Primary malignant melanoma of the gastrointestinal (GI) tract is an epithelial malignancy originating from melanocytes.¹ Melanocytes are derived from melanoblasts of the neural crest and migrate to the distal ileum via the omphalomesenteric canal to the distal ileum.² In the GI tract, metastatic melanoma is most commonly found in the small intestine (51%–71%), stomach (27%), colon (22%), and esophagus (5%).^3,4 Primary malignant melanoma of the GI tract is extremely rare, and occurrences involving the esophagus are even rarer, accounting for approximately 0.1% to 0.5% of all esophageal malignancies.⁵ It occurs in patients between the ages of 60 and 70 years and is twice as prevalent in men as in women. More than 90% of malignant melanomas of the esophagus occur mainly in the middle to distal third of the esophagus, which is speculated to be due to the high local concentration of melanocytes.⁶ In comparison to other primary esophageal cancers, it progresses rapidly and has a poor prognosis. At the time of diagnosis, approximately 40.9% of patients already present with metastatic lesions; the average survival duration is 10 to 13 months, and the 5-year survival rate is 0% to 4%.⁷

It is essential to rule out metastatic malignant melanoma by comprehensively analyzing the patient’s history and physical examination, including the skin, eyes, and anus, which can be the initial sites of melanoma, before establishing a diagnosis of primary malignant melanoma of the esophagus. Through a full-body physical examination, the patient, in this case, was also confirmed to have no additional melanoma-suspected primary lesions. Endoscopic findings of primary esophageal melanoma typically reveal a lobulated, dark-colored tumor with intact mucosa or occasional ulcerations.⁸ If a metastatic lesion is ruled out, the subsequent diagnosis is obtained through histopathologic examination. Given its frequent misdiagnosis as a poorly differentiated carcinoma, obtaining a sufficient number of specimens during tissue biopsy is important. The histopathologic diagnostic criteria for esophageal melanoma include the presence of melanin granules inside the tumor cells as well as melanocytes in the overlying esophageal epithelial layer.⁸ In addition, accurate diagnosis can be obtained through immunohistochemical staining, which often reveals positive antibody-specific cytoplasmic reactivity to HMB-45 and S-100 proteins, and negative results for cytokeratin or carcinoembryonic antigen.⁹ In CT images, melanoma is frequently observed as a bulky mass compressing the adjacent mediastinal structures. Differential diagnoses, including spindle cell carcinoma, leiomyosarcoma, and esophageal lymphoma, should be established. F-18 FDG PET-CT detects melanoma as an FDG-avid lesion, making it an efficient diagnostic tool for confirming the disease burden. The patient was diagnosed with primary malignant melanoma of the esophagus with distant lymph node metastasis. The patient received seven months of palliative chemotherapy with pembrolizumab, but the disease progressed with esophageal stenosis and tracheal invasion. Chemotherapy was discontinued as the patient’s condition deteriorated. The patient died eight months after being diagnosed with progressive disease.