A Case of Primary Gastric Melanoma Exhibiting a Rare BRAF V600R Mutation

Abstract

Introduction: Malignant melanoma of the gastrointestinal tract is usually a metastasis from a cutaneous source. Primary gastric melanoma is an extremely rare clinical entity, with few reported cases worldwide. It is often advanced at time of diagnosis and is associated with a dismal outcome. Background: A 76 year old gentleman presenteded with a one month history of fatigue and exertional dyspnoea. Laboratory investigations indicated an anaemia, with a haemoglobin level of 11.0g/dl. Subsequent gastroscopy visualised a large, atypical, crater-like ulcerated lesion distal to the cardia in the proximal stomach. Provisional histology was suggestive of a poorly differentiated adenocarcinoma but subsequent cyto-morphology and immunophenotyping were consistent with melanoma, with positive S100 protein, HMB45 and Melan A. Further molecular genetic testing revealed a V600R mutation in the BRAF gene, which is the first primary gastric melanoma with this mutation to be reported in the literature. Given the rarity of the findings, an extensive secondary work-up was undertaken, which concluded the diagnosis primary gastric melanoma. Discussion: Primary gastric melanoma is a rare disease that can present similarly to other upper gastrointesinal lesions, with weight loss, abdominal pain, malena, and anaemia. Given its rarity, the pathogenesis is poorly understood. Lesions are often endoscopically atypical. Important points to note would include the absence of a primary lesion, as supported by a full skin examination and PET-CT findings, which can help to delineate the limitation to the stomach, thus helping to inform subsequent management. LEARNING POINTS• Primary gastric melanoma (PGM) is a rare clinical entity.• Work-up including skin and ophthalmic examination is important to exclude a primary cutaneous source, as this helps dictate both prognosis and subsequent management, including whether surgical resection is advisable.• Immunophenotyping and genetic testing inform management but, despite advances in therapy, the prognosis of PGM and other mucosal melanomas remains poor.

Melanoma metastasis mimicking gastric cancer: a challenge that starts from diagnosis

“…In the literature there at least six cases of gastric melanoma misdiagnosed as gastric cancer ( Table 1 ). 6 , 7 , 24 – 27 Three authors 6 , 24 , 25 were able spontaneously to correct the first diagnosis of gastric cancer to gastric melanoma before making any therapeutic decisions. Bahat et al .…”

“…To the best of our knowledge this is the third case of melanoma with gastric involvement treated with BRAF inhibitors. 24 , 29 BRAF is one of the most significant gene mutations in cutaneous melanoma (approximately 50%) but is rare in mucosal forms of the disease. 30 The presence of skin lesions and substantial disease burden in a case of poorly differentiated gastric cancer must raise the suspicion of an incorrect histological diagnosis.…”

Primary Gastric Malignant Melanoma

“…Mucosal melanomas comprise approximately 1.3% of all melanocytic malignancies [ 3 ]. Primary gastric malignant melanoma (PGMM), a subtype of mucosal melanoma, is extremely rare [ 4 ]. So far, in the literature, 25 cases have been reported worldwide [ 5 ].…”

“…PGMM has been reported to occur in older patients with an average age of 71 years, often at an advanced stage, and is characterized by a worse prognosis [ 2 ] due to the tendency to grow faster and more aggressively than metastatic tumors, perhaps due to the rich lymphovascular supply available in the intestinal mucosa [ 6 ]. PGMM clinical manifestations are similar to other upper gastrointestinal (GI) lesions, such as weight loss, abdominal pain, anemia, nausea, and melaena due to GI bleeding [ 4 , 7 ]. Histologic diagnosis of melanoma requires the exclusion of metastasis from a primary cutaneous or ocular lesion, with full skin and eye examination by a dermatologist and an ophthalmologist, to rule out another primary source, as this influences both the prognosis and further management of the patient, including whether surgical resection is advisable [ 4 ].…”

“…PGMM clinical manifestations are similar to other upper gastrointestinal (GI) lesions, such as weight loss, abdominal pain, anemia, nausea, and melaena due to GI bleeding [ 4 , 7 ]. Histologic diagnosis of melanoma requires the exclusion of metastasis from a primary cutaneous or ocular lesion, with full skin and eye examination by a dermatologist and an ophthalmologist, to rule out another primary source, as this influences both the prognosis and further management of the patient, including whether surgical resection is advisable [ 4 ]. The extremely low incidence and lack of awareness of this disease may also contribute to the misdiagnosis by phy­sicians and pathologists, especially in cases lacking a known primary lesion and when the tumor tissue excised with biopsy contains no melanin pig­mentation, such as the one we present.…”