Ménétrier's disease (MD) is a rare, acquired premalignant condition characterized by hypertrophic gastropathy. Its defining features include giant gastric rugal folds, predominantly in the fundus and body of the stomach, foveolar hyperplasia with glandular atrophy, and a protein-losing gastropathy leading to hypoalbuminemia and peripheral edema. The pathogenesis is primarily driven by the overactivation of the epidermal growth factor receptor (EGFR) signaling pathway, most commonly due to the overexpression of its ligand, transforming growth factor-alpha (TGF-α). The clinical presentation varies significantly between pediatric and adult populations. In children, the disease is often acute, self-limiting, and strongly associated with Cytomegalovirus (CMV) infection. In adults, it typically follows a chronic and progressive course, carrying a significant risk for the development of gastric adenocarcinoma. Diagnosis is challenging and relies on a combination of endoscopic visualization, histopathological analysis of deep or full-thickness biopsies, and advanced imaging techniques such as endoscopic ultrasound (EUS) to differentiate it from its mimics, which include gastric lymphoma and infiltrative carcinoma. Management strategies have evolved from supportive care, such as high-protein diets and treatment of associated infections like Helicobacter pylori, to targeted molecular therapies. The monoclonal antibody Cetuximab, which blocks EGFR, has emerged as a highly effective treatment, capable of inducing clinical and histological remission. Somatostatin analogues like octreotide and lanreotide also offer symptomatic control by inhibiting growth factor signaling. For patients with refractory symptoms, severe complications, or malignant transformation, surgical intervention via partial or total gastrectomy remains the definitive treatment. This review provides a detailed examination of the current understanding of the molecular underpinnings, diverse clinical spectrum, diagnostic modalities, and therapeutic landscape of MD.

Giant hypertrophic gastropathy with Epstein-Barr virus encoded small RNA positive in a child

Gastrointestinal neoplasms are rare in dogs and cats, primarily comprising adenocarcinomas, lymphomas, leiomyomas, leiomyosarcomas, and gastrointestinal stromal tumors (GISTs). In the current literature epidemiological data are scars. The aim of this study was to identify the epidemiological and the pathological features of these neoplasms in dogs and cats. Epidemiological data were collected from the databases of two laboratories in Romania, covering a period of 10 years. A total of 192 cases of neoplastic and neoplastic-like lesions were selected and subjected to statistical analysis. Older animals were more predisposed for chronic hypertrophic pyloric gastropathy (CHPG) (mean age of 11.14 years) and gastric polyps (mean age of 9.6 years), while younger individuals showed a higher incidence for feline gastrointestinal eosinophilic sclerosing fibroplasia (FGIESF), with a mean age of 7.25 years for the lesions located in the stomach and 5.25 years in the intestine. Additionally, CHPG and FGIESF were more prevalent in males. Dogs were the main species affected by benign neoplasms, including adenomas (22%) and adenomatous polyps/pedunculated adenomas (5%), primarily located in the anorectal junction, as well as leiomyomas (8%) with gastric involvement. In dogs, malignant neoplasms accounted for 69%, with adenocarcinomas representing 39%, followed by lymphomas (12%), and GIST (9%). In cats, 98.82% of neoplasms were represented by malignant tumors, with lymphomas being the most frequently diagnosed (77%). Both adenocarcinomas in dogs and lymphomas in cats were more common in males, accounting for 61.76% and 52.31% of cases, respectively, with the intestine being the most frequently affected site. This is the first epidemiological study in Romania to examine both the gastrointestinal tract in dogs and cats, including neoplastic-like lesions. The definitive diagnosis of gastrointestinal masses requires histological and molecular analyses.

