Primary melanoma of the gastrointestinal tract

Primary melanomas of the gastrointestinal tract are rare malignancies, representing less than 2% of all melanomas and 37% of mucosal melanomas. They arise de novo from the mucosal gastrointestinal epithelium, most frequently in the anorectum and esophagus. Their etiology is unclear: Unlike cutaneous melanomas, they are not associated with ultraviolet exposure while genetic predisposition, chronic inflammation, and immune deficiency are among suspected risk factors. They show a relatively low tumor mutational burden with KIT gene mutations being the most common alteration. Symptoms are based on tumor location and may include abdominal pain, bleeding, weight loss, nausea and vomiting, difficulty swallowing in esophageal melanomas, or bowel obstruction. The diagnosis relies on endoscopic studies and cross-sectional imaging. Surgery represents the mainstay of treatment in localized disease and may also provide palliation in more advanced stages. Due to their aggressive nature, adjunctive treatments such as immunotherapy and targeted therapy are often employed while chemotherapy is of limited value. Prognosis is poor, with median survival often below one year in more severe cases. Early detection and novel treatments, including cancer vaccines, immunotherapy combinations, and personalized medicine approaches, are promising to improve survival and quality of life.