Ménétrier’s disease: a narrative review of molecular pathogenesis, clinical spectrum and evolving therapeutic strategies

Ménétrier's disease (MD) is a rare, acquired premalignant condition characterized by hypertrophic gastropathy. Its defining features include giant gastric rugal folds, predominantly in the fundus and body of the stomach, foveolar hyperplasia with glandular atrophy and a protein-losing gastropathy leading to hypoalbuminemia and peripheral edema. The pathogenesis is primarily driven by the overactivation of the epidermal growth factor receptor (EGFR) signaling pathway, most commonly due to the overexpression of its ligand, transforming growth factor-alpha (TGF-α). The clinical presentation varies significantly between pediatric and adult populations. In children, the disease is often acute, self-limiting and strongly associated with cytomegalovirus (CMV) infection. In adults, it typically follows a chronic and progressive course, carrying a significant risk for the development of gastric adenocarcinoma. Diagnosis is challenging and relies on a combination of endoscopic visualization, histopathological analysis of deep or full-thickness biopsies and advanced imaging techniques such as endoscopic ultrasound (EUS) to differentiate it from its mimics, which include gastric lymphoma and infiltrative carcinoma. Management strategies have evolved from supportive care, such as high-protein diets and treatment of associated infections like Helicobacter pylori, to targeted molecular therapies. The monoclonal antibody cetuximab, which blocks EGFR, has emerged as a highly effective treatment, capable of inducing clinical and histological remission. Somatostatin analogues like octreotide and lanreotide also offer symptomatic control by inhibiting growth factor signaling. For patients with refractory symptoms, severe complications or malignant transformation, surgical intervention via partial or total gastrectomy remains the definitive treatment. This review provides a detailed examination of the current understanding of the molecular underpinnings, diverse clinical spectrum, diagnostic modalities and therapeutic landscape of MD.