Background: The association of intravenous prostacyclin therapy, essential for improving prognosis and survival in pulmonary arterial hypertension (PAH), with gastric epithelial neoplasms is uncertain. This study aimed to analyze the clinicopathologic features of gastric neoplasms in patients with PAH undergoing continuous intravenous prostacyclin therapy. Methods: We screened the registry of patients with pulmonary hypertension who visited the NHO Okayama Medical Center. Of the patients with PAH managed between January 2003 and December 2022, those who underwent esophagogastroduodenoscopy (EGD) were assessed for gastric neoplasms. Their clinical, endoscopic, and histopathological data were reviewed. Results: Among the 186 patients with PAH, 56 underwent EGD, revealing 4 patients (aged 37-50 years) with gastric epithelial neoplastic lesions. All four patients received continuous intravenous prostacyclin therapy for a median of 151 months. Of the 98 patients who received prostacyclin, 28 patients underwent EGD; the incidence of gastric epithelial neoplasms was 4.1% (4/98) and the endoscopic detection rate was 14.3% (4/28). All patients had multiple tumors against a background of hypertrophic gastropathy (histologically being foveolar epithelial hyperplasia), with shared features of distal location, elevated morphology, and absent submucosal invasion. However, lymph node metastasis was observed in one lesion. By immunohistochemistry, the tumors exhibited gastric-predominant mucus phenotype and were managed by surgical or endoscopic resection without recurrence. Conclusions: The consistent clinicopathologic features of these cases suggest an association between continuous intravenous prostacyclin therapy and the development of hypertrophic gastropathy with potential progression to gastric epithelial neoplasia. Further prospective clinical trials are warranted to ensure safer prostacyclin use.

To describe the use, complications and outcome of Finney or Jaboulay pyloroplasties for the treatment of benign gastric outlet lesions in dogs and cats. The medical records of dogs and cats surgically treated with Finney or Jaboulay pyloroplasty for benign gastric outflow tract disease in three institutions between January 1, 2015 and August 31, 2023 were retrospectively reviewed. Eight dogs and five cats were diagnosed with benign obstructive or perforating gastric outlet lesions, including chronic hypertrophic pyloric gastropathy (n = 4), perforating pyloro-duodenal peptic ulcer (4), sub-obstructive pyloro-duodenal eosinophilic sclerosing fibroplasia (2) and antral or proximal duodenal obstructive mass (3). Nine cases were treated using hand-sewn Finney pyloroplasty and four cases were treated using stapled Jaboulay pyloroplasty. No major complications were recorded. Cases were followed for a median of 16.1 [11 to 29.6] months. At the last follow-up, the outcome was excellent in all cases, with no clinical signs recorded and no medical treatment required. This case series suggests that Finney and Jaboulay pyloroplasties were safe and effective procedures for the surgical treatment of benign obstructive or perforating gastric outlet lesions in dogs and cats.

Acquired hypoproteinemic, hypertrophic gastropathy also known as Menetrier’s disease is one of the infrequently encountered disorders in clinical practice. Understanding of the pathogenesis, diagnostic features and course of this disease is important as the symptoms may closely resemble a variety of other conditions like malignancies. one of the case control studies, the disease is found to be associated with increased mortality and can predispose to adenocarcinoma

We present a case report describing the diagnosis and management of a patient who presents with a rare diagnosis of Menetrier’s disease. This condition poses a diagnostic challenge to clinicians due to its nonspecific clinical presentation and is oftentimes misdiagnosed for more common gastric disorders. Menetrier’s disease is characterized by gastric mucosal hypertrophy and subsequent protein loss, resulting in gastric symptoms and widespread edema. While the etiology remains unclear, notable associations have been observed with Helicobacter pylori infection and overexpression of transforming growth factor alpha. The management often involves supportive measures with medical and surgical interventions for refractory cases and when necessary. This report includes a comprehensive review of the literature on the clinical presentation, diagnostic approach, and management of this rare disease. By documenting such cases in the medical literature, we aim to enhance the clinician’s ability to recognize and manage this disorder, thereby preventing the development of more severe manifestations such as diabetes mellitus. Menetrier’s disease is a rare disorder that should be suspected in patients with upper gastrointestinal complaints and hypertrophied gastric mucosa. With a rather broad differential diagnosis consisting of Zollinger-Ellison syndrome, hypertrophic lymphocytic gastritis, hypertrophic hypersecretory gastropathy, gastric adenocarcinoma, gastric polyps, infections such as histoplasmosis and tuberculosis, autoimmune-like inflammatory conditions such as sarcoidosis, and more commonly, gastrointestinal disease, it is often overlooked in the diagnostic workup. Therefore, it is crucial for clinicians to conduct a thorough evaluation and maintain a high clinical suspicion when there is concurrent H.pylori infection and/or imaging findings suggestive of hypertrophied gastric mucosa to avoid missing this disease.

