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Lu T, Liu JX, Xia Y, Zhao Y. Clinical, endoscopic and histopathological observation of a rare case of esophageal submucosal gland duct adenoma: A case report. World J Gastrointest Endosc 2025; 17:105238. [PMID: 40291130 PMCID: PMC12019125 DOI: 10.4253/wjge.v17.i4.105238] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/16/2025] [Revised: 03/10/2025] [Accepted: 03/27/2025] [Indexed: 04/14/2025] Open
Abstract
BACKGROUND Esophageal submucosal gland duct adenoma (ESGDA) is very rare, and easily diagnosed as adenocarcinoma. CASE SUMMARY A 70-year-old man presented with abdominal discomfort and intermittent dull pain during swallowing for 10 days. Digestive endoscopy revealed a polypoid bulge at the esophago-gastric junction, which was resected by endoscopic submucosal dissection (ESD). Routine pathological examination showed intestinal metaplasia of the glandular epithelium on the mucosal surface, with serous tumor-like complex glands in the submucosa which showing significant hyperplasia. This initially diagnosis was early gastric adenocarcinoma. However, we still observed a few points that did not meet the criteria for cancer such as lack of malignant features. Following multidisciplinary discussion and consultation with the experienced specialist pathologists, we finally diagnosed the lesion as a rare ESGDA by further immunohistochemistry. The follow-up examination results for the patient were satisfactory, with no evidence of tumor recurrence. And we summarize the ESGDAs reported in the literature, aiming to enhance understanding of this tumor type. CONCLUSION ESGDA is a benign tumor that can be cured by ESD. Accurate diagnosis can prevent unnecessary extensive therapeutic interventions.
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Affiliation(s)
- Ting Lu
- Department of Pathology, Nanjing Medical University Affiliated Taizhou People’s Hospital, Jiangsu Taizhou People’s Hospital, Taizhou 225300, Jiangsu Province, China
| | - Jun-Xing Liu
- The Second Clinical Medical College, Xuzhou Medical University, Xuzhou 221004, Jiangsu Province, China
| | - Yin Xia
- Department of Pathology, Nanjing Medical University Affiliated Taizhou People’s Hospital, Jiangsu Taizhou People’s Hospital, Taizhou 225300, Jiangsu Province, China
| | - Yan Zhao
- Department of Pathology, Nanjing Medical University Affiliated Taizhou People’s Hospital, Jiangsu Taizhou People’s Hospital, Taizhou 225300, Jiangsu Province, China
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Zhao C, Su BJ, Lin WZ, He AF, Hui DY, Liu HL, Chen H, Xiao MY, Chen JN, Li HF, Zheng JY, Wang WJ, Huang Y, Shao CK. An emerging entity of gastric adenocarcinoma: clinicopathological features and differential diagnosis of gastric adenocarcinoma of fundic-gland type in 25 retrospective cases. Virchows Arch 2025:10.1007/s00428-025-04075-9. [PMID: 40100386 DOI: 10.1007/s00428-025-04075-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/15/2024] [Revised: 02/23/2025] [Accepted: 03/04/2025] [Indexed: 03/20/2025]
Abstract
Gastric adenocarcinoma of fundic-gland type (GA-FG) is a rare gastric cancer with an extremely low rate of vascular and lymph node metastases. It can be cured with endoscopic submucosal dissection (ESD). However, inadequate understanding of GA-FG may lead to overtreatment, negatively impacting patient quality of life. We analyzed the clinical, endoscopic, and pathological characteristics of 25 cases of GA-FG. Immunohistochemical markers (CEA, MUC2, MUC5AC, MUC6, H + /K + ATPase, Pepsinogen-I, CgA, P53, and Ki67) were used to differentiate GA-FG from conventional gastric adenocarcinoma (CGA), neuroendocrine tumor (NET), gastric adenocarcinoma of fundic-gland mucosa type (GA-FGM), and other related conditions. The expression of β-catenin and Yes-associated protein (YAP) was also analyzed. All 25 GA-FG cases were located in the proximal stomach, with maximum diameter ranging from 4 to 20 mm. Histologically, the tumors displayed branching, mutual pulling or fusion of glandular duct structures, occasional sieve-like patterns, and mild cellular atypia. Some cases exhibited foveolar hyperplasia, with indistinct boundaries between proliferating and normal epithelium. The absence of an abrupt transition at low magnification was a critical feature to distinguish GA-FG from GA-FGM. Immunophenotypically, GA-FG resembled gastric-type adenocarcinoma with a low Ki67 index. The wild-type expression of P53 and varying Ki67 intensity patterns were helpful for diagnosing non-neoplastic hyperplasia. Abnormal β-catenin nuclear expression was found in 1 case, while 6 out of 12 showed positive YAP expression. GA-FG is a well-differentiated adenocarcinoma mimicking gastric fundic glands growth patterns. Accurate diagnosis of GA-FG is essential to accurate treatment and avoid oversurgery.
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Affiliation(s)
- Chang Zhao
- Department of Pathology, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510630, China
| | - Bo-Jin Su
- Department of Pathology, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510630, China
| | - Wei-Zhen Lin
- Department of Pathology, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510630, China
| | - An-Fang He
- Department of Pathology, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510630, China
| | - Da-Yang Hui
- Department of Pathology, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510630, China
| | - Hai-Ling Liu
- Department of Pathology, The Six Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510655, China
| | - Hui Chen
- Department of Pathology, Guangdong Provincial Key Laboratory of Major Obstetric Diseases, Guangdong Provincial Clinical Research Center for Obstetrics and Gynecology, The Third Affiliated Hospital, Guangzhou Medical University, Guangzhou, 510150, China
| | - Ming-Ya Xiao
- Department of Gastroenterology, Changsha Hospital of Traditional Chinese Medicine, Changsha, 410000, China
| | - Jian-Ning Chen
- Department of Pathology, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510630, China
| | - Hai-Feng Li
- Department of Pathology, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510630, China
| | - Jin-Yue Zheng
- Department of Pathology, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510630, China
| | - Wei-Jia Wang
- Department of Pathology, Yuedong Hospital of the Third Affiliated Hospital, Sun Yat-sen University, Meizhou, 514700, China.
| | - Yan Huang
- Department of Pathology, The Six Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510655, China.
| | - Chun-Kui Shao
- Department of Pathology, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510630, China.
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Shinozaki-Ushiku A, Koinuma D, Nakayama A, Nawa J, Fujishiro M, Ushiku T. Diffuse Cyclin D1 and SPINK1 Expression in Gastric Oxyntic Gland Neoplasms: Promising Diagnostic Markers Identified Using Spatial Transcriptome Analysis. Mod Pathol 2025; 38:100719. [PMID: 39863113 DOI: 10.1016/j.modpat.2025.100719] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/22/2024] [Revised: 01/12/2025] [Accepted: 01/15/2025] [Indexed: 01/27/2025]
Abstract
Oxyntic gland neoplasms typically arise in Helicobacter pylori-naive stomachs and are composed predominantly of chief cells, with a smaller component of parietal cells. Their pathologic diagnosis can be challenging owing to minimal cellular atypia. Especially in biopsy specimens with a limited tumor volume or when pathologists have limited experience in diagnosing this neoplasm, distinguishing them from normal oxyntic glands can be difficult, and no reliable diagnostic markers are currently available. In this study, single-cell spatial transcriptome analysis successfully identified significant upregulation of CCND1 and SPINK1 in all 6 analyzed cases of oxyntic gland neoplasms compared with normal oxyntic glands. Immunohistochemical analysis confirmed this finding in 21 endoscopically resected cases of oxyntic gland neoplasms, demonstrating that cyclin D1 and serine peptidase inhibitor Kazal type 1 (SPINK1) were diffusely expressed in oxyntic gland neoplasms, whereas their expression was scarcely observed in normal oxyntic glands, with a few of them showing weak to moderate staining. Even in biopsy specimens, these 2 markers highlighted the tumor areas and clearly distinguished neoplastic from normal oxyntic glands. Nonneoplastic foveolar epithelia and mucous neck cells also showed positive staining for both cyclin D1 and SPINK1. In addition, a mild increase in cyclin D1 expression and patchy or mosaic expression of SPINK1 were observed in fundic gland polyps, H. pylori-associated gastritis, and pyloric gland adenomas, whereas a diffuse staining pattern was specific to oxyntic gland neoplasms. These observations suggest that cyclin D1 and SPINK1 are reliable markers in differentiating oxyntic gland neoplasms from nonneoplastic oxyntic glands and pyloric gland adenomas. Cyclin D1 is commonly used for immunostaining in many pathology departments, and owing to its higher sensitivity and specificity compared with SPINK1, it is considered the best diagnostic marker.
