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BACKGROUND/AIM: The long-term use of proton pump inhibitors (PPIs) has been reported to be strongly associated with the development of fundic gland polyps (FGPs). Conversely, a few cases of gastric hyperplastic polyps (GHPs) associated with PPI use have been reported. We experienced a case of PPI-associated multiple GHPs with uncontrollable bleeding. CASE REPORT: A 64 year old man with a history of rheumatoid arthritis presented to the hospital with complaints of vertigo and black stools. Blood tests revealed anemia and hypoproteinemia. Esophagogastroduodenoscopy (EGD) showed blood and black residue accumulated in the stomach. The source of the bleeding was multiple hyperplastic polyps. Bleeding could be stopped even with fasting, and total blood transfusions amounted to 28 units of RBCs were required in 18 days. After the cessation of PPI, EGD showed that the polyps had almost disappeared. Pathological diagnosis of resected polyp was hyperplastic polyp, which was characterized by capillary hyperplasia and edema. Gastrin receptors were over-expressed in the foveolar epithelium and not in the capillaries. Methotrexate (MTX)-induced portal hypertensive gastroenteropathy was revealed during follow-up. We consider that the effect of portal hypertension may have caused the capillary hyperplasia. CONCLUSION: Although PPI-related polyps are usually fundic gland polyps and do not cause life-threatening adverse events, we experienced PPI-related GHPs in which hemostasis was difficult to control.

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A 90-year-old man on maintenance hemodialysis was admitted due to severe symptomatic anemia. Biopsies under esophagogastroduodenoscopy demonstrated that the cause of anemia was intermittent blood oozing from multiple gastric hyperplastic polyps. Even after successful eradication of Helicobacter pylori, he showed hypergastrinemia (480 pg/mL) owing to esomeprazole (proton-pump inhibitor) therapy for the past 4.5 years to treat reflux esophagitis. Seven months after we switched esomeprazole to famotidine (H2-receptor antagonist), those gastric polyps and anemia were remarkably ameliorated with lowered gastrin levels. This case indicates that long-term use of a proton-pump inhibitor triggers chronic hypergastrinemia, leading to gastric hyperplastic polyps and subsequent severe anemia.

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BACKGROUND: Foveolar-type gastric adenoma (FGA) occurs in Helicobacter pylori (Hp)-naïve individuals and morphologically mimics Hp-naïve gastric hyperplastic polyp (HpN-GHP). FGA is often difficult to distinguish from HpN-GHP even by biopsy, due to its low-grade histologic atypia. We conducted a retrospective study to create an endoscopic diagnostic index. METHODS: We analyzed 51 FGAs in 41 patients and 36 HpN-GHPs in 24 patients. All lesions were photographed by white-light endoscopy (WLE) and narrow-band imaging with magnification endoscopy (NBIME). Three experts and three non-experts reviewed the WLE and WLE+NBIME images to assess six items for lesion diagnosis. We analyzed correlations between the diagnostic items and histologic features and compared the diagnostic accuracy between modalities. We created a composite diagnostic index and calculated its accuracy and consistency. RESULTS: FGAs more frequently showed the following features vs. HpN-GHPs: bright-red color (94.1% vs. 44.4%), peripheral hyperplasia (58.8% vs. 8.3%), papillary/gyrus-like microstructure (96.1% vs. 33.3%), visible capillaries (70.6% vs. 38.9%), and demarcation line (98.0% vs. 41.7%) (P < 0.05). White-zone thickening was seen only in HpN-GHPs (52.8%). Diagnostic accuracy (mean, WLE vs. WLE+NBIME) was 90.8 ± 1.1% vs. 93.5 ± 2.4% (P = 0.15) for experts and 88.5 ± 3.0% vs. 86.6 ± 3.5% (P = 0.51) for non-experts. When satisfying the four criteria (bright-red color, papillary/gyrus-like microstructure, demarcation line, and absent white-zone thickening), sensitivity and specificity for FGA were 90.2% and 94.4%, respectively, with a kappa value of ≥ 0.6 for interobserver diagnostic agreement. CONCLUSIONS: Composite diagnostic index contributes to the reproducible, accurate, preoperative differential diagnosis of FGA and HpN-GHP.

