Mucosal Melanoma: Epidemiology, Biology and Treatment

Abstract

Mucosal melanoma is an exceedingly rare variant of cutaneous melanoma that, due to its rarity, is poorly described and infrequently studied. Primary sites of origin include the head and neck, anorectum and vulvovaginal regions. It is uniquely different from cutaneous melanoma with respect to epidemiology, etiology, pathogenesis and prognosis. The etiology and pathogenesis remain unclear. Unlike cutaneous melanoma, exposure to UV light is not an apparent risk factor. Furthermore, distinct molecular features including a lower incidence of BRAF oncogene mutations but a higher incidence of KIT oncogene mutations suggest divergent genetic etiologies. Mucosal melanomas generally present at a later stage, are more aggressive and carry a worse prognosis regardless of the stage at diagnosis. Establishing standardized treatment guidelines has been challenging due to the rarity of the disease. Early detection provides the best chance at survival but is often difficult due to anatomic location. Surgery remains the primary therapeutic intervention if complete resection is technically feasible given the anatomic location. Radiotherapy may be used to achieve local control when resection is not feasible, or adjuvantly to enhance locoregional control, but most studies have failed to demonstrate an improvement in overall survival. There are no consensus guidelines on the optimal systemic therapy, and regimens are often extrapolated from data based on therapies used to treat advanced cutaneous melanoma. Clinical trials, particularly utilizing newer targeted therapies and immunotherapies, are investigating novel treatment approaches.

Primary mucosal melanoma of the head and neck in Denmark, 1982–2012: Demographic and clinical aspects. A retrospective DAHANCA study

“…Though, this field is rapidly progressing [24]. Recent studies of MMs have shown distinct molecular features compared to cutaneous melanoma.…”

“…BRAF-inhibition of cutaneous melanoma in a phase III trial showed improved rates of overall and progression-free survival [28]. However, only about 10% of patients with MM have BRAF V600 mutations and the question is whether these patients will see the same response as seen in patients with cutaneous melanoma [24]. Immunotherapy has proven effective in the treatment of advanced cutaneous melanoma.…”

“…Ipilimumab, an IgG antibody, has in a randomized phase III trial showed a survival advantage in melanoma patients with metastatic disease. In this particular study a few MM patients were represented [29], but until now there have never been any randomized trials of ipilimumab in a population solely with MM patients [24]. However, the development of targeted therapy and immunotherapy is of great clinical interest and may provide new treatment regimes for patients with MM and MMHN.…”

Malignant melanoma of sun-protected sites: a review of clinical, histological, and molecular features

“…For example, 66% of patients with mucosal melanoma arising on the larynx or pharynx report a history of smoking, and anorectal melanoma appears to be more common in patients with HIV. 16,64 CONCLUSION In summary, our review of the literature suggests important clinical and histological similarities between acral and mucosal melanomas. Whereas cutaneous melanomas may be somewhat common in women before the age of 50, sun-protected subtypes are rarely diagnosed before the seventh and eighth decades of life.…”

“…In fact, these subtypes represent a disproportionally high percentage of melanomas in blacks, Asians, and Hispanics, owing to the overall low incidence of sun-related melanomas in these groups. 15,16 …”