Abstract
Malignant melanoma represents the most aggressive type of skin cancer. Modern therapies, including targeted agents and immune checkpoint inhibitors, have changed the dismal prognosis that characterized this disease. However, most evidence was obtained by studying patients with frequent subtypes of cutaneous melanoma (CM). Consequently, there is an emerging need to understand the molecular basis and treatment approaches for unusual melanoma subtypes. Even a standardized definition of infrequent or rare melanoma is not clearly established. For that reason, we reviewed this challenging topic considering clinical and molecular perspectives, including uncommon CMs—not associated with classical V600E/K BRAF mutations—malignant mucosal and uveal melanomas, and some unusual independent entities, such as amelanotic, desmoplastic, or spitzoid melanomas. Finally, we collected information regarding melanomas from non-traditional primary sites, which emerge from locations as unique as meninges, dermis, lymph nodes, the esophagus, and breasts. The aim of this review is to summarize and highlight the main scientific evidence regarding rare melanomas, with a particular focus on treatment perspectives.
Highlights
Malignant melanoma is one of the most aggressive cancers once it becomes metastatic, an early identification has a high impact on prognoses
The five-year survival rate is less than 25% in this population, which may be explained by different factors, including the limitation of early visual detection compared to cutaneous melanoma (CM), and anatomical factors that hamper a complete resection [102,103]
Fujimori et al described one of the first case reports of a patient with BRAF-mutant Primary intracranial and meningeal melanomas (PIMMs) treated with vemurafenib and nivolumab, with no clinical benefit [216]
Summary
Malignant melanoma is one of the most aggressive cancers once it becomes metastatic, an early identification has a high impact on prognoses. The five-year survival rate is less than 25% in this population, which may be explained by different factors, including the limitation of early visual detection compared to CM, and anatomical factors that hamper a complete resection [102,103] This uncommon subtype has been considered as a distinctive entity since recent genomic studies have supported the notion that UV-light plays a limited role in carcinogenesis [104,105]. In contrast to the increasing rate of CM cases observed in the last years, the incidence of UM has remained relatively stable at approximately five per million since the 1970s [154] This subtype is especially prevalent among white patients with light-colored eyes [155]. UM shows a remarkably low mutational burden, except for iris melanomas that have been associated with UV-induced DNA damage
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