• Adenocarcinoma
• Endoscopic mucosal resection
• Gastric fundus
• Immunohistochemistry
• Stomach neoplasm

• Humans
• Stomach Neoplasms/pathology
• Stomach Neoplasms/surgery
• Stomach Neoplasms/diagnosis
• Male
• Aged
• Female
• Middle Aged
• Adenoma/pathology
• Adenocarcinoma/pathology
• Aged, 80 and over
• Adult

• chief cell
• endoscopic mucosal resection
• endoscopic submucosal dissection
• gastric adenocarcinoma of the fundic gland type
• magnifying endoscopy with narrow‐band imaging

• gastric adenocarcinoma of fundic-gland type
• oxyntic gland adenoma
• oxyntic gland neoplasm

• Humans
• Retrospective Studies
• Prevalence
• Stomach Neoplasms/epidemiology
• Stomach Neoplasms/pathology
• Gastric Fundus/pathology
• Gastric Mucosa/pathology

• Chief cells, gastric
• Endoscopic submucosal dissection
• Gastric cancer

• Humans
• Stomach Neoplasms/diagnosis
• Stomach Neoplasms/surgery
• Helicobacter Infections
• Helicobacter pylori
• Adenocarcinoma/diagnosis
• Adenocarcinoma/surgery

Gastric adenocarcinoma of fundic gland type (GA-FG) is a newly discovered type of gastric cancer in recent years, and it is a form of well-differentiated malignancy unlike conventional intestinal and diffuse gastric cancers. It is expected that GA-FG will account for an increasing proportion of all gastric cancers, but the current lack of knowledge among endoscopists and clinicopathologists may lead to misdiagnosis.

To increase the diagnostic yield of GA-FG and reduce missed diagnosis and misdiagnosis, we conducted a systematic review of the endoscopic, clinical, and pathological features of GA-FG.

The clinical, pathological, and endoscopic data of patients with GA-FG reported in the Chinese and English literature published between January 2007 and March 2022 were collected from PubMed and CNKI and retrospectively analyzed.

Data related to a total of 322 lesions in 320 patients with GA-FG were collected from 67 articles. Most of the lesions were located in the upper third of the stomach (81.6%), with an average lesion size of 9.66 mm (1 mm-85 mm), and approximately 76.88% of the lesions had an elevated gross morphology. Microvascular dilatation and disorganized or thickened microglandular structures were observed on the surface of the lesions by narrow band imaging. The main cell differentiation type accounted for approximately 74.84% of all lesions, which significantly expressed MUC6 and pepsinogen.

The incidence of GA-FG is low. Endoscopic complete resection and surgical operation can achieve curative resection. The prognosis is good, but it tends to be misdiagnosed. The diagnosis should be combined with its clinicopathological characteristics to reduce the rate of misdiagnosis and missed diagnosis.

• Gastric adenocarcinoma of fundic gland type
• Clinical characteristics
• Pathology
• Endoscopy

• AGS cell transfection
• Gastric carcinoma of fundic gland
• Immunohistochemistry
• NKX2-1/TTF-1
• Transcriptome analysis

• Humans
• Thyroid Nuclear Factor 1/genetics
• Genes, Homeobox
• Stomach Neoplasms/genetics
• Stomach Neoplasms/pathology
• Adenocarcinoma/genetics
• Adenocarcinoma/pathology
• Gene Expression Profiling

• 21K15940 Japan Society for the Promotion of Science
• 20K16952 Japan Society for the Promotion of Science

• gastric adenocarcinoma of fundic gland type
• h+/k+-atpase
• pepsinogen-i

• Adenocarcinoma/surgery
• Female
• Gastric Mucosa
• Gastroscopy
• Humans
• Male
• Stomach Neoplasms/surgery

• Gastric adenocarcinoma of fundic-gland mucosa type
• Gastric adenocarcinoma of fundic-gland type
• Gastric epithelial neoplasm of fundic-gland mucosa lineage
• Oxyntic gland adenoma

• Aged
• Cell Lineage
• Female
• Humans
• Male
• Middle Aged
• Pain Measurement/methods
• Pain Measurement/statistics & numerical data
• Polyps/classification
• Polyps/pathology
• Retrospective Studies
• Stomach Neoplasms/classification
• Stomach Neoplasms/pathology

• JSPS KAKENHI

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.

• Chief cells
• Endoscopic diagnosis
• Endoscopic submucosal dissection
• Gastric adenocarcinoma of the fundic gland type
• Pathological diagnosis
• Pepsinogen-I

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.

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.

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.

