Severe induction of aberrant DNA methylation by nodular gastritis in adults.

BACKGROUND: Nodular gastritis (NG) is characterized by marked antral lymphoid follicle formation, and is a strong risk factor for diffuse-type gastric cancer in adults. However, it is unknown whether aberrant DNA methylation, which is induced by atrophic gastritis (AG) and is a risk for gastric cancer, is induced by NG. Here, we analyzed methylation induction by NG. METHODS: Gastric mucosal samples were obtained from non-cancerous antral tissues of 16 NG and 20 AG patients with gastric cancer and 5 NG and 6 AG patients without, all age- and gender-matched. Genome-wide methylation analysis and expression analysis were conducted by a BeadChip array and RNA-sequencing, respectively. RESULTS: Clustering analysis of non-cancerous antral tissues of NG and AG patients with gastric cancer was conducted using methylation levels of 585 promoter CpG islands (CGIs) of methylation-resistant genes, and a large fraction of NG samples formed a cluster with strong methylation induction. Promoter CGIs of CDH1 and DAPK1 tumor-suppressor genes were more methylated in NG than in AG. Notably, methylation levels of these genes were also higher in the antrum of NG patients without cancer. Genes related to lymphoid follicle formation, such as CXCL13/CXCR5 and CXCL12/CXCR4, had higher expression in NG, and genes involved in DNA demethylation TET2 and IDH1, had only half the expression in NG. CONCLUSIONS: Severe aberrant methylation, involving multiple tumor-suppressor genes, was induced in the gastric antrum and body of patients with NG, in accordance with their high gastric cancer risk.

Regression of Autoimmune Gastritis after Eradication of Helicobacter pylori.

We report a case of autoimmune gastritis (AIG) in which gastric mucosal atrophy improved with Helicobacter pylori eradication. Based on endoscopic findings (advanced gastric atrophy with vascular visibility and diffuse redness in remnant oxyntic mucosa), a woman in her 40s was suspected of having AIG coexisting with an active H. pylori infection. This was confirmed by a positive anti-parietal cell antibody (PCA, 1:160), an elevated serum gastrin level (638 pg/mL), and positive anti-H. pylori antibody (Hp Ab, 15.5 U/mL) and H. pylori stool antigen tests. Seven months after eradication, reduced vascular visibility and disappearance of diffuse redness on endoscopy and reduced PCA (1:40) and Hp Ab (5.1 U/mL) titers were observed, although histopathological findings (basal-predominant lymphocytic infiltration, destruction of parietal and chief cells, pseudopyloric metaplasia, and enterochromaffin-like cell hyperplasia) were consistent with AIG. Endoscopy 26 months after eradication showed further improvement in atrophic findings in the gastric corpus and histopathological recovery of parietal and chief cells in fundic glands. Serum gastrin levels returned to normal (64 pg/mL), and the PCA titer fell further (1:20).

Evolving Autoimmune Gastritis Initially Hidden by Active Helicobacter pylori Gastritis.

Autoimmune gastritis (AIG) and Helicobacter pylori (H. pylori) gastritis are considered different diseases but exhibit overlapping features. We herein report a case of evolving AIG that had been initially hidden by active H. pylori gastritis. The patient was diagnosed with active H. pylori gastritis and received first-line eradication therapy in 2014 and successful second-line therapy in 2017. She was suspected of having early-stage AIG in 2019 based on the endoscopic finding of salmon roe-like nodular lesions on the greater curvature of the corpus. Parietal cell antibody was positive and the serum gastrin level was slightly elevated. Although subsequent endoscopy in 2020 revealed no significant changes in gastric atrophy, a sharp rise in the serum gastrin level was noted. A biopsy specimen taken from a nodular lesion showed pseudohypertrophy of residual parietal cells, lymphocytic infiltration, and enterochromaffin-like (ECL) cell hyperplasia. Upon retrospective reviews, endoscopic and serological findings obtained before eradication were consistent with active H. pylori gastritis. However, endoscopic salmon roe-like nodular lesions were detected in close-up views. In addition, lymphocytic destruction of fundic glands, pseudopyloric metaplasia, and ECL cell hyperplasia was histopathologically identified on a background of full-thickness inflammation, which suggested that early-stage AIG had coexisted with active H. pylori gastritis.

Early autoimmune gastritis presenting with a normal endoscopic appearance.

