Distinguishing Ménétrier's disease from its mimics

Abstract

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...

Severe hypoproteinemia as a harbinger of Ménétrier's disease in autoimmune pancreatitis

“…In this setting, endoscopic evaluation with histological examination of gastric biopsy material, including a full--thickness mucosal biopsy of the involved mucosa, may be helpful to establish prompt diagnosis allowing appropriate and timely therapy. 4 We speculate that there may be some relation between AIP and Ménétrier's disease explained by the sharing of a common genetic factor.…”

“…discussion Ménétrier's disease is characteristically associated with protein-losing gastropathy and hypochlorhydria, the latter possibly related to overexpression of transforming growth factor-alpha. 4 Patients may present with epigastric pain, dyspepsia, vomiting, anorexia, diarrhea, weight loss, gastrointestinal bleeding, peripheral edema and typically significant hypoalbuminemia secondary to a loss of albumin into the gastric lumen, as well as an exacerbated loss of enteric protein. 1,5 Gastric fold thickening is the most notable feature of Ménétrier's disease.…”

“…The diagnostic procedure of choice is upper endoscopy showing giant rugal folds that involve the fundus and the body of the stomach, generally with antral sparing, confirmed by tissue diagnosis of biopsy material. 1,4 Optimal treatment of this disease is elusive, because the condition is rare and controlled trials are lacking. Many pharmacological approaches have provided occasional therapeutic benefits but inconsistent, such as anti-secretory agents (e.g., histamine-2 blockers, proton pump inhibitors and anti-cholinergic drugs), glucocorticoids, octreotide, Helicobacter pylori eradication and monoclonal antibody against the epidermal growth factor receptor.…”

“…Many pharmacological approaches have provided occasional therapeutic benefits but inconsistent, such as anti-secretory agents (e.g., histamine-2 blockers, proton pump inhibitors and anti-cholinergic drugs), glucocorticoids, octreotide, Helicobacter pylori eradication and monoclonal antibody against the epidermal growth factor receptor. 3,4 Currently, subtotal or total gastrectomy seems to be the only curative treatment, but is reserved for individuals in whom medical management failed or who experienced severe complications such as refractory or persistent bleeding, persistent loss of protein, or if malignancy could not be excluded. 1,5 Ménétrier's disease associated with AIP may pose a diagnostic challenge because both conditions can present overlapping features, which can make it difficult to establish timely diagnosis and prompt treatment.…”

Ménétrier’s Disease: a Rare Entity Which Mimicks Gastric Cancer

“…Ménétrier's disease is a rare, acquired hypertrophic gastropathy of unknown etiology [1], in several situations associated with Helicobacter pylori (HP) or Cytomegalovirus (CMV) infection [2,3]. There are also patients in whom neither HP nor CMV were detected.…”