Gastric Foveolar‐Type Hyperplastic Polyp of the Duodenum With GNAS and KRAS Mutations: A Potential Precursor to Neoplasia

ABSTRACT We report a gastric foveolar‐type hyperplastic polyp of the duodenum harboring mutations in the GNAS and KRAS genes. The lesion was incidentally detected during a routine upper gastrointestinal endoscopy in a man in his 50s. It appeared as a 10‐mm elevated lesion located at the superior duodenal angle. The surrounding mucosa showed no endoscopic evidence of gastric foveolar metaplasia (GFM) or heterotopic gastric mucosa (HGM). Endoscopic mucosal resection was performed as diagnostic treatment. Histopathology showed a diffuse, monotonous proliferation of gastric foveolar‐type epithelial cells without cytological dysplasia, and immunohistochemical analysis showed diffuse positivity for MUC5AC. Genetic analysis revealed activating mutations in both the GNAS and KRAS genes. Based on these findings, the final diagnosis was a gastric foveolar‐type hyperplastic polyp harboring GNAS and KRAS mutations. Such mutations have also been reported in pyloric gland adenomas and gastric‐type duodenal adenocarcinomas. Proximal non‐ampullary duodenal epithelial tumors are often linked to a gastric‐type mucin phenotype with higher malignant potential. Potential precursor lesions for carcinomas proximal to the ampulla include GFM and HGM. This case supports the hypothesis that some duodenal lesions with the gastric‐mucin phenotype may harbor molecular alterations typically associated with neoplastic processes despite their non‐neoplastic appearance, suggesting a potential role as precursors to neoplasia.