This report describes a patient with early-stage autoimmune gastritis (AIG) presenting with a normal endoscopic appearance. A 66-year-old man with autoimmune thyroiditis was suspected of having AIG because of a previous history of vitamin B12 deficiency when receiving steroid therapy for interstitial pneumonia 5 years earlier. At presentation, he tested positive for anti-parietal cell antibody (1:320) and anti-intrinsic factor antibody, but not for vitamin B12 deficiency. His gastrin level was elevated (338 pg/mL), but his pepsinogen (PG) I level (56.1 ng/mL) and PGI/PGII ratio (7.6) were normal. Endoscopically, neither atrophic nor inflammatory changes were observed. Histopathologic examination, however, showed mild atrophic changes with dense lymphocytic infiltration in the deep lamina propria and focal destruction of parietal cells in the greater curvature of the corpus. PGI-positive/MUC6-positive pseudo-pyloric metaplasia was observed in the area from which H+/K+-ATPase-positive parietal cells had disappeared. Chromogranin A immunostaining showed linear hyperplasia of enterochromaffin-like cells. By contrast, atrophic changes were not evident in the lesser curvature of the corpus, except for mild lymphocytic infiltration around and into the fundic glands. These serological and histopathological findings suggested that the patient had early-stage AIG with a normal endoscopic appearance.

A case of autoimmune gastritis with fundic gland polyp-like pseudopolyps presenting with nodular enterochromaffin-like cell hyperplasia.

Pseudopolyps, a type of remnant oxyntic mucosa on a background of corpus-restricted mucosal atrophy, are a characteristic endoscopic finding in autoimmune gastritis (AIG). Linear or nodular enterochromaffin-like (ECL) cell hyperplasia, a characteristic histopathological finding of AIG, is not generally found in pseudopolyps. We report a case of AIG with fundic gland polyp (FGP)-like pseudopolyps containing nodular ECL cell hyperplasia. A 64-year-old man underwent esophagogastroduodenoscopy, which revealed atrophic changes limited to the corpus, with a normal antrum. The greater curvature was less atrophic than the lesser curvature. Sessile or semipedunculated polypoid lesions were observed on the greater curvature and on the anterior and posterior walls of the corpus. The polypoid lesions resembled FGPs, although some were larger than FGPs generally are. Histologically, non-atrophic fundic glands with parietal cell pseudohypertrophy were observed in the upper regions of the polypoid lesions. By contrast, at the base of the lesions, where linear and nodular ECL cell hyperplasia was identified by immunohistochemical staining, destruction of fundic glands with lymphocytic infiltration, loss of parietal cells, and pseudopyloric metaplasia was observed. Anti-parietal cell antibody positivity and hypergastrinemia confirmed the diagnosis of AIG with pseudopolyps. FGP-like pseudopolyps can, therefore, be present with nodular ECL cell hyperplasia in AIG.

Multiple Pseudopolyps Presenting as Reddish Nodules Are a Characteristic Endoscopic Finding in Patients with Early-stage Autoimmune Gastritis.

We herein report two cases of autoimmune gastritis without complete atrophy of the corpus. Both were positive for anti-parietal cell antibodies. Endoscopic examinations indicated that atrophic changes were predominant in the lesser curvature of the corpus in both cases. In one, the greater curvature was covered with pseudopolyp-like nodules, whereas the greater curvature of the other showed multiple similar nodules and mildly atrophic mucosa. Histopathological examinations of these nodules showed focal and patchy atrophy and preserved fundic glands with parietal cell pseudohypertrophy. Follow-up endoscopy and a repeated biopsy demonstrated the development of gastric atrophy on the greater curvature in both cases.

A Rare Combination of Gastric Mucosa-associated Lymphoid Tissue Lymphoma, Autoimmune Gastritis, Thyroiditis, Hemolysis, and Systemic Lupus Erythematosus.

We herein report a case with the rare combination of mucosa-associated lymphoid tissue lymphoma (MALT lymphoma) of the stomach, autoimmune gastritis (AIG), autoimmune thyroiditis, autoimmune hemolytic anemia (AIHA), and systemic lupus erythematosus. A 68-year-old woman was diagnosed with gastric MALT lymphoma associated with Helicobacter pylori (H. pylori) infection and AIG. Complete remission of the MALT lymphoma was achieved by H. pylori eradication and radiotherapy. Three years after the diagnosis of MALT lymphoma, the patient developed AIHA and anti-nuclear and anti-Smith autoantibody-positive lupus serositis, which were successfully managed with prednisolone administration.