Epidemiology and Molecular Profile of Mucosal Melanoma: A Population-Based Study in Southern Europe

SIMPLE SUMMARY: There are few population-based studies focused on the epidemiology of mucosal melanoma, a rare neoplasm. Its poor prognosis, the different etiology from cutaneous melanoma and the lack of effective treatment beyond corrective surgery, make the knowledge of the mutational profile of this type of cancer a useful tool in understanding its natural history and also for the investigation of new target therapies. The aim of our population-based study is to analyze the incidence and survival of mucosal melanoma, which mainly arises from the head and neck sphere, genitourinary tract and rectal area, and to carry out the mutational analysis of selected cases. We used the Girona Cancer Registry database, which registered all cancer cases in Girona, a province of Spain in southern Europe, during the period of 1994–2018. ABSTRACT: Background: Mucosal melanoma is a rare neoplasm on which few epidemiological population-based studies have been published. A good surgical approach is the standard treatment, but the prognosis is worse than that of skin melanoma. The analysis of mucosal melanoma’s mutational profile can help to develop target therapies in advanced disease or adjuvant settings. Methods: We analyzed the database of the Cancer Registry of Girona, a region located in the north-east of Spain, in the period of 1994–2018. We selected cases of primary invasive melanoma, excluding those located in the skin, eye, central nervous system and an unknown primary site. Epidemiological analysis included incidence and survival. Mutational profile analysis was performed with a custom gene panel. Results: Forty-two patients were identified: 14 (33%) had vulvar-vaginal melanoma, 15 (35.7%) had rectal melanoma, 12 (28.6%) had melanoma located in the head and neck sphere and 1 male patient had a urethral melanoma. European age-standardized incidence rates for vulvar-vaginal, rectal and head and neck melanoma were 0.09, 0.1 and 0.09 cases/100,000 inhabitant-years, respectively. Five-year observed survival rates were 37.5%, 20% and 25% for these types of cancers. NRAS Q61 was the most frequent mutation found. Conclusion: Our study confirms the steady incidence and low survival of mucosal melanomas in a region of southern Europe. NRAS and NF1 play a role in the molecular landscape of mucosal melanoma. MEK and PI3K/mTOR inhibitors could be reasonable treatment options and are being studied in clinical trials.