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Affiliation(s)
- Aya Shinozaki-Ushiku
- Department of Pathology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan; Department of Integrative Genomics, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Daizo Koinuma
- Department of Pathology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Atsuhito Nakayama
- Department of Pathology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Junichi Nawa
- Department of Pathology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Mitsuhiro Fujishiro
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Tetsuo Ushiku
- Department of Pathology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
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Shibagaki K, Kushima R, Sekine S, Mishiro T, Kotani S, Miyaoka Y, Ishimura N, Araki A, Ohnuma H, Niino D, Ishihara S. Spectrum of gastric neoplasms in Helicobacter pylori-naïve patients. Dig Endosc 2025. [PMID: 39844451 DOI: 10.1111/den.14980] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/11/2024] [Accepted: 11/26/2024] [Indexed: 01/24/2025]
Abstract
Chronic Helicobacter pylori (Hp) infection is the largest etiological factor for gastric cancer, but in recent years the reports of Hp-naïve gastric neoplasms (HpNGNs) have increased as the Hp-infected population in Japan has been declining. The histopathologic spectrum of HpNGNs differs significantly from that of conventional Hp-infected gastric neoplasms. Molecularly, the former harbor considerably fewer genetic and epigenetic abnormalities, reflecting the absence of chronic inflammatory conditions in the gastric mucosa. The majority of HpNGNs fall within several specific histological entities; each arise from particular background mucosa. Most originate from the fundic gland mucosa and have a gastric immunophenotype, as seen in foveolar-type gastric adenoma (FGA), oxyntic gland adenoma (OGA)/gastric adenocarcinoma of fundic gland type (GA-FG), signet-ring cell carcinoma (SRCC), and sporadic fundic gland polyp with dysplasia (FGPD). In contrast, tumors arising from the pyloric or cardiac gland mucosa have a diverse immunophenotype, as seen in intestinal-type gastric dysplasia (IGD) and gastric cardiac carcinoma. FGA, FGPD, SRCC, and IGD are mostly found as small intramucosal lesions. OGA/GA-FG frequently progresses to invasive carcinoma, but only a few have lymph node metastases. Thus, these tumors are regarded as precancerous lesions by Western pathologists, while in Japan they tend to be diagnosed as carcinomas, even in cases of low-grade dysplasia. Gastric cardiac carcinomas, on the other hand, are often found as advanced carcinomas and harbor a high malignant biological potential. A new diagnostic framework for gastric neoplasms is required in the present era of Hp-naïve individuals in Japan.
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Affiliation(s)
- Kotaro Shibagaki
- Department of Endoscopy, Shimane University Hospital, Shimane, Japan
| | - Ryoji Kushima
- Department of Pathology, Shiga University of Medical Science, Shiga, Japan
| | - Shigeki Sekine
- Department of Pathology, Keio University School of Medicine, Tokyo, Japan
| | - Tsuyoshi Mishiro
- Department of Gastroenterology, Faculty of Medicine, Shimane University, Shimane, Japan
| | - Satoshi Kotani
- Department of Gastroenterology, Faculty of Medicine, Shimane University, Shimane, Japan
| | - Yoichi Miyaoka
- Department of Endoscopy, Shimane Prefectural Central Hospital, Shimane, Japan
| | - Norihisa Ishimura
- Department of Gastroenterology, Faculty of Medicine, Shimane University, Shimane, Japan
| | - Asuka Araki
- Department of Pathology, Shimane University Hospital, Shimane, Japan
| | - Hideyuki Ohnuma
- Department of Pathology, Shimane Prefectural Central Hospital, Shimane, Japan
| | - Daisuke Niino
- Department of Endoscopy, Shimane Prefectural Central Hospital, Shimane, Japan
| | - Shunji Ishihara
- Department of Gastroenterology, Faculty of Medicine, Shimane University, Shimane, Japan
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Goel A, Agrawal K, Mukherjee U, Singla V. Fundic gland adenocarcinoma. BMJ Case Rep 2024; 17:e261983. [PMID: 39631917 DOI: 10.1136/bcr-2024-261983] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/07/2024] Open
Abstract
Gastric malignancy is one of the most common malignancies diagnosed worldwide. Over the past many decades, extensive research has been made into the risk factors, pathogenesis and prognosis of gastric adenocarcinoma. However, gastric adenocarcinoma of the fundic gland (GA-FG) has been recently defined, and not much is known about its risk factors and pathogenesis. Since the first case, which was reported in 2007, only 195 cases have been described in the literature to date. The rarity of the lesion is the cause of unawareness of this entity among reporting pathologists, often leading to its misdiagnosis. Existing literature shows that the risk factors, pathogenesis and even the prognosis of GA-FG are remarkably different from gastric adenocarcinoma. Hence, early and correct diagnosis can have a significant impact on patient management and outcomes.
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Affiliation(s)
- Akash Goel
- Department of Gastroenterology, Hepatology and Endoscopy, Max Super Speciality Hospital Saket, New Delhi, Delhi, India
| | - Komal Agrawal
- Department of Histopathology, Max Super Speciality Hospital Saket, New Delhi, Delhi, India
| | - Urmi Mukherjee
- Department of Histopathology, Max Super Speciality Hospital, New Delhi, Delhi, India
| | - Vikas Singla
- Department of Gastroenterology, Hepatology and Endoscopy, Max Super Speciality Hospital Saket, New Delhi, Delhi, India
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Kelly P, Lauwers GY. Polyps and tumour‐like lesions of the stomach. MORSON AND DAWSON'S GASTROINTESTINAL PATHOLOGY 2024:195-226. [DOI: 10.1002/9781119423195.ch12] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/06/2025]
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Hayasaka J, Hoteya S, Takazawa Y, Kikuchi D, Araki A. Antacids and reflux esophagitis as a risk factor for gastric neoplasm of fundic-gland type: A retrospective, matched case-control study. J Gastroenterol Hepatol 2024; 39:1580-1585. [PMID: 38641971 DOI: 10.1111/jgh.16577] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/22/2023] [Revised: 03/17/2024] [Accepted: 04/01/2024] [Indexed: 04/21/2024]
Abstract
BACKGROUND AND AIM Since the first report of gastric adenocarcinoma of the fundic-gland type in 2010, the clinicopathological characteristics of gastric neoplasm of the fundic-gland type (GNFG) have become clearer; however, their risk factors remain unclear. This exploratory study aimed to identify the risk factors for GNFG. METHODS We conducted a single-center, retrospective, matched case-control study using medical information recorded at our health management center from January 2014 to July 2023. During this period, 39 240 people underwent upper gastrointestinal endoscopy. GNFG were extracted as cases and matched to controls, according to age and sex, in a 1:8 ratio, excluding those with a history of gastrointestinal surgery and those with a history or comorbidity of cancer. Univariate analysis was used to compare patient background and endoscopic findings. Multivariable analysis was performed, adjusting for factors with P values < 0.1 and antacid use. RESULTS A total of 20 GNFG cases and 160 matched healthy controls were included. In the univariate analysis, only reflux esophagitis was significantly more common in GNFG (40.0% vs 18.1%; P = 0.036). Factors antacids and duodenitis had P values < 0.1. Logistic regression analysis was performed, adjusting for antacids, reflux esophagitis, and duodenitis. Antacids and reflux esophagitis were the independent risk factors for GNFG (odds ratio = 3.68 [95% confidence interval: 1.04-11.91] and 3.25 [95% confidence interval: 1.11-9.35]). CONCLUSIONS Although the sample of patients with GNFG was small, antacids and reflux esophagitis were identified as a risk factor. The pathogenesis of antacids and reflux esophagitis may be involved in the development of GNFG.
