A Case of Oxyntic Gland Neoplasm Incidentally Found During Upper Endoscopic Screening

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Korean J Helicobacter Up Gastrointest Res. 2026;26(2):239-244

Publication date (electronic) : 2026 June 8

doi : https://doi.org/10.7704/kjhugr.2025.0078

Ji Yoon Kim¹, Joo Hyun Lim^,1,2

¹Department of Internal Medicine, Healthcare Research Institute, Seoul National University Hospital Healthcare System Gangnam Center, Seoul, Korea

²Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea

Corresponding author Joo Hyun Lim, MD, PhD Department of Internal Medicine, Healthcare Research Institute, Seoul National University Hospital Healthcare System Gangnam Center, 152 Teheran-ro, Gangnam-gu, Seoul 06236, Korea E-mail: limz00@gmail.com

Received 2025 November 5; Revised 2026 February 11; Accepted 2026 February 12.

Abstract

INTRODUCTION

With advances in immunohistochemistry for pathologic diagnosis, a new histological subtype of gastric neoplasm, oxyntic gland neoplasm (OGN), has been identified. Tsukamoto et al. [1] first reported a case of adenocarcinoma with chief cell differentiation in 2007. Subsequently, Ueyama et al. [2] proposed the term “gastric adenocarcinoma of the fundic gland type (GA-FG)” in 2010 to describe this novel entity of gastric adenocarcinoma, based on a series of similar cases exhibiting chief cell differentiation. According to the WHO classification, lesions confined to the mucosa are designated as oxyntic gland adenoma (OGA), whereas those showing submucosal invasion are categorized as GA-FG [3]. OGN represents a relatively rare subtype of gastric neoplasm, with limited cases and available data. Because of its nonspecific endoscopic appearance, it can be difficult to differentiate from other lesions such as fundic gland polyps and gastric neuroendocrine tumors [4]. These factors contribute to the diagnostic challenge of OGN. In this report, we present a case of GA-FG that was incidentally detected during a surveillance upper endoscopy, aiming to enhance the understanding of this rare gastric neoplasm.

CASE REPORT

A 57-year-old male patient underwent routine health surveillance with no apparent symptoms. He had no significant past medical history and was non-smoker with no notable history of alcohol consumption. The patient had been undergoing surveillance upper gastrointestinal endoscopy every two to three years. The patient received Helicobacter pylori eradication therapy six years earlier for chronic atrophic gastritis with H. pylori infection confirmed by PCR assay, and successful eradication was verified by a urea breath test. The previous examination, performed three years earlier, revealed chronic atrophic gastritis (Kimura Takemoto Classification C3) with intestinal metaplasia. Laboratory tests, including blood chemistry, liver and renal function tests, as well as tumor markers (CA 19-9 and CEA), were within normal limits. An endoscopic examination revealed a single hyperemic erosion on the greater curvature of the upper body, along with chronic atrophic gastritis (C3) and intestinal metaplasia. The lesion measured approximately 0.3 cm in diameter and appeared slightly elevated, with hyperemic erosion on its surface (Fig. 1). A biopsy was performed under the impression of a single erosion. Histopathologic examination showed fundic gland proliferation with 1) mild architectural atypia and 2) findings indefinite for submucosal invasion, suggestive of a fundic gland neoplasm (OGA vs. GA-FG) (Fig. 2). The patient was referred for further management, and endoscopic mucosal resection using the cap-assisted method (EMR-C) was performed the next month, without any procedure-related adverse events (Fig. 3). The pathologic evaluation of the resected specimen revealed an adenocarcinoma of the fundic gland type, measuring 0.5×0.4×0.2 cm, with submucosal invasion (450 μm). En-bloc resection was successfully achieved, and no lymphovascular invasion was identified. The pathologic stage was pT1b (Fig. 4). Post-EMR stomach CT performed one week later showed no evidence of residual tumor or metastasis. Follow-up endoscopy performed three months later demonstrated a well-healed post-EMR scar, with no evidence of recurrent or residual lesion. The patient is scheduled for a 1-year follow-up endoscopy.

