Adult-onset Ménétrier's disease is strongly associated with Helicobacter pylori (H. pylori) infection and an elevated risk of carcinogenesis. Cases of early-stage gastric cancer developed in H. pylori-negative Ménétrier's disease are extremely rare. We report a case of early gastric cancer in H. pylori-negative Ménétrier's disease that was curatively resected with endoscopic submucosal dissection (ESD).

A 60-year-old woman was referred to our hospital after her medical examination detected anemia. Contrast-enhanced upper gastrointestinal (UGI) radiography revealed translucency of the nodule-aggregating surface with giant rugae. Blood tests showed hypoproteinemia and were negative for serum H. pylori immunoglobulin G antibodies. The 99mTc-DTPA-human serum albumin scintigraphy showed protein loss from the stomach. UGI endoscopy showed a 40-mm protruding erythematous lesion on giant rugae of the greater curvature of lower gastric body, suggesting early-stage gastric cancer due to Ménétrier's disease. En bloc resection with ESD was performed for diagnosis and treatment. Histology of ESD showed well-differentiated tubular adenocarcinoma. The cancer was confined to the mucosa, and complete curative resection was achieved. Foveolar hyperplasia and atrophy of the gastric glands were observed in non-tumor areas, histologically corresponding to Ménétrier's disease. Three years after ESD, gastric cancer had not recurred, and Ménétrier's disease remained in remission with spontaneous regression of giant gastric rugae.

Complete curative resection was achieved through ESD in a patient with early-stage gastric cancer and H. pylori-negative Ménétrier's disease.

To describe four cases of an uncommon type of acalculous cholecystitis/cholangitis characterized by increased intraepithelial lymphocytes within the biliary epithelium.

Cases were prospectively compiled during regular surgical pathology sign-out. Clinical information was obtained from the electronic medical record and the gross appearance from the surgical pathology reports. Microscopic examination was performed with emphasis on the type, location, and distribution of the inflammatory pattern; presence of intraepithelial lymphocytes (>30 per 100 biliary cells); and presence of metaplasia and epithelial hyperplasia. Immunohistochemical stains for CD3, CD8, and IgG4 were performed in some cases.

All patients were adults who had either biliary pain or obstructive symptoms. All gallbladders had a relatively normal gross appearance and did not contain gallstones or biliary sludge. Microscopic examination showed numerous intraepithelial lymphocytes in the biliary epithelium. The mucosa was frequently expanded by dense inflammatory cell infiltrates. The inflammatory process was more severe in the infundibulum and bile ducts than in the body of the gallbladder. The intraepithelial lymphocytes were CD3+, CD8+. IgG4+ plasma cells were absent.

The term lymphocytic cholecystitis/cholangitis is proposed. The potential clinical implications and pathogenesis of this inflammatory pattern and the differential diagnosis with other forms of acalculous cholecystitis are discussed.

Ménétrier's disease is a rare premalignant disorder of the stomach with no proven effective medical therapy. Increased epidermal growth factor 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 epidermal growth factor receptor signaling, in nine 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 seven patients who completed the 1-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 1-month trial elected to continue treatment, and four subsequently showed near-complete histological remission. Cetuximab should be considered as first-line therapy for Ménétrier's disease.

Increased numbers of intraepithelial lymphocytes (lymphocytosis) can be found in the esophagus, stomach, small intestine, and colon in a variety of clinical circumstances. This review, directed at practicing pathologists, portrays the normal resident lymphocyte population in the mucosa of each segment of the digestive tract and discusses the different situations that may result in quantitative or qualitative alterations of intraepithelial lymphocytes. Esophageal lymphocytosis has not been fully characterized and its clinical significance, if any, awaits definition. Thus, this diagnosis is presently discouraged. In the stomach, it is particularly important to exclude Helicobacter pylori infection and celiac sprue before diagnosing lymphocytic gastritis. Duodenal lymphocytic infiltrates, inextricably tied with alterations of the villous architecture of the mucosa, are often caused by gluten sensitivity. However, similar morphologic changes may be caused by a vast array of other conditions that must be carefully considered and excluded. Lymphocytic and collagenous colitis are most often unexplained, but their frequent association with autoimmune conditions or certain medications deserve a thorough investigation in each case. Using a combination of histologic and clinical clues, a cause for the intraepithelial lymphocytic infiltration can be identified in many instances. As some of the associated conditions are amenable to effective treatment, the importance of diligently seeking such associations before resorting to a diagnosis of primary lymphocytosis is emphasized.

