At present there is no universally accepted classification for gastritis. The first successful classification (The Sydney System) that is still commonly used by medical professionals was first introduced by Misiewicz et al in Sydney in 1990. In fact, it was the first detailed classification after the discovery of Helicobacter pylori by Warren and Marshall in 1982. In 1994, the Updated Sydney System was proposed during the International Workshop on the Histopathology of Gastritis followed by the publication in The American Journal of Surgical Pathology by Dixon et al. Using the new classification, distinction between atrophic and nonatrophic gastritis was revised, and the visual scale grading was incorporated. According to the Updated Sydney System Classification, atrophic gastritis is categorized into multifocal (H. pylori, environmental factors, specific diet) and corpus-predominant (autoimmune). Since metaplasia is a key histological characteristic in patients with atrophic gastritis, it has been recommended to use the word "metaplastic" in both variants of atrophic gastritis: autoimmune metaplastic atrophic gastritis (AMAG) and environmental metaplastic atrophic gastritis. Although there are many overlaps in the course of the disease and distinction between those two entities may be challenging, the aim of this review article was to describe the etiology, epidemiology, pathogenesis, diagnosis, clinical manifestations and treatment in patients with AMAG. However, it is important to mention that H. pylori is the most common etiologic factor for the development of gastritis in the world.

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Autoimmune atrophic gastritis: current perspectives.

Autoimmune gastritis (AIG) is a chronic immune-mediated, inflammatory condition that involves the destruction of the gastric oxyntic mucosa through the autoimmune-mediated loss of parietal cells, with replacement by atrophic and metaplastic tissue. Diagnosing AIG is important, given the need for ongoing clinical management and vigilance with respect to downstream complications, the most serious of which is gastric adenocarcinoma. Other clinical consequences include gastric neuroendocrine tumors, consequences related to decreased gastric acid and decreased intrinsic factor due to parietal cell destruction and antibodies against intrinsic factor (e.g. micronutrient deficiencies), as well as concomitant autoimmune disorders. Considering the prevalence of AIG and the potential for severe clinical outcomes, it is important to engage in efforts to reduce practice pattern variability related to diagnosis and management. Accordingly, herein, we review of the epidemiology, pathogenesis, clinical presentation of AIG, including both gastric and extragastric manifestations, and provide an overview of clinical management.

https://journals.sagepub.com/doi/pdf/10.1177/17562848211038771

Autoimmune gastritis, with or without pernicious anemia: epidemiology, risk factors, and clinical management

Gastric biopsies are often submitted with as clinical question Helicobacter pylori (HP) infection. Regularly, the morphology suggests a HP infection but the organism is not detected in special stains. This review presents a practical approach to deal with such biopsies. The first step is to exclude a false negative result of the search for HP, by ensuring that both antral and oxyntic mucosa are present, by the use of sensitive stains, identification of marked reactive changes, such as intestinal, pseudo-pyloric, pancreatic metaplasia that may suggest a diagnosis of (HP associated or autoimmune) atrophic gastritis, and finally identification of signs of the use of proton pump inhibitors (PPI) as in such biopsies, HP may sometimes be found only within parietal cells. The differential diagnosis should include lymphocytic gastritis, other diseases affecting the stomach, such as inflammatory bowel disease (IBD), vasculitis, granulomatous disease, viral infection, such as cytomegalovirus (CMV) or more rarely Epstein-Barr virus (EBV) infection, or other bacterial infections, such as Enterococcus and Treponema pallidum. Clinical input may be required to ensure the patient is not taking medication that may cause gastritis, such as antibiotics used for HP eradication or common medications that cause a form of gastropathy. When these have been excluded, a known cause has not been found and in such a case, the term idiopathic focal/diffuse gastritis can be used.