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Affiliation(s)
- Junnosuke Hayasaka
- Department of Gastroenterology, Toranomon Hospital, Tokyo, Japan
- Okinaka Memorial Institute for Medical Research, Tokyo, Japan
| | - Shu Hoteya
- Department of Gastroenterology, Toranomon Hospital, Tokyo, Japan
| | | | - Daisuke Kikuchi
- Department of Gastroenterology, Toranomon Hospital, Tokyo, Japan
| | - Akihiro Araki
- Health Management Center, Toranomon Hospital, Tokyo, Japan
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8
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Suto D, Sato K, Yoshida M, Ota H, Otake T, Osawa Y, Nakazato Y, Ohdaira H, Suzuki Y, Kohgo Y. Gastric carcinoma of the fundic gland type developed 32 years after Helicobacter pylori eradication for duodenal ulcer: a case report. Ann Med Surg (Lond) 2024; 86:4227-4230. [PMID: 38989225 PMCID: PMC11230769 DOI: 10.1097/ms9.0000000000002192] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/06/2024] [Accepted: 05/08/2024] [Indexed: 07/12/2024] Open
Abstract
Introduction Gastric cancer has been reported to occur with mild to moderate mucosal atrophy, particularly after the eradication of Helicobacter pylori (HP) more than 10 years previously. However, no conclusion has been reached on how many years of esophagogastroduodenoscopy should be performed after HP eradication. Presentation of case This was a case of gastric carcinoma of the fundic gland type (GCFGT) 32 years after the eradication of HP, which is the longest posteradication period reported. A 62-year-old male patient was diagnosed with GCFGT after HP eradication and regular esophagogastroduodenoscopy, which revealed a white raised lesion on the anterior wall of the upper part of the body. Endoscopic submucosal dissection was performed for GCFGT, and the vertical and horizontal margins were negative. Clinical discussion In this case, HP was eradicated in 1990, and GCFGT developed 32 years later. To the best of our knowledge, this is the longest case in which gastric cancer appeared after HP eradication. HP eradication therapy for a duodenal ulcer was first reported in 1990, supporting that this is the longest case. Conclusions This is the first case of gastric cancer more than 20 years after the eradication of HP. The endoscopic findings of this case are typical of GCFGT and may be useful when encountering such cases in the future. Therefore, the risk of gastric cancer should be considered for an extended period even after the eradication of HP, and regular esophagogastroduodenoscopy is recommended even after the eradication of HP.
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Affiliation(s)
| | | | | | - Hiroyoshi Ota
- Department of Biomedical Laboratory Sciences, Shinshu University School of Medicine, Matsumoto, Japan
| | | | | | - Yoshimasa Nakazato
- Department of Pathology, International University of Health and Welfare Hospital, Nasushiobara, Tochigi
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Hayasaka J, Hoteya S, Suzuki Y, Ochiai Y, Mitsunaga Y, Odagiri H, Masui A, Kikuchi D, Takazawa Y. Comparison of Prognosis and Metachronous Gastric Tumor Rates After Endoscopic Submucosal Dissection Between Gastric Neoplasm of Fundic Gland Type Neoplasms and Conventional Gastric Adenocarcinoma. Cureus 2024; 16:e58467. [PMID: 38765360 PMCID: PMC11099554 DOI: 10.7759/cureus.58467] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 04/16/2024] [Indexed: 05/22/2024] Open
Abstract
INTRODUCTION Gastric neoplasm of the fundic gland type (GNFG) is a tumor with a good prognosis. However, since it has not been compared with conventional gastric adenocarcinoma (CGA), it is unknown whether it has a good prognosis or requires surveillance after treatment. The purpose of this study was to determine the prognosis and metachronous gastric tumor rates compared with those of CGA. METHODS We conducted a single-center, retrospective, matched-cohort study using our database from January 2010 to December 2021. We extracted GNFG data from the endoscopic submucosal dissection (ESD) database and matched patients with conventional early gastric cancer as controls in a 1:4 ratio by age and sex. GNFG and CGA were compared for the overall survival (OS), disease-specific survival, progression-free survival, and metachronous gastric tumor rates. RESULTS Overall, 43 lesions were GNFG and 164 CGAs were matched. There were three deaths in the GNFG group and 11 deaths in the CGA group. There was no significant difference in the OS between the two groups (P=0.81). The five-year OS rates for the GNFG and CGA groups were 90.9% and 92.9%, respectively. No disease-specific deaths or recurrences were observed in either group. There was no significant difference in the cumulative metachronous gastric tumor rate between the two groups (P=0.17). The cumulative five-year metachronous gastric tumor rates for the GNFG and CGA groups were 6.6% and 2.5%, respectively. CONCLUSIONS The prognosis for GNFG is good, however, not better than that for CGA. The metachronous gastric tumor rate after ESD in GNFG was not lower than that in CGA. Therefore, after ESD, GNFG may need to be managed in the same way as CGA.
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Affiliation(s)
| | - Shu Hoteya
- Gastroenterology, Toranomon Hospital, Tokyo, JPN
| | - Yugo Suzuki
- Gastroenterology, Toranomon Hospital, Tokyo, JPN
| | | | | | | | - Akira Masui
- Gastroenterology, Toranomon Hospital, Tokyo, JPN
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Liu L, Zhang X, Fan X, Zhu X. Genetic analysis of fundic gland‑type gastric adenocarcinoma. Mol Clin Oncol 2023; 19:82. [PMID: 37745263 PMCID: PMC10512195 DOI: 10.3892/mco.2023.2678] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/20/2023] [Accepted: 08/17/2023] [Indexed: 09/26/2023] Open
Abstract
This study aimed to analyze the molecular characteristics of gastric adenocarcinoma of the fundic-gland type (GAFG) and explore the possible mechanism of tumor development. Samples from 10 Chinese patients with GAFG were collected at the Peking University International Hospital and Liaocheng People's Hospital between January 2015 and March 2022. The nucleic acid sequence of Epstein Barr virus-encoded RNA (EBV-EBER) was detected by in situ hybridization. Genetic mutation information for GNAS, KRAS, NRAS, BRAF, PIK3CA, TP53, APC, CTNNB1, HER2, MLH1, MSH2, MSH6, and PMS2 was obtained by Next-Generation Sequencing, and the relevant literature was reviewed. A total of eight instances of missense mutations were detected, consisting of seven cases with GNAS mutations, two cases with KRAS mutations, and one case with a TP53 mutation. Additionally, two patients had simultaneous missense mutations in GNAS and KRAS. Nonsynonymous mutations in APC, CTNNB1, NRAS, BRAF, PIK3CA, HER2, MLH1, MSH2, MSH6, or PMS2 were not observed in any cases. In addition, all tumors were EBER-negative. GAFG exhibits diversity at the molecular level, and GNAS mutations are more common than KRAS mutations, TP53 mutations, and microsatellite instability. To date, no association between EBV/HER2 and GAFG has been found.
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Affiliation(s)
- Lei Liu
- Department of Pathology, Peking University International Hospital, Beijing 102206, P.R. China
| | - Xuedong Zhang
- Department of Pathology, Liaocheng People's Hospital, Liaocheng, Shandong 252000, P.R. China
| | - Xue Fan
- Department of Gastroenterology, Peking University International Hospital, Beijing 102206, P.R. China
| | - Xiaoyun Zhu
- Department of Pathology, Peking University International Hospital, Beijing 102206, P.R. China
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11
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Asahara H, Takao T, Asahara Y, Asahara M, Motomura D, Sakaguchi H, Yoshizaki T, Ikezawa N, Takao M, Morita Y, Toyonaga T, Komatsu M, Kushima R, Kodama Y. Clinicopathological Features and the Prevalence of Oxyntic Gland Neoplasm: A Single-center Retrospective Study. Intern Med 2023; 62:2763-2774. [PMID: 36792200 PMCID: PMC10602823 DOI: 10.2169/internalmedicine.0552-22] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/04/2022] [Accepted: 12/14/2022] [Indexed: 02/16/2023] Open
Abstract
Objective We explored the clinicopathological characteristics and disease frequency of oxyntic gland neoplasms (OGNs). Methods We retrospectively evaluated the data of patients pathologically diagnosed with OGN at an internal medicine clinic. Patients A total of 13,240 upper gastrointestinal endoscopies were performed on 7,488 patients between December 1, 2017, and March 31, 2021. Results We identified 27 patients with 30 histopathologically confirmed OGNs, yielding a disease frequency of 0.36% (27/7,488). Furthermore, multiple simultaneous lesions were found in 3 of 27 patients (11%). One (3.3%) of the 30 lesions was present in the antrum, whereas the remaining lesions occurred in the body of the stomach. Nine (33%) of the 27 patients had no history of Helicobacter pylori infection, whereas the remaining 18 (67%) were either currently or had been previously infected. Nevertheless, 27/30 lesions (90%) still occurred in non-atrophied regions. After endoscopic treatment, a histopathological examination of the resected specimens revealed submucosal infiltration in 8 (44%) of the 18 lesions; however, none of the lesions showed submucosal desmoplasia. For all patients with submucosal involvement, only observation was performed. There were no recurrent lesions found on follow-up. Conclusion The period prevalence of OGN was 0.36%, which is much higher than previously reported. The discovery of a small submucosal appearing lesion with a faded yellow or white color and dilated microvasculature, especially in a non-atrophic area of the stomach, should raise suspicion for an OGN, which can be endoscopically managed.
