Ménétrier's disease

Key points

• Giant hypertrophic gastropathy with massive foveolar hyperplasia of gastric mucosa
• Predominantly affects the body and fundus, spares the antrum
• Hallmark: protein-losing gastropathy causing hypoalbuminaemia
• Increased risk of gastric adenocarcinoma (up to 15%)
• Self-limiting in children (often post-CMV infection); chronic and progressive in adults

Epidemiology & risk factors

• Rare; peak incidence in adults aged 40-60 years, male predominance
• Paediatric form associated with CMV infection (self-limiting)
• Adult form linked to overexpression of TGF-alpha acting on EGFR
• No strong genetic predisposition; sporadic occurrence
• H. pylori infection implicated in some cases

Pathophysiology

• TGF-alpha overexpression → EGFR activation → massive foveolar (surface mucous cell) hyperplasia with glandular atrophy
• Replacement of parietal and chief cells → hypochlorhydria and reduced pepsinogen
• Increased mucosal permeability → transmucosal protein loss → hypoalbuminaemia
• Distinguish from: Zollinger-Ellison (parietal cell hyperplasia, hyperchlorhydria) and lymphocytic gastritis

Clinical features

• Epigastric pain, nausea, vomiting, anorexia, weight loss
• Peripheral oedema secondary to hypoalbuminaemia
• GI bleeding (occult or overt)
• Diagnosis confirmed by full-thickness gastric biopsy (endoscopic mucosal biopsies often insufficient)

Imaging / investigations

Barium meal / upper GI series

• Markedly enlarged, tortuous gastric rugal folds ("brain-like" or "cerebriform" appearance)
• Predominantly in body and fundus; antrum typically spared
• Excessive mucus may coat the mucosal surface

CT

• Diffuse gastric wall thickening with prominent, thickened rugal folds
• Enhancing, polypoid mucosal folds in body/fundus
• No significant lymphadenopathy (helps distinguish from lymphoma)
• May see ascites if significant hypoalbuminaemia

Endoscopy

• Giant, hypertrophied rugal folds that do not flatten with air insufflation
• Excessive mucus production
• Full-thickness biopsy required for definitive diagnosis

Labs

• Low serum albumin, low gastric acid output
• Normal to low serum gastrin (vs elevated in ZES)

Differentials

• Gastric lymphoma - wall thickening + lymphadenopathy, crosses pylorus
• Zollinger-Ellison syndrome - rugal fold thickening but with hyperchlorhydria, elevated gastrin, involves body/fundus AND antrum/duodenum
• Gastric carcinoma (linitis plastica) - rigid, non-distensible stomach, narrowed lumen
• Lymphocytic gastritis - thickened folds but distinct histology
• Gastric varices - submucosal, enhancing serpentine structures on CT

Management

• Supportive: high-protein diet, albumin replacement
• Cetuximab (anti-EGFR monoclonal antibody) - emerging targeted therapy in adults
• Eradication of H. pylori if co-infection present
• Total gastrectomy - definitive treatment for refractory cases or malignant transformation
• Paediatric (CMV-associated): supportive care, typically self-resolves