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The fifth edition of the World Health Organization (WHO) classification of digestive system tumours was published in 2019. The classification of invasive carcinoma is basically the same as in the fourth edition, but the description of each histological type has been updated, and some rare subtypes such as micropapillary carcinoma, gastric adenocarcinoma of the fundic gland type and undifferentiated carcinoma have been added and explained. Although this classification did not provide specific numerical criteria for the diagnosis of signet-ring cell carcinoma in poorly cohesive carcinoma, an additional study defined signet-ring cell carcinoma as having more than 90% signet-ring cells. The molecular classification of gastric cancer (Epstein-Barr virus-positive type, microsatellite instability type, genomically stable type, chromosomally unstable type) was additionally introduced. Many pages in the present classification have been devoted to precancerous lesions, and this article focuses on foveolar-type adenoma/dysplasia.Die fünfte Ausgabe der Klassifikation von Tumoren des Verdauungssystems durch die Weltgesundheitsorganisation (WHO) wurde 2019 veröffentlicht. Dabei ist die Klassifikation invasiver Karzinome prinzipiell gleich wie in der vierten Auflage, es erfolgte aber bei der Beschreibung der histologischen Typen eine Aktualisierung und die Ergänzung einiger seltener Subtypen wie das mikropapillärer Karzinom, das Magenadenokarzinom vom Fundusdrüsentyp und das undifferenzierte Karzinom. Obwohl diese Klassifikation keine spezifischen prozentualen Kriterien für die Diagnose des Siegelringzellkarzinoms bei nichtkohäsivem Karzinom lieferte, wurde in einer zusätzlichen Studie das Siegelringzellkarzinom als mehr als 90 % Siegelringzellen enthaltend definiert. Die molekulare Klassifikation von Magenkarzinomen (Epstein-Barr-Virus-positiver Typ – Mikrosatelliteninstabilitätstyp – genomisch stabiler Typ – chromosomal instabiler Typ) wurde zusätzlich eingeführt. In der WHO-Klassifikation wurde den Präkanzerosen viel Raum gewidmet. Der vorliegende Artikel konzentriert sich auf das Adenom/die Dysplasie vom foveolären Typ.

Gastric adenocarcinoma of fundic-gland type (GA-FG) was first proposed as a new entity of gastric adenocarcinoma in 2010. Subsequently, gastric adenocarcinoma of fundic-gland mucosa type (GA-FGM) was reported as a subtype of gastric adenocarcinoma. This study aimed to investigate the endoscopic findings of GA-FGM and to evaluate the differences between GA-FGM and GA-FG. This was a single-center retrospective study. Participants were selected from patients with gastric cancer treated at Fukuoka University Chikushi Hospital, between September 2007 and May 2020. Patients histologically diagnosed with GA-FGM or GA-FG were enrolled, and endoscopic findings were analyzed in detail. A total of 12 GA-FGM lesions (12 patients) and 14 GA-FG lesions (13 patients) were analyzed. The two lesion types showed similar features: most lesions were of elevated type, located in the upper stomach, and developed in the stomach without Helicobacter pylori infection. On conventional endoscopy using the dye-spraying method, well-demarcated fine granular areas were observed in 7 GA-FGM lesions (58%) but not in any GA-FG lesions, with a significant difference between the two groups (P = 0.001). Magnifying endoscopy with narrow-band imaging (NBI) showed that 11 GA-FGM lesions (92%) met the diagnostic criteria for cancer according to the vessel plus surface classification system, whereas none of the GA-FG lesions met the same criteria (0%, 0/14) (P = 0.001). Our results suggest that magnifying endoscopy with NBI is a potentially useful method for the diagnosis of GA-FGM.