Fig. 1.

Initial endoscopic image of incidentally detected oxyntic gland neoplasm. A slightly elevated lesion measuring approximately 0.3 cm with hyperemic erosion on its surface was noted on the greater curvature of the high body.

Fig. 2.

Histologic image of the biopsy. A: Fundic gland proliferation is noted (H&E, ×200). B: High power view showing mild architectural atypia with predominantly chief cell–like cells and fewer parietal cell–like cells (H&E, ×400). H&E, haematoxylin and eosin stain.

Fig. 3.

Endoscopic mucosal resection using the cap-assisted method was performed.

Fig. 4.

Histopathologic image of the endoscopically resected lesion. A: Gross image of the resected specimen. B: Low-power view of the whole section showing a fundic gland–like structure (H&E, ×100). C: Medium magnification view showing tubular glands with mild architectural atypia, composed predominantly of chief cell–like cells and fewer parietal cell–like cells (H&E, ×200). D: High magnification view showing smooth muscle invasion (H&E, ×400). H&E, haematoxylin and eosin stain.

DISCUSSION

In this report, we presented a case of an asymptomatic individual diagnosed with OGN during screening endoscopy and treated with EMR-C. OGN is a relatively rare condition that includes OGA, GA-FG, and the recently identified gastric adenocarcinoma of fundic-gland mucosa type (GA-FGM) [5]. Gastric neoplasms with oxyntic gland differentiation consist of cells showing mild cytonuclear atypia, differentiating into chief cells and, to a lesser extent, parietal cells. Intramucosal tumors with biologically benign behavior are classified as OGA, whereas those with submucosal invasion are categorized as GA-FG. Among the latter, tumors showing differentiation not only into fundic glands but also into foveolar epithelium and mucous glands are classified as GA-FGM, which display atypical histological features associated with more aggressive biological behavior [6,7]. A retrospective study investigating 136 patients with 150 OGA and GA-FG lesions performed a multivariate logistic regression analysis, which suggested that a lesion size ≥5 mm, elevated morphology, and the absence or closed type of atrophy were factors distinguishing GA-FG from OGA [8].

The exact prevalence of OGN has not been established. Earlier studies have reported the prevalence rates of less than 0.01%, while some recent reports have found rates as high as 0.047% and even 0.36% [5,9]. The higher prevalence observed in recent studies may be attributed to advances in knowledge and diagnostic experience among endoscopists and pathologists. A review of 29 OGN cases reported a median patient age of 65 years, with males accounting for 58.6% of cases. Most lesions exhibited a superficially elevated or subepithelial tumor-like appearance on endoscopy. The majority were located in the upper parts of the stomach, predominantly in the body region horizontally and on the greater curvature side cross-sectionally. They were also found in non-atrophic areas of the stomach, suggesting a distinct pathogenesis from conventional gastric adenoocarcinoma [3].

Because most lesions are small and difficult to distinguish from other entities such as gastric neuroendocrine tumors or fundic gland polyps, histopathologic evaluation, particularly immunohistochemical staining, is essential for accurate diagnosis. Histologically, OGN consists of well-differentiated columnar cells resembling fundic gland cells, with mildly enlarged nuclei and a pale gray-blue basophilic cytoplasm [3]. Immunohistochemical markers useful for differential diagnosis include pepsinogen I for chief cells, H⁺/K⁺-ATPase for parietal cells, MUC-5AC for surface epithelial cells, and MUC-6 for mucous neck or pyloric gland cells [5]. Typical OGA and GA-FG are positive for MUC-6 and negative for MUC-5AC, while also showing positivity for pepsinogen I and H⁺/K⁺-ATPase [3,9]. However, GA-FGM, considered a higher-grade variant, may exhibit MUC-5AC positivity, indicating differentiation toward gastric foveolar epithelium (Table 1) [7]. A study analyzing OGN based on invasion depth found that tumors confined to the mucosa were small (2–9 mm) and exhibited only mild cytonuclear atypia. Even tumors with submucosal invasion tended to retain a low-grade malignant profile when atypical histological features were absent. In contrast, submucosally invasive tumors with atypical features showed abnormal cellular differentiation, including mucous neck and foveolar epithelial components, and were associated with lymphovascular invasion and deeper submucosal infiltration. Overall, OGN is generally regarded as a neoplasm with low malignant potential; however, a subset characterized by atypical histological features may exhibit more aggressive behavior [6]. A retrospective study of pathologically diagnosed OGNs reported very low Ki-67 labeling indices in all endoscopically resected cases, including those with submucosal invasion, further supporting the notion that OGN has low malignant potential [9].