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Gastric hyperplastic polyps (GHP) are frequently found to be benign polyps and have been considered to have a low carcinogenic potential. The characteristics of the hyperplastic polyp-associated gastric cancer (HPAGC) remain unclear. Therefore, we analyzed samples from 102 GHP patients and identified 20 low-grade atypical GHPs (19.6%), 7 high-grade atypical GHPs (6.9%), and 5 intramucosal cancer samples (4.9%). GHP atypia was more common in the elderly and increased with increasing polyp size. In particular, polyps larger than 1 cm were associated with a higher grade and cancer. Furthermore, mucus production decreased with increasing atypia. Although no correlation was found between atypia and Helicobacter pylori infection or intestinal metaplasia, enhanced proliferative ability (Ki-67) did correlate with atypia, as did nuclear 8-hydroxy-2'-deoxyguanosine levels. Interestingly, 4-hydroxynonenal levels in granulation tissue and the area ratio of granulation tissue within polyps also correlated with GHP atypia. In five cases of HPAGC, three cases exhibited caudal type homeobox transcription factor (CDX2)-positive cells and a mixed mucin phenotype, which is considered to be related to H. pylori infection. By contrast, two cases were CDX2 negative, with a gastric mucin phenotype, and H. pylori infection was not observed in the tumor or the surrounding mucosa. In these cases, a v-raf murine sarcoma viral oncogene homolog B1 (BRAF) mutation (V600E) was detected. All cancer samples showed high stemness and p53 protein accumulation, but no KRAS mutations. The molecular and phenotypic characteristics of the cases characterized by BRAF mutations may represent a novel subtype of HPAGC, reflecting a conserved pathway to oncogenesis that does not involve H. pylori infection. These findings are worthy of further investigation in a large-scale study with a substantial cohort of HPAGC patients to establish their clinical significance.

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Here, we report on a rare case of gastric hyperplastic polyps which disappeared after the discontinuation of proton pump inhibitor (PPI). The patient was an 83-year-old woman with liver cirrhosis and portal hypertension, along with gastroesophageal reflux disease treated by PPI. An initial upper gastrointestinal endoscopy showed unique polypoid lesions in the greater curvature of the stomach. Biopsy specimens of the lesions were diagnosed as hyperplastic polyps and she was followed. One year later, a second endoscopy showed that the lesions had increased in number and size, and an endoscopic mucosal resection (EMR) was performed for the main polyps. The resected specimens indicated a proliferation of foveolar epithelium cells with an increase of capillary ectasia and parietal cell hyperplasia, which was thought to be induced by hypergastrinemia from the PPI. Three months after the EMR, she was admitted because of bleeding from the remaining polyps along with an increase in new polyps. After conservative treatment, PPI was stopped and rebamipide was used. One year and 6 months later, an endoscopy showed the complete disappearance of all gastric polyps.

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INTRODUCTION: Gastric hyperplastic polyps are common stomach lesion and these polyps are generally benign. However, they can undergo malignant transformation. Most reported cases of malignant transformation of gastric hyperplastic polyps have been to well or moderately differentiated adenocarcinoma, and those transformed into poorly differentiated adenocarcinoma are extremely rare. No case has been reported that has changed to diffuse type adenocarcinoma with lymphatic invasion. PRESENTATION OF CASE: A 48-year-old woman presented with worsening anemia. A polyp was seen in the gastric cardia seven years prior to presentation. Helicobacter pylori infection was also found at that time. She underwent upper gastrointestinal endoscopy and biopsy of the polyp revealed signet ring cell carcinoma. Total gastrectomy was performed due to concern about possible invasion into the submucosal layer and there was no evidence of distant metastases. Histologic examination revealed both poorly differentiated adenocarcinoma and signet ring cell carcinoma surrounded by hyperplastic epithelium at the head of the polyp. Lymphatic invasion was also found, and malignant cells were limited to the mucosa. DISCUSSION: Gastric hyperplastic polyps are commonly associated with chronic gastritis which is related to Helicobacter pylori infections. Gastric hyperplastic polyps are generally benign and rarely undergo malignant transformation to adenocarcinoma with differentiated histology. The gastric hyperplastic polyp in this patient transformed to poorly differentiated adenocarcinoma with lymphatic invasion. CONCLUSION: Even small polyps may become poorly differentiated adenocarcinoma with invasion, so close follow-up or endoscopic resection are recommended as well as eradication of Helico Pylori infection when appropriate.