The aim of this study was to reveal the histological features of oxyntic gland adenomas and gastric adenocarcinoma of the fundic-gland type (GA-FG). We retrospectively examined the histological features of 126 lesions of oxyntic gland adenoma and/or GA-FG in 116 patients. The prevalence of oxyntic gland adenomas and GA-FG was approximately equal. The majority of the lesions were resected by endoscopic mucosal resection using a diathermic snare (EMR, n = 42) or endoscopic submucosal dissection (ESD, n = 72). Histologically, there were no lesions with invasion at the level of the muscularis propria or deeper, and lymphovascular invasion was present in 1.6%. Of the ESD and EMR specimens, there were no lesions that were positive for vertical margins. Among the eight GA-FG patients with deep (≥ 500 μm) submucosal invasion, six were treated with endoscopic resection alone, and no recurrence was documented. No patients died of the disease during the median follow-up period of 14.5 months. In conclusion, all lesions were confined to the mucosa or submucosa and were negative for vertical margins. Lymphovascular invasion was present in only 1.6% of the patients. Thus, we believe that endoscopic resection is a suitable initial treatment method for oxyntic gland adenoma and GA-FG.

Gastric adenocarcinoma of fundic gland type is known to originate from the gastric mucosa of the fundic gland region without intestinal metaplasia. It is difficult to detect during endoscopy and diagnose histopathologically. The development of immunohistochemistry has enabled the diagnosis of gastric adenocarcinoma of fundic gland type by gastric phenotype. A 34-year-old man visited us for treatment of a 5 cm-sized low-grade dysplasia in the gastric fundus which was incidentally found during a health check-up endoscopy. Endoscopic submucosal dissection was performed successfully, and the final histopathology showed gastric adenocarcinoma of fundic gland type. Herein, we report a rare case of gastric adenocarcinoma of fundic gland type and its endoscopic and histopathologic findings.

Gastric adenocarcinoma of the fundic gland mucosa type (GA-FGM) was proposed as a new variant of gastric adenocarcinoma of the fundic gland type (GA-FG). However, at present, the influence of Helicobacter pylori and the speed of progression and degree of malignancy in GA-FGM remain unclear. Herein, we report the first case of intramucosal GA-FGM that was endoscopically observed before and after H. pylori eradication over 15 years. The lesion showed the same tumor size with no submucosal invasion and a low MIB-1 labeling index 15 years after its detection using endoscopy. The endoscopic morphology changed from 0-IIa before H. pylori eradication to 0-IIa+IIc and then 0-I after H. pylori eradication. These findings suggest that the unaltered tumor size reflects low-grade malignancy and slow growth, and that the endoscopic morphology is influenced by H. pylori eradication.

Significant atrophic gastritis in the fundic gland region is a well-known endoscopic finding observed in autoimmune gastritis (AIG). The endoscopic features of early AIG have not been reported. Iron deficiency, vitamin B12 deficiency, anemia, or neurological symptoms may not be observed in the early stages of AIG, and it may thus be difficult to diagnose early AIG based on clinical findings. We treated a 50-year-old Japanese female whose condition was suspected to be early AIG. The endoscopic findings showed normal gastric pyloric gland mucosa, and diffuse reddened and edematous gastric fundic gland mucosa. Pathologically, local infiltration of lymphocytes and decrease of parietal cells was present in a deep part of the gastric fundic gland mucosa. Blood tests showed that the titer of parietal cell antibody (PCA) was 1:320 and the gastrin level was 820 pg/ml. We determined that the patient had AIG because she also had Hashimoto’s disease, the PCA titer was high, the serum gastrin level was slightly increased, and inflammation was observed only in the gastric body on the endoscopic images. To the best of our knowledge, this is the first case report of endoscopic findings that suggest early AIG, before atrophic changes were observed.

Gastric polyps can be truly neoplastic but most polypoid dysplastic lesions are manifestations of gastritis-associated dysplasia that happens to form a polypoid lesion rather than true adenomas arising in normal background mucosa as is typically observed in the colon. However, the term adenoma has been used over the years to describe polyps with intestinal and pyloric gland differentiation, and this terminology is entrenched in our lexicon. In this review, we briefly discuss the issue of terminology, gastritis, and the following polyp types: intestinal type adenoma, pyloric gland adenoma, foveolar adenoma, and oxyntic gland adenoma (also termed oxyntic gland neoplasm and adenocarcinoma of fundic gland type.