Menetrier’s disease is a rare condition of the stomach characterized by giant mucosal folds in the gastric fundus and body, diminished acid secretory capacity, and a protein-losing state with hypoalbuminemia. It is also called protein-losing hypertrophic gastropathy. It was first described by the French pathologist Pierre Menetrier in 1888. Menetrier’s disease has also a recognized premalignant potential although the precise risk of progression to gastric cancer is not known. Several studies reported regression of disease after treatment with the monoclonal antibody against the EGFR receptor. But the only satisfactory treatment has historically been and remains the surgical intervention with total or partial gastrectomy.A case report of A 10-year male presented to the emergency room with a history of progressively increasing abdominal pain on and off for 1 month with epigastric region fullness, nausea, and vomiting. Generalized edema was noted on examination. An abdominal ultrasound examination was performed, and the patient was found to have diffuse mucosal thickening of the gastric wall with prominent rugal folds and echogenic mucosal lining with generalized subcutaneous edema and mild ascites. The patient underwent surgery and the diagnosis was confirmed by the histopathological report.

Histamine Signaling Is Essential for Tissue Macrophage Differentiation and Suppression of Bacterial Overgrowth in the Stomach

Menetrier’s disease (MD) is a rare hypertrophic gastropathy clinically characterized by digestive signs as epigastric pain, nausea, vomiting and diarrhea, with hypoalbuminemia and anemia, endoscopically by giant rugal folds and histologically by tortuous foveolar hyperplasia with dilated glands and hypertrophic muscularis mucosae. The current study presents a case of MD in 44 year-old-man admitted to the hospital of Hassan II in Fez, Morocco with epigastralgia, vomiting and weight loss. Physical examination fond a pale face and anemia in laboratory studies. A total gastrectomy was performed given the resistance to treatment and the persistence of symptoms, as well as the suspect endoscopic aspect. Macroscopic examination showed hypertrophic and polyploid gastric mucosa resembles cerebral convolutions. Histological examination showed a foveolar hyperplasia, tortuosity and dilatation of the glands. Hypertrophic muscularis mucosae with smooth muscle bundles extending into the lamina propria have also been observed. MD is considered as precancerous condition, and is associated with an increased risk of gastric cancer. This is a retrospective study of MD to describe his clinical, endoscopic and histological features, showing also the difficulty of the histological diagnosis.

Giant peptic ulcers have a poor prognosis and are associated with more frequent bleeding, together with very high morbidity. The prognosis worsens if it also spreads to the duodenum, with probable involvement of adjacent organs such as the pancreas. The most serious complication of these is perforation, this being the first manifestation is up to a third cases. A 62-year-old male patient with a history of high blood pressure, progressive cognitive disorder, and complications related to alcohol abuse and smoking. The patient came to the emergency room complaining of frequent stools mixed with blood. Ten hours after admission, he experienced massive hematemesis, followed by cardiorespiratory arrest and death. An autopsy was requested. In the pylorus and the first portion of the duodenum, an ulcerated lesion measuring 6.5 × 5 cm was identified, with smooth and raised edges, a fibrinoid bottom and a blackish appearance. During the histological study, an abrupt transition between the mucosa and the ulcerated area was observed, with involvement of the pancreas, the ampulla of Vater and adjacent tissues. Signs of hypersecretory hypertrophic gastropathy were found, with no signs of malignancy or associated Helicobacter pylori. Complicated giant peptic ulcers represent a medical emergency associated with increased morbidity, mortality, and costs. The variability of the associated symptoms makes it difficult in certain cases to identify the risk of massive bleeding, which eventually manifests as significant hematemesis due to vascular involvement. Complications, such as perforation and penetration, are important mortality risks, which make up a wide spectrum of signs and symptoms that precede a fatal outcome, which correspond to the autopsy findings of the case presented here. Key word: Autopsy, peptic ulcer, hemorrhage.

