scholarly journals Clinicopathological and Endoscopic Features of Raspberry-Shaped Gastric Cancer in Helicobacter pylori-Uninfected Patients

Digestion ◽  
2020 ◽  
pp. 1-8
Author(s):  
Noboru Yatagai ◽  
Hiroya Ueyama ◽  
Muneo Ikemura ◽  
Ryota Uchida ◽  
Hisanori Utsunomiya ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Gastric Adenocarcinoma ◽  
Submucosal Tumor ◽  
Clinicopathological Characteristics ◽  
Fundic Gland ◽  
Histopathological Classification ◽  
Histological Characteristics ◽  
Greater Curvature ◽  
H Pylori ◽  
Tumor Shape

<b><i>Background:</i></b> Gastric adenocarcinoma of foveolar type (GA-FV) is a raspberry-shaped gastric cancer (RSGC) and garners much attention as <i>H. pylori</i> (<i>Hp</i>)-uninfected gastric cancer. However, the classification and clinicopathological and endoscopic features of RSGCs in <i>Hp</i>-uninfected patients are poorly defined. We designed a new histopathological classification of RSGC and compared them via endoscopic and clinicopathological characteristics. <b><i>Summary:</i></b> From 996 patients with early gastric cancers resected by endoscopy in our hospital, we studied 24 RSGC lesions from 21 (2.4%) <i>Hp</i>-uninfected patients. RSGCs were classified into 3 histological types as follows: GA-FV (<i>n</i> = 19), gastric adenocarcinoma of fundic gland type (GA-FG, <i>n</i> = 2), and gastric adenocarcinoma of fundic gland mucosa type (GA-FGM, <i>n</i> = 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. <b><i>Key Messages:</i></b> RSGCs in <i>Hp</i>-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.

scholarly journals Pathological Diversity of Gastric Cancer from the Viewpoint of Background Condition

Digestion ◽  
2021 ◽  
pp. 1-9
Author(s):  
Hiroyuki Abe ◽  
Tetsuo Ushiku
Keyword(s):  
Gastric Cancer ◽  
Gastric Carcinoma ◽  
Atrophic Gastritis ◽  
Gastric Adenocarcinoma ◽  
Chronic Atrophic Gastritis ◽  
Signet Ring Cell ◽  
Diffuse Gastric Cancer ◽  
Fundic Gland ◽  
Histological Characteristics ◽  
H Pylori

<b><i>Background:</i></b> The prevalence of <i>Helicobacter pylori</i> infection and chronic atrophic gastritis is decreasing in Japan, which has led to a decline in the incidence of gastric cancer. However, there are various subtypes of gastric cancer that arise from the background mucosa without <i>H. pylori</i> infection, and their histological characteristics are distinct from those of gastric cancer with chronic atrophic gastritis. <b><i>Summary:</i></b> In this review, after a brief overview of conventional gastric carcinoma with <i>H. pylori</i> infection, including its molecular classification, histological characteristics of gastric cancer after eradicating <i>H. pylori</i> are described. The clinicopathological characteristics of gastric cancer independent of <i>H. pylori</i> infection are then explained. Autoimmune gastritis (type A gastritis) increases the risk of gastric adenocarcinoma and neuroendocrine tumors. Gastric carcinoma without <i>H. pylori</i> infection has various histological subtypes, including fundic gland-type adenocarcinoma (oxyntic gland adenoma), foveolar-type adenocarcinoma/adenoma, signet ring cell carcinoma, and adenocarcinoma of the esophagogastric junction. In addition, some familial gastric cancer syndromes, including hereditary diffuse gastric cancer, familial adenomatous polyposis, and gastric adenocarcinoma and proximal polyposis of the stomach, are also discussed. <b><i>Key Messages:</i></b> Although the incidence of gastric cancer will decrease in the near future, the diversity of gastric cancer pathology will be enhanced because <i>H. pylori</i>-negative gastric cancer will have a significant impact on the clinical practice guidelines for gastric cancer. Gastroenterologists and pathologists should be aware of the morphological diversity of <i>H. pylori</i>-negative gastric cancer, and attention should be paid to the status of the background gastric mucosa while examining gastric cancer.