Introduction: Since inflammatory cells, such as lymphocytes and plasma cells, normally inhabit the stomach, the border between normal and mild inflammation is difficult to visually determine using the updated Sydney system scale of gastritis. Additionally, eosinophils in the gastric mucosa must be counted to diagnose eosinophilic gastritis. We aimed to determine the normal number of inflammatory cells in patients with endoscopically normal mucosa and without Helicobacter pylori infections. Methods: We assessed patients aged 20–79 years, who had undergone upper gastrointestinal endoscopy at Kawasaki Medical School Hospital between January 2010 and December 2014. Inflammatory cells were counted in 1,000 μm2 fields of pyloric and fundic gland mucosal biopsy specimens. We finally included 325 (male, n = 141; female, n = 184; average age = 49.3 years) patients without inflammation who had H. pylori-negative endoscopic results and negative histological findings interpreted based on the updated Sydney System and the Kyoto classification of gastritis. Results: The average numbers of nucleated cells were 83.3 ± 14.2 and 65.4 ± 12.6/mm2 in the pyloric and fundic gland mucosae, respectively. Inflammatory cells were significantly more abundant in the pyloric mucosa than in the fundic gland mucosa (p < 0.05). Age and sex distribution did not significantly differ. Eosinophils were absent or scanty in the gastric mucosae of both glands in all patients. Conclusion: We determined the absolute values of inflammatory cells, including eosinophils, in normal mucosae of pyloric and fundic glands. These findings could be important in defining gastric mucosal inflammation, including eosinophilic gastritis diagnosis.

Background: Gastric adenocarcinoma of foveolar type (GA-FV) is a raspberry-shaped gastric cancer (RSGC) and garners much attention as H. pylori (Hp)-uninfected gastric cancer. However, the classification and clinicopathological and endoscopic features of RSGCs in Hp-uninfected patients are poorly defined. We designed a new histopathological classification of RSGC and compared them via endoscopic and clinicopathological characteristics. Summary: From 996 patients with early gastric cancers resected by endoscopy in our hospital, we studied 24 RSGC lesions from 21 (2.4%) Hp-uninfected patients. RSGCs were classified into 3 histological types as follows: GA-FV (n = 19), gastric adenocarcinoma of fundic gland type (GA-FG, n = 2), and gastric adenocarcinoma of fundic gland mucosa type (GA-FGM, n = 3). Most of the lesions were found at the greater curvature of the upper or middle third of the stomach. GA-FV lesions were homogeneously reddish and frequently accompanied with a whitish area around the tumor and an irregular microvascular (MV) pattern; these features were confirmed histopathologically by the presence of homogeneous neoplastic foveolar epithelium with foveolar hyperplasia around the tumors. GA-FG lesions might be heterogeneously reddish with a submucosal tumor shape and regular MV pattern; these were confirmed by the presence of covered or mixed nonneoplastic epithelium on deeper regions of tumors. GA-FGM lesions might be homogeneously reddish and occasionally had a submucosal tumor shape and irregular MV pattern; these were confirmed by the presence of homogeneous neoplastic foveolar epithelium on deeper regions of the tumors. Key Messages: RSGCs in Hp-uninfected patients are classified into 3 histopathological types. For accurate diagnosis of RSGCs, it may be necessary to fully understand endoscopic features of these lesions based on these histological characteristics and to take a precise biopsy.