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Affiliation(s)
- Hikari Asahara
- Department of Gastroenterology, Kobe Red Cross Hospital, Japan
| | - Toshitatsu Takao
- Department of Gastroenterology, Kobe University Graduate School of Medicine, Japan
| | | | | | - Douglas Motomura
- Division of Gastroenterology, Department of Medicine, University of British Columbia, Canada
| | - Hiroya Sakaguchi
- Department of Gastroenterology, Kobe University Graduate School of Medicine, Japan
| | - Tetsuya Yoshizaki
- Department of Gastroenterology, Kobe University Graduate School of Medicine, Japan
| | - Nobuaki Ikezawa
- Department of Gastroenterology, Kobe University Graduate School of Medicine, Japan
| | - Madoka Takao
- Department of Gastroenterology, Kobe University Graduate School of Medicine, Japan
| | - Yoshinori Morita
- Department of Gastroenterology, Kobe University Graduate School of Medicine, Japan
| | - Takashi Toyonaga
- Department of Gastroenterology, Kobe University Graduate School of Medicine, Japan
| | - Masato Komatsu
- Division of Diagnostic Pathology, Kobe University Graduate School of Medicine, Japan
| | - Ryoji Kushima
- Department of Pathology, Shiga University of Medical Science Hospital, Japan
| | - Yuzo Kodama
- Department of Gastroenterology, Kobe University Graduate School of Medicine, Japan
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12
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Krooks J, Thaker H, Qiu S, Reep G, He J. Oxyntic Gland Adenoma in a Patient With Refractory Reflux. Cureus 2023; 15:e38577. [PMID: 37284353 PMCID: PMC10239566 DOI: 10.7759/cureus.38577] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 05/04/2023] [Indexed: 06/08/2023] Open
Abstract
A 58-year-old African American male was referred for endoscopic evaluation due to a persistent nine-year history of reflux. Previous endoscopy nine years ago revealed a small hiatal hernia and chronic gastritis caused by Helicobacter pylori (H. pylori), which was treated with triple therapy. During the current endoscopic evaluation, findings consistent with reflux esophagitis were identified, along with the discovery of an incidental 6 mm sessile polyp in the gastric fundus. Pathological examination revealed the presence of an oxyntic gland adenoma (OGA). Otherwise, the stomach was found to be unremarkable endoscopically and histologically. OGA is a rare gastric neoplasm that is primarily observed in Japan, with very few reported cases in North America. Studies have suggested a potential association with antacids, while the role of H. pylori in the development of OGA remains controversial. Our patient's OGA was completely resected during the endoscopy, with no recurrence noted on the three-month follow-up.
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Affiliation(s)
- Jolie Krooks
- Pathology, University of Texas Medical Branch, Galveston, USA
| | | | - Suimin Qiu
- Pathology, University of Texas Medical Branch, Galveston, USA
| | - Gabriel Reep
- Gastroenterology and Hepatology, University of Texas Medical Branch, Galveston, USA
| | - Jing He
- Pathology, University of Texas Medical Branch, Galveston, USA
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Iwamuro M, Kusumoto C, Nakagawa M, Matsueda K, Kobayashi S, Yoshioka M, Inaba T, Toyokawa T, Sakaguchi C, Tanaka S, Tanaka T, Okada H. Lesion size, elevated morphology, and non or closed-type atrophy are predictive factors for gastric adenocarcinoma of the fundic gland type rather than oxyntic gland adenoma. J Gastrointest Oncol 2023; 14:554-562. [PMID: 37201070 PMCID: PMC10186535 DOI: 10.21037/jgo-22-870] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/07/2022] [Accepted: 03/02/2023] [Indexed: 03/18/2023] Open
Abstract
BACKGROUND An oxyntic gland neoplasm confined to the mucosal layer (T1a) is classified as an oxyntic gland adenoma, whereas that with submucosal invasion (T1b) is defined as gastric adenocarcinoma of the fundic gland type (GA-FG). METHODS To reveal the differences in clinical features between them, we retrospectively investigated 136 patients with 150 oxyntic gland adenoma and GA-FG lesions. RESULTS The univariate analysis revealed that the mean size (GA-FG vs. oxyntic gland adenoma, 7.7±5.4 vs. 5.5±3.1 mm), the prevalence of elevated morphology (79.1% vs. 51.8%), black pigmentation within the lesion (23.9% vs. 9.6%), and non or closed-type atrophy (81.2% vs. 65.1%) were different between the two groups. A multivariate logistic regression analysis revealed that ≥5 mm lesion size (odds ratio, 2.96; 95% confidence interval: 1.21-7.23), elevated morphology (odds ratio, 2.40; 95% confidence interval: 1.06-5.45), and no or closed-type atrophy (odds ratio, 2.49; 95% confidence interval: 1.07-5.80) were factors in distinguishing GA-FG from oxyntic gland adenoma. When oxyntic gland neoplasms with no or one feature were judged as oxyntic gland adenomas and those with two or three features were judged as GA-FG, the sensitivity and specificity were 85.1% and 43.4% for GA-FG, respectively. CONCLUSIONS We identified three possible distinctive features of GA-FG compared to oxyntic gland adenoma: lesion size ≥5 mm, elevated morphology, and no or closed-type atrophy.
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Affiliation(s)
- Masaya Iwamuro
- Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Okayama, Japan
| | - Chiaki Kusumoto
- Department of Gastroenterology, Nippon Kokan Fukuyama Hospital, Fukuyama, Hiroshima, Japan
| | - Masahiro Nakagawa
- Department of Endoscopy, Hiroshima City Hospital, Hiroshima, Hiroshima, Japan
| | - Kazuhiro Matsueda
- Department of Gastroenterology and Hepatology, Kurashiki Central Hospital, Kurashiki, Okayama, Japan
| | - Sayo Kobayashi
- Department of Internal Medicine, Fukuyama City Hospital, Fukuyama, Hiroshima, Japan
| | - Masao Yoshioka
- Department of Internal Medicine, Okayama Saiseikai General Hospital, Okayama, Okayama, Japan
| | - Tomoki Inaba
- Department of Gastroenterology, Kagawa Prefectural Central Hospital, Takamatsu, Kagawa, Japan
| | - Tatsuya Toyokawa
- Department of Gastroenterology, National Hospital Organization Fukuyama Medical Center, Fukuyama, Hiroshima, Japan
| | - Chihiro Sakaguchi
- Department of Endoscopy, National Hospital Organization Shikoku Cancer Center, Matsuyama, Ehime, Japan
| | - Shouichi Tanaka
- Department of Gastroenterology, National Hospital Organization Iwakuni Clinical Center, Iwakuni, Yamaguchi, Japan
| | - Takehiro Tanaka
- Department of Pathology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama, Okayama, Japan
| | - Hiroyuki Okada
- Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Okayama, Japan
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Guo BZ, Liu ZZ, Shen GF, Zhu F, Lian HF, Li X, Zheng JY, Li JP, Deng SM, Huang R. Clinicopathological features of gastric adenocarcinoma of fundic gland type. Shijie Huaren Xiaohua Zazhi 2023; 31:244-248. [DOI: 10.11569/wcjd.v31.i6.244] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 03/28/2023] Open
Abstract
BACKGROUND 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.
AIM 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.
METHODS 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.
RESULTS 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.
CONCLUSION 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.
