Reassessing ménétrier’s disease: diagnostic variability, molecular subtypes, and implications for precision therapy

The recent review by Zhang et al. provided an authoritative overview of Ménétrier’s disease (MD) but left several methodological and biological aspects underexplored.1 The most significant limitation was the reliance on case reports lacking standardised histological and microbiological criteria. In the reviewed cohort, fewer than one-third of cases included dual Helicobacter pylori and cytomegalovirus testing, and nearly half lacked specialised staining,1 probably inflating the apparent proportion of infection-negative MD. Reconsidered in this context, the apparent decline in infection-associated MD may reflect incomplete diagnostic assessment rather than a true epidemiological shift. The absence of quantitative synthesis and extended follow-up further constrained the evaluation of therapeutic durability and cancer risk,1 despite evidence that chronic mucosal remodelling and hypoalbuminaemia predict malignant transformation.2,3 Recent molecular studies have expanded the pathogenic framework of MD. Transcriptomic analyses demonstrated that Hedgehog pathway activation can occur independently of epidermal growth factor receptor (EGFR) signalling, delineating distinct epithelial phenotypes.4 Concurrently, overexpression of Claudin 18.2 (CLDN18.2) has been identified in infection-negative, EGFR-intermediate disease, indicating a potential role for Claudin-targeted therapy.5 Together, these findings support a tri-modal molecular model comprising infection-driven, EGFR-dominant, and CLDN18.2-enriched forms, replacing the traditional adult–paediatric dichotomy. Recognising this heterogeneity is essential for precision-based management that aligns pathway activation with targeted interventions and structured biomarker-informed surveillance.