The Thousand Faces of Malignant Melanoma: A Systematic Review of the Primary Malignant Melanoma of the Esophagus

Simple Summary Primary malignant melanoma of the esophagus (PMME) represents a fairly described and represented entity in the literature, although only in the middle of the last century was it recognized as actually existing. In this systematic review we address the history of PMME starting from 1906, the year in which Bauer made the first description of this entity, passing through his first demonstration on an autopsy series by De Pava et al. and we come to the most recent notions of molecular biology and immunotherapy. Primary Malignant Melanoma of the Esophagus (PMME) is an extremely rare cancer of the esophagus, accounting for 0.1-0.8% of all oro-esophageal cancers and <0.05% of all melanoma subtypes, with an estimated incidence of 0.0036 cases per million/year. We conduct a careful analysis of the literature starting from 1906 to the beginning of 2022, searching the PubMed, Science.gov, Scopus and Web of Science (WoS) databases. A total of 457 records were initially identified in the literature search, of which 17 were duplicates. After screening for eligibility and inclusion criteria, 303 publications were ultimately included, related to 347 patients with PMME. PMME represents a very rare entity whose very existence has been the subject of debate for a long time. Over time, an increasing number of cases have been reported in the literature, leading to an increase in knowledge and laying the foundations for a discussion on the treatment of this pathology, which still remains largely represented by surgery. In recent times, the possibility of discovering greater mutations in gene hotspots has made it possible to develop new therapeutic strategies of which nivolumab is an example. Future studies with large case series, with clinicopathological and molecular data, will be necessary to improve the outcome of patients with PMME.