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Gastric cancers that fulfill the Japanese criteria for curative endoscopic resection show a low risk of lymph node (LN) metastasis. Here, we report a case of LN metastasis from early gastric cancer that fulfilled the curative criteria. A 74-year-old Japanese woman was referred to our hospital for treatment of early gastric cancer identified at the site of a hyperplastic polyp that had been diagnosed 10 years prior to presentation. Contrast-enhanced computed tomography did not show any lymphadenopathy and laparoscopy-assisted distal gastrectomy was performed. Histopathological examination revealed a predominantly moderately differentiated adenocarcinoma that measured 15 mm in size and was confined to the mucosa. However, a single metastatic regional LN was observed. A few cancer cells showed positive staining for alpha-fetoprotein. It should be noted that early gastric cancer can be accompanied by LN metastasis even if it fulfills the criteria for curative endoscopic resection.

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Gastric cancers that fulfill the Japanese criteria for curative endoscopic resection show a low risk of lymph node (LN) metastasis. Here, we report a case of LN metastasis from early gastric cancer that fulfilled the curative criteria. A 74-year-old Japanese woman was referred to our hospital for treatment of early gastric cancer identified at the site of a hyperplastic polyp that had been diagnosed 10 years prior to presentation. Contrast-enhanced computed tomography did not show any lymphadenopathy and laparoscopy-assisted distal gastrectomy was performed. Histopathological examination revealed a predominantly moderately differentiated adenocarcinoma that measured 15 mm in size and was confined to the mucosa. However, a single metastatic regional LN was observed. A few cancer cells showed positive staining for alpha-fetoprotein. It should be noted that early gastric cancer can be accompanied by LN metastasis even if it fulfills the criteria for curative endoscopic resection.

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Objective To analyze the serum gastric function and Helicobacter pylori ( HP ) infection in patients with gastric hyperplastic polyps and gastric fundic gland polyps.Methods From December 2017 to December 2018, 135 patients with gastric polyps and pathologically confirmed gastric hyperplastic polyps and gastric fundic gland polyps were enrolled in the hospital of Xuzhou Medical University.Among them, 68 patients with hyperplastic polyps, 67 cases of the gastric fundic gland polyps.Serum Hp antibodies ( UreA, UreB, VacA, CagA antibodies ) were qualitatively detected by immunoblotting.Eighty patients with chronic superficial gastritis were selected as the control group.Three groups of serum pepsinogen?I ( PG?I),pepsinogen?Ⅱ( PG?Ⅱ),gastrin were detected by enzyme?linked immunosorbent assay (ELISA).Gastrin?17( G?17) and calculate PGⅠ and PGⅡ ratio( PGR).Results The levels of serum PGⅡ(13.13(8.15,20.30) μg ／L) and G17 (8.44(3.72,27.17) pmol／L) in the gastric hyperplastic polyp group were higher than those in the control group (9.16(5.56,15.14) μg／L and 1.83(0.87,5.95) pmol／L) ( P＜0.05),and the PGR level was lower than the control group ( P＜0.05);serum PGI ( 120.12 ( 86.72,174.70) μg／L), PGII ( 11.92 ( 7.27,22.26) μg／L),G17 ( 5.68 ( 1.79, 14.65) pmol／L) in the gastric fundic gland polyp group was higher than the control group (( 101.32 (79.17,131.33) μg ／L,9.16 ( 5.56,15.14) μg ／L,1.83 ( 0.87,5.95) pmol／L) ( P 均＜0.05)) ( P＜0.05); serum G17 (8.44(3.72,27.17) pmol／L) level in gastric hyperplastic polyp group was higher than gastric fundus polyp group (5.68(1.79,14.65) pmol／L) ( P＜0.05); Hp infection rate in gastric hyperplastic polyp group61.76%(42／68)was higher than that in the gastric fundic gland polyp group40.30%(27／67) (P＜0.05),and type I Hp was the main one (P＜0.05).The serum PGⅡ and G17 levels in the gastric hyperplastic polyp group were higher than those of Hp negative ( all P＜0.05).There were no significant differences in serum PGI, PGⅡ, G17, and PGR levels between the HP?positive and negative?positive patients in the gastric fundus polyp group.The serum PGI and PGR levels in the hypertrophic polyp group were higher than those in the HPⅡ type ( all P＜0.05).There was no significant difference in the levels of serum PGⅠ,PGⅡ,G17,and PGR between the gastric fundic gland polyps group and the type Ⅱ.Conclusion Serum PG and G17 levels in patients with gastric hypertrophic polyps and gastric fundic gland polyps are higher than those in patients with chronic superficial gastritis.Patients with gastric hyperplastic polyps have higher HP infection rate and abnormal gastric function than gastric fundic gland polyps.