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Iwamuro M, Kusumoto C, Nakagawa M, Matsueda K, Kobayashi S, Yoshioka M, Inaba T, Toyokawa T, Sakaguchi C, Tanaka S, Tanaka T, Okada H. Endoscopic features of oxyntic gland adenoma and gastric adenocarcinoma of the fundic gland type differ between patients with and without Helicobacter pylori infection: a retrospective observational study. BMC Gastroenterol 2022; 22:294. [PMID: 35692036 PMCID: PMC9188703 DOI: 10.1186/s12876-022-02368-w] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/15/2022] [Accepted: 06/06/2022] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND The endoscopic features of oxyntic gland adenoma and gastric adenocarcinoma of the fundic gland type have not been fully investigated in relation to Helicobacter pylori infection status. We compared the morphology, color, and location of these lesions between patients with and without H. pylori infection. METHODS We retrospectively enrolled 165 patients (180 lesions) from 10 institutions. We divided the patients into the (i) Hp group (patients with current H. pylori infection [active gastritis, n = 13] and those with past infection [inactive gastritis, n = 76]) and (ii) uninfected group (H. pylori-uninfected patients, n = 52). We compared the clinical and endoscopic features of the two groups. We also performed an analysis between (i) lesions with atrophy of the surrounding gastric mucosa (atrophy group) and (ii) lesions without atrophy of the surrounding gastric mucosa (non-atrophy group). RESULTS The average age was older in the Hp group than in the uninfected group (68.1 ± 8.1 vs. 63.4 ± 8.7 years, p < 0.01). Although the difference was not statistically significant (p = 0.09), multiple lesions were observed in 9 of 89 patients (10.1%) in the Hp group and in only 1 of 52 patients (1.9%) in the uninfected group. Meanwhile, significant differences were observed in the prevalence of lesions located in the gastric fornix or cardia (uninfected group: 67.3% vs. Hp group: 38.0%, p < 0.01), with an elevated morphology (80.0% vs. 56.0%, p < 0.01), with a subepithelial-like appearance (78.2% vs. 42.0%, p < 0.01), and with a color similar to that of the peripheral mucosa (43.6% vs. 25.0%, p = 0.02). The male-to-female ratio, lesion size, and presence or absence of vascular dilatation or black pigmentation on the surface were not different between the two groups. In the analysis comparing lesions with and without mucosal atrophy, the prevalence of multiple lesions was significantly higher (p = 0.02) in the atrophy group (5/25 patients, 20.0%) than in the non-atrophy group (7/141 patients, 5.0%). CONCLUSIONS The endoscopic features of oxyntic gland adenoma and gastric adenocarcinoma of the fundic gland type differ between patients with and without H. pylori infection.
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Affiliation(s)
- Masaya Iwamuro
- Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku, Okayama, Okayama, 700-8558, Japan.
| | - Chiaki Kusumoto
- Department of Gastroenterology, Nippon Kokan Fukuyama Hospital, 1844 Tsunoshita, Daimon-cho, Fukuyama, Hiroshima, Japan
| | - Masahiro Nakagawa
- Department of Endoscopy, Hiroshima City Hospital, 7-33 Motomachi, Naka-ku, Hiroshima, 730-8518, Japan
| | - Kazuhiro Matsueda
- Department of Gastroenterology and Hepatology, Kurashiki Central Hospital, 1-1-1 Miwa, Kurashiki, Okayama, 710-8602, Japan
| | - Sayo Kobayashi
- Department of Internal Medicine, Fukuyama City Hospital, 5-23-1 Zao-cho, Fukuyama, Hiroshima, 721-8511, Japan
| | - Masao Yoshioka
- Department of Internal Medicine, Okayama Saiseikai General Hospital, 2-25 Kokutai-cho, Kita-ku, Okayama, Okayama, 700-8511, Japan
| | - Tomoki Inaba
- Department of Gastroenterology, Kagawa Prefectural Central Hospital, 1-2-1 Asahi-cho, Takamatsu, Kagawa, 760-8557, Japan
| | - Tatsuya Toyokawa
- Department of Gastroenterology, Fukuyama Medical Center, 4-14-17 Okinogami-cho, Fukuyama, Hiroshima, 720-8520, Japan
| | - Chihiro Sakaguchi
- Department of Endoscopy, National Hospital Organization Shikoku Cancer Center, 160 Kou, Minamiumemoto-cho, Matsuyama, Ehime, 791-0280, Japan
| | - Shouichi Tanaka
- Department of Gastroenterology, Iwakuni Clinical Center, 1-1-1 Atago-cho, Iwakuni, Yamaguchi, 740-8510, Japan
| | - Takehiro Tanaka
- Department of Pathology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku, Okayama, Okayama, 700-8558, Japan
| | - Hiroyuki Okada
- Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku, Okayama, Okayama, 700-8558, Japan
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Luo R, Huang W, Chen L, Liu Y, Xu L, Zhang X, Xu C, Hou Y. SP70 is a potential biomarker to identify gastric fundic gland neoplasms. World J Surg Oncol 2022; 20:132. [PMID: 35468832 PMCID: PMC9036694 DOI: 10.1186/s12957-022-02564-8] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/19/2021] [Accepted: 03/11/2022] [Indexed: 12/13/2022] Open
Abstract
Background Gastric neoplasms with fundic gland differentiation include oxyntic gland adenomas (OGAs) and gastric adenocarcinomas of fundic gland type (GA-FGs). Due to their well-differentiated and similar morphology with normal fundic glands, it is usually challenging to identify these lesions in pathological diagnosis, especially in biopsy specimens. This study aims to explore and verify the potential role of a newly developed monoclonal antibody (McAb) NJ001 (SP70) in differentiating fundic neoplasms from non-neoplastic fundic gland lesions. Methods Twenty-three cases of histological confirmed gastric fundic gland neoplasms were obtained, including 12 cases of OGAs and 11 of GA-FGs. Fifty cases of fundic gland polyps (FGPs) were taken as the control group. Six cases of well-differentiated gastric neuroendocrine tumors (NETs) (easily misdiagnosed) were also obtained. Key clinicopathological information was collected. SP70 immunostaining was performed (with para-tumor normal fundic glands as internal control). The positive intensity and staining pattern of SP70 were analyzed and compared. Results In normal gastric mucosa, SP70 was strongly and diffusely stained on the cytoplasm in fundic glands, but not in the foveolar epithelium. Therefore, a zonal distribution of SP70 was observed in normal mucosa. FGPs (50/50, 100%) shared a similar expression pattern with normal fundic glands. In fundic gland neoplasms, a significant down-expression of SP70 was observed in both OGAs and GA-FGs. The positive rate of SP70 in fundic gland neoplasms (6/23, 26.1%) was significantly lower than that in FGPs (100%) (P<0.0001). There was no difference in SP70 expression between OGAs (3/12, 25.0%) and GA-FGs (3/11, 27.2%) group (P>0.05). In these 6 NET cases, SP70 was weak to moderate intensity in the majority of tumor cells (with a different expression pattern). Conclusion Down-expression of SP70 is a specific feature to fundic gland neoplasms including OGAs and GA-FGs. Therefore, SP70 can serve as a potential biomarker in the identification and differential diagnosis of fundic gland neoplasms.
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Affiliation(s)
- Rongkui Luo
- Department of Pathology, Zhongshan Hospital, Fudan University, No. 180 Fenglin Rd, Xuhui District, Shanghai, 200032, People's Republic of China
| | - Wen Huang
- Department of Pathology, Zhongshan Hospital, Fudan University, No. 180 Fenglin Rd, Xuhui District, Shanghai, 200032, People's Republic of China
| | - Lingli Chen
- Department of Pathology, Zhongshan Hospital, Fudan University, No. 180 Fenglin Rd, Xuhui District, Shanghai, 200032, People's Republic of China
| | - Yalan Liu
- Department of Pathology, Zhongshan Hospital, Fudan University, No. 180 Fenglin Rd, Xuhui District, Shanghai, 200032, People's Republic of China
| | - Lei Xu
- Department of Pathology, Zhongshan Hospital, Fudan University, No. 180 Fenglin Rd, Xuhui District, Shanghai, 200032, People's Republic of China
| | - Xiaolei Zhang
- Department of Pathology, Zhongshan Hospital, Fudan University, No. 180 Fenglin Rd, Xuhui District, Shanghai, 200032, People's Republic of China
| | - Chen Xu
- Department of Pathology, Zhongshan Hospital, Fudan University, No. 180 Fenglin Rd, Xuhui District, Shanghai, 200032, People's Republic of China.
| | - Yingyong Hou
- Department of Pathology, Zhongshan Hospital, Fudan University, No. 180 Fenglin Rd, Xuhui District, Shanghai, 200032, People's Republic of China.
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Kakumoto A, Kuroda H, Jamiyan T, Shimakawa T, Masunaga A. Gastric Adenocarcinoma of the Fundic Gland Type: A Case Report. AMERICAN JOURNAL OF CASE REPORTS 2021; 22:e933474. [PMID: 34853292 PMCID: PMC8650407 DOI: 10.12659/ajcr.933474] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/09/2022]
Abstract
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 PDGFRa 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.