Introduction: 5-fluorouracil is a potent antimetabolite chemotherapeutic medication used for treatment of various malignancies . Using this agent result in toxic effect mainly in the lining of digestive tract. To ameliorate 5 FU toxic effect ginger was implicated in this study.Aim of the Work: To evaluate the microscopic effect of 5-fluorouracil on gastric fundus mucosa in rat models . and to study the possible beneficial role of ginger in the ameliorations of these changes. Material and Methods: Forty-eight adult male albino rates were divided into four groups: group I (control), group II received ginger orally in a dose of 200 mg/kg/day , group III received 5-fluorouracil (15 mg/kg) intraperitoneally and group IV received 5 FU and Ginger as previous doses for 5 days. The fundic part of stomach was excised and subjected to light and electron microscopic studies.Results: In 5 FU treated group, the fundic gastric mucosa showed multiple areas of tissue loss , congested dilated blood vessels and extravasated red blood cells and mononuclear infiltration were seen between fundic gland cells. Parietal cells showed ballooned appearance, vacuolated cytoplasm, and pykontic nuclei. PAS/ Alcian blue stained sections showed marked reduction in both alcian blue and PAS positive reaction. There was strong positive cytoplasmic reaction in the apical and middle parts of the fundic glands for caspase 3 while large number of parietal cells were stained positive for Cox 2. These histological findings were improved after ginger administration. Histomorphometric study revealed significant weight reduction, increased mucosal ulcer depth, decreased mucosal thickness and increased number of parietal cells in 5 FU treated group when compared to control group. Conclusion: 5FU causes gastric damage in rat model. Ginger supplementation could be used to alleviate the damaging pathological effect on gastric fundus.

Gastric neoplasms exhibiting oxyntic gland differentiation typically are composed of cells with mild cytonuclear atypia differentiating to chief cells and to a lesser extent, parietal cells. Such tumors with atypical features have been reported also and terminology for this entity remains a matter of considerable debate. We analyzed and classified 26 tumors as oxyntic gland neoplasms within mucosa (group A, eight tumors) and with submucosal invasion. The latter was divided further into those with typical histologic features (group B, 14 tumors) and atypical features, including high-grade nuclear or architectural abnormality and presence of atypical cellular differentiation (group C, four tumors). Groups A and B tumors shared similar histologic features displaying either a chief cell predominant pattern characterized by monotonous chief cell proliferation, or a well-differentiated mixed cell pattern showing admixture of chief and parietal cells resembling fundic gland. In addition, group C tumors displayed atypical cellular differentiation, including mucous neck cell and foveolar epithelium. Moderate or even marked cytological atypia was noted in group C, whereas it was usually mild in the other groups except for three group B tumors with focal moderate atypia. More than 1000 μm submucosal invasion and lymphovascular invasions were recognized only in group C. Mutation analyses identified KRAS mutation in one group C tumor as well as GNAS mutation in in one group A and group B tumors. Intramucosal tumors appear to behave biologically benign and should be classified as "oxyntic gland adenoma". Those with submucosal invasion also have low malignant potential; however, a subset will have atypical features associated with aggressive histologic features and should be designated as "adenocarcinoma of fundic gland type". Especially, we suggest "adenocarcinoma of fundic gland mucosa type" for tumors with submucosal invasion exhibiting atypical cellular differentiation, because the feature is likely to be a sign of aggressive phenotype.

Background: The characteristics of Helicobacter pylori (HP) infection-negative gastric cancer (HPINGC) have not been well documented because of the rareness. The aim of this study was to classify HPINGC endoscopically and clinicopathologically. Methods: This retrospective study included 1,741 early gastric cancer lesions and evaluated their HP infection status. Expression levels of MUC5AC, MUC6, MUC2, CD10, p53, MIB-1, pepsinogen-I, H+/K+ ATPase, chromogranin A, E-cadherin, and gastrin were evaluated in tumors by immunohistochemistry (IHC). Results: Among the analyzed lesions, 19 (1.1%) were diagnosed as HPINGC and classified into 6 types: undifferentiated (5 lesions), fundic gland (2 lesions), cardiac gland (1 lesion), pyloric gland (3 lesions), foveolar (5 lesions), and mixed (3 lesions) types. Undifferentiated lesions were of pale color, with unclear demarcation and decreased E-cadherin expression. Fundic-type lesions were tan to reddish in color, with submucosal tumor-like protrusions, and positive for pepsinogen-I and H+/K+ ATPase. The cardiac gland type was located in the gastroesophageal junction and was positive for MUC6 and pepsinogen-I. Pyloric gland-type lesions were of the same color as normal mucosa, with mild elevation and unclear demarcation, likely positive for CD10 and chromogranin A. Foveolar epithelial-type lesions were white and elevated, with defined demarcation, and contained MUC5AC-positive cells. Mixed-type lesions, showing various staining patterns in IHC, had both elevated and depressed shape and reddish color. Conclusion: Endoscopic observation and IHC were useful for classifying the characteristics of HPINGC, which may preserve the characteristics of its region of origin.