Table 1.

Histologic features and immunohistochemical profiles of oxyntic gland neoplasms

Initially, OGN was thought to occur exclusively in patients without H. pylori infection. However, as in our case, subsequent studies have demonstrated that OGN can also occur in previously infected patients, particularly in non-atrophic regions, regardless of H. pylori status [9]. The role of H. pylori infection in OGN, however, remains unclear. A retrospective observational study categorizing OGN patients by H. pylori infection status and mucosal atrophy revealed that OGNs share similar carcinogenic and biological characteristics irrespective of infection status. Nonetheless, H. pylori-uninfected cases were more frequently located in the gastric fundus or cardia, presenting as elevated, subepithelial-like lesions with a coloration similar to that of the surrounding mucosa. In contrast, patients with current or past infection tended to present with flat lesions in atypical locations rather than in the upper third of the stomach. Multiple lesions were also significantly more common in the atrophic group than in non-atrophic group [10]. Due to its histologic similarity to fundic gland polyps, the relationship between OGN and proton pump inhibitor (PPI) use warrants further investigation, as fundic gland polyps are known to develop with long-term PPI therapy [9].

Currently, there are no established guidelines for OGN treatment. Most OGNs have non-tumorous epithelial cells covering the tumor surface, making superficial biopsy a diagnostic challenge [3]. OGN is also notable for its potential to infiltrate the submucosal layer even when very small [9]. Therefore, endoscopic resection of all detected OGNs, regardless of size, may be justified. EMR-C and endoscopic submucosal dissection (ESD) are often commonly employed, both achieving high en bloc resection rates. A retrospective histological review of endoscopically resected OGNs found that all lesions treated with either EMR or ESD were confined to the mucosa or submucosa, had negative vertical margins, and demonstrated lymphovascular invasion in only 1.6% of cases [11]. Another retrospective study comparing precut EMR and ESD for the treatment of OGN reported no significant differences between the two methods in terms of en bloc resection, complete resection, or curative resection rates [5]. Given its simplicity and effectiveness, EMR-C may be preferred for small lesions, as it avoids the technical complexity and time requirements associated with ESD [3,8]. In our case, the lesion was small, measuring approximately 0.3 cm in diameter, with relatively well-defined margins and no findings suggestive of deep invasion; therefore, EMR-C was considered an appropriate treatment option.

Currently, there are no established guidelines for post-resection surveillance of OGN. However, previous studies have shown that OGNs have a low malignant potential, with a low likelihood of deep invasion and lymphovascular invasion [11]. A study evaluating appropriate endoscopic surveillance strategies following curative resection of early gastric cancer recommended intensive surveillance within 6 months, followed by annual surveillance for at least 5 years [12]. As complete resection was achieved in our case, we adopted this surveillance strategy. Accordingly, a short-term follow-up endoscopy was performed 3 months after the resection, and a 1-year follow-up endoscopy is scheduled.

In conclusion, OGN is a rare subset of gastric neoplasms that are generally non-aggressive but can demonstrate malignant potential. Although its diagnosis has increased due to greater awareness among endoscopists and pathologists, many aspects of this entity remain to be elucidated. Further studies with larger cohorts and long-term follow-up are required to establish optimal management strategies and clarify the long-term outcomes of OGN.

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