The diagnosis of gastritis

After Babylonian confusion over the histological classification of gastritis, the Sydney system brought standardization and reproducibility to the diagnostic field of gastric biopsies. Even some shortcomings do not reduce the importance of the Sydney system for classification of gastritis. Essentially gastritis is a purely histological diagnosis. Herein we describe further diagnostic criteria for the diagnosis of gastritis and show the time-dependent changes in frequencies of various types of gastritis over more than 25 years at the Institute of Pathology in Bayreuth. Pathologists should be encouraged to address the etiology of inflammatory infiltrates to enhance the clinical value of a histological diagnosis on gastric biopsies.     

Lymphocytic gastritis versus varioliform gastritis. A historical series revisited

A historical series of varioliform gastritis published in 1978 by Lambert et al. (Digestion 1978; 17: 159-167) was revisited by two pathologists. The histological preparations from 35 patients were reread and interpreted in the light of endoscopic data found in the files. The results demonstrate a strict correlation between clinical diffuse varioliform gastritis and a recently recognized histopathological entity--lymphocytic gastritis, which is characterized by intense lymphocytic infiltration of the surface and foveolar epithelium. The rare discrepancies occur in Crohn's disease and in varioliform gastritis limited to part of the stomach, mostly the antrum.     

Observer variation in the assessment of chronic gastritis according to the Sydney system

The main aims of the Sydney system for the classification of gastritis are to improve uniformity in histopathological reporting and to provide a flexible matrix of rules for grading the histological features. We sought to determine the level of interobserver agreement between pathologists in the application of the Sydney system. Three histopathologists independently examined H & E, alcian blue/PAS and modified Giemsa stained sections of two antral and two corpus gastric biopsies from 69 consecutive dyspeptic patients. After elimination of five unsuitable cases, each observer graded chronic inflammation, polymorph activity, atrophy, intestinal metaplasia and Helicobacter pylori density in the antrum and corpus on a 0–3 scale according to the Sydney system criteria. The pairwise agreement on final diagnosis and the overall and conditional agreement on histological grades were examined by kappa statistics. Agreement on the final diagnosis ranged from 83–94% with kappa values of 0.699 ('good') to 0.887 ('excellent'). Conditional probability of agreement on a diagnosis of H. pylori positive gastritis was 99%, but wider disagreements were apparent in the recognition of H. pylori negative gastritis, reactive gastritis and even normal biopsies. Overall agreement for grade ranged from 70% for antral atrophy to 94% for intestinal metaplasia in the corpus with 'moderate' or 'good' kappa values. We conclude that the diagnostic and grading criteria described in the Sydney system can be applied consistently by histopathologists. The findings underline its potential usefulness in routine practice.     

Pathology,diagnostics, and classification of medulloblastoma

Medulloblastoma (MB) is the most common CNS embryonal tumor. While the overall cure rate is around 70%, patients with high‐risk disease continue to have poor outcome and experience long‐term morbidity. MB is among the tumors for which diagnosis, risk stratification, and clinical management has shown the most rapid advancement. These advances are largely due to technological improvements in diagnosis and risk stratification which now integrate histomorphologic classification and molecular classification. MB stands as a prototype for other solid tumors in how to effectively integrate morphology and genomic data to stratify clinicopathologic risk and aid design of innovative clinical trials for precision medicine. This review explores the current diagnostic and classification of MB in modern neuropathology laboratories.     

''Corkscrew-like''bacteria associated with gastritis

Gastric spiral bacteria morphologically unlike Campylobacter pylori have recently been described in patients with gastritis. We report an additional case. These organisms are as yet unnamed, remain uncultured and are morphologically similar to organisms present in the gastric mucosa of various mammalian species. Their possible role in the pathogenesis of gastritis is discussed.     

