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 may at times be difficult to establish. Firm diagnostic criteria for MD are proposed by delineating the clinicopathological features that best differentiate MD from its mimics.

Method: 48 patients referred to Vanderbilt University Medical Center for consideration of enrolment in a clinical trial of treatment of patients with MD with cetuximab were evaluated for a definitive diagnosis by assessing the clinical presentation, pertinent laboratory values and histopathological features.

Results: MD was confirmed in 25 of the 48 patients (52%). The remaining 23 patients were considered to be mimics of MD, the most common diagnoses being gastric polyps or polyposis syndromes (13/23, 57%). Gastric slides were available from 40 of the 48 patients for detailed histological analysis (22/25 MD and 18/23 non-MD). Foveolar hyperplasia, glandular tortuosity and dilation, and a marked reduction in parietal cell number were present in all 22 cases of MD. 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 patients with MD was characterised by significantly younger age of onset, male predominance and increased vomiting compared with non-MD patients, and a lower prevalence of anaemia compared with MD patients with polyps. There was a trend towards increased frequency of peripheral oedema in patients with MD compared with non-MD patients.

Conclusions: MD is most accurately diagnosed by clinicohistopathological analysis including oesophagogastroduodenoscopy with gastric pH, appropriate laboratory tests (complete blood count, serum albumin, serum gastrin, Helicobacter pylori and cytomegalovirus serology) and full-thickness mucosal biopsy of the involved gastric mucosa.

Figure 1

The most common clinical complaints associated with MD (blue), total non-MD (red) and non-MD with polyps (yellow). *p = 0.01; p value for difference in vomiting between MD and non-MD with polyps was 0.051. **p = 0.016. Dotted lines represent range of normal values.

Figure 2

Comparison of relevant lab values. A. Serum albumin; B. Gastric pH; Serum gastrin. Dotted lines signify normal range. Median values are designated with a bar for each group.

Figure 3

Histological features of MD and its mimics. A. Low power H&E of MD showing relative preservation of mucosal architecture with foveolar hyperplasia, tortuosity and dilatation of the glands, smooth muscle hyperplasia and decreased numbers of parietal cells. B. High power view of MD showing clusters of eosinophils (arrows). C. Low power H&E of JPS polyp. D. High power view of JPS polyp showing oedematous stroma and lack of smooth muscle hyperplasia. E. Hyperplastic polyp. F. PPI effect (arrow points to parietal cell snouting). Size bar = 50μm.

Figure 4

Cancer in the setting of MD. A. Low power view showing typical features of MD with arrow pointing to a focus of cancer. B. Multiple small foci of cancer seen in the lymphovascular space. Size bar = 50μm.

Figure 5

Endoscopic views of MD (A&B) versus a polyposis syndrome (C&D). A. Giant rugal folds with surface erosions and overlying mucus in MD. B. Mucus bridge across the lumen upon retroflex view of the fundus in MD. C. Translucent cluster of polyps lacking thick mucus accumulation in polyposis syndrome. D. Translucent polyps covering the mucosal surface in polyposis syndrome.

Figure 6

Clinicopathological decision-making tree for the diagnosis of MD.