There are two forms of chronic pyloric hypertrophic gastropathy (GHPC), the first one being of congenital origin, which is the benign pyloric muscle hypertrophy, where the increase in cell volume occurs in the cells of the muscle layer; and the second one being acquired, which consists of hypertrophy of the mucosa of the gastric antrum, where this increase occurs in the mucous layer; both cause delayed gastric emptying as it results in stenosis of the pyloric lumen. This work aims to bring the literature review of both forms of GHPC. The definitive diagnosis of both is made from complementary imaging exams, especially endoscopy and biopsy; it’s very important to make the differential diagnosis for other diseases that present similar clinical signs, where the main one is vomiting right after the meal. The treatment of choice is surgical correction using the pyloroplasty technique, which requires monitoring the patient in the post-surgical period and the prognosis is usually favorable.

Ménétrier's disease (MD) (also known as giant hypertrophic gastritis or hypoproteinemic hypertrophic gastropathy) is a rare premalignant entity characterized by markedly hypertrophied mucosal folds of the fundus and the gastric corpus typically associated with , hypochlorhydria, protein losing enteropathy causing hypoalbuminemia and anemia. However, the natural history of MD in adults remains unclear and is rarely reported in the literature. Its constellation of classic symptoms includes nausea, vomiting, abdominal pain and peripheral edema, and it is associated with increased risk of gastric cancer. Nevertheless, its pathophysiology is not yet fully understood and clinical and endoscopic diagnosis can be difficult to establish. Malignant transformation in MD should not be overlooked, and regular monitoring of the gastric mucosa via endoscopy is necessary.

We describe a case of hypertrophic gastropathy (Ménétrier’s like disease) with metastatic gastric adenocarcinoma in a seven-year-old intact female Labrador Retriever dog. The animal suddenly presented with emesis and died. Gross lesions included a marked diffuse thickening of the gastric mucosa and an ulcerated transmural neoplastic mass in the gastric body. Gastric body and fundus were affected by foveolar hyperplasia with loss of chief and parietal cells replaced by mucous cells and marked dilatation of gastric glands. An area of gastric adenocarcinoma with submucosal lymphatic vessels invasion was also present and metastases were observed in the gastric lymph nodes, small intestine, pancreas, lung and liver. Due to its similarity with other gastric proliferative disorders, including this condition in the list of differentials is a necessary step in the diagnostic investigation of canine gastropathies.

Hypertrophic pyloric gastropathy with Helicobacter spp. in a dog

BackgroundMénétrier-like disease is a rare hypertrophic canine gastropathy, reported in only seven dogs. Clinical signs are vomiting, anorexia and weight loss. Macroscopically, giant cerebriform gastric mucosal folds are typically seen in the corpus and fundus of the stomach. Histopathologically, fundic mucous cell hyperplasia and loss of parietal and chief cells are typical.Case presentationA nine-year-old spayed female Pointer had a history of intermittent vomiting, marked weight loss and hypoalbuminaemia. A gastroduodenoscopy was performed three times within three months with macroscopic changes remaining the same. The gastric mucosa of the corpus, fundus and proximal antrum was markedly irregular, with cerebriform mucosal folds. In the first gastric biopsies, histopathology revealed a moderate granulomatous gastritis, with a severe manifestation of Helicobacter-like organisms. Treatment for Helicobacter spp. decreased the vomiting slightly. The dog was diagnosed with concurrent leishmaniosis; the conventional anti-Leishmania treatment decreased the vomiting moderately, the hypoalbuminaemia resolved and the dog gained weight back to a normal body condition. Granulomatous gastritis was not present in the gastric biopsies after these treatments. The dog increased vomiting when palliative treatment (maropitant citrate, ondansetron and esomeprazole) was discontinued, and thus, full-thickness biopsies of the stomach were taken and Ménétrier-like disease was diagnosed. The affected area was too large to be surgically removed; thus, palliative treatment was reinstated. The dog remained clinically well 39 months after the first clinical presentation.ConclusionsThis is the first report of Ménétrier-like disease in a dog with a simultaneous manifestation of granulomatous gastritis, helicobacteriosis and leishmaniosis. The clinical signs decreased after treatment of helicobacteriosis and leishmaniosis, but vomiting remained probably as a sign of Ménétrier-like disease. Treatment options for dogs are surgical removal of the abnormal area or palliative treatment. In humans, promising results for a cure have been shown with cetuximab treatment, a human monoclonal antibody, but no canine antibody is commercially available yet. The dog here was doing well 39 months after first presentation, which is the longest reported survival time for Ménétrier-like disease with only palliative treatment in dogs. Full-thickness biopsies are preferred in macroscopic hypertrophic lesions of the stomach for better assessment of Ménétrier-like disease.

