular malignant melanoma.