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We experienced two cases of adenocarcinoma coexisting with a hyperplastic polyp arising from Helicobacter pylori-negative normal gastric mucosa. The first case was of a 59-year-old man. Esophagogastroduodenoscopy revealed a protruding lesion measuring 4 mm in diameter on the greater curvature of the middle gastric body. The second case was of a 47-year-old man. Esophagogastroduodenoscopy showed a protruding lesion measuring 5 mm located at the greater curvature of the upper gastric body. The absence of atrophic changes in the entire gastric mucosa was confirmed endoscopically in both cases. Multiple H. pylori tests were all negative. Endoscopically, these protruding lesions appeared as reddish, semipedunculated polyps. Hyperplastic polyps were suspected based on white light endoscopic findings. Magnified endoscopy with narrow band imaging could not predict the coexistence of cancer. However, histopathological examination of the resected specimen revealed focal cancer at the surface of the gastric hyperplastic polyps. Considering the possibility that cancer may be coexisting in polyps, when reddish polyps are detected in H. pylori-negative normal gastric mucosa, it is important to perform a biopsy, or a careful follow-up endoscopy.

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Gastric hyperplastic polyps are usually solitary, their development is supposed to be associated with excessive proliferation of foveolar cells. It is essential to differentiate hyperplastic polyps from other sporadic polyps (adenomatous and fundic gland polyps) and lesions, included in familial polyposis syndromes. The frequency of adenocarcinoma in large gastric hyperplastic polyps (more than 1-2 cm in size) is about 2,1%. This article includes case report of gastric adenocarcinoma arised in large hyperplastic polyp in a 56-year-old patient. On histological examination a well-differentiated adenocarcinoma without invasion in the peduncle was identified. Immunohistochemically cells of adenocarcinoma showed elevated expression of claudin-3, CDX2, p53 and Ki67 compared to hyperplastic glands and dysplastic areas of the polyp. Also focal expression of MUC2 was revealed in adenocarcinoma. Expression of MUC5AC, CD44 and cyclin D1 was less prominent in cancer areas compared to hyperplastic and dysplastic glands. Levels of expression of claudin-1, claudin-4 and ß-catenin were equal in adenocarcinoma and hyperplastic structures. Control endoscopic examination with following morphologic examination was performed three months after surgical operation. No signs of tumor growth were identified.

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A 56-year-old man with gastroesophageal reflux disease (GERD) was referred to our hospital. Esophagogastroduodenoscopy (EGD) revealed no evidence of any polypoid lesions in the stomach, and the patient had no history of Helicobacter pylori infection. He received omeprazole (20 mg) once daily for the GERD. EGD was performed at 1 year after the start of omeprazole administration, and this time, gastric hyperplastic polyps (GHPs) were detected. The GHPs increased in size as the omeprazole treatment continued, but they markedly decreased in size following omeprazole discontinuation. Thus, the administration of proton pump inhibitors may be a risk factor for the development of GHP independent of H. pylori infection.

