# Cobblestone-like Gastric Mucosal Changes on Endoscopy in Dogs with a History of Prolonged Proton Pump Inhibitor Therapy

## TL;DR

This study identifies a benign gastric mucosal pattern in dogs linked to long-term proton pump inhibitor use, which can mimic more serious conditions.

## Contribution

The study characterizes a new reactive gastropathy in dogs associated with prolonged proton pump inhibitor therapy.

## Key findings

- Histopathology showed foveolar hyperplasia and cystic dilation of fundic glands without neoplasia.
- Most dogs improved clinically after reducing or stopping omeprazole, suggesting a reversible condition.
- Follow-up endoscopy showed variable improvement, indicating the condition may regress over time.

## Abstract

Gastric mucosal hypertrophy in dogs is an uncommon condition that may resemble more serious disorders such as gastric neoplasia. This study describes seven canine cases characterized by a cobblestone-like thickening of the gastric mucosa observed during endoscopy. The aim of our study was to better characterize the clinical, endoscopic, and histopathologic features of this pattern and to investigate its potential relationship with prolonged proton pump inhibitor (PPI) therapy. Histological examination revealed superficial and foveolar hyperplasia, with occasional cystic dilation of fundic glands and hyperplasia of parietal cells, and no evidence of neoplasia. Most dogs improved clinically after omeprazole withdrawal or tapering. Follow-up endoscopy, available in two dogs, showed marked improvement in the dog re-evaluated after six months, whereas only minimal changes were observed in the dog re-evaluated after three months. These findings suggest that this pattern represents a benign, potentially regressive reactive gastropathy possibly related to chronic acid suppression. Recognizing this appearance may alert veterinarians to consider reactive causes in the differential diagnosis; however, endoscopic findings alone are insufficient to reliably distinguish reactive from proliferative or neoplastic gastric disease, and histopathologic evaluation of gastric biopsy samples is required for definitive diagnosis.

This study describes the clinicopathological features of seven canine cases showing a diffuse cobblestone-like gastric mucosal pattern on endoscopy. Cases were retrospectively retrieved from endoscopic databases (2017–2025). Clinical data, treatment history, endoscopic findings, and histology were reviewed. Endoscopically, all dogs exhibited thickened, irregular, and poorly distensible gastric folds. Histopathologic examination showed mild-to-moderate foveolar hyperplasia, variable cystic dilation of the fundic glands, mild chronic lymphoplasmacytic inflammation, and interstitial fibrosis. Parietal-cell population was variably increased and predominant (hyperplasia). Because these features can overlap widely among reactive and hyperplastic gastropathies, interpretation required correlation with clinical and endoscopic findings in addition to histopathology. All dogs had a history of prolonged omeprazole administration, and most showed clinical improvement after dose reduction or treatment withdrawal. Follow-up endoscopy in two dogs documented divergent outcomes, with marked improvement in one dog and only minimal changes in the other. These findings suggest that this cobblestone-like pattern represents a benign, reactive, and potentially regressive gastropathy, possibly associated with chronic acid suppression. Recognition of this appearance may assist clinicians in differentiating reactive gastropathy from proliferative or neoplastic conditions and supports prudent use of long-term proton pump inhibitors in dogs with chronic gastrointestinal disease.