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.

A captive 16-year-old male camel (Camelus ferus bactrianus) was euthanized after a prolonged period of inappetence leading to cachexia. At necropsy, there was a 7 cm large, tan, firm, well-demarcated nodule in the tunica muscularis and serosa of the distal region of C3. Histologically, a gastric adenocarcinoma was diagnosed. Numerous metastases were found in the liver and the hepatic lymph nodes, in the wall of the portal vein and the aorta, in the lung, heart, and pleura parietalis. Osseous metaplasia was found within the pleural and aortic metastases. In the mucosa of the glandular region of the C3 compartment a diffuse marked hypertrophy of rugae resembling cerebral convolutions was observed. The lesion was characterized by glandular hyperplasia and stromal inflammation and oedema. These changes closely resembled Menétrier's disease described in humans. To our knowledge, this is the first report of concomitant metastatic gastric adenocarcinoma and gastric hyperplasia in a camel.

Most gastric polyps, adenocarcinomas, carcinoids, and B cell lymphomas arise on a gastric mucosa damaged by long-standing chronic gastritis. The most common form of chronic gastritis is caused by infection with Helicobacter pylori. All patients with H. pylori infection develop lymphoid aggregates with germinal centers that interact intimally with the gastric mucosa (mucosa-associated lymphoid tissue [MALT]); these follicles are the condition sine qua non for the development of primary B cell mantle lymphomas, also known as MALT lymphomas. As the infection progresses, atrophy of the gastric mucosa develops in a subset of patients, which is replaced by an intestinal-type epithelium (intestinal metaplasia). On this background, dysplasia and adenocarcinomas of the intestinal type may develop. When atrophy is sufficiently severe to impair acid production, the gastrin-producing cells of the antrum increase their secretion of gastrin and stimulate endocrine cells in the corpus, which may eventually proliferate, become dysplastic, and give raise to carcinoids. This development is more frequent in advanced cases of autoimmune gastritis associated with pernicious anemia. On this background, there is also extensive epithelial hyperplasia and the formation of hyperplastic or inflammatory polyps, a small percentage of which may become dysplastic and progress to adenocarcinoma. Chronic exposure of the corpus mucosa to pancreaticoduodenal secretions ("bile reflux") causes reactive mucosal changes that may predispose to neoplasia. Thus, the progression of inflammation to atrophy to metaplasia, and in some cases chronic chemical injury, may give rise, at different times and under the influence of other, unknown stimuli, to most types of gastric tumors. Other types of gastritis, including lymphocytic and granulomatous gastritis, are rare and have not been associated with gastric neoplasia. Awareness of these associations, appropriate treatment policies, and implementation of endoscopic surveillance programs would dramatically reduce the incidence of most types of gastric neoplasms and would allow the detection of many tumors at a stage when endoscopic resection or conservative treatment would still be possible.

Menetrier's disease is an uncommon condition of unknown aetiology. We describe two cases of male identical twins with haematemesis aged 29 and 35 years that exhibited a similar and particular form of this hyperplastic gastropathy. Their stomachs showed confluent polypoid mucosal projections affecting mainly the gastric fundus and the antrum. To the best of our knowledge, only four previous cases have been reported in a familial setting, and this is the first documented example of an occurrence in twins. These two cases suggest the possibility of a genetic predisposition for this condition.

The purpose of this review is to highlight two types of gastritis that have recently received much greater attention: lymphocytic gastritis and the gastritis associated with Crohn's disease. Lymphocytic gastritis is a distinctive pattern of inflammation that resembles that seen in celiac disease and lymphocytic colitis. It is associated with a diverse and unusual group of disorders in their own right, as well as having a possible relationship (real or phantom) with H. pylori infection. With respect to Crohn's disease, there is a growing recognition that, much more common than gastric granulomas, is the existence in one third or more of patients of a highly focal non-H. pylori gastritis. This recognition may help secure the diagnosis of Crohn's disease where it is equivocal, especially in children, in whom follow-up radiography and endoscopy cannot be done as readily as in adults.