Intraepithelial Melanoma in the Stomach After Treatment With Immune Checkpoint Blockade Therapy

Abstract

Melanoma is the most common tumor to metastasize to the gastrointestinal tract, commonly affecting the small intestine, colon, and anorectum. Primary mucosal melanoma can arise in any gastrointestinal site, most frequently affecting anorectal mucosa. Melanoma involving the gastric mucosa, specifically, is exceedingly rare and carries a poor prognosis with a median survival of 5 months. The presence of atypical melanocytes exclusively within gastric epithelium has not been previously described. We report a case of a 52-year-old man with widespread BRAFV600E mutant metastatic melanoma who was referred to our institution for immune checkpoint antibody-blockade therapy. The patient had previously been treated with BRAF inhibitors, and despite initial response to therapy, developed resistance leading to disease progression and multiorgan involvement including the liver, spleen, and axial skeleton. Immune checkpoint antibody blockade with ipilimumab and pembrolizumab has been shown to induce significant tumor regression in patients with melanoma by upregulating T-cell activity and removing the natural check on the host immune response. After his first dose of combination therapy, the patient underwent an upper gastrointestinal tract endoscopy for severe nausea and was found to have 2 pigmented lesions within the gastric body, one of which was biopsied. The biopsy showed gastric body-fundic type mucosa with melanophages and scattered atypical intraepithelial melanocytes within the lamina propria, which were strongly positive for S100, HMB45, SOX10, and MITF. A Fontana-Masson silver stain was performed for confirmation. The finding of predominantly atypical intraepithelial melanocytes associated with melanin pigment was interpreted as metastatic melanoma to the stomach with some regression in response to immune checkpoint blockade therapy.

Checkpoint inhibition immunotherapy for advanced local and systemic conjunctival melanoma: a clinical case series

“…In review of the published literature using the terms conjunctiva, melanoma, BRAF, KIT, pembrolizumab, ipilimumab, interferon and genetics, we found a 2016 study on the efficacy of anti-PD-1 agents in acral and mucosal melanomas supported its use in clinical practice [21, 22]. In contrast, a 2017 study concluded that checkpoint inhibition for advanced mucosal melanoma revealed no clinical response and disease progression [23].…”

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

“…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.…”

Melanin-Targeted PET Imaging With 18F-PFPN for Identifying Gastric Metastatic Melanoma

“…Melanoma is the most common tumor to metastasize to the gastrointestinal tract, commonly affecting the small intestine, colon, and anorectum. 3,4 Melanoma involving the stomach is extremely rare, and the prognosis is generally poor. 5 In this case, the patient had a primary lesion in the occipital skin, progressed without sentinel lymph node metastasis but displayed mucosal lentiginous metastases in the stomach.…”

“…Further pathological biopsy of gastric cardia, fundus, and body tissue identified as metastases of melanoma ( B ). Melanoma is the most common tumor to metastasize to the gastrointestinal tract, commonly affecting the small intestine, colon, and anorectum 3,4 . Melanoma involving the stomach is extremely rare, and the prognosis is generally poor 5 .…”