The differential diagnosis of Helicobacter pylori negative gastritis

There are two types of pyloric gland-like metaplasia in the corpus of stomach: pyloric and pseudopyloric metaplasias. They show the same morphology as the original pyloric glands in H&E staining. Pseudopyloric metaplasia is positive for pepsinogen (PG) I immunohistochemically, whereas pyloric metaplasia is negative. Recently, spasmolytic polypeptide-expressing metaplasia (SPEM) is proposed for pyloric gland-like metaplasia mainly in animal experiments. SPEM expresses trefoil factor family 2 (TFF2) and is often considered synonymous with pseudopyloric metaplasia. We reviewed consecutive 22 Japanese patients with autoimmune gastritis (AIG) to investigate TFF2 expression in pyloric and pseudopyloric metaplasias by counting all pyloric gland-like glands in biopsy specimens taken from greater curvature of the middle corpus according to the Updated Sydney System. Pyloric metaplasia was seen in all the 22 cases, and pseudopyloric metaplasia was found in 15 cases. Of 1567 pyloric gland-like glands in all the cases, 1381 (88.1%) glands were pyloric metaplasia glands, and the remaining 186 (11.9%) glands were pseudopyloric metaplasia glands. TFF2 expression was observed in pyloric or pseudopyloric metaplasia glands in 20 cases. TFF2 expression was recognized in 409 of 1381 (26.9%) pyloric metaplasia glands and 27 of 186 (14.5%) pseudopyloric metaplasia glands (P<0.01, chi-square test). In conclusion, SPEM was not always the same as pseudopyloric metaplasia in human AIG, and the majority of metaplasia in AIG was not pseudopyloric but pyloric metaplasia.

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Pyloric, pseudopyloric, and spasmolytic polypeptide-expressing metaplasias in autoimmune gastritis: a case series of 22 Japanese patients.

Autoimmune atrophic gastritis (AAG) is a chronic disease that can progress to gastric cancer (GC). To better understand AAG pathology, this proteomics study investigated gastric proteins whose expression levels are altered in this disease and also in GC. Using two-dimensional difference gel electrophoresis (2D-DIGE), we compared protein maps of gastric corpus biopsies from AAG patients and controls. Differentially abundant spots (|fold change|≥ 1.5, P < 0.01) were selected and identified by LC–MS/MS. The spots were further assessed in gastric antrum biopsies from AAG patients (without and with Helicobacter pylori infection) and from GC patients and unaffected first-degree relatives of GC patients. 2D-DIGE identified 67 differentially abundant spots, with 28 more and 39 less abundant in AAG-corpus than controls. LC–MS/MS identified these as 53 distinct proteins. The most significant (adjusted P < 0.01) biological process associated with the less abundant proteins was “tricarboxylic acid cycle”. Of the 67 spots, 57 were similarly differentially abundant in AAG-antrum biopsies irrespective of H. pylori infection status. The differential abundance was also observed in GC biopsies for 14 of 28 more abundant and 35 of 39 less abundant spots, and in normal gastric biopsies of relatives of GC patients for 6 and 25 spots, respectively. Immunoblotting confirmed the different expression levels of two more abundant proteins (PDIA3, GSTP gene products) and four less abundant proteins (ATP5F1A, PGA3, SDHB, PGC). This study identified a proteomics signature of AAG. Many differential proteins were shared by GC and may be involved in the progression of AAG to GC.

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Proteomics signature of autoimmune atrophic gastritis: towards a link with gastric cancer.