• Gastric adenocarcinoma of the fundic gland
• Multiple lesions
• Pepsinogen-I
• Endoscopic submucosal dissection
• Case report

• Adenocarcinoma/pathology
• Atrophy/pathology
• Gastric Mucosa/pathology
• Gastritis/pathology
• Helicobacter Infections/pathology
• Helicobacter pylori/physiology
• Humans
• Intestines/pathology
• Metaplasia/pathology
• Stomach Neoplasms/pathology

Gastric adenocarcinoma of the fundic gland (chief cell-predominant type, GA-FG-CCP) is a rare variant of well-differentiated adenocarcinoma, and has been proposed to be a novel disease entity. GA-FG-CCP originates from the gastric mucosa of the fundic gland region without chronic gastritis or intestinal metaplasia. The majority of GA-FG-CCPs exhibit either a submucosal tumor-like superficial elevated shape or a flat shape on macroscopic examination. Narrow-band imaging with endoscopic magnification may reveal a regular or an irregular microvascular pattern, depending on the degree of tumor exposure to the mucosal surface. Pathological analysis of GA-FG-CCPs is characterized by a high frequency of submucosal invasion, rare occurrences of lymphatic and venous invasion, and low-grade malignancy. Detection of diffuse positivity for pepsinogen-I by immunohistochemistry is specific for GA-FG-CCP. Careful endoscopic examination and detailed pathological evaluation are essential for early and accurate diagnosis of GA-FG-CCP. Nearly all GA-FG-CCPs are treated by endoscopic resection due to their small tumor size and low risk of recurrence or metastasis.

• Narrow-band imaging
• Pepsinogen-I
• Fundic gland
• Gastric adenocarcinoma
• Chief cell

• Adenocarcinoma/diagnosis
• Adenocarcinoma/pathology
• Biomarkers, Tumor
• Biopsy
• Chief Cells, Gastric/pathology
• Diagnosis, Differential
• Gastric Fundus/cytology
• Gastric Fundus/pathology
• Gastric Fundus/surgery
• Gastroscopy/methods
• Humans
• Immunohistochemistry
• Laparoscopy/methods
• Narrow Band Imaging/methods
• Neoplasm Recurrence, Local
• Pepsinogen A/immunology
• Polyps/diagnosis
• Practice Guidelines as Topic
• Stomach Neoplasms/diagnosis
• Stomach Neoplasms/pathology
• Stomach Neoplasms/surgery

Gastric adenocarcinoma of the fundic gland type (GA-FG) is a rare entity that has only recently been described and defined. There is ongoing controversy regarding the malignant potential of this lesion. We report the case of a GA-FG in a 49-year-old Caucasian man who was referred to endoscopy for management of an incidentally found gastric polyp. Endoscopy showed a single polypoid lesion in the gastric fundus which was successfully removed with endoscopic resection. Grossly, the polyp measured 1.1 cm in greatest dimension. Microscopic examination showed irregularly branched neoplastic glands covered with a nonneoplastic foveolar epithelium. The continuity between the neoplastic glands and the fundic glands is clearly identified, indicating the tumor arose from the fundic glands. The tumor cells exhibited occasional oxyntic cytoplasm with enlarged atypical nuclei. The tumor invaded the submucosa with complete disruption of the muscularis mucosae and mild lymphocytic and fibroblastic stromal reaction. No necrosis, mitosis, or lymph-vascular invasion was identified. Although some authors have proposed reclassification of GA-FGs as oxyntic gland polyps/adenomas, in light of several reported cases with submucosal invasion as well as lymphatic invasion, we maintain that this neoplasm is best categorized as an extremely well-differentiated adenocarcinoma to reflect its invasive potential.

• Helicobacter pylori
• chief cell
• fundic gland
• gastric adenocarcinoma
• pepsinogen I

A 77-year-old woman underwent an upper gastrointestinal (UGI) endoscopy screening examination, and a 10-mm reddish, submucosal tumor-like lesion was found on the posterior wall of the fornix. Biopsy was performed, but there was no evidence of malignancy, so annual follow-up by UGI endoscopy was decided upon. After 12 years, examination of another biopsy specimen revealed an adenocarcinoma of the fundic gland type. There had been no significant change in the size or shape of the lesion over the long follow-up period. Endoscopic submucosal dissection (ESD) was performed, and en bloc resection was achieved. Histopathologically, the tumor appeared as a flat elevated lesion measuring 11 × 10 mm. It was composed of irregularly shaped glands and invaded the submucosa up to 300 µm. Immunohistochemical examination involving specific antibodies to pepsinogen I, MIST-1, MUC6, and H⁺/K⁺-ATPase confirmed the fundic gland differentiation of the irregularly shaped glands together with a very low Ki-67 labeling index. Thus, gastric adenocarcinoma of the fundic gland type (GAFG) was diagnosed. Four years have passed since the ESD, and there has been no recurrence. To the best of our knowledge, this is the first report of the long-term natural history of GAFG. Over the 12 years, no morphologic changes were observed; the tumor remained within the submucosal layer. Our observations in this case strengthen the notion that GAFG is a specific type of gastric adenocarcinoma of low-grade malignancy.