Introduction and aim: Adequately preserved slides and tissue blocks in pathology archives, when re-reviewed and associated with patient charts, are important tools to further assess prevalence changes and associations of certain pathologies. Our aim was to identify whether proton-pump inhibitor (PPI) use, dose, and duration of use were associated with gastric polyps and their phenotypes in a case-control study. Methods: The slides from patients with a morphologic diagnosis of either hyperplastic polyps or fundic gland polyps were retrieved from the 1980, 1990, 2000, 2010, and 2016 surgical pathology files at a tertiary care hospital in Mexico City and re-evaluated. Cases were paired by age and sex with patients that underwent endoscopy and gastric mucosa biopsy in the same year, with no evidence of polyps. Results: A total of 133 (3.8%) patients with gastric polyps were identified from 3,499 gastric biopsies taken in the abovementioned years and compared with 133 paired controls. Dyspepsia was more prevalent in the controls (p = 0.002) and abdominal pain was more prevalent in the patients with gastric polyps (p = 0.001). PPI use (OR 7.7, 95% confidence interval, 4.4-13.3) and taking more than one PPI medication (OR 4.9, 95% confidence interval, 1.09-22.3) were significantly associated with the presence of gastric polyps. The fundic gland phenotype in the oxyntic mucosa was more frequently associated with PPI use (p

Patient: Male, 78-year-old Final Diagnosis: Fundic gland adenocarcinoma Symptoms: Tumor Medication:— Clinical Procedure: — Specialty: Pathology Objective: Rare coexistence of disease or pathology Background: Gastric adenocarcinoma of the fundic gland type (GAFG) is an extremely rare neoplasm that consists of a mixed proliferation of oxyntic and chief cells. Differential diagnosis of GAFG is difficult in the absence of infiltration. Here, we report a case of GAFG and discuss the clinicopathological features. Case Report: A 78-year-old man was diagnosed with gastritis and reflux esophagitis, status after esophagectomy for carcinoma of the esophagus in 2015. The patient underwent repeated gastric biopsies in 2017 and an atypical epithelium was observed, but no diagnosis was confirmed. There was no evidence of tumor extension in the submucosa. The tumor was resected via endoscopic mucosal resection, and pathological examination was performed. Microscopic findings revealed an oxyntic-type gastric mucosa with atypical dense or dilated glands with abundant pale basophilic cytoplasm and round nuclei with prominent nucleoli. The majority of the tumor cells resembled chief cells, suggesting they were derived from gastric fundic glands. However, the tumor appeared to have no submucosal infiltration or focal stromal desmoplastic reaction. Sections stained positive for MUC6 and pepsinogen-I in chief cells, and H+/K+ ATPase and PDGFRα in parietal cells, but were mostly negative for CDX2, chromogranin A, synaptophysin, and CD10. Sections stained for mib-1 expressed very low proliferative activity, with an average of 10%. Staining for TP53 overexpression was negative. Conclusions: Immunostaining markers are a supportive tool for histological diagnosis of GAFG. However, if there is no infiltration, as in our case, it is difficult to consider it as a malignant tumor. Further elucidation is needed in the future, including an officially accepted diagnostic name.