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Affiliation(s)
- Akinari Kakumoto
- Department of Diagnostic Pathology, Tokyo Women's Medical University, Medical Center East, Tokyo, Japan
| | - Hajime Kuroda
- Department of Diagnostic Pathology, Tokyo Women's Medical University, Medical Center East, Tokyo, Japan
| | - Tsengelmaa Jamiyan
- Department of Pathology and Forensic Medicine, Mongolian National University of Medical Sciences, Ulaanbaatar, Mongolia
| | - Takeshi Shimakawa
- Department of Surgery, Tokyo Women's Medical University, Medical Center East, Tokyo, Japan
| | - Atsuko Masunaga
- Department of Diagnostic Pathology, Tokyo Women's Medical University, Medical Center East, Tokyo, Japan
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Ueyama H, Yao T, Akazawa Y, Hayashi T, Kurahara K, Oshiro Y, Yamada M, Oda I, Fujioka S, Kusumoto C, Fukuda M, Uchita K, Kadota T, Oono Y, Okamoto K, Murakami K, Matsuo Y, Kato M, Maehata T, Yahagi N, Yasuhara Y, Yada T, Uraushihara K, Yamane T, Matsuo T, Ito M, Maruyama Y, Osako A, Ono S, Kato M, Yagi K, Hashimoto T, Tomita N, Tsuyama S, Saito T, Matsumoto K, Matsumoto K, Watanabe S, Uemura N, Chiba T, Nagahara A. Gastric epithelial neoplasm of fundic-gland mucosa lineage: proposal for a new classification in association with gastric adenocarcinoma of fundic-gland type. J Gastroenterol 2021; 56:814-828. [PMID: 34268625 PMCID: PMC8370942 DOI: 10.1007/s00535-021-01813-z] [Citation(s) in RCA: 27] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/24/2021] [Accepted: 07/10/2021] [Indexed: 02/04/2023]
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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Affiliation(s)
- Hiroya Ueyama
- Department of Gastroenterology, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-Ku, Tokyo, 113-8421, Japan.
| | - Takashi Yao
- Department of Human Pathology, Juntendo University Graduate School of Medicine, Tokyo, Japan
| | - Yoichi Akazawa
- Department of Gastroenterology, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-Ku, Tokyo, 113-8421, Japan
| | - Takuo Hayashi
- Department of Human Pathology, Juntendo University School of Medicine, Tokyo, Japan
| | - Koichi Kurahara
- Department of Gastroenterology, Matsuyama Red Cross Hospital, Ehime, Japan
| | - Yumi Oshiro
- Department of Pathology, Matsuyama Red Cross Hospital, Ehime, Japan
| | - Masayoshi Yamada
- Endoscopy Division, National Cancer Center Hospital, Tokyo, Japan
| | - Ichiro Oda
- Endoscopy Division, National Cancer Center Hospital, Tokyo, Japan
| | - Shin Fujioka
- Division of Gastroenterology, Fukuoka Red Cross Hospital, Fukuoka, Japan
| | - Chiaki Kusumoto
- Department of Gastroenterology, Nippon Kokan Fukuyama Hospital, Hiroshima, Japan
| | - Masayoshi Fukuda
- Department of Gastroenterology and Hepatology, Tokyo Medical and Dental University, Tokyo, Japan
| | - Kunihisa Uchita
- Department of Gastroenterology, Kochi Red Cross Hospital, Kochi, Japan
| | - Tomohiro Kadota
- Department of Gastroenterology and Endoscopy, National Cancer Center Hospital East, Chiba, Japan
| | - Yasuhiro Oono
- Department of Gastroenterology and Endoscopy, National Cancer Center Hospital East, Chiba, Japan
| | - Kazuhisa Okamoto
- Department of Gastroenterology, Faculty of Medicine, Oita University, Oita, Japan
| | - Kazunari Murakami
- Department of Gastroenterology, Faculty of Medicine, Oita University, Oita, Japan
| | - Yasumasa Matsuo
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, St. Marianna University School of Medicine, Kanagawa, Japan
| | - Motohiko Kato
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan
- Division of Research and Development for Minimally Invasive Treatment, Cancer Center, Keio University School of Medicine, Tokyo, Japan
| | - Tadateru Maehata
- Division of Research and Development for Minimally Invasive Treatment, Cancer Center, Keio University School of Medicine, Tokyo, Japan
| | - Naohisa Yahagi
- Division of Research and Development for Minimally Invasive Treatment, Cancer Center, Keio University School of Medicine, Tokyo, Japan
| | - Yumiko Yasuhara
- Department of Diagnostic Pathology, Kyoto-Katsura Hospital, Kyoto, Japan
| | - Tomoyuki Yada
- Department of Gastroenterology & Hepatology, National Center for Global Health and Medicine, Kohnodai Hospital, Chiba, Japan
| | - Koji Uraushihara
- Department of Gastroenterology and Hepatology, Showa General Hospital, Tokyo, Japan
| | - Tetsumi Yamane
- Department of Diagnostic Pathology, Tottori Red Cross Hospital, Tottori, Japan
| | - Taiji Matsuo
- Department of Endoscopy, Hiroshima University Hospital, Hiroshima, Japan
| | - Masanori Ito
- Department of General Internal Medicine, Hiroshima University Hospital, Hiroshima, Japan
| | - Yasuhiko Maruyama
- Department of Gastroenterology, Fujieda Municipal General Hospital, Shizuoka, Japan
| | - Ayumi Osako
- Department of Gastroenterology, Tottori Seikyo Hospital, Tottori, Japan
| | - Shoko Ono
- Department of Gastroenterology, Hokkaido University Hospital, Hokkaido, Japan
| | - Mototsugu Kato
- Department of Gastroenterology, National Hospital Organization Hakodate National Hospital, Hokkaido, Japan
| | - Kazuyoshi Yagi
- Department of Gastroenterology and Hepatology, Uonuma Institute of Community Medicine, Niigata University Medical and Dental Hospital, Niigata, Japan
| | - Takashi Hashimoto
- Department of Esophageal and Gastroenterological Surgery, Juntendo University School of Medicine, Tokyo, Japan
| | - Natsumi Tomita
- Department of Esophageal and Gastroenterological Surgery, Juntendo University School of Medicine, Tokyo, Japan
| | - Sho Tsuyama
- Department of Human Pathology, Juntendo University School of Medicine, Tokyo, Japan
| | - Tsuyoshi Saito
- Department of Human Pathology, Juntendo University School of Medicine, Tokyo, Japan
| | - Kohei Matsumoto
- Department of Gastroenterology, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-Ku, Tokyo, 113-8421, Japan
| | - Kenshi Matsumoto
- Department of Gastroenterology, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-Ku, Tokyo, 113-8421, Japan
| | - Sumio Watanabe
- Department of Gastroenterology, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-Ku, Tokyo, 113-8421, Japan
| | - Naomi Uemura
- Department of Gastroenterology & Hepatology, National Center for Global Health and Medicine, Kohnodai Hospital, Chiba, Japan
| | - Tsutomu Chiba
- Department of Gastroenterology and Hepatology, Kyoto University Graduate School of Medicine, Kyoto, Japan
- Kansai Electric Power Hospital, Osaka, Japan
| | - Akihito Nagahara
- Department of Gastroenterology, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-Ku, Tokyo, 113-8421, Japan
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Geospatial Assessments of DNA Adducts in the Human Stomach: A Model of Field Cancerization. Cancers (Basel) 2021; 13:cancers13153728. [PMID: 34359626 PMCID: PMC8345122 DOI: 10.3390/cancers13153728] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/01/2021] [Revised: 07/21/2021] [Accepted: 07/22/2021] [Indexed: 12/11/2022] Open
Abstract
BACKGROUND Field cancerization is a popular concept regarding where cancer cells arise in a plane, such as the opened-up gastrointestinal mucosa. The geospatial distribution of DNA adducts, some of which are believed to initiate mutation, may be a clue to understanding the landscape of the preferred occurrence of gastric cancer in the human stomach, such that the occurrence is much more frequent in the lesser curvature than in the greater curvature. METHODS Seven DNA adducts, C5-methyl-2'-deoxycytidine, 2'-deoxyinosine, C5-hydroxymethyl-2'-deoxycytidine, N6-methyl-2'-deoxyadenosine, 1,N6-etheno-2'-deoxyadenosine, N6-hydroxymethyl-2'-deoxyadenosine, and C8-oxo-2'-deoxyguanosine, from different points and zones of the human stomach were semi quantitatively measured by liquid chromatography/tandem mass spectrometry. The differences in the quantity of these DNA adducts from the lesser and greater curvature, the upper, middle and lower third zones, the anterior and posterior wall of the stomach, and the mucosae distant from and near the tumor were compared to determine whether the location preference of cancer in the stomach could be explained by the distribution of these DNA adducts. Comparisons were conducted considering the tumor locations and operation methods. CONCLUSIONS Regarding the DNA adducts investigated, significant differences in quantities and locations in the whole stomach were not noted; thus, these DNA adducts do not explain the preferential occurrence of cancer in particular locations of the human stomach.