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Gastric polyps become a major clinical problem because of high prevalence and tendency to malignant transformation of some of them. The development of gastric hyperplastic polyps results from excessive proliferation of foveolar cells accompanied by their increased exfoliation, and they are macroscopically indistinguishable from other polyps with lower or higher malignant potential. Panendoscopy allows detection and differentiation of gastric polyps, usually after obtaining histopathological biopsy specimens. Unremoved gastric hyperplastic polyps may enlarge and sometimes spontaneously undergo a sequential progression to cancer. For this reason, gastric hyperplastic polyps larger than 5 mm in size should be removed in one piece. After excision of polyps with atypical focal lesion, endoscopic surveillance is suggested depending on histopathological diagnosis and possibility of confirming the completeness of endoscopic resection. Because of the risk of cancer development also in gastric mucosa outside the polyp, neighboring fragments of gastric mucosa should undergo microscopic investigations. This procedure allows for identification of patients who can benefit most from oncological endoscopic surveillance. If Helicobacter pylori (H. pylori) infection of the gastric mucosa is confirmed, treatment strategies should include eradication of bacteria, which may prevent progression of intestinal metaplasia. The efficacy of H. pylori eradication should be checked 3-6 mo later.

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Hyperplastic polyps of the stomach are routinely encountered during upper endoscopy and often arise in the setting of abnormal surrounding mucosa, particularly Helicobacter pylori, autoimmune gastritis, and reactive gastropathy. Not infrequently gastroenterologists fail to biopsy the surrounding mucosa, thus determining the underlying etiology of the gastric hyperplastic polyp can be difficult. Recently, the Rodger C. Haggitt Gastrointestinal Pathology Society published guidelines on the use of special stains. The society guidelines indicate that H pylori are not usually present in hyperplastic polyps and special stains in this setting may have limited utility. We analyzed the histologic features of 32 gastric hyperplastic polyps in which the nonpolypoid mucosa demonstrated H pylori gastritis. A consecutive series of 50 hyperplastic polyps in which no surrounding mucosa was sampled was also analyzed. When H pylori are identified in biopsies of the nonpolypoid mucosa, it is also commonly present within the polyp tissue (22/32, 69%). The majority of H pylori organisms were identified on routine hematoxylin and eosin stain (16/22, 72%). In contrast, H pylori were only seen in 2/50 consecutive hyperplastic polyps in which the surrounding mucosa was not sampled. Compared with the hyperplastic polyps that lack the organisms, H pylori associated hyperplastic polyps more commonly had dense lymphoplasmacytic inflammation (P = .0001) and neutrophils within gastric epithelium (P = .036). Polyp location, number, size, and presence of intestinal metaplasia was not associated with H pylori These results provide empirical data to guide evaluation of hyperplastic polyps for H pylori.

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This paper reports a rare case of early adenocarcinoma within the gastric hyperplastic polyp, that was completely resected during an endoscopic procedure, and discusses current recommendations in such cases. Endoscopic resection of polyps with focal dysplasia or cancer is commonly indicated, as long as the procedure can be performed safely. After complete excision of a polyp with atypical focal lesion, endoscopic surveillance is suggested. The frequency of surveillance endoscopy should depend on the precise histopathological diagnosis and possibility of confirming the completeness of the endoscopic resection. If the completeness of the procedure is confirmed both macro- and microscopically, gastric resection does not have to be performed. A follow-up esophago-gastroduodenoscopy should be performed at 1 year and then at 3 years.

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UNLABELLED: Gastric hyperplastic polyps (GHP) are the most common type of polyps occurring in the stomach. Although GHP are broadly interpreted as benign lesions, they may progress to dysplasia and adenocarcinoma. OBJECTIVE: In this study, we aimed to identify genomic mutations that characterize and may drive malignant transformation in GHP by using next-generation sequencing. Eight GHP (2 with dysplasia, 1 indefinite for dysplasia and 5 without dysplasia) were studied. Only large polyps (>1cm) with gastric differentiation were included in this study, while adenomatous polyps (intestinal-type) were excluded. Immunohistochemistry for MUC2, MUC5A, MUC6, CDX2, p53, and Ki67 was performed. DNA was extracted from formalin-fixed paraffin-embedded sections and sequenced for the detection of somatic mutations. Multiplex sequencing was done with the TrueSeq Amplicon Cancer Panel in the MiSeq platform. Variant annotation and visualization were performed using NextGENe (SoftGenetics) software. No pathogenic mutations were detected in GHP without dysplasia. TP53 gene mutations were the most common alteration in dysplastic GHP (2 of 2 dysplastic cases). PIK3CA mutation was identified in a GHP with pyloric-type dysplasia, whereas foveolar-type dysplasia carried TP53 mutations. In conclusion, TP53 gene mutations are a common alteration in the early dysplastic stage during malignant transformation of GHP. GHP with dysplasia may show dual differentiation. In our study, pyloric-type dysplasia was associated with a PIK3CA alteration whereas foveolar dysplasia carried TP53 mutations. The identification of carcinoma-associated mutations in large GHP provides additional evidence of their neoplastic potential and emphasizes the need for their complete resection and follow-up.

