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Review
. 2020 Aug 21;12(9):2362.
doi: 10.3390/cancers12092362.

Uncommon Subtypes of Malignant Melanomas: A Review Based on Clinical and Molecular Perspectives

Matías Chacón  1 , Yanina Pfluger  1 , Martín Angel  1 , Federico Waisberg  1 , Diego Enrico  1
Affiliations
Review

Uncommon Subtypes of Malignant Melanomas: A Review Based on Clinical and Molecular Perspectives

Matías Chacón et al. Cancers (Basel). .

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.

Keywords: acral melanoma; amelanotic melanoma; desmoplastic melanoma; immunotherapy; mucosal melanoma; rare melanomas; spitzoid melanoma; targeted therapy; uncommon melanomas; uveal melanoma.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Schematic summary of the most relevant mutations, key features, and treatment options of rare melanomas. For each subtype, mutations are ordered by their prevalence. Main treatment strategies were ordered according to the decreasing efficacy outcomes, including the overall response rate, progression-free survival, and overall survival. Abbreviations: TMB, tumor mutational burden; UV, ultraviolet radiation; Mut, mutation; Amp, amplification; KIT, receptor tyrosine kinase (c-Kit); VEGFR, vascular endothelial growth factor receptor. *Fusion kinases involving ALK, ROS1, NTRK1, NTRK3, MET, RET, BRAF, and MAP3K8.
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References

    1. Thoelke A., Willrodt S., Hauschild A., Schadendorf D. Primary extracutaneous malignant melanoma: A comprehensive review with emphasis on treatment. Onkologie. 2004;27:492–499. doi: 10.1159/000080372. - DOI - PubMed
    1. Chang A.E., Karnell L.H., Menck H.R. The National Cancer Data Base report on cutaneous and noncutaneous melanoma: A summary of 84,836 cases from the past decade. The American College of Surgeons Commission on Cancer and the American Cancer Society. Cancer. 1998;83:1664–1678. doi: 10.1002/(SICI)1097-0142(19981015)83:8<1664::AID-CNCR23>3.0.CO;2-G. - DOI - PubMed
    1. McLaughlin C.C., Wu X.-C., Jemal A., Martin H.J., Roche L.M., Chen V.W. Incidence of noncutaneous melanomas in the U.S. Cancer. 2005;103:1000–1007. doi: 10.1002/cncr.20866. - DOI - PubMed
    1. Pires da Silva I., Wang K.Y.X., Wilmott J.S., Holst J., Carlino M.S., Park J.J., Quek C., Wongchenko M., Yan Y., Mann G., et al. Distinct Molecular Profiles and Immunotherapy Treatment Outcomes of V600E and V600K BRAF-Mutant Melanoma. Clin. Cancer Res. 2019;25:1272–1279. doi: 10.1158/1078-0432.CCR-18-1680. - DOI - PMC - PubMed
    1. Long G.V., Menzies A.M., Nagrial A.M., Haydu L.E., Hamilton A.L., Mann G.J., Hughes T.M., Thompson J.F., Scolyer R.A., Kefford R.F. Prognostic and clinicopathologic associations of oncogenic BRAF in metastatic melanoma. J. Clin. Oncol. 2011;29:1239–1246. doi: 10.1200/JCO.2010.32.4327. - DOI - PubMed