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Iwamuro M, Kusumoto C, Nakagawa M, Kobayashi S, Yoshioka M, Inaba T, Toyokawa T, Hori S, Tanaka S, Matsueda K, Tanaka T, Okada H. Endoscopic resection is a suitable initial treatment strategy for oxyntic gland adenoma or gastric adenocarcinoma of the fundic gland type. Sci Rep 2021; 11:7375. [PMID: 33795810 PMCID: PMC8016920 DOI: 10.1038/s41598-021-86893-w] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/28/2020] [Accepted: 03/15/2021] [Indexed: 01/14/2023] Open
Abstract
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.
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Affiliation(s)
- Masaya Iwamuro
- Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku, Okayama, Okayama, 700-8558, Japan.
| | - Chiaki Kusumoto
- Department of Gastroenterology, Nippon Kokan Fukuyama Hospital, 1844 Tsunoshita, Daimon-cho, Fukuyama, Hiroshima, 721-0927, Japan
| | - Masahiro Nakagawa
- Department of Internal Medicine, Hiroshima City Hospital, 7-33 Motomachi, Naka-ku, Hiroshima, 730-8518, Japan
| | - Sayo Kobayashi
- Department of Internal Medicine, Fukuyama City Hospital, 5-23-1 Zao-cho, Fukuyama, Hiroshima, 721-8511, Japan
| | - Masao Yoshioka
- Department of Internal Medicine, Okayama Saiseikai General Hospital, 2-25 Kokutai-cho, Kita-ku, Okayama, Okayama, 700-8511, Japan
| | - Tomoki Inaba
- Department of Gastroenterology, Kagawa Prefectural Central Hospital, 1-2-1 Asahi-cho, Takamatsu, Kagawa, 760‑8557, Japan
| | - Tatsuya Toyokawa
- Department of Gastroenterology, Fukuyama Medical Center, 4-14-17 Okinogami-cho, Fukuyama, Hiroshima, 720-8520, Japan
| | - Shinichiro Hori
- Department of Endoscopy, National Hospital Organization Shikoku Cancer Center, 160 Kou, Minamiumemoto-cho, Matsuyama, Ehime, 791-0280, Japan
| | - Shouichi Tanaka
- Department of Gastroenterology, Iwakuni Clinical Center, 1-1-1 Atago-cho, Iwakuni, Yamaguchi, 740-8510, Japan
| | - Kazuhiro Matsueda
- Department of Gastroenterology and Hepatology, Kurashiki Central Hospital, 1-1-1 Miwa, Kurashiki, Okayama, 710-8602, Japan
| | - Takehiro Tanaka
- Department of Pathology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku, Okayama, Okayama, 700-8558, Japan
| | - Hiroyuki Okada
- Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku, Okayama, Okayama, 700-8558, Japan
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Abstract
Background: We aimed to provide insight into the actual frequencies of gastric adenoma types and their association with gastritis status and associated mucosal changes with a focus on Helicobacter infection and the operative link on gastritis assessment (OLGA)/operative link on gastric intestinal metaplasia assessment (OLGIM) staging. Methods: From the archive of the Institute of Pathology in Bayreuth, we collected a consecutive series of 1058 gastric adenomas diagnosed between 1987 and 2017. Clinicopathological parameters retrieved from diagnostic reports included adenoma type and localization, associated mucosal changes in antrum and corpus (i.e., type of gastritis, the extent of intestinal metaplasia and atrophy), gender, date of birth, and date of diagnosis. Results: Intestinal-type adenoma was the most frequent adenoma (89.1%), followed by foveolar-type adenoma (4.3%), pyloric gland adenoma (3.4%), adenomas associated with hereditary tumor syndromes (2.8%), and oxyntic gland adenoma (0.4%). Adenomas were found in the background of Helicobacter pylori (H. pylori) gastritis in 23.9%, Ex-H. pylori gastritis in 36.0%, autoimmune gastritis in 24.8%, chemical reactive gastritis in 7.4%, and others in 0.1%. More than 70% of patients with gastric adenomas had low-risk stages in OLGA and OLGIM. Conclusions: We found a higher frequency of foveolar-type adenoma than anticipated from the literature. It needs to be questioned whether OLGA/OLGIM staging can be applied to all patients.
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Li C, Wu X, Yang S, Yang X, Yao J, Zheng H. Gastric adenocarcinoma of the fundic gland type: clinicopathological features of eight patients treated with endoscopic submucosal dissection. Diagn Pathol 2020; 15:131. [PMID: 33097069 PMCID: PMC7585219 DOI: 10.1186/s13000-020-01047-2] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/14/2020] [Accepted: 10/15/2020] [Indexed: 02/08/2023] Open
Abstract
BACKGROUND Gastric adenocarcinoma of the fundic gland type (GA-FG) has been added to the 2019 edition of the World Health Organization's list of digestive system-associated cancers. This lesion differentiates toward the fundic gland and mostly involves chief cell-predominant differentiation with low-grade cytology. Clinicians and pathologists are still unaware of this rare disease; consequently, some cases are incorrectly diagnosed. This study aimed to investigate the clinicopathological features of GA-FG using retrospective analyses of endoscopic and pathological findings. MATERIALS AND METHODS Samples were collected from patients diagnosed with GA-FG. The clinical courses of all patients were monitored prospectively and reviewed retrospectively. Available clinical information, endoscopic features, pathological appearance, and follow-up data were assessed. Immunohistochemistry [mucin (MUC) 2, MUC5, MUC6, P53, CDX2, Ki67, SYN, CD56, CGA, β-catenin, and pepsinogen-I] was examined using Envision two-step method. RESULTS Eight cases of endoscopic submucosal dissection (ESD) were obtained from our institution. Patient age ranged from 48 to 80 years (mean, 65 years). Some patients were on acid-suppressing medication. Most lesions were located in the upper third (n = 7) and one was in the middle third of the stomach. Six lesions were of the superficial flat type, whereas two were of the superficial elevated type. Narrow-band imaging using magnifying endoscopy showed irregular microvascular patterns (MVPs) in four cases and regular MVPs in the remaining cases. All lesions were primarily solitary and ~ 6 mm in diameter (largest, 12 mm). The main body of the tumors were localized in the mucosal layer, of which six cases invade into the submucosal layer. Well-formed glands of chief cells were predominant. Tumor cells were positive for pepsinogen-I, MUC6, SYN, and CD56. Lymphatic and vascular infiltration and metastatic and recurrent disease were not observed in any case. CONCLUSION GA-FG, a well-differentiated adenocarcinoma with mild atypia, can be completely removed using ESD, with a favorable prognosis in patients.
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Affiliation(s)
- Chengfang Li
- Department of Pathology, Affiliated Hospital of Zunyi Medical University, Guizhou, 563003, China
| | - Xinglong Wu
- Department of Pathology, Affiliated Hospital of Zunyi Medical University, Guizhou, 563003, China
| | - Shuang Yang
- Department of Pathology, Affiliated Hospital of Zunyi Medical University, Guizhou, 563003, China
| | - Xiaorong Yang
- Department of Pathology, Affiliated Hospital of Zunyi Medical University, Guizhou, 563003, China
| | - Jin Yao
- Department of Pathology, Affiliated Hospital of Zunyi Medical University, Guizhou, 563003, China
| | - Hong Zheng
- Department of Pathology, Affiliated Hospital of Zunyi Medical University, Guizhou, 563003, China.
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Sato Y, Sato T, Matsushima J, Fujii A, Ono Y, Suda T, Katayama Y, Ban S. Histopathologic Change of a Case of Gastric Oxyntic Neoplasm (Gastric Adenocarcinoma of Fundic Gland Mucosa Type) Through 5 Years With Concurrent Other Oxyntic Gland Lesions. Int J Surg Pathol 2020; 29:557-564. [PMID: 33030084 DOI: 10.1177/1066896920962574] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Some gastric epithelial neoplasms show predominant chief cell differentiation (oxyntic gland neoplasms), in which the entity of "gastric adenocarcinoma of fundic gland type" was firstly designated, whereas a possible more aggressive subgroup "gastric adenocarcinoma of fundic gland mucosa type" (GA-FGM) was subsequently proposed. However, the histopathologic progression mode of these neoplasms has not been sufficiently reported. In this article, we describe a case of GA-FGM in which we could observe its progression during 5 years. The tumor was removed by endoscopic submucosal dissection 5 years after the first biopsy, which had already shown a feature of oxyntic gland neoplasm. During the follow-up period, the endoscopy revealed little change in the tumor appearance. However, the histology of endoscopic submucosal dissection showed submucosal extension with its histological progression. Besides, other oxyntic gland neoplasms of the stomach were observed metachronously or synchronously, giving an implication about a common pathogenetic basis of these lesions.
