Ménétrier disease (ORPHA:2494)
Ménétrier disease (MD) is a rare premalignant hyperproliferative gastropathy characterized by massive overgrowth of foveolar cells in the gastric lining, resulting in large gastric folds, and manifesting with epigastric pain, nausea, vomiting, peripheral edema and, less commonly, anorexia and weight loss.
Epidemiology
Exact prevalence and incidence data are not available. MD appears to affect males slightly more than females.
Clinical description
The usual age of onset is between 30 and 60 years (average 55 years), although cases in childhood have been reported. The childhood variant often involves sudden onset and spontaneous regression. In adults, onset is often insidious with a wide spectrum of clinical manifestations. Affected patients typically present with abdominal pain, vomiting and nausea. Edema of peripheral tissues is often found. Other symptoms include asthenia, anorexia, and weight loss. Some individuals with MD are only mildly affected or are asymptomatic. Loss of protein from the gastrointestinal tract leads to hypoalbuminemia and peripheral edema. Mucosal ulceration is also described and can result in gastrointestinal bleeding. Disease course tends to be progressive, leading to gastric adenocarcinoma in 2-15% of cases. Complications include severe or recurrent infections and vascular thromboembolism.
Etiology
The etiology is currently unknown but is thought to be acquired and to involve enhanced epidermal growth factor receptor (EGFR) signaling in the gastric mucosa with local overproduction of transforming growth factor-alpha (TGF-alpha). In children, some MD cases have been linked to cytomegalovirus (CMV) and in adults some have been linked to Helicobacter pylori; however, the possible role of these infections remains to be elucidated. Rare familial cases point to a possible genetic component. The mechanism(s) underlying carcinogenesis in MD remain unknown.
Diagnostic methods
MD is suspected on the basis of the constellation of clinical signs and symptoms but there are no formal diagnostic criteria. Diagnosis requires gastroscopic examination (showing enlarged gastric folds primarily involving the gastric corpus) with biopsy, preferably of full thickness gastric mucosa, which reveals characteristic histological features (extensive foveolar hyperplasia with corkscrew morphology in the absence of distortion of overall linear architecture, decreased or absent parietal cells, variable amounts of chronic inflammation with scattered clusters of eosinophils, and scattered strands of smooth muscle between mucous glands). Gastric acid secretion is generally markedly decreased or absent, while gastric mucous secretion is elevated. Serum gastrin levels remain relatively normal.
Differential diagnosis
Differential diagnoses include Zollinger-Ellison syndrome (see this term), hypertrophic hypersecretory gastropathy, hypertrophic lymphocytic gastritis, infiltrating neoplasm, polyps, and polyposis syndromes (e.g. juvenile polyposis syndrome, Peutz-Jeghers syndrome, and gastric adenocarcinoma and proximal polyposis of the stomach; see these terms).
Genetic counseling
MD is an acquired gastropathy but a genetic predisposition with autosomal dominant inheritance has been suggested in a few families.
Management and treatment
There is no recommended standard treatment. In some patients, treatment may be limited to supportive care with a high-protein diet. Inconsistent results have been achieved with anticholinergic drugs, acid suppression therapy, treatment against CMV infection in children, and H. pylori eradication in adults. Treatment with cetuximab, an EGFR neutralizing monoclonal antibody, has been successfully carried out. If there is concern about malignant transformation or in severe cases, partial or total gastrectomy may be required. Although there is no official recommendation, endoscopic surveillance may be offered every 1-3 years.
Prognosis
MD tends to be a progressive disorder. Most of the patients ultimately require gastrectomy, either due to worsening symptoms or the risk of developing gastric cancer. The risk of malignant transformation is not well characterized.

                            Last update: 
                            October 2016


                            - Expert reviewer(s): 
                            Dr Won Jae HUH  - Pr ROBERT J. COFFEY