A 14-y-old spayed female Labrador Retriever was presented with an 8-mo history of chronic vomiting. Abdominal ultrasound and gastrointestinal endoscopy revealed a mass protruding into the gastric lumen, with cytologic features suggestive of sarcoma. A partial gastrectomy was performed; the gastric body and antrum were thickened, with a cerebriform appearance of the mucosal surface. Histologic examination revealed a submucosal neoplastic proliferation of fusiform cells variably arranged in irregular bundles and scattered whorls. Fusiform cells strongly reacted to antibodies against vimentin, S100, and neuron-specific enolase; glial fibrillary acidic protein was moderately and multifocally expressed. Pancytokeratin, KIT, α-smooth muscle actin, and desmin were nonreactive. Histologic and immunohistochemical findings suggested a diagnosis of gastric sarcoma with features referable to a non-GIST (gastrointestinal stromal tumor), non-smooth muscle NIMT (non-angiogenic, non-lymphogenic intestinal mesenchymal tumor). The overlying gastric mucosa was thickened by elongated and dilated gastric glands, predominantly lined by intensely periodic acid-Schiff-stained mucous cells. This altered mucosal architecture was suggestive of Ménétrier-like disease. Although this disease has been hypothesized to predispose to gastric adenocarcinoma in dogs, an association with gastric sarcoma has not been documented previously in the veterinary literature, to our knowledge.

Risk factors contributing to the transformation of chronic atrophic gastritis into gastric cancer are analyzed. Detection and monitoring of patients with precancerous conditions/lesions (precancerous changes), proper screening of H. pylori make early diagnosis of gastric cancer real. Features of precancerous conditions are given in order of increasing risk of developing gastric cancer. Adenomatous polyps of the stomach take the first place. Subsequent precancerous conditions include: cancer of the operated stomach, Menetria disease (hypertrophic gastropathy), B12-deficient anemia, and gastric ulcer. A definition of intestinal metaplasia subtypes is proposed as a risk factor for gastric cancer, dividing into complete and incomplete one, taking into account reduction in the expression of gastric mucins MUC1, MUC5AC and MUC6. Currently, the development of gastric cancer (mainly of the “intestinal type”) is considered as a multistage process involving the sequence of mucosal change, such as chronic inflammation, atrophy, intestinal metaplasia, dysplasia and adenocarcinoma. Role of the organism’s genetic susceptibility to H. pylori infection, factors of pathogenicity contributing to epithelial metaplasia, are analyzed. Role of Toll-like type 4 receptors (TLR4) involved in the recognition of H. pylori is clarified. It is with this type of receptors that the development of an excessive immune response of the host is associated, resulting in damage to the mucous membrane in H. pylori-infected individuals. In particular, carriers of TLR4+896A> G polymorphism have a more severe atrophy of the stomach and degree of inflammation, as well as an increased risk of non-cardiac gastric cancer.

La enfermedad de Ménétrier, también conocida como gastritis hipertrófica gigante o gastropatía hipertrófica hipoproteinémica, es una entidad poco frecuente, caracterizada por una gastroenteropatía perdedora de proteínas, hipoclorhidria y engrosamiento de los pliegues mucosos del fondo y el cuerpo gástrico; es causante de un grupo clásico de síntomas que incluyen náuseas, vómitos, dolor abdominal y edema periférico; se asocia con un mayor riesgo de cáncer gástrico, sin embargo, su fisiopatología aún no está del todo esclarecida y su diagnóstico, clínico y endoscópico, puede llegar a ser difícil de establecer, por lo que se describe un caso clínico y se presenta una revisión sucinta de la literatura.