• Endoscopic submucosal dissection (ESD)
• Gastric adenocarcinoma of fundic gland type (GAFG)
• Natural history

Both gastric adenocarcinoma of fundic gland type (ADC-FG) and carcinoma with lymphoid stroma (lymphoepithelioma-like carcinoma, LELC) are relatively rare. Epstein-Barr virus (EBV) has been implicated in the pathogenesis of LELC. However, the pathogenesis of ADC-FG, as well as the role of EBV in the carcinogenesis of LELC, remain unclear and under debate. The current study presents a case of concurrent ADC-FG and LELC in the stomach in a 69-year-old man. Total gastrectomy was performed, and two separate masses were identified. Upon histological and immunohistochemical examination, the mass located in the lower body was determined to be LELC and the mass in the upper body was diagnosed as ADC-FG. The lesions were characterized by different mucin phenotypes and EBV in situ results. In the lower-body mass, EBV in situ hybridization expression was diffusely strongly positive, but MUC2, MUC5AC, MUC6, and CD10 were all negative. On the other hand, in the upper-body mass, the results were positive for MUC6 but negative for MUC2, MUC5AC, CD10, and EBV by in situ hybridization. The remaining gastric tissue was unremarkable, and perigastric lymph node metastases were absent. Seven months after the gastrectomy, a postoperative computed tomography scan revealed no recurrence or metastasis.

• Adenocarcinoma of fundic gland type
• Carcinoma with lymphoid stroma
• Stomach

Gastric adenocarcinoma of fundic gland type (GA-FG) with chief cell differentiation was recently proposed as an extremely rare type of gastric adenocarcinoma. Here, we report 4 cases of GA-FG with chief cell differentiation. Endoscopic features included a submucosal tumor shape or a flat shape, whitish discoloration and dilated vessels on the surface. The tumors were located in the upper or middle third of the stomach. All cases were preoperatively diagnosed as GA-FG by biopsy, and endoscopic submucosal dissection was performed. Resected specimens revealed well-differentiated adenocarcinomas resembling chief cells. Tumor cells were diffusely positive for pepsinogen-I, but partially positive for H⁺/K⁺-ATPase in scattered locations around the tumor margin. Despite the presence of minimal invasion of the carcinoma into the submucosal layer, which was observed in two cases, neither lymphatic nor venous invasion was detected in any of the cases. Finally, all cases showed less aggressive clinical behavior with low grade malignancy.

• Early gastric cancer
• Low grade malignancy
• Fundic gland type
• Chief cells
• Endoscopic submucosal dissection

• chief cells
• fundic gland
• gastric polyp
• oxyntic gland
• stomach neoplasm

Gastric adenocarcinoma is one of the most common malignancies worldwide. Histochemical and immunohistologic analyses classify the phenotypes of gastric adenocarcinoma into several groups based on the variable clinical and pathologic features. A new and rare variant of gastric adenocarcinoma with chief cell differentiation (GA-CCD) has recently been recognized. Studies reporting the distinct clinicopathologic characteristics proposed the term oxyntic gland polyp/adenoma because of the benign nature of the GA-CCD. Typically, GA-CCD is a solitary mucosal lesion that develops either in the gastric cardia or fundus. Histologically, this lesion is characterized by tightly clustered glands and anastomosing cords of chief cells. Immunohistochemically, GA-CCD is diffusely positive for mucin (MUC) 6 and negative for MUC2 and MUC5AC. However, other gastric tumors such as a gastric neuroendocrine tumor or fundic gland polyp have been difficult to exclude. Because GA-CCD tends to be endoscopically misdiagnosed as a neuroendocrine tumor or fundic gland polyp, comprehensive assessment and observation by an endoscopist are strongly recommended. Herein, we report a rare case of oxyntic gland adenoma endoscopically mimicking a gastric neuroendocrine tumor that was successfully removed by endoscopic mucosal resection.

• Chief cell differentiation
• Gastric carcinoma
• Mucin 6
• Neuroendocrine tumor
• Oxyntic gland adenoma

• Adenoma/chemistry
• Adenoma/classification
• Adenoma/pathology
• Adenoma/surgery
• Aged
• Biomarkers, Tumor/analysis
• Biopsy
• Diagnosis, Differential
• Endosonography
• Gastrectomy
• Gastroscopy
• Humans
• Immunohistochemistry
• Male
• Mucin-6/analysis
• Neuroendocrine Tumors/pathology
• Parietal Cells, Gastric/chemistry
• Parietal Cells, Gastric/pathology
• Predictive Value of Tests
• Stomach Neoplasms/chemistry
• Stomach Neoplasms/classification
• Stomach Neoplasms/pathology
• Stomach Neoplasms/surgery
• Terminology as Topic