scholarly journals Diagnostic limitations of magnifying endoscopy with narrow-band imaging in early gastric cancer

2020 ◽  
Vol 08 (10) ◽  
pp. E1233-E1242
Author(s):  
Kohei Matsumoto ◽  
Hiroya Ueyama ◽  
Takashi Yao ◽  
Daiki Abe ◽  
Shotaro Oki ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Early Gastric Cancer ◽  
Gastric Adenocarcinoma ◽  
Narrow Band ◽  
Narrow Band Imaging ◽  
Magnifying Endoscopy ◽  
Clinicopathological Features ◽  
Fundic Gland ◽  
Undifferentiated Adenocarcinoma ◽  
Histological Characteristics

Abstract Background and study aims Magnifying endoscopy with narrow band imaging (M-NBI) has made a huge contribution to endoscopic diagnosis of early gastric cancer (EGC). However, we sometimes encountered false-negative cases with M-NBI diagnosis (i. e., M-NBI diagnostic limitation lesion: M-NBI-DLL). However, clinicopathological features of M-NBI-DLLs have not been well elucidated. We aimed to clarify the clinicopathological features and histological reasons of M-NBI-DLLs. Patients and methods In this single-center retrospective study, M-NBI-DLLs were extracted from 456 EGCs resected endoscopically at our hospital. We defined histological types of M-NBI-DLLs and analyzed clinicopathologically to clarify histological reasons of M-NBI-DLLs. Results Of 456 EGCs, 48 lesions (10.5 %) of M-NBI-DLLs were enrolled. M-NBI-DLLs was classified into four histological types as follows: gastric adenocarcinoma of fundic-gland type (GA-FG, n = 25), gastric adenocarcinoma of fundic-gland mucosal type (GA-FGM, n = 1), differentiated adenocarcinoma (n = 14), and undifferentiated adenocarcinoma (n = 8). Thirty-nine lesions of M-NBI-DLLs were H. pylori-negative gastric cancers (39/47, 82.9 %). Histological reasons for M-NBI-DLLs were as follows: 1) completely covered with non-neoplastic mucosa (25/25 GA-FG, 8/8 undifferentiated adenocarcinoma); 2) well-differentiated adenocarcinoma with low-grade atypia (1/1 GA-FGM, 14/14 differentiated adenocarcinoma); 3) similarity of surface structure (10/14 differentiated adenocarcinoma); and 4) partially covered and/or mixed with a non-neoplastic mucosa (1/1 GA-FGM, 6/14 differentiated adenocarcinoma). Conclusions Diagnostic limitations of M-NBI depend on four distinct histological characteristics. For accurate diagnosis of M-NBI-DLLs, it may be necessary to fully understand endoscopic features of these lesions using white light imaging and M-NBI based on these histological characteristics and to take a precise biopsy.

scholarly journals Two Distinct Etiologies of Gastric Cancer: Infection and Autoimmunity

2021 ◽  
Vol 9 ◽  
Author(s):  
Stella G. Hoft ◽  
Christine N. Noto ◽  
Richard J. DiPaolo
Keyword(s):  
Gastric Cancer ◽  
T Cells ◽  
Gastric Adenocarcinoma ◽  
Inflammatory Diseases ◽  
The United States ◽  
Autoimmune Gastritis ◽  
Gastric Disease ◽  
Increased Risk ◽  
H Pylori ◽  
Gastrointestinal Ulceration

