Acral Melanoma

Abstract

Compared with the US melanoma incidence rate of 21.1 per 100 000 population from2006 through 2010, a low incidence rateofmelanoma(≤1/100 000)wasreported inEastAsiancountries includingTaiwan,China, Japan,Korea,HongKong,and Singapore. The most common subtype in these countries was acral lentiginous melanoma, which comprised approximately50%to58%ofcutaneousmelanoma.1-6 Incontrast, acral lentiginousmelanoma represented 2% to 3%of allmelanoma among Western populations. Cutaneous acral lentiginousmelanomausually presents in areaswith little to no sun exposure (such as palms, soles, and nail apparatus). Another sun exposure–independent melanoma is mucosal melanoma, which comprised 22% of melanoma in China in 2011.3 ComparedwithWestern countries, where superficial spreadingmelanomacomprisedapproximately 50%to70%,only approximately 5% to 37% of cutaneous melanoma was superficial spreading melanoma in East Asia, where sun-seeking behavior is not as popular as in Western countries. In Asian countries, cutaneous melanoma tends to be diagnosed at an advanced stageand results in low5-year survival rates (Table). UV light exposure has been implicated as a major etiology in the development of melanoma. The defense mechanisms that protect human skin against UV radiation involve melanin synthesis and active repair mechanisms. DNA is the major target of direct or indirect UV-induced cellular damage. UV-induced DNA photoproducts are able to cause specific mutations in genes susceptible to developing skin cancers. Recent molecular genetic investigations have revealed thatmelanomas fromsun-exposedareas showedfrequentmutations in either theBRAF orNRAS gene. In contrast,BRAF or NRASmutations were infrequent in melanomas arising from non–sun-exposedareas, suchas acral skin,nail apparatus, and mucosa. Instead, these types of melanomas showed a higher degreeof chromosomal aberrations; specifically, genomic amplifications involving small portionsof chromosomearms.7 In acral melanoma, the most frequently amplified region was chromosome 11q13, which contains the CCND1 gene. This region has not been well studied in Asian melanoma. The etiology of acral melanoma in Asia remains to be determined. Inanetiological studyofacralmelanomas fromAustralia, an increased risk was associated with penetrating injuryof the feet orhands (relative risk [RR], 5.0) andwithheavy exposure to agricultural chemicals (RR, 3.6).8 These risk factors could be also true in other Asian countries. In this issue, Jung and coauthors4 reported the characteristics of 177 acral melanomas in Korea. This is an important article that explores thepossiblecausesofacralmelanomainEastAsia.Based on theobservational study, theauthorsdemonstratedahigher incidenceofacralmelanomaatmorephysicallypressuredsites (such as the center area of the heels and inner forefoot) than non–physically pressured areas in the acral skin. The authors also observed that acral melanoma tended to spread along naturally occurring creases of the skin. They concluded that chronic physical pressure could influence the incidence and spreading pattern of acral melanoma. Among the 52 patients that provided their trauma history, 15 (29%) patients had evident histories of previous trauma on their sites ofmelanoma. Thisobservationseemstobeconsistentwith theworkofGreen andcoauthors8 suggesting traumaasa risk factorof acralmelanoma. It should be noted that the study by Jung et al4 is observational. Further research with a case-control study is needed to determine the extent and impact of trauma on the developmentofacralmelanoma.Nonetheless, thestudysheds light on the possible etiology of acral melanoma in East Asia. Related article page 1281