Endocrine cell growths in atrophic body gastritis. Critical evaluation of a histological classification

The aim of the present study was to evaluate the correspondence of the classification of non-antral endocrine cell growths proposed by Solcia and co-workers with clinical features and non-endocrine mucosal changes. For this purpose, 94 cases of newly diagnosed atrophic body gastritis were investigated using endoscopic biopsies and compared with 18 control subjects. The patients were subdivided into the following four groups according to the most severe pattern of endocrine cell proliferation found in the body mucosa, as shown by chromogranin A immunostaining: group 1, normal pattern (7 cases, 7·5 per cent); group 2, simple hyperplasia (6 cases, 6·5 per cent); group 3, linear hyperplasia (24 cases, 25·8 per cent); group 4; micronodular hyperplasia (56 cases, 60·2 per cent). Adenomatoid hyperplasia was found in only one case, thus precluding further analysis. Patients in groups 1 and 2 had lower acid secretion, higher gastrin level, and higher mean scores in all histopathological variables of chronic gastritis considered by the Sydney system when compared with controls, but did not differ among them in any parameter investigated. When compared with groups 1 and 2, patients of groups 3 and 4 showed higher values of circulating gastrin, higher scores of glandular atrophy, and lower values of acid secretion and of mononuclear and neutrophil inflammatory cell infiltration. Moreover, group 4 patients differed significantly from those of group 3 in their higher gastrin levels and atrophy scores, and lower scores of neutrophil cell infiltration. On the basis of these results, it is proposed that for practical purposes the normal and the simple hyperplasia patterns may be incorporated into a single group. It is concluded that this classification in its simplified form, based on a qualitative histological approach, shows clinical relevance without the need to perform expensive, time-consuming morphometric evaluations. © 1997 John Wiley & Sons, Ltd.     

Mucosal mast cells in reflux gastritis and chronic (type B) gastritis

The histological features that characterize alkaline reflux gastritis are typical of the histamine-mediated response to tissue injury. We have investigated this in nine patients with symptomatic reflux gastritis following partial gastrectomy for duodenal ulcer by determining the gastric mucosal mast cell count before and after Roux-en-Y biliary diversion. Following diversion, the histological picture changed from that of reflux gastritis to type B chronic gastritis in all cases. The mean mucosal mast cell count in all patients was 47.57/mm2 before diversion and 123.33/mm2 after diversion (P less than 0.05). Analysis of the paired data, in which eight out of nine patients showed a rise in mucosal mast cell numbers following bile diversion, also showed a significant difference before and after surgery (P less than 0.01). The gastric mucosal mast cell count is significantly less in reflux gastritis than in type B chronic gastritis. This is most likely to be due to increased degranulation, which would explain why striking vascular changes occur in the absence of inflammatory cell infiltration in reflux gastritis.     

An experimental study into the cause of acute haemorrhagic gastritis in cirrhosis

To clarify the role of endotoxaemia and congestion of the stomach in the development of acute haemorrhagic gastritis in cirrhotic patients and to investigate the mechanisms of gastric mucosal haemorrhage, the present study was undertaken using rats. Congestion of the stomach was produced by the ligation of gastric veins. Congestion of the stomach or endotoxaemia could not produce gastric mucosal haemorrhage by itself. However, petechial haemorrhage was induced when endotoxin was given to the rats with congestion of the stomach, and the gastric mucosal haemorrhage was largely prevented by administration of gabexate mesilate, an anti-kallikrein drug. Administration of bromelain, which releases prekallikrein and high molecular weight kininogen, instead of endotoxin, also induced gastric mucosal haemorrhage. These findings suggest that the cause of acute haemorrhagic gastritis may be the coexistence of endotoxaemia and congestion of the stomach due to liver cirrhosis and portal hypertension. The mechanisms of the haemorrhage may be as follows: Endotoxin-induced bradykinin acts on the dilated capillaries and small veins in the mucosa and markedly increases their permeability.     

Immune response to Helicobacter pylori and its association with the dynamics of chronic gastritis in the antrum and corpus

The aim of the study was to establish possible factors which play a role in progression of gastritis to atrophic gastritis in long-term follow-up among the Estonian population, to assess the association between the host immune response and different Helicobacter pylori antigens and autoantigens in relation to the histological parameters of gastritis in the antrum and corpus. ELISA and immunoblot were used for detection of IgG to H. pylori acid glycine-extracted cell surface proteins, CagA protein, and H. pylori HSP60. Anticanalicular autoantibodies (ACAB) in the serum were evaluated according to Faller et al. (1996). Apoptosis was evaluated using the TUNEL method. Study subjects were 1958 persons from an unselected Estonian population, and 70 persons from a sample from Saaremaa Island, who had been investigated over a period of 18 years. Seropositivity for CagA was a sign of gastritis activity [OR=14.8 (4.5-50.3)] and atrophy [OR=7.0 (2.1-23.1)] and might predict development of atrophy, particularly in the corpus [OR=7.1 (1.8-27.7)]. The prevalence of ACAB increased significantly with duration of H. pylori gastritis from 22% in 1985 to 46% in 1997 (p=0.004). Immune response to H. pylori HSP60 indicates chronic inflammation in the antrum (p=0.003). Apoptosis of gastric epithelial cells is largely dependent on grade of activity of gastritis, and, particularly in the antrum, on grade of H. pylori colonization (p=0.01; p=0.02), but is not associated with development of atrophy. Seropositivity for different H. pylori antigens (CagA, HSP 60) serves as a marker of different histological manifestations in the antrum and corpus mucosa.     

