Ménétrier’s disease (MD) is a rare type of hypertrophic gastropathy involving the body of the stomach, which was initially described in 1888 (1). It is characterized by thickening of the gastric mucosa in the form of giant rugal folds, hypochlorhydria and protein loss. The classic symptoms of MD include abdominal pain, nausea, vomiting and peripheral oedema (2). It occurs in two forms, depending on the patient’s age; in adult males aged ~55 years, it presents as a progressive disease with an asymptomatic onset. However, in early childhood, it develops abruptly and resolves spontaneously. While the development of MD is associated with the cytomegalovirus (CMV) infection in the case of infants, the cause of MD in adults remains unknown (3–5). Previous studies demonstrate the coexistence of MD with infections (Helicobacter pylori, CMV, herpes simplex, human immunodeficiency virus [HIV], Mycoplasma pneumoniae) (4,6–9) as well as non-specific inflammatory diseases (including ulcerative colitis) (10). However, the administration of targeted therapy in these disorders has not provided any benefits concerning the treatment of MD. Furthermore, the coexistence of MD with different types of cancer has been documented in >50 cases. It remains unknown as to whether cancer develops from MD, whether the disease is a premalignant condition and what the possible mechanism of carcinogenesis is. In the current study, a patient with MD and advanced gastric cancer is described and a review of the literature is presented, which indicates that MD should be recognized as a premalignant condition. The studywas approved by the ethics committee of the Medical University of Białystok, (Białystok, Poland) and the patient provided written informed consent.

Since MD is rare and difficult to discriminate from other hypertrophic gastropathies, Rich et al (2) proposed an algorithm for its recognition. According to the algorithm, the diagnosis of MD should be based on a comprehensive collection of data concerning clinical, endoscopic, laboratory and histopathological findings. The most common symptoms of MD include abdominal pain, nausea, vomiting and oedema, in addition to serum albumin loss. Endoscopically, histopathological examination demonstrates a thickened gastric mucosa. Additionally, the gastric pH must be evaluated; in MD the pH is often alkaline. The characteristic microscopic features are as follows: Parallel mucosal gland ducts, tortuosity and dilatation, foveolar hyperplasia, a reduced number of parietal cells, infiltration of eosinophils and/or plasma cells, smooth muscle hyperplasia and oedema. The laboratory assessments, including complete blood count, serum protein, serum gastrin as well as serologic tests for H. pylori and CMV should also be performed (2). In the present case, the patient belonged to a group of MD patients with less pronounced clinical symptoms, who did not exhibit protein loss. The elevated number of parietal cells observed in the histopathological examination was the predominant difference. However, other characteristic features facilitated the diagnosis of MD.

As yet it has been impossible to determine the number of diagnosed cases of MD due to a lack of accurate incidence data. However, >50 cases of MD presenting with coexisting gastric cancer have been documented since 1983. Until 1990, ~30 cases had been described and Hsu et al (13) documented that a higher percentage of up to 18 cases of MD coexisted with early gastric cancer. Cases of MD coexisting with cancer documented after 1991 were collected as part of the present study; out of 16 MD cases, three were with early stage cancer, seven were with advanced stage cancer and six contained no evidence of the cancer stage (Table I) (14–24). Such statistics may be due to the patients’ origin. The majority of cases described by Hsu et al (13) originate from Japan, where screening for cancer is widely developed and early changes are more frequently diagnosed. Histologically, a predominance of poorly differentiated adenocarcinomas were identified during the literature search in the present study. In addition, in 2007, Choi et al (20) demonstrated a case of MD coexisting with squamous cell carcinoma. In the studies identified during the literature search, the patients were aged >40 years and nine out of the 12 cases described were male.

The risk of malignancy in MD was described in 1991 as 6–10% of the incidence rate (13). A premalignant condition is defined as a disease that may develop into a malignancy. This percentage is considered to be adequate to regard MD as a premalignant condition. Currently, it is not possible to determine and confirm this rate due to the low incidence of the disease and a lack of registration of all cases of MD.

In MD it is also unclear whether a tumour is formed on hyperplastic growth or develops as a de novo lesion. Usually, and in the cases that were presented in the literature, the two changes are diagnosed simultaneously during histological imaging. However, it was 1983 when Wood et al (25) described a man with MD who developed early gastric cancer 3.5 years following diagnosis. Furthermore, Ramia et al (19) reported a patient with advanced gastric cancer and MD, who was diagnosed with MD 13 years prior to the cancer diagnosis. In the abovementioned cases, the cancer developed subsequent to the diagnosis of MD. In the patient in the present study, the cancer was identified in the biopsy material, whereas MD was confirmed later in the postoperative specimen. Macroscopically, there were two distinct gastric tumours ~3 cm apart, which were connected to each other by infiltration that indicated independent growth. A morphological similarity of tumour growth to the cystic gland ducts in MD was observed. Histologically, the cancerous glands appeared to be enormous cystic formations with ingrowing papillary structures of cancer cells (Fig. 4). This provides further evidence for the hypothesis that cancer may arise from MD.

The poorly understood pathogenesis of MD that results in a lack of appropriate treatment strategies is another point in favour of recognising MD as a premalignant lesion. Currently, symptomatic treatment, anticholinergic agents, acid suppression, octreotides and prednisone are predominantly administered for its treatment (5). Furthermore, theories of bacterial (H. pylori, Mycoplasma pneumoniae) and viral infections (CMV, herpes simplex, HIV) have been proposed, which are associated with chronic inflammation of the gastric mucosa and result in further abnormal recovery in the form of hyperplasia (4–9). However, due to a lack of clinical trials, the benefits of targeted treatment for these infections in adults are not well known. A theory of increased epidermal growth factor receptor signalling associated with transforming growth factor-α overproduction has also been presented and treatment with monoclonal antibodies has been proposed (2). However, the optimum therapeutic procedure for MD is a gastrectomy, specifically in those patients with uncontrolled protein loss, bleeding and a high risk for coexisting cancer. A partial or total gastrectomy is performed depending on anastomosis, clinical observations and the cancer stage (17).

In conclusion, MD should be treated with particular attention and regarded as a premalignant condition due to the previously documented cases of its coexistence with gastric cancer, as well as the lack of knowledge regarding its pathogenesis and effective therapeutic management. This condition should not be overlooked, and the clinician and the patient should be aware that it is necessary to monitor the lesion via regular endoscopic biopsy examinations.