Gastric cancer is a leading cause of mortality worldwide. The risk of developing gastric adenocarcinoma, which comprises &gt;90% of gastric cancers, is multifactorial, but most associated with Helicobacter pylori infection. Autoimmune gastritis is a chronic autoinflammatory syndrome where self-reactive immune cells are activated by gastric epithelial cell autoantigens. This cause of gastritis is more so associated with the development of neuroendocrine tumors. However, in both autoimmune and infection-induced gastritis, high risk metaplastic lesions develop within the gastric mucosa. This warrants concern for carcinogenesis in both inflammatory settings. There are many similarities and differences in disease progression between these two etiologies of chronic gastritis. Both diseases have an increased risk of gastric adenocarcinoma development, but each have their own unique comorbidities. Autoimmune gastritis is a primary cause of pernicious anemia, whereas chronic infection typically causes gastrointestinal ulceration. Both immune responses are driven by T cells, primarily CD4+ T cells of the IFN-γ producing, Th1 phenotype. Neutrophilic infiltrates help clear H. pylori infection, but neutrophils are not necessarily recruited in the autoimmune setting. There have also been hypotheses that infection with H. pylori initiates autoimmune gastritis, but the literature is far from definitive with evidence of infection-independent autoimmune gastric disease. Gastric cancer incidence is increasing among young women in the United States, a population at higher risk of developing autoimmune disease, and H. pylori infection rates are falling. Therefore, a better understanding of these two chronic inflammatory diseases is needed to identify their roles in initiating gastric cancer.

scholarly journals Clinicopathological characteristics of Barrett's carcinoma, cardia carcinoma type II and distal gastric carcinoma: Influence of observed parameters on the five-year postoperative survival of patients

2009 ◽  
Vol 137 (5-6) ◽  
pp. 249-254
Author(s):  
Ivan Jovanovic ◽  
Tamara Alempijevic ◽  
Tomica Milosavljevic ◽  
Dragan Popovic ◽  
Milos Bjelovic ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Survival Rate ◽  
Gastric Adenocarcinoma ◽  
Clinicopathological Characteristics ◽  
Clinicopathological Parameters ◽  
Cancer Type ◽  
Cardia Cancer ◽  
Tumour Invasion ◽  
Barrett’S Cancer ◽  
Distal Gastric Cancer

Introduction. In the past two decades, the increased frequency of distal esophageal adenocarcinoma, esophagogastric junction and proximal gastric adenocarcinoma has been observed. The vast majority of these tumours are diagnosed in advanced stages, when the prognosis is poorer than in other gastric cancers. Objective. The aim of our study was to analyze the demographic and clinicopathological characteristics of patients operated on for Barrett's, cardia and distal gastric adenocarcinomas, as well as to study the influence of manifestations of each cancerogenetic indication on the studied clinicopathological parameters and to analyze the 5-year survival rate of patients surgically treated for cardia adenocarcinoma in relation to the patients operated on for distal gastric adenocarcinoma. Methods. We analyzed gender and age, tumour type, depth of tumour invasion, involvement of blood and lymph vessels in 66 patients surgically treated at the Centre for Oesophageal Surgery of the Institute for Digestive Diseases of the Belgrade Clinical Centre. Results. Except for significant differences in the depth of tumour invasion during surgery, there were no other statistically significant differences between the studied groups of patients. In the patients operated on for Barrett's and cardia cancers, the tumours invaded more deeply the wall layers, i.e. they were significantly more invasive than the distal gastric tumour. The lymph node involvement was present in 87.5% of patients with Barrett's cancer, in 80% with cardia cancer and in 87% with distal gastric cancer. The 3-year survival rate of patients operated on for cardia cancer was 47.4% and the 5-year survival rate was 31.6%, while the 3-year survival rate of patients operated on for distal gastric cancer was 46.2% and the 5-year survival rate was 34.6%. These differences were not statistically significant (Wilcoxon 0,036; p=0,85). Singly, the patients' gender, cancer type and the degree of tumour differentiation had no influence on the length of patients' postsurgical survival rate. Conclusion. At the time of diagnosis cardia cancer and cancers developed at the location of the Barrett's oesophagus, developed significant deeper per continuitatem than gastric cancer. There were no other differences in regard to the analyzed clinicopathological parameters among the tumours of these three locations, and there was no difference between the 3-year and 5-year survival rate between the patients operated on for gastric cancer and cardia cancer. Each studied clinicopathological parameter had no influence on the illness course.