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In spite of the evidence that the malignant transformation of gastric hyperplastic polyps (HPs) is a rare event, it must always be taken into account during diagnosis. The aim of the current study was to clarify the mechanism of the malignant transformation of gastric hyperplasia polyps, with focus on phenotypic expression, cell proliferation and p53 overexpression. Immunohistochemistry for mucin phenotypic markers, including MUC1, MUC2, MUC5AC, MUC6, tight junction factors (claudin-3, -4 and -18), an intestinal phenotypic marker [caudal type homeobox 2 (Cdx2)], Ki-67 proliferative index and p53 overexpression, was performed on archival specimens of gastric polyps excised from six patients. Histologically, the intermingled components of several lesions were present in these polyps. Furthermore, the cancer components were predominantly differentiated adenocarcinoma. Immunohistochemically, all hyperplastic components expressed MUC5AC, but did not exhibit positivity for MUC2. Additionally, the majority of hyperplastic components were immunonegative for claudin-3, while claudin-3 positivity was observed in the majority of areas of dysplasia and carcinoma. Expression of claudin-4 was also observed in the majority of cases and claudin-18 was preserved in the hyperplastic, dysplastic and adenocarcinomatous lesions of all cases. Nuclear accumulation of Cdx2 was detected in almost all the samples with dysplasia and carcinoma, while nuclear p53 was detected in 24-80% of the dysplastic areas and >85% of the cancer components. The Ki-67 labeling index appeared to correlate with neoplastic progression. The observations provided evidence that the mechanism underlying malignant transformation of gastric HPs may occur by multistep carcinogenesis, such as the hyperplasia-adenoma (dysplasia)-adenocarcinoma sequence, and these neoplastic cells may acquire various phenotypes during this process.

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The endoscopic findings of gastric hyperplastic polyps (HPs) with dysplasia have not been well-defined, and the clinical significance of these lesions, including their malignant potential, is unclear. In this report, we describe a case of a white opaque substance (WOS)-positive gastric HP with dysplasia. A 76-year-old woman was referred to our hospital for endoscopic resection of a gastric HP. Upper endoscopy revealed a 25-mm whitish and reddish polypoid lesion on the greater curvature in the lower third of the stomach. The whitish part was diagnosed as a WOS using conventional and magnifying endoscopy with narrow band imaging. An examination of the biopsy specimen indicated that the lesion was a typical gastric HP. However, because of its color and the presence of a WOS, we suspected that this lesion was an atypical gastric HP. Therefore, we performed a polypectomy. Histopathologically, diffuse low- to high-grade dysplasia was found on the surface of the polyp. We performed immunohistochemical staining using a monoclonal antibody specific for adipophilin as a marker of lipid droplets (LDs). LDs were detected in approximately all of the neoplastic cells, especially in the surface epithelium of the intervening apical parts and were located in the subnuclear cytoplasm of the neoplastic cells. According to endoscopic and histopathological findings, the WOS-positive epithelium indicated dysplasia of the gastrointestinal phenotype, which could absorb lipids. The presence of a WOS in a gastric HP may be considered an endoscopic finding that is predictive of the neoplastic transformation of a gastric HP. We suggest that a WOS-positive gastric HP should be resected endoscopically to investigate its neoplastic transformation.

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Gastric hyperplastic polyps are generally considered benign lesions, although rare cases of adenocarcinoma have been reported. Although, the underlying mechanism of carcinogenesis in gastric hyperplastic polyps is still uncertain, most malignant polyps are seen to originate from dysplastic epithelium rather than from hyperplastic epithelium. Herein, we report the case of a woman diagnosed with adenocarcinoma that originated from a hyperplastic gastric polyp that was successfully removed by endoscopic submucosal dissection. In this case, we observed adenomatous changes around the cancerous component.