Abstract Ménétrier's disease is a rare acquired protein-losing premalignant hypertrophic gastropathy characterized by giant gastric rugal folds, decreased acid secretion, increased gastric mucus production, and hypoalbuminemia. Microscopically, it is characterized by massive foveolar hyperplasia, oxyntic gland atrophy, and repatterning of cell specification. Spasmolytic polypeptide-expressing metaplasia (SPEM) is a more widely prevalent premalignant gastric lesion, and it is associated with chronic inflammatory conditions such as Helicobacter pylori infection. SPEM is microscopically similar to Ménétrier's disease except for absence of massive foveolar hyperplasia. We previously reported transgenic mice overexpressing the EGF receptor (EGFR) ligand, TGF-α, phenocopy Ménétrier's disease, that TGF-α is overexpressed in the stomach of Ménétrier's disease patients, and that the EGFR-neutralizing monoclonal antibody (mAb), cetuximab, is the first effective medical therapy for Ménétrier's disease. In a proteomic analysis of gastric tissue of Ménétrier's disease patients, we observed decreased levels of the Notch ligand, Jagged1, after cetuximab treatment. The aim of this study was to examine whether Notch signaling is a downstream target of EGFR signaling and whether it contributes to the pathogenesis of Ménétrier's disease and/ or SPEM. TGF-α transgenic mice (MT-TgfaTg) were used as a Ménétrier's disease mouse model. High-dose tamoxifen injection (5 mg intraperitoneal tamoxifen injection per 20 g body weight for 3 days) was used as a SPEM mouse model. Egfr protein reporter mouse line (EgfrEmgfp/Emgfp) was used to investigate the distribution of endogenous Egfr. Chief cell-specific reporter mouse line (Mist1CreERT2/+; Rosa26mTmg/+) was crossed with MT-TgfaTg for chief cell lineage tracing. We tested whether Notch signaling is activated in the stomach of Ménétrier's disease and SPEM mouse models by Hes-1 immunofluorescent staining. Then we tested whether Notch activation is reduced by MM-151, a cocktail of EGFR mAbs that blocks mouse EGFR, and/ or dibenzazepine (DBZ), a γ-secretase inhibitor in the gastric mucosa of MT-TgfaTg mice. We also examined the level of foveolar hyperplasia and proliferation, and the number of parietal and chief cells in the MT-TgfaTg mice using markers: UEA1 (foveolar pit cell), Ki-67 (proliferation), H+/K+ ATPase (parietal cell), GSII (neck cell), and gastric intrinsic factor (chief cell). Expression levels and distribution of endogenous Egfr protein were increased in the gastric mucosa of both Ménétrier's disease and SPEM mouse models. Nuclear Hes-1 expression was upregulated in the pit, isthmus, and neck compartments in the stomach of both mouse models compared to wild-type mice. Lineage tracing of chief cells in MT-TgfaTg mice showed that they were also positive for neck cell marker, GSII, which is a characteristic of SPEM. Number of nuclear Hes-1 positive cells was decreased by MM-151 and/ or DBZ treatment in MT-TgfaTg mice. Also, MM-151 and/ or DBZ treatment led to decreased foveolar hyperplasia and proliferation, and increased numbers of parietal and chief cells in the gastric mucosa of MT-TgfaTg mice. This study shows that the gastric mucosa of MT-TgfaTg mice also has a characteristic of SPEM for the first time. Both Ménétrier's disease and SPEM mouse models show increased EGFR and Notch signaling in the stomach. It was also shown that the activation of EGFR signaling is sufficient and necessary for the activation of Notch signaling in MT-TgfaTg mice. This study suggests that Notch signaling activated by EGFR signaling contributes, at least in part, to the pathogenesis of Ménétrier's disease and SPEM. Moreover, these findings suggest that blockade of Notch signaling may be a novel therapeutic strategy for Ménétrier's disease and SPEM. Citation Format: Won Jae Huh, Robert J. Coffey. EGF receptor-activated Notch signaling contributes to pathogenesis of premalignant gastric lesions [abstract]. In: Proceedings of the AACR Special Conference: Advances in Modeling Cancer in Mice: Technology, Biology, and Beyond; 2017 Sep 24-27; Orlando, Florida. Philadelphia (PA): AACR; Cancer Res 2018;78(10 Suppl):Abstract nr A34.