DETERMINATION OF HELICOBACTER PYLORI CAGA GENE AND VACA GENOTYPES IN PATIENTS WITH GASTRIC CANCER

2013 ◽  
pp. 118-125
Author(s):  
Quy Hung Le ◽  
Thi Minh Thi Ha
Keyword(s):  
Gastric Cancer ◽  
Helicobacter Pylori ◽  
Signet Ring Cell ◽  
Tubular Adenocarcinoma ◽  
Negative Group ◽  
Caga Gene ◽  
Positive Group ◽  
Histopathological Classification ◽  
Vaca Gene ◽  
H Pylori

Background: H. pylori is the first cause of gastric cancer (GC). However, the role of cagA gene and vacA gene in GC is still controversial. This study is aimed at determining the rates of H. pylori infection, cagA gene, vacA genotypes in patients with GC; and evaluating the relationship between cagA gene, vacA genotypes and endoscopic and histopathological features of gastric cancer. Patients and methods: Fifty eight GC patients and one hundred and sixteen non-GC patients (controls) were enrolled. Infection of H. pylori was determined by PCR. cagA gene and vacA genotypes were determined by Multiplex PCR. Results: The rate of H. pylori was found in 55.2% in GC group. The rate of cagA gene and vacA gene in GC patients H. pylori positive were found in 78.1% and 100%, respectively. vac A genotypes s1/m1, s1/m2 and s1/m1m2 were found in 34.4%; 50% and 15.6%, respectively. The risk of GC of cagA positive group was higher than cagA negative group, with OR = 4,5; 95%CI = 1.6-12.2. The risk of GC of vacA s1/m1, cagA positive group was higher than vacA s1/m1, cagA negative group, OR = 7.1; 95%CI = 1.4-36. A statistically significative difference of rate of cagA positive was found between Borrmann III/IV group (100%) and Borrmann I/II group (46.2%). A statistically significative difference of rate of cagA positive was found between the tubular adenocarcinoma group (100%) and signet-ring cell carcinoma (44.4%, p = 0,002), and mucinous adenocarcinoma (50%, p =0,024). Conclusion: Gene cagA and vacA s1/m1 genotype were both risk factors in GC. A significative differences of rate of cagA positive were found between Borrmann groups, and between groups of WHO histopathological classification. Key words: cagA gene and vacA genotype, Helicobacter pylori, gastric cancer

Effect of helicobacter pylori on prognosis of curatively resected gastric cancers in a population with high prevalence: Short-term results of a prospective study.

2011 ◽  
Vol 29 (4_suppl) ◽  
pp. 152b-152b
Author(s):  
H. Hur ◽  
J. Y. Kim ◽  
Y. B. Kim ◽  
Y. A. Lim ◽  
Y. K. Cho ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Gastric Adenocarcinoma ◽  
Curative Resection ◽  
Disease Free Survival ◽  
Enzyme Linked Immunosorbent Assay ◽  
Free Survival ◽  
H Pylori ◽  
Predicting Factor ◽  
Disease Free

152b Background: Although two prospective studies reported that negative H pylori is associated with good prognosis in Western countries, these results are not generally acceptable due to regional differences in H pylori virulence and incidence of gastric cancer. Here, we prospectively assessed the correlation between H pylori status of patients who underwent curative resection for treatment of gastric adenocarcinoma and their prognosis in Korea, where H pylori is highly prevalent in the population. Methods: Between 2006 and 2007, 192 patients who had undergone curative resection for treatment of gastric adenocarcinoma were prospectively enrolled. Of these patients, 18 patients were excluded due to inexact evaluation of H pylori status, and 174 patients were finally analyzed. Serologic testing for H pylori was assessed using an enzyme-linked immunosorbent assay kit for IgG, and histological presence was identified using Giemsa stain. Results: Of 174 patients, 111 patients (63.8%) who showed both serologically and histologically positive results were confirmed as having positive H pylori infection. H pylori status was not correlated with overall or disease-free survival. In term of patients who were diagnosed with AJCC stage III or IV, disease-free survival of patients with positive H pylori status was a significant predicting factor for recurrence longer than that of negative patients (p = 0.019). Negative H pylori status became a predicting factor for recurrence in multivariable analysis (RR = 2.724, 95% C.I.: 1.192-6.228). Conclusions: H pylori status did not show correlation with clinicopathologic factors of gastric adenocarcinoma in Korea. However, negative H pylori may be a predictive factor for recurrence in patients diagnosed with gastric adenocarcinoma of advanced status. Therefore, in H pylori endemic areas, patients diagnosed with locally advanced gastric cancer accompanied by negative H pylori status should be considered for an aggressive treatment strategy and close follow-up. In addition, correlation in an early stage should be confirmative through the results of longer follow-up. No significant financial relationships to disclose.

