OBJECTIVE-Ménétrier's disease (MD) is a rare hypertrophic gastropathy characterised by giant rugal folds, hypochlorhydria, protein loss and a classic constellation of symptoms -nausea, vomiting, abdominal pain and peripheral oedema. It is considered a clinical diagnosis that, at times, may be difficult to establish. We propose firm diagnostic criteria for MD by delineating the clinicopathological features that best differentiate MD from its mimics. DESIGN-Forty-eight patients referred to Vanderbilt University Medical Center for consideration of enrolment in a clinical trial to treat MD patients with cetuximab were evaluated for a definitive diagnosis by assessment of clinical presentation, pertinent laboratory values and histopathological features.RESULTS-MD was confirmed in 25/48 (52%) of the patients. We designated the remaining 23 patients as mimics of MD; the most common diagnoses among the MD mimics were gastric polyps or polyposis syndromes (13/23, 57%). Gastric slides were available from 40 of 48 cases for detailed histological analysis (22/25 MD cases and 18/23 non-MD cases). Foveolar hyperplasia, glandular tortuosity and dilatation, and a marked reduction in parietal cell number were present in all 22 MD cases; lamina propria smooth muscle hyperplasia and oedema characterised most cases (18/22 and 19/22, respectively); more than half had prominent eosinophils (11/22) and/or plasma cells (12/22) in the lamina propria. The clinical presentation of MD patients was characterised by significantly younger age at onset, male predominance and increased vomiting compared to non-MD, and lower prevalence of anaemia compared to non-MD with polyps; there was trend towards increased frequency of peripheral oedema in MD versus non-MD.CONCLUSIONS-MD is most accurately diagnosed by clinicohistopathological analysis including esophagogastroduodenoscopy with gastric pH, appropriate laboratory tests (complete blood count, serum albumin, serum gastrin, H. pylori and cytomegalovirus serology) and full thickness mucosal biopsy of the involved gastric mucosa.Corresponding Author: Robert Coffey, robert.coffey@vanderbilt.edu, Tel: 615-343-6228, Fax: 615-343-1591 however, each has yielded inconsistent benefits, and none have been evaluated in a clinical trial. [9][10][11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26] The only definitive treatment is total gastrectomy. A recently published clinical trial from our group reported that MD patients treated with cetuximab, a monoclonal antibody to the epidermal growth factor receptor (EGFR), showed significant clinical and biochemical improvement in all 7 patients that completed the one-month trial with subsequent histological reversion to normal or near normal in 4 of these patients. [27][28][29] The pathogenesis of MD is related to increased EGFR signalling in the stomach. In vitro, administration of transforming growth factor-α (TGF-α), one of seven mammalian EGFR ligands, stimulates gastric epithelial growth, inhibits acid production and increases mucin levels...

Ménétrier’s disease is a rare, premalignant disorder of the stomach with no proven effective medical therapy. Increased epidermal growth factor (EGF) receptor signaling has been implicated in the pathogenesis of Ménétrier’s disease. We conducted a single-arm clinical trial with cetuximab, a monoclonal antibody that blocks EGF receptor signaling, in 9 individuals with clinically and histologically documented severe Ménétrier’s disease that impaired quality-of-life to the extent that gastrectomy was being considered. Of the 7 patients who completed the one-month course of treatment, all showed statistically significant improvement both clinically (quality-of-life indices) and biochemically (increased parietal cell mass and gastric acidity). Furthermore, all seven patients who completed the one-month trial elected to continue treatment, and four subsequently showed near complete histological remission. Cetuximab should be considered first line therapy for Ménétrier’s disease.

The gastrointestinal epithelium does much more than provide a physical barrier between the intestinal lumen and our internal milieu. It is actively engaged in absorption and secretion of salt and water via ion transporters, exchangers and selective ion channels. It is also a continuously self-renewing epithelium that undergoes ordered growth and differentiation along its vertical axis. From this dual perspective, we will consider the actions of the ERBB family of ligands and receptors in the maintenance of gastrointestinal homeostasis and discuss instances when the actions of this family go awry such as in cancer and Ménétrier's disease.

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