Clinicopathological features of syphilitic gastritis in Korean patients

Syphilitic gastritis is difficult to diagnose without a history of syphilis, because endoscopic and microscopic findings can simulate gastric cancer or lymphoma. Herein are reported two cases of syphilitic gastritis and analysis of the clinicopathological characteristics of 11 cases in Korean subjects, including nine previously reported ones. The two present patients were 25‐ and 32‐year‐old men with epigastric pain. The gastroduodenoscopy features were similar: multiple erosive or ulcerative lesions in whole gastric mucosa. Microscopically, gastric mucosa contained severe chronic active gastritis involving submucosa with crypt abscesses, venulitis and granulomas, suggesting unusual infectious gastritis. Numerous spirochetes were identified on silver staining, and serological tests for syphilis were reactive in both patients. They were treated with benzathin penicillin, and follow‐up gastric biopsy specimens indicated non‐specific chronic gastritis without evidence of syphilis. Of the 11 Korean patients with syphilitic gastritis, six were female and five were male (mean age, 31.7 years). The most common symptom was epigastric pain and all patients had diffuse erosive, ulcerative or infiltrative lesions on gastroduodenoscopy. Syphilitic gastritis should be considered in young patients with epigastric pain who have diffuse gastric involvement such as erosion or shallow ulcer on endoscopy and unusually extensive chronic active gastritis on microscopy, even if the history of syphilis is not clear.     

Xanthogranulomatous gastritis with pseudosarcomatous changes

Reported herein is a rare case of xanthogranulomatous inflammation of the gastric wall occurring in a 77-year-old man. Two submucosal lesions presented as rapidly enlarging nodules, and biopsy showed interweaving bundles of spindle cells with numerous atypical cells with marked nuclear pleomorphism. The differential diagnosis from mesenchymal malignancies, particularly from a malignant gastrointestinal stromal tumor, was difficult and immunohistochemical investigations could not improve the diagnostic accuracy of HE histology alone. Thus, an erroneous diagnosis of malignancy was made and a partial gastrectomy was performed. On macroscopic examination of the resected material, spontaneous regression of the lesions was observed and microscopic examination showed characteristic features of xanthogranulomatous inflammation; large numbers of foamy histiocytes including multinucleated giant cells were admixed with chronic inflammatory cells and fibrous reaction. Although the precise pathogenesis could not be elucidated, recognition of this unusual morphological appearance is of importance to avoid an overdiagnosis of malignancy.     

Severe gastritis in the Peruvian Andes

OBJECTIVE: To compare the Helicobacter pylori-associated pathology in gastric biopsies taken from patients living at sea level with those taken from patients living at high altitude. METHODS AND RESULTS: We included 38 patients from a hospital in the Andean city of La Oroya, Peru, located at 3700 m in altitude, and 40 control patients taken from Comas Clinic located in the city of Lima at sea level. Fibrepanendoscopy and multiple biopsies were performed in all the patients followed by histopathological examination. In the antrum, patients from the Andean town had a higher prevalence of glandular lymphoid adherence lesions, active germinal centres, moderate to severe chronic atrophic gastritis, intestinal metaplasia and moderate to severe total deep gland loss, than did patients from the coastal town. Furthermore, the severity of the histological lesions seen in the gastric body and cardia was significantly greater in the high-altitude patients than in those from sea level. CONCLUSION: This study suggests that the severity of H. pylori-associated gastric lesions seen on histopathological examination is greater in patients living at high altitude, the cause of which is most probably multifactorial but nonetheless principally altitude related.     