scholarly journals In VitroActivity of 2-methoxy-1,4-naphthoquinone and Stigmasta-7,22-diene-3β-ol fromImpatiens balsaminaL. against Multiple Antibiotic-ResistantHelicobacter pylori

2011 ◽  
Vol 2011 ◽  
pp. 1-8 ◽  
Author(s):  
Yuan-Chuen Wang ◽  
Wan-Yu Li ◽  
Deng-Chyang Wu ◽  
Jeh-Jeng Wang ◽  
Cheng-Hsun Wu ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Helicobacter Pylori ◽  
Gastric Adenocarcinoma ◽  
Bactericidal Activity ◽  
Indigenous Medicine ◽  
Impatiens Balsamina ◽  
Ph Values ◽  
H Pylori ◽  
Dose Dependent ◽  
Group 1

Infection withHelicobacter pyloriis strongly associated with gastric cancer and gastric adenocarcinoma. WHO classifiedH. pylorias a group 1 carcinogen in 1994.Impatiens balsaminaL. has been used as indigenous medicine in Asia for the treatment of rheumatism, fractures and fingernail inflammation. In this study, we isolated anti-H. pyloricompounds from this plant and investigated their anti- and bactericidal activity. Compounds of 2-methoxy-1,4-naphthoquinone (MeONQ) and stigmasta-7,22-diene-3β-ol (spinasterol) were isolated from the pods and roots/stems/leaves ofI. balsaminaL., respectively. The minimum inhibitory concentrations (MICs) and minimum bactericidal concentrations (MBCs) for MeONQ were in the ranges of 0.156–0.625 and 0.313–0.625μg mL−1, respectively, and in the ranges of 20–80 μg mL−1both of MICs and MBCs for spinasterol against antibiotic (clarithromycin, metronidazole and levofloxacin) resistantH. pylori. Notably, the activity of MeONQ was equivalent to that of amoxicillin (AMX). The bactericidalH. pyloriaction of MeONQ was dose-dependent. Furthermore, the activity of MeONQ was not influenced by the environmental pH values (4–8) and demonstrated good thermal (121°C for 15 min) stability. MeONQ abounds in theI. balsaminaL. pod at the level of 4.39% (w/w db). In conclusion, MeONQ exhibits strong potential to be developed as a candidate agent for the eradication ofH. pyloriinfection.

scholarly journals Gastritis, Gastric Polyps and Gastric Cancer

2021 ◽  
Vol 22 (12) ◽  
pp. 6548
Author(s):  
Helge Waldum ◽  
Reidar Fossmark
Keyword(s):  
Gastric Cancer ◽  
Term Treatment ◽  
Fundic Gland ◽  
Carcinogenic Effect ◽  
Gastric Polyps ◽  
Ecl Cell ◽  
Increased Risk ◽  
Long Term Treatment ◽  
Degree Of Malignancy ◽  
H Pylori

