RESUMO
BACKGROUND: Subungual melanoma (SM) is an unusual type of melanocytic tumor affecting the nail apparatus. The mutational prevalence of the most prominently mutated genes in melanoma has been reported in small cohorts of SM, with unclear conclusions on whether SM is different from the rest of melanomas arising in acral locations or not. Hence, the molecular profile of a large series of SM is yet to be described. OBJECTIVES: The aim of this study was to describe the molecular characteristics of a large series of SM and their association with demographic and histopathological features. METHODS: Patients diagnosed with SM between 2001 and 2021 were identified from six Spanish and Italian healthcare centers. The mutational status for BRAF, NRAS, KIT, and the promoter region of TERT (TERTp) were determined either by Sanger sequencing or next-generation sequencing. Clinical data were retrieved from the hospital databases to elucidate potential associations. RESULTS: A total of 68 SM cases were included. Mutations were most common in BRAF (10.3%) and KIT (10%), followed by NRAS (7.6%), and TERTp (3.8%). Their prevalence was similar to that of non-subungual acral melanoma but higher in SM located on the hand than on the foot. CONCLUSIONS: To date, this study represents the largest cohort of SM patients with data on the known driver gene mutations. The low mutation rate supports a different etiopathogenic mechanism for SM in comparison of non-acral cutaneous melanoma, particularly for SM of the foot.
Assuntos
Melanoma , Doenças da Unha , Neoplasias Cutâneas , Telomerase , Humanos , Melanoma/patologia , Neoplasias Cutâneas/genética , Neoplasias Cutâneas/diagnóstico , Proteínas Proto-Oncogênicas B-raf/genética , Proteínas Proto-Oncogênicas c-kit/genética , Regiões Promotoras Genéticas/genética , Mutação , Doenças da Unha/genética , Análise Mutacional de DNA , Telomerase/genética , Proteínas de Membrana/genética , GTP Fosfo-Hidrolases/genéticaRESUMO
BACKGROUND: Acral location of melanomas is associated with poor survival. It can be due, at least in part, to the fact that acral lentiginous melanoma, a distinct melanoma subtype, has a particular biological profile and a bad clinical behavior. However, since almost 50% of acral melanomas are not of acral lentiginous melanoma subtype, the worse clinical behavior could also be attributable to the intrinsic characteristics of the location. OBJECTIVE: This study aimed to investigate if melanomas of the lower limb excluding acral lentiginous melanoma differ by location. METHODS: This retrospective, observational study recruited patients from an oncology referral center in Spain. We included 285 patients with superficial spreading and nodular melanomas of the lower limb. We compare melanomas by site, clinical and pathological characteristics, and the differences by location of disease-free and melanoma-specific survival by the Kaplan-Meier method and Cox proportional hazard method. RESULTS: Patients with melanomas on the foot, compared to those on the rest of the limb, were older and reported having suffered less sunburns; the melanoma more frequently appeared in areas that had been rarely sun exposed, were more frequently of nodular type, presented thicker tumors, with more ulceration, less regression, and more advanced stage of the disease. Foot location increased the risk of relapse and decreased melanoma-specific survival. CONCLUSION: Melanoma development in foot is less related to sun exposure and is associated with pathological features that can account for the worse prognosis and poorer survival.