Cu is a metallic element that widely spread over in the environment, which have raised wide concerns about the potential toxic effects and public health threat. The objective of this study aimed to investigate the impression of copper (Cu)-triggered toxicity on mitochondrial dynamic, oxidative stress, and unfolded protein response (UPRmt) in fundic gland of pigs. Weaned pigs were randomly distributed into three groups, fed with different Cu of 10 mg/kg (control group), 125 mg/kg (group I), and 250 mg/kg (group Ⅱ). The trial persisted for 80 days and the fundic gland tissues were collected for further researches. Moreover, the markers participated to mitochondrial dynamic, UPRmt，and oxidative stress in fundic gland were determined. Results revealed that vacuolar degeneration were observed in the treated groups contrast with control group, and the Cu level was boosted with the increasing intake of Cu. Besides that, the levels of CAT, TRX, H2O2, and G6PDH were reduced in group Ⅰ and group Ⅱ, the mRNA levels of NRF2, HO-1, SOD-1, CAT, SOD-2, GSR, GPX1, GPX4, and TRX in the treated groups were promoted contrast to control group. Furthermore, the protein expression of KEAP1 was dramatically decreased, and the protein expression of NRF2, TRX and HO-1 were markedly enhanced in group Ⅰ and Ⅱ at 80 days. Moreover, the mRNA and protein expression levels of MFN1, MFN2, and OPA1 down-regulated and protein level of DRP1 was increased with the adding levels of Cu. Nevertheless, the UPRmt-related mRNA levels of CLPP, HTRA-2, CHOP, HSP10, and HSP60 were enhanced dramatically in Cu treatment group compared with control group. In general, our current study demonstrated that excessive absorption of Cu in fundic gland were related with stimulating UPRmt, oxidative stress, and the NRF2 interceded antioxidant defense. These results could afford an updated evidence on molecular theory of Cu-invited toxicity.

Background Gastric adenocarcinoma of fundic-gland type (GA-FG) is a rare variant of gastric neoplasia. However, the etiology, classification, and clinicopathological features of gastric epithelial neoplasm of fundic-gland mucosa lineage (GEN-FGML; generic term of GA-FG related neoplasm) are not fully elucidated. We performed a large, multicenter, retrospective study to establish a new classification and clarify the clinicopathological features of GEN-FGML. Methods One hundred GEN-FGML lesions in 94 patients were collected from 35 institutions between 2008 and 2019. We designed a new histopathological classification of GEN-FGML using immunohistochemical analysis and analyzed via clinicopathological, immunohistochemical, and genetic evaluation. Results GEN-FGML was classified into 3 major types; oxyntic gland adenoma (OGA), GA-FG, and gastric adenocarcinoma of fundic-gland mucosa type (GA-FGM). In addition, GA-FGM was classified into 3 subtypes; Type 1 (organized with exposure type), Type 2 (disorganized with exposure type), and Type 3 (disorganized with non-exposure type). OGA and GA-FG demonstrated low-grade epithelial neoplasm, and GA-FGM should be categorized as an aggressive variant of GEN-FGML that demonstrated high-grade epithelial neoplasm (Type 2 > 1, 3). The frequent presence of GNAS mutation was a characteristic genetic feature of GEN-FGML (7/34, 20.6%; OGA 1/3, 33.3%; GA-FG 3/24, 12.5%; GA-FGM 3/7, 42.9%) in mutation analysis using next-generation sequencing. Conclusions We have established a new histopathological classification of GEN-FGML and propose a new lineage of gastric epithelial neoplasm that harbors recurrent GNAS mutation. This classification will be useful to estimate the malignant potential of GEN-FGML and establish an appropriate standard therapeutic approach.

Background In recent years, there have been reports of a new histological type of gastric cancer, termed gastric adenocarcinoma of the fundic gland (GA-FG). This disease entity presents differentiation towards the fundic gland, especially chief cell-predominant differentiation (GA-FG-CCP). GA-FG-CCP easily invades into the submucosa but rarely shows metastasis. The reports mostly describe primarily single lesions. Herein, we report a case with multiple lesions, and summarize the clinicopathologic characteristics of multiple cases. Case summary A 55-year-old woman underwent upper gastrointestinal endoscopy screening. Two whitish lesions on the anterior wall of the gastric corpus and the gastric fundus were detected. The patient had previously received Helicobacter pylori eradication therapy. The mucosa was characterized as grade C-2 atrophic gastritis. We diagnosed the patient with multiple GA-FG (GA-FG-CCP) by hematoxylin and eosin (HE) staining and immunohistochemical staining of the endoscopic biopsy. Upon performing endoscopic submucosal dissection (ESD), one lesion was not found, but the scar from the biopsy was visible; the mucularis mucosa of the biopsy and ESD-resected specimen were intact. The two lesions showed no lymphatic nor venous invasion. The resection performed appeared to be relatively curative. Conclusion Cases of multiple GA-FG-CCP are very rare in clinical practice. Most of its clinicopathologic characteristics are similar to those of a single lesion. Our case provides diagnostic and therapeutic information about GA-FG-CCP with multiple lesions.