Gastric cancer is still an important disease causing many deaths worldwide, although there has been a marked reduction in prevalence during the last few decades. The decline in gastric cancer prevalence is due to a reduction in Helicobacter pylori infection which has occurred for at least 50 years. The most probable mechanism for the carcinogenic effect of H. pylori is hypergastrinemia since H. pylori infected individuals do not have increased risk of gastric cancer before the development of oxyntic atrophy. When atrophy has developed, the carcinogenic process continues independent of H. pylori. Autoimmune gastritis also induces oxyntic atrophy leading to marked hypergastrinemia and development of ECL cell neoplasia as well as adenocarcinoma. Similarly, long-term treatment with efficient inhibitors of acid secretion like the proton pump inhibitors (PPIs) predisposes to ECL cell neoplasia of a different degree of malignancy. Contrasting the colon where most cancers develop from polyps, most polyps in the stomach have a low malignant potential. Nevertheless, gastric polyps may also give rise to cancer and have some risk factors and mechanisms in common with gastric cancer. In this overview the most common gastric polyps, i.e., hyperplastic polyps, adenomatous polyps and fundic gland polyps will be discussed with respect to etiology and particularly use of PPIs and relation to gastric carcinogenesis.

scholarly journals [ARTICLE PARTIAL RETRACTION] PREVALENCE OF HELICOBACTER PYLORI INFECTION IN DYSPEPTIC PATIENTS AND ITS ASSOCIATION WITH CLINICAL RISK FACTORS FOR DEVELOPING GASTRIC ADENOCARCINOMA

2019 ◽  
Vol 56 (1) ◽  
pp. 66-70
Author(s):  
Stéfani Sousa BORGES ◽  
Amanda Ferreira Paes Landim RAMOS ◽  
Aroldo Vieira de MORAES FILHO ◽  
Carla Afonso da Silva Bitencourt BRAGA ◽  
Lilian Carla CARNEIRO ◽  
...  
Keyword(s):  
Risk Factors ◽  
Gastric Cancer ◽  
Helicobacter Pylori ◽  
High Risk ◽  
Gastric Adenocarcinoma ◽  
Public Health Problem ◽  
Clinical Risk Factors ◽  
International Agency ◽  
Clinical Risk ◽  
H Pylori

ABSTRACT BACKGROUND: In Brazil, particularly in the underdeveloped localities, the prevalence of Helicobacter pylori (H. pylori) infections can range up to 90%. These rates are higher in older individuals and vary by country region. H. pylori infections are linked to the development of gastric pathologies, namely mild to moderate gastritis, gastroenteritis, peptic ulcer, intestinal metaplasia, and gastric cancer. In 1994, this organism was classified by the International Agency for Research on Cancer (IARC) as pertaining to the Group 1 carcinogen for gastric adenocarcinoma etiology. Gastric cancer represents a significant public health problem, being the fourth most common malignant tumor and the second largest cause of cancer-related deaths. OBJECTIVE: To investigate the prevalence of H. pylori infection in dyspeptic patients and determine the link between clinical risk factors and gastric adenocarcinoma diagnosis. METHODS: Polymerase chain reaction (PCR) analysis was employed for molecular diagnosis of gastric tissue biopsies collected from 113 dyspeptic patients at the University Hospital of Federal University of Goiás. Molecular analyses allowed the identification of H. pylori infections. Furthermore, histopathological examinations were performed to determine the clinical risks of developing gastric malignancies. RESULTS: The test results identified 69 individuals older than 44 years, from 75 (66.4%) positive H. pylori infection samples. The prevalence of gastric adenocarcinoma in this study was 1.3%. Among the infected patients, six (8.2%) had high risk, and 67 (91.8%) had a low risk of developing gastric cancer (P<0.05). CONCLUSION: This study shows a high prevalence of H. pylori infection and identifies its contribution to gastric inflammations, which in the long term are manifested in high-risk clinical factors for the development of gastric adenocarcinoma.

scholarly journals Gastric epithelial neoplasm of fundic-gland mucosa lineage: proposal for a new classification in association with gastric adenocarcinoma of fundic-gland type

2021 ◽  
Author(s):  
Hiroya Ueyama ◽  
Takashi Yao ◽  
Yoichi Akazawa ◽  
Takuo Hayashi ◽  
Koichi Kurahara ◽  
...  
Keyword(s):  
Gastric Adenocarcinoma ◽  
Clinicopathological Features ◽  
Low Grade ◽  
Fundic Gland ◽  
New Classification ◽  
Histopathological Classification ◽  
Gland Type ◽  
Epithelial Neoplasm

Abstract 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.

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