The histopathological diagnosis of autoimmune gastritis (AG) in its early stages can be a diagnostic challenge. Even some advanced cases with complete atrophy of the corpus mucosa may be difficult to recognize. To establish the diagnosis of autoimmune gastritis, several histological features should be assessed and combined with immunostains for enterochromaffin cell-like (ECL) cells and G-cells. The main histological criteria include a mononuclear infiltrate within the lamina propria, foci of destruction of oxyntic glands, intestinal metaplasia (IM), pyloric metaplasia, and parietal cell pseudohypertrophy. These criteria were evaluated in our series of 25 patients with achlorhydria and/or megaloblastic anemia. Some of our patients presented with nonspecific gastrointestinal symptoms. The age ranged between 46 and 79 years; one male patient was only 31 years old. Histologically, the corpus mucosa displayed in all cases chronic inflammation with focal complete IM and advanced pyloric metaplasia. In 4 patients, oxyntic glands were destructed in some sites. There was a pancreatic metaplasia of acinar type in 2 patients and a minimal focal pseudohypertrophy of parietal cells in the 31-year-old man. A tubular adenoma with a low-grade dysplasia was found in one female patient. Immunohistochemically, chromogranin-A highlighted linear or nodular hyperplasia of ECL cells in 19 patients, and adenomatoid ECL hyperplasia in one case (80%). In the remaining cases hyperplasia of ECL cells could not be recognized from their normal count. In 13 cases (52%) a few ECL cells were seen also in IM. Regarding associated pathology, in one woman with nodular ECL cell hyperplasia, a gastric carcinoid was removed endoscopically. The reaction with gastrin antibody revealed in 11 cases (44%) a small number of G cells in IM in the corpus mucosa. In 18 patients, antral mucosa was examined as well. In 8 patients, the mucosa was normal; in 10 cases, a mild chronic inactive gastritis was diagnosed, and in 15 patients G-cell hyperplasia was found. In accordance with other studies, we show that the diagnosis of AG may be established microscopically in endoscopic specimens of the gastric body mucosa when histologic features and immunohistochemical detection of ECL and G cell hyperplasia are combined.

Autoimmune gastritis. A clinicopathologic study of 25 cases.

The histologic diagnosis of reflux esophagitis is still complicated by the lack of a consensus opinion on what is the normal mucosa in the area of the gastroesophageal junction (GEJ). Most authors consider GEJ as the junction between the squamous and the cardiac epithelium. The cardiac mucosa is composed of mucinous or mixed mucinous-oxyntic glands. These glands are in fact indistinguishable from metaplastic mucosa that arises in the distal esophagus in consequence of gastroesophageal reflux (GER). The cardiac mucosa shows invariably chronic inflammatory changes referred to as "carditis". The cause of "carditis" is GER and/or Helicobacter pylori (HP) infection. In our series of 120 endoscopic biopsies of the GEJ and distal esophagus the cardia type mucosa (CM) was always present. In 15 cases, it was accompanied by oxyntocardiac mucosa. Both mucosa types showed chronic inflammation that is after exclusion of HP infection regarded as a strong diagnostic sign of the gastroesophageal reflux disease (GERD). In two cases with clinical symptoms of GERD, a few HP were found on the CM. Therefore we diagnosed them as GERD with secondary HP infection. In 17 cases, CM displayed intestinal metaplasia (IM) predominantly of incomplete type and no dysplasia. This IM expressed MUC6 in the glandular zone of the mucosa like it did in the neighboring glands, whereas in the surface and foveolar epithelium the MUC6 was negative or only slightly and focally positive. On the other hand, IM in the surface and foveolar epithelium was reactive for MUC5AC. The positivity and distribution of CK7 and CK20 was very similar in the Barrett's mucosa, cardiac mucosa and antral mucosa. In one specimen of esophagus resected for adenocarcinoma, CM with incomplete IM was found in the vicinity of the tumor. Squamous metaplastic epithelium was often seen near the orifices of submucosal esophageal glands in these areas, indicating the metaplastic nature of the glandular mucosa in the distal esophagus. In the GEJ of 5 autopsy cases of children with spastic quadriplegia (age range 7-10 years) CM in a short segment (0.5-3 mm in length), probably of metaplastic origin was identified, showing chronic inactive inflammation.

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Z Benes

Papers

Autoimmune gastritis. A clinicopathologic study of 25 cases.

Histopathologic changes in gastroesophageal reflux disease. A study of 126 bioptic and autoptic cases.