Coexisting early gastric adenocarcinomas of pyloric gland-type and intestinal-type with different genetic mutations in the setting of autoimmune gastritis.

Abstract

We report a 58-year-old female with no significant symptoms who was found to have two distinct gastric lesions during routine endoscopy: a 15 mm lesion in the fundus, diagnosed as gastric adenocarcinoma of pyloric gland mucosa-type (GA-PGM), and a 30 mm cauliflower-like mass in the gastric body, identified as well-differentiated tubular adenocarcinoma with gastrointestinal mixed type (GA-TAC), accompanied by multifocal neuroendocrine cell hyperplasia in the background of autoimmune gastritis (AIG). Molecular analysis revealed distinct genetic alterations between the two tumors despite arising within the same gastric background: GA-PGM harbored a KRAS p.Q61H mutation and MDM2 amplification, whereas GA-TAC showed a KRAS p.G12D mutation along with STK11 and additional alterations. This case reports the unusual coexistence of GA-PGM and GA-TAC in the setting of AIG, with the two lesions presenting distinct clinicopathologic and molecular characteristics. Our findings support the hypothesis that these two tumor subtypes originate from distinct metaplastic cell lineages through independent tumorigenic pathways, and add to the limited clinical evidence for the rare entity, GA-PGM.