Metastatic Duodenal and Jejunal Melanoma With BRAF V600K Mutation

Background Melanoma, the most invasive skin cancer with the highest risk of death in the United States, frequently harbors BRAF V600K mutations in cutaneous types, whereas mucosal melanomas are associated with SF3B1, KIT, or NF1 mutations. Although melanoma usually metastasizes to the brain, liver, lungs, and lymph nodes, small intestinal metastases are rare and often present late with nonspecific symptoms. Metastatic lesions can cause obstruction or bleeding, requiring prompt medical intervention. We present a unique case of BRAF V600K mutated metastatic duodenal and jejunal melanoma, highlighting diagnostic and therapeutic challenges. Case Description A male in his fifth decade of life with a history of upper back melanoma diagnosed in 2019, which was treated with wide local excision and sentinel lymph node biopsy, presented to our institution in the summer of 2024 with severe iron deficiency anemia, melena, and night sweats. The original primary had a Breslow depth of 2.4 mm, ulceration, and a negative sentinel lymph node biopsy, consistent with stage IIB disease (pT3bN0M0). Subsequent enteroscopy revealed two nodules in the distal duodenum and proximal jejunum, respectively. The lesions appeared dysplastic and inflamed, and biopsies were obtained from both segments. Immunohistochemistry demonstrated SOX‐10 and HMB‐45 positivity, confirming melanoma. Additionally, molecular analyses identified a BRAF V600K mutation in each specimen. Further imaging revealed regional nodal metastases and FDG‐avid mesenteric masses near the duodenojejunal junction. In the fall of 2024, he underwent a partial jejunal resection followed by immunotherapy with nivolumab and ipilimumab. At a 5‐month follow‐up, the patient continues on immunotherapy and is receiving advanced palliative care. Conclusion This case is important because it points to the consideration of metastatic melanoma in patients with a cutaneous melanoma history and gastrointestinal (GI) symptoms. BRAF V600K mutation testing was crucial in determining metastasis versus primary GI melanoma. Comprehensive endoscopic, histologic, and genetic evaluations, including BRAF V600K mutation testing, are mandatory for diagnosis and treatment planning. Considering the rarity of small bowel melanoma metastases, continued research is warranted.