Relationship of TT virus and Helicobacter pylori infections in gastric tissues of patients with gastritis

Blood and gastric tissue biopsies of 34 patients with gastritis were tested for the presence of TT virus (TTV), a ubiquitous virus found in the blood of most humans. Thirty-one of these patients were TTV positive, and 27 patients had virus in both tissues. In addition, 13 of the patients who had TTV in gastric tissue were Helicobacter pylori positive. There was an association of higher TTV titers in gastric tissues of patients who were H. pylori positive than in those in whom the bacterium could not be detected. Furthermore, this association was stronger in H. pylori-positive patients with the presence of the cagA protein. Of 10 specimens in which genogroup determination was carried out in the gastric corpus, 5/5 that were H. pylori positive showed the presence of TTV genogroup 3, while for those that were H. pylori negative, 5/5 showed the presence of genogroup 1t. By contrast, genogroup 1 was found in the corpus of only one H. pylori-positive patient, and genogroup 3 in only one H. pylori-negative patient. The histological severity of gastritis did correlate significantly with loads in the gastric tissues. There was no significant difference in TTV titer in blood of patients regardless of H. pylori infection status. These findings pique interest in clarifying the role of TTV, alone or in association with H. pylori infection, in the pathogenesis of gastritis.     

Histological features do not define NSAID-induced gastritis

Nonsteroidal anti-inflammatory drug (NSAID) use is a common cause of peptic ulcer. This study investigated the nature, frequency, and topographic distribution of histological abnormalities of the gastric mucosa associated with chronic NSAID use. A set of 3 to 11 mapped gastric biopsy specimens were obtained from 108 chronic users of NSAIDs and 61 controls. Each specimen was graded from 0 to 3 for each of the following features: foveolar hyperplasia, smooth muscle fibers, edema, neutrophils, intestinal metaplasia, eosinophils, mononuclear cells, mucosal hemorrhage, atrophy, and Helicobacter pylori. We found that foveolar hyperplasia, considered one of the characteristic features of chemical gastropathy, was absent in 66% of NSAID users. Foveolar hyperplasia was present in 37 NSAID users (34%) and in 10 controls (18%); prominent smooth muscle fibers were found in 51 NSAID users (47%) and 10 of the controls (16%). Concurrent H pylori gastritis obscured the histopathologic changes of NSAID use. All other parameters, including H pylori infection rate (57% v 51%) were similar in NSAID users and controls. We conclude that the histological features characteristic of NSAID users were present only in a subset of patients. No single histological feature can be used to characterize or diagnose chemical gastropathy and no simple set of diagnostic criteria can be applied for this purpose.     

Vascular endothelial growth factor and neo-angiogenesis in H. pylori gastritis in humans

Host response plays a major role in the pathogenesis of Helicobacter pylori-induced gastroduodenal disease including adenocarcinoma of the distal stomach. Vascular endothelial growth factor (VEGF) is an important modulator of gastric mucosal repair and is overexpressed in gastric cancer. The present study sought to evaluate the expression of VEGF in the gastric mucosa of H. pylori-infected and H. pylori-non-infected dyspeptic patients. Fifteen H. pylori-infected and 15 H. pylori-non-infected dyspeptic patients were studied. Diagnosis of H. pylori infection was based on rapid urease test and histology. VEGF protein expression was assessed by western blotting. VEGF mRNA expression was assessed by RT-PCR. VEGF localization in the gastric mucosa and neo-angiogenesis were determined by immunohistochemistry. VEGF protein and mRNA expression was significantly greater in H. pylori-infected than in non-infected patients. Immunohistochemistry showed that VEGF expression was more intense in the gastric gland compartment of H. pylori-infected mucosa than in the non-infected mucosa. The increase in VEGF expression was associated with a significant increase in neo-angiogenesis as assessed by determination of CD34-positive micro-vessels. H. pylori gastritis is therefore associated with up-regulation of VEGF expression, which parallels the increased formation of blood vessels in the gastric mucosa. It is postulated that increased VEGF expression and neo-angiogenesis may contribute to H. pylori-related gastric carcinogenesis.     

Cytomegalovirus gastritis with perforation and gastrocolic fistula formation

A 76-year-old man with lymphoma involving cervical and mediastinal lymph nodes and abdomen was treated by radiotherapy and chemotherapy. He subsequently developed cytomegalovirus gastritis and gastric ulcers with a gastrocolic fistula and a jejuno-jejunal fistula, necessitating a partial gastrectomy. The pathogenesis of cytomegalovirus gastritis and its complications are discussed.