Sporadic pyloric gland adenoma associated with a large fundic gland polyp: genetic evidence for stepwise progression

Pyloric gland adenoma (PGA) is an uncommon variant of gastric adenoma exhibiting pyloric gland/mucous neck cell differentiation. We present a sporadic PGA associated with a large fundic gland polyp (FGP) in a woman in her 40 s without Helicobacter pylori infection. The polyp, measuring 25 mm in size, was located in the middle gastric body and was removed by endoscopic submucosal dissection. Histological examination revealed three morphologically distinct components: FGP, FGP with large cysts, and PGA. A genetic analysis identified a truncating APC mutation in all the three components, supporting their histogenetic relationship. Additionally, a GNAS mutation was detected in two components, FGP with large cysts and PGA, whereas a KRAS mutation was exclusively found in the PGA component. Thus, despite the unusual presentation, the PGA component harbored prototypical genetic alterations. The differential genetic alterations observed in the three components imply that they represent stepwise progression from FGP to PGA.