BACKGROUND Gastric adenocarcinoma of fundic gland type (GA-FG) has recently been proposed as a novel histological type of gastric cancer. CASE SUMMARY We report a case of GA-FG in a 77-year-old Chinese woman with epigastric distention who was referred to endoscopy for the management of an incidentally found submucosal tumor-like elevated lesion in the lower part of the gastric body. The tumor occurred after Helicobacter pylori (H. pylori) eradication therapy without long-term use of proton pump inhibitors. Complete and curable removal of the tumor was performed by endoscopic submucosal dissection. Histopathological findings showed numerous cells with basophilic cytoplasm and mildly atypical nuclei-like chief cells of the fundic gland. The tumor was observed to have the so-called “endless glands” pattern of the well-differentiated mixed phenotype. A safe resection margin without lymphatic and venous invasion was observed. As the tumor occurred after H. pylori eradication therapy, it is unknown whether there was a relationship with H. pylori eradication. The patient will be followed up by periodic gastroscopic observation. CONCLUSION In conclusion, we report a case of GA-FG after H. pylori eradication therapy without long-term proton pump inhibitors use. Further analysis of similar cases will reveal the clinical behavior of GA-FG.

A 73-year-old man with prior history of duodenal ulcer has been undergoing periodic upper gastrointestinal endoscopy since 1999. In 2017, a 25-mm submucosal tumor-like protrusion was detected in the lesser curvature of the upper stomach; histological examination of the lesion revealed gastric adenocarcinoma of fundic gland type. En bloc resection was achieved using endoscopic submucosal dissection. The patient was histopathologically diagnosed with gastric adenocarcinoma of fundic gland type arising from heterotopic gastric glands. Immunohistochemical staining was positive for MUC5AC, MUC6, pepsinogen I, and proton pump but negative for MUC2 and CD10. Moreover, the patient’s Ki-67 labeling index score was extremely low. The presence of MUC5AC indicated that the tumor differentiated to the foveolar epithelium and fundic glands. Gastric adenocarcinoma of fundic gland type that differentiates to several directions has a higher malignant potential than the disease that differentiates to chief cells. A retrospective review of the patient’s previous endoscopic examination revealed that the submucosal tumor-like protrusion existed since 2000; tumor size increased from 8 mm in 2000 to 25 mm in 2017. The present case is rare in that the carcinoma arose from heterotopic gastric glands. Moreover, the 19-year follow-up revealed that the tumor differentiated to the foveolar epithelium, considered as having high-grade malignancy.

We investigated the clinicopathological features, diagnosis and differential diagnosis of a patient with gastric adenocarcinoma of the fundic gland type (GA-FG). Endoscopic examination, histomorphological and pathological features were assessed in a 38-year female patient with GA-FG, who presented with upper abdominal pain. Upon endoscopic examination, we observed a smashed area around the cardia. Biopsy and pathological examinations revealed tumor tissue similar to fundic glands composed of parietal and chief cells. Endoscopic submucosal dissection was then performed and the tumor was found to infiltrate into the submucosa. GA-FG is a new tissue type of gastric cancer with unique clinicopathological features, with a good prognosis, and no tendency to relapse. Key Words: Gastric adenocarcinoma, Fundic gland type, Endoscopy.