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Affiliation(s)
- Yoko Sato
- Department of Pathology, Dokkyo Medical University Saitama Medical Center, Koshigaya, Saitama, Japan
| | - Taiki Sato
- Department of Pathology, Dokkyo Medical University Saitama Medical Center, Koshigaya, Saitama, Japan
| | - Jun Matsushima
- Department of Pathology, Dokkyo Medical University Saitama Medical Center, Koshigaya, Saitama, Japan
| | - Akiko Fujii
- Department of Pathology, Dokkyo Medical University Saitama Medical Center, Koshigaya, Saitama, Japan
| | - Yuko Ono
- Department of Pathology, Dokkyo Medical University Saitama Medical Center, Koshigaya, Saitama, Japan
| | - Toshikuni Suda
- Department of Gastroenterology, Dokkyo Medical University Saitama Medical Center, Koshigaya, Saitama, Japan
| | - Yasumi Katayama
- Department of Gastroenterology, Dokkyo Medical University Saitama Medical Center, Koshigaya, Saitama, Japan
| | - Shinichi Ban
- Department of Pathology, Dokkyo Medical University Saitama Medical Center, Koshigaya, Saitama, Japan
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Ushiku T, Kunita A, Kuroda R, Shinozaki-Ushiku A, Yamazawa S, Tsuji Y, Fujishiro M, Fukayama M. Oxyntic gland neoplasm of the stomach: expanding the spectrum and proposal of terminology. Mod Pathol 2020; 33:206-216. [PMID: 31375767 DOI: 10.1038/s41379-019-0338-1] [Citation(s) in RCA: 43] [Impact Index Per Article: 8.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/14/2018] [Revised: 07/06/2019] [Accepted: 07/10/2019] [Indexed: 01/02/2023]
Abstract
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.
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Affiliation(s)
- Tetsuo Ushiku
- Department of Pathology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
| | - Akiko Kunita
- Department of Pathology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Ryohei Kuroda
- Department of Pathology, Center Hospital of the National Center for Global Health and Medicine, Tokyo, Japan
| | - Aya Shinozaki-Ushiku
- Department of Pathology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Sho Yamazawa
- Department of Pathology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Yosuke Tsuji
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Mitsuhiro Fujishiro
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Masashi Fukayama
- Department of Pathology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
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Yu YN, Yin XY, Sun Q, Liu H, Zhang Q, Chen YQ, Zhao QX, Tian ZB. Gastric adenocarcinoma of fundic gland type after Helicobacter pylori eradication: A case report. World J Clin Cases 2019; 7:1696-1702. [PMID: 31367629 PMCID: PMC6658382 DOI: 10.12998/wjcc.v7.i13.1696] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/23/2019] [Revised: 04/29/2019] [Accepted: 05/11/2019] [Indexed: 02/05/2023] Open
Abstract
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.
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Affiliation(s)
- Ya-Nan Yu
- Department of Gastroenterology, the Affiliated Hospital of Qingdao University, Qingdao 266003, Shandong Province, China
| | - Xiao-Yan Yin
- Department of Gastroenterology, the Affiliated Hospital of Qingdao University, Qingdao 266003, Shandong Province, China
| | - Qi Sun
- Department of Pathology, the Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing 210008, Jiangsu Province, China
| | - Hua Liu
- Department of Gastroenterology, the Affiliated Hospital of Qingdao University, Qingdao 266003, Shandong Province, China
| | - Qi Zhang
- Department of Gastroenterology, the Affiliated Hospital of Qingdao University, Qingdao 266003, Shandong Province, China
| | - Yun-Qing Chen
- Department of Pathology, the Affiliated Hospital of Qingdao University, Qingdao 266003, Shandong Province, China
| | - Qing-Xi Zhao
- Department of Gastroenterology, the Affiliated Hospital of Qingdao University, Qingdao 266003, Shandong Province, China
| | - Zi-Bin Tian
- Department of Gastroenterology, the Affiliated Hospital of Qingdao University, Qingdao 266003, Shandong Province, China
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Benedict MA, Lauwers GY, Jain D. Gastric Adenocarcinoma of the Fundic Gland Type: Update and Literature Review. Am J Clin Pathol 2018; 149:461-473. [PMID: 29648578 DOI: 10.1093/ajcp/aqy019] [Citation(s) in RCA: 41] [Impact Index Per Article: 5.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
OBJECTIVES Gastric adenocarcinoma of the fundic gland type (GA-FG) is a newly described entity with a lack of awareness amongst general surgical pathologists and this review highlights the key features and controversies associated with this uncommon neoplasm. METHODS A literature search through PubMed using synonyms for GA-FG was conducted to obtain 111 cases. RESULTS GA-FG is a well-differentiated neoplasm of oxyntic mucosa, that is comprised of chief cells and parietal cells. Chief cell differentiation is highlighted with Muc-6, RUNX3, and pepsinogen. Parietal cells are highlighted with H+/K+ ATPase and PDGFRA-α. Association with Helicobacter infection, chronic gastritis, intestinal metaplasia, or gastric atrophy is not seen. Most GA-FGs are confined to the mucosa. Deeper invasion, lymphovascular invasion, nodal metastasis, and extragastric spread are uncommon. CONCLUSIONS GA-FGs are rare lesions that typically follow a benign course. However, despite features of malignancy in some cases, complete surgical excision, sometimes with endoscopic mucosal resection, seems adequate treatment.
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Affiliation(s)
- Mark A Benedict
- Department of Pathology, Yale University School of Medicine, New Haven, CT
| | - Gregory Y Lauwers
- Department of Pathology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL
| | - Dhanpat Jain
- Department of Pathology, Yale University School of Medicine, New Haven, CT
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Nassereddine H, Poté N, Théou-Anton N, Lamoureux G, Fléjou JF, Couvelard A. A gastric MANEC with an adenocarcinoma of fundic-gland type as exocrine component. Virchows Arch 2017; 471:673-678. [PMID: 28653202 DOI: 10.1007/s00428-017-2178-z] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/03/2017] [Revised: 05/25/2017] [Accepted: 06/11/2017] [Indexed: 12/14/2022]
Affiliation(s)
- Hussein Nassereddine
- AP-HP and DHU UNITY, Département de Pathologie Bichat-Beaujon, Paris, France. .,Département de Pathologie, Hôpital Bichat, 46 rue Henri Huchard, 75018, Paris, France.
| | - Nicolas Poté
- AP-HP and DHU UNITY, Département de Pathologie Bichat-Beaujon, Paris, France.,Université Paris Diderot, Paris, France
| | | | - Gaële Lamoureux
- Département de Pathologie, Hôpital de Meulan-les-Mureaux, Meulan-en-Yvelines, France
| | | | - Anne Couvelard
- AP-HP and DHU UNITY, Département de Pathologie Bichat-Beaujon, Paris, France.,Université Paris Diderot, Paris, France
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The Japanese Viewpoint on the Histopathology of Early Gastric Cancer. ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY 2016; 908:331-46. [PMID: 27573779 DOI: 10.1007/978-3-319-41388-4_16] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Japanese histopathologists have traditionally had greater opportunity to study the histology and clinical course of early gastric cancer because of technological developments including double contrast radiography and endoscopy systems, combined with the higher incidence of gastric cancer in the general population in Japan. Endoscopic resection is now considered best practice for treatment of early gastric cancers with a negligible risk of lymph node metastasis. Histopathologic evaluation plays a critical role in assessing the likelihood of lymph node metastasis on endoscopically resected specimens. There remains disparity between Western and Japanese histopathologists in the conceptual approach to the histopathologic evaluation of neoplastic lesions in the upper gastrointestinal tract, in particular regarding lesions straddling the borderline between noninvasive and invasive disease. Although in routine practice, the clinical impact of these conceptual differences is small, this disparity does complicate international exchange of datasets and the development of globally applicable formal definitions. Here we review the current practice in histological diagnosis of early gastric cancer in Japan and discuss some of the conceptual differences between Japanese and Western histopathological assessment of lesions in the neoplastic stomach.
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