Beyond Gastritis and Before Cancer: the Strange Case of Ménétrier’s Disease

A 73-year-old man complained of epigastric discomfort, dysphagia, and weight loss of 8 kg over the prior 2 months; he denied hematemesis, hematochezia, melena, diarrhea, fever, or any other symptoms. The patient had severe leg weakness with intermittent bladder and bowel incontinence caused by a spinal cord compressing D6 fracture, hypertension, a repaired abdominal aortic aneurysm, and recurrent venous thromboembolism, for which a filter was inserted in the inferior cava vein. There was neither personal and family history of allergy, nor any gastrointestinal disorders, including cancer and peptic ulcer disease. The physical examination was unrevealing: the vital signs were normal and stable, and laboratory studies were normal except for a hemoglobin 9.8 g/dl, hematocrit 38.8%, total protein 6.9 g/dl, and albumin 3.0 g/dl. A computed tomography of the abdomen showed thickened gastric walls, an air fluid level in the lower esophagus, and abundant intraperitoneal fluid around the liver and the spleen, and in the pelvis. Endoscopy of the upper gastrointestinal tract revealed an almost complete obstruction of the gastric lumen by giant folds of the mucosa with rugae closely resembling cerebral convolutions with a finely nodular (cobblestone) appearance (Fig. 1). There was abundant and thick mucus, and an ulcerated mass was partially obstructing the pyloric outlet (not shown). Microscopy of multiple biopsies of gastric giant folds showed mucosal and foveolar hypertrophy, elongated crypts, dilated gastric glands, some of which were lined by a large number of mucous cells, and glandular cysts extending into the submucosa. There was no evidence of mucosal or submucosal inflammation, ulcers, or granulomata and no eosinophilic infiltration throughout the entire thickness of specimens. The stains for mycobacteria and fungi were negative, and cultures grew no organisms. We considered all these histological findings diagnostic of Menetrier’s disease. Microscopy of biopsies of the pyloric mass showed a poorly differentiated carcinoma. Proton pump inhibitors, corticosteroids, and parenteral nutrition were started; the patient refused surgery and was discharged to a hospice. Hypertrophic gastropathy can be caused by a wide spectrum of disorders ranging from Zollinger–Ellison syndrome to sarcoidosis, syphilis, and eosinophilic gastroenteritis; however, giant gastric folds associated with foveolar hyperplasia are more likely due to Menetrier’s disease than other causes of hypertrophic gastropathy [1]. Menetrier’s disease is a rare disease, characterized by enlargement of the gastric mucosal folds that primarily affect the body of the stomach, whereas the gastric antrum is usually saved [1]. Microscopy shows proliferation of the gastric glands with preservation of nuclear polarity and cystic dilatation of their basilar portion. In extensive cases, the mucous-secreting cells are present in the glands deep in the mucosa and replace the normal chief and parietal cells. Inflammation in the lamina propria is modest although the enlarged folds are subject to erosion and can show superficial ulcers with granulation tissue and an influx of neutrophils into the lamina propria. A patchy accumulation of eosinophils in the lamina propria is an under appreciated feature of Menetrier’s disease even though eosinophils are sometimes the predominant inflammatory cells; lamina propria lymphocytes may also be mildly increased. The muscularis mucosa is thickened and disorganized, with strands of smooth muscle extending into the lamina propria, as well as prolapse of the enlarged folds. G. Famularo (&) M. R. Sajeva L. Gasbarrone Department of Internal Medicine, San Camillo Hospital, Circonvallazione Gianicolense, 00152 Rome, Italy e-mail: gfamularo@scamilloforlanini.rm.it