Distinct Patterns of Acral Melanoma Based on Site and Relative Sun Exposure

Abstract

Acral melanoma is distinct from melanoma of other cutaneous sites, yet there is considerable variation within this category. To better define this variation, we assessed melanomas occurring on dorsal (n = 21), volar (n = 9), and subungual/interdigital (n = 13) acral skin as well as acral nevi (n = 24) for clinical, histologic, and molecular features. Melanomas on dorsal acral surfaces demonstrated clear differences compared with volar and subungual/interdigital melanomas. The latter two groups exhibited significantly less frequent BRAF mutations (P = 0.01), were significantly less likely to have the superficial spreading histologic subtype (P = 0.01), occurred in older patients (P = 0.05), and had more frequent involvement in non-Caucasians (P = 0.01). These differences can be explained by differing levels of UV exposure. Subungual/interdigital melanomas had the most diverse group of oncogenic mutations including PIK3CA (2/13), STK11 (2/13), EGFR (1/13), FGFR3 (1/13), and PTPN11 (1/13). In addition, subungual/interdigital melanomas had a significantly higher frequency of copy number aberrations (67%) than other subgroups (P = 0.02), particularly in CDK4 and cyclin D1, and were less likely to have BRAF mutations or a superficial spreading histologic subtype (P = 0.05) compared with volar acral melanomas. Although based on a limited sample size, differences between volar and subungual/interdigital melanomas in our study may be the result of differing levels of UV exposure.

The Clinicopathological and Survival Profiles Comparison Across Primary Sites in Acral Melanoma

“…Among 1157 AM patients, 68.5% of patients were reported as sole melanoma at diagnosis in our study. The constitution percentages of different primary sites were consistent with the reports of Haugh et al and Curtin et al 12,17 With respect to age, the overall median age of the patients at time of diagnosis was 56 and the sole group had an older median/mean age than the other two groups, which is similar to another study result. 17 Nunes et al 10 analyzed 157 Brazilian AM patients; the age at diagnosis was older than ours and the age distribution between palms and nail beds was similar.…”

“…On the other hand, an analysis of 177 AM patients in Korea 11 showed that the ulceration proportion in the subungual group was higher. Haugh et al 12 detected the gene mutational profile in AM patients and found that nail bed melanoma was more likely to have CDK4 copy number aberration and lower frequency of BRAF mutation than melanoma originating on palms. Another report 13 showed that the prevalence of BRAF mutation between palm and other subgroups in AM was similar but the NRAS mutation frequency was significantly higher in palm melanoma.…”

Immunohistochemical BRAF V600E Expression and Intratumor BRAF V600E Heterogeneity in Acral Melanoma: Implication in Melanoma-Specific Survival

“…Acral melanoma is rare in Caucasian populations, while it is the most common subtype of melanoma in Asian, African, and Latin American populations [2]. Although several genomic profiling studies of melanoma have been conducted, the numbers of acral melanoma cases in these were limited [11][12][13][14][15]. Furthermore, the genetic heterogeneity of acral melanoma has not been fully investigated.…”

Genetic alterations in primary melanoma in Taiwan

“…Malignant melanoma is classified based on its anatomical site and degree of ultraviolet (UV) light exposure . Acral melanoma (AM) occurs on nonhairy acral skin (palms, soles and nail beds) and is not thought to be linked to UV radiation . Among white people, AMs constitute around 10% of all cases of melanoma.…”