Due to their similarity to humans, studies regarding gastric ulcers in pigs have become of great interest. It is known that Helicobacter spp. is related to the occurrence of these ulcers, as they possess a high prevalence in pigs. This study aimed to associate gastric lesions findings naturally occurring in minipigs related to or not related to the presence of Helicobacter spp., through the ultra-rapid urease test and immunohistochemical analysis, reaffirming the disease in swine as a natural biomedical model for human cases. For this, samples of formalin-fixed paraffin-embedded gastric tissues from 40 minipigs were obtained at the Laboratório de Morfologia e Patologia Animal (LMPA) in the Universidade Estadual do Norte Fluminense (UENF). Regarding the ultra-rapid urease test, no animal was positive in all regions. However, 18 were positive in at least one: six (15%) were positive in the aglandular region, eight (20%) in the antrum region, 13 (32.5%) in the region of the cardiac gland, and one (2.5%) in the region of the fundic gland. Regarding immunohistochemical analysis, only one animal was positive in all regions, and 32 animals were positive in at least one: four (10%) were positive in the aglandular region, 10 (25%) in the antrum region, 23 (57.5%) in the region of the cardiac gland, and three (7.5%) in the region of the fundic gland. The gastric lesion findings showed a close relationship with Helicobacter spp., enriching the laboratory animal pathologies list. The immunostaining of the bacteria not associated with gastric lesions in certain regions demonstrated the saprophytic and opportunisitic nature of Helicobacter. RESUMO: Por sua semelhança com a da espécie humana, a úlcera gástrica nos suínos tem despertado muito interesse. Sabe-se que o Helicobacter spp. está relacionado à ocorrência dessas úlceras, apresentando alta prevalência. Este estudo teve como objetivo associar as lesões gástricas, de ocorrência natural em miniporcos, à presença, ou não, de Helicobacter spp., por meio do teste ultra-rápido da urease e da análise imunohistoquímica, reafirmando a enfermidade em suínos como modelo biomédico natural para os casos em humanos. Para este fim, foram utilizados histossetes de tecido gástrico de 40 minipigs obtidos no Laboratório de Morfologia e Patologia Animal (LMPA) da Universidade Estadual do Norte Fluminense (UENF). Em relação ao teste ultra-rápido da urease, nenhum animal foi positivo em todas as regiões, entretanto, 18 foram positivos em pelo menos uma: seis foram positivos na região aglandular, oito na região do antro, 13 na região das glândulas cárdicas e um na região das glândulas fúndicas. Em relação à análise imuno-histoquímica, somente um animal foi positivo em todas as regiões e 32 animais foram positivos em pelo menos uma: quatro foram positivos na região aglandular, 10 na região do antro, 23 na região das glândulas cárdicas e três na região das glândulas fúndicas. As lesões gástricas demonstraram estreita relação com o Helicobacter spp. em miniporcos, enriquecendo a lista de patologias de animais de laboratório. A imunomarcação da bactéria não associada à lesão, em certas regiões gástricas, demonstra seu caráter saprofítico e oportunista.

Introduction: The aim of this study was to study the relationship between the formation of gastric fundic gland polyp and gastric hyperplastic polyp (HP) and the changes of gastric juice microenvironment. Methods: The proton-pump inhibitor (PPI) applications to patients were recorded. Gastric juices and biopsy polyps were collected for pathological examination, H. pylori tests, biomarkers, and MUC1, MUC2, MUC5AC expression measurement. Results: Among 34,892 patients, the detection rate of gastric fundic gland polyps was significantly higher than that of gastric HPs (p < 0.01). The incidence rate of gastric fundic gland polyp and gastric HP in PPI users (n = 3,886) was higher than that of non-PPI users (p < 0.01). The occurrence of polyp was positively related to the duration of PPI application and the H. pylori-positive rate. The bile reflux rate between fundic gland polys group (17.61%) and HPs (28.67%) was significantly different (p < 0.01). The levels of gastric juice Gastrin-17, epidermal growth factor (EGF) and MUC2 from patients with gastric fundic gland polyps and gastric HPs were higher than those in the control group (p < 0.01). However, patients with gastric fundic gland polyps and HPs had significantly lower gastric juice PGE2 and MUC5AC (p < 0.01). Conclusion: PPI application, H. pylori infection, and bile reflux are the potential risk factors for formation of fundic gland polyps and HPs. The potential mechanism of polyps’ formation can be related to the levels of Gastrin-17, EGF, MUC2, PGE2, and MUC5AC in gastric juice.