Gastric adenocarcinoma with submucosal invasion occurs in a sporadic fundic gland polyp of a Helicobacter pylori-uninfected patient on proton pump inhibitor

Abstract

Gastric fundic gland polyps (FGPs) are common benign lesions, typically found in Helicobacter pylori (HP)-uninfected stomachs. While syndromic FGPs resulting from genetic diseases may exhibit dysplasia, sporadic FGPs rarely develop into adenocarcinomas. Here, we present the first case of invasive gastric adenocarcinoma that occurred in a sporadic FGP in an HP-uninfected patient. A 77-year-old man on proton pump inhibitor (PPI) therapy for 6 years developed an enlarged reddish FGP. The absence of atrophic changes in the entire gastric mucosa was confirmed endoscopically and multiple HP tests were negative. After PPI discontinuation, the lesion initially reduced in size from 25 to 15 mm in 1 month; however, malignancy was suspected because of rapid enlargement and persistent discoloration. En bloc resection was performed by endoscopic mucosal resection. Histological examination confirmed FGP and submucosal adenocarcinoma with a depth of approximately 700 μm, negative for lymphovascular invasion, and negative resection margins. A subsequent distal gastrectomy confirmed the absence of residual disease or lymph node metastases. The unusual endoscopic findings of rapid enlargement and reddish tone pushed us to perform endoscopic treatment, which resulted in a correct diagnosis and appropriate treatment.

Keywords: Helicobacter pylori negative; Fundic gland polyp; Stomach neoplasms.

Fig. 1

Endoscopic findings. a 6 years before referral at family doctor showed only several fundic gland polyps (FGPs). b 4 years before at family doctor showed a gradual increase in the number and lesion size of FGPs. c Just before referral at family doctor showed an enlarged reddish polypoid lesion. d White light imaging revealed a partially reddish polypoid lesion 25 mm in size surrounded by isochromatic FGPs in the greater curvature of the gastric body. e Close observation of the former. f In retroflex view, the posterior wall side was reddish and uneven on the surface. g With chromoendoscopy with indigo carmine. h Magnifying endoscopy with narrow band imaging of the reddish area. i One month later, the reduction in the previously identified polypoid lesion and the surrounding FGPs. j During endoscopic mucosal resection procedure. k Post-resection wound surface. l Resected tumor specimen

Fig. 2

Histopathological findings of the EMR specimen a Semi-macro images of the entire lesion in the resected specimen indicating the lesion to be a submucosal adenocarcinoma and no tumor involvement of the resection margins. b High magnification of a cancerous area. Tumor cells formed branching tumor glands and exhibited round, enlarged, hyperchromatic nuclei, with a diagnosis of well-differentiated adenocarcinoma (magnification × 200). c Higher magnification of submucosal invasion (magnification × 100). d Desmin stain indicated that a muscularis mucosa and adenocarcinoma had infiltrated the submucosal layer (magnification × 100). e The boundary between adenocarcinoma and FGP. The area to the left of the dashed line is adenocarcinoma, and the area to the right is FGP (magnification × 200)

Fig. 3

Immunohistochemical findings of the adenocarcinoma component (magnification × 100). a Positive expression of MUC5AC. b Positive expression of MUC6. c Partial positive expression for MUC2 expression of MUC2. d Negative expression of CD10 e Ki-67 was diffusely positive. f β-Catenin accumulation was observed in the cell membrane. g Overexpression of p53 was observed