This was the first study to report the disease prevalence rate per patient among those undergoing endoscopy, which has great significance. We discovered 30 oxyntic gland neoplastic lesions in 27 patients over a 40-month period between December 2017 and March 2021 at the Asahara Clinic (a single facility). The rate of identification of these lesions per number of patients undergoing upper gastrointestinal endoscopy was 0.36% (27/7488). Second, our results showed that OGNs metastasized to adjoining areas in 11% of patients (3/27). While OGNs are characterized with early submucosal infiltration. In this study, despite locating the lesions being found while they were quite small with a median pathological size (width) of 5 mm (2–8), submucosal infiltration occurred in 47% (8 /17) of the lesions.
According to WHO Classification of Gastric Carcinoma (Fifth edition), the exact frequency of OGNs is unknown . The previous report listed as a reference have reported a value of < 0.01% on the frequency of OGNs . This 0.01% figure was calculated as the proportion of 30,182 individuals who underwent yearly check-up endoscopies during a period of 3 years and 11 months. However, this rate was not an accurate prevalence because some individuals underwent multiple screenings during the study period. We estimated the incidence of OGNs as 0.36% (27/7488) for the entire cohort of 7488 patients. Screening by experienced endoscopist with a high-definition endoscope might lead to more frequent detection of OGNs.
Thirteen lesions in 13 patients diagnosed with OGNs had been previously imaged during endoscopy. From this, we concluded that diagnosis of oxyntic gland neoplasm was difficult if an endoscopist and a pathologist performing the diagnosis were not familiar with both the endoscopic and histological images of the oxyntic gland neoplasm. Should endoscopists and pathologists become aware of OGNs, their identification/incidence rates would improve.
OGNs have been reported as slow-growing tumors  At the same time, cases of lymph node metastasis and OGNs with advanced cancer have also been reported [13, 14]. We should carefully examine each case such that these rare lesions are not missed during gastric screening.
It has been reported that the endoscopic image of the oxyntic gland neoplasm is a yellowish, gently rising elevated lesion characterized by dilation of microvessels on the surface . The manifestations of these characteristics may vary based on the size of the oxyntic gland neoplasm. As the lesion grows, the above findings manifest. However, at the microlesion stage, its characteristics are as follows: the lesion is flat, its color ranges from a dull, pale yellow to normal color tones, and the microvasculature runs from the periphery of the tumor towards the center. Furthermore, we believe that during observation with narrow band imaging (NBI) and magnification, a slightly dilated, circular crypt opening supports the presence of an oxyntic gland neoplasm 【Figure 1】.
Xanthomas are examples of lesions that are endoscopically similar to OGNs. Xanthomas are pale yellow in color, similar to OGNs. However, their surface is finely granular, and they do not involve dilation of microvessels, which distinguishes them from the endoscopic image of OGNs. Dilated images of microvessels are also observed on the surface of neuroendocrine tumors. However, neuroendocrine tumors are more hemispherical than oxyntic gland neoplasm and, unlike oxyntic gland neoplasm, often occur in a background of autoimmune gastritis.
When we recognize xanthoma-like lesions or neuroendocrine tumors in the stomach without atrophy, we should carefully examine them after considering oxyntic gland neoplasm in the differential diagnosis.
It has been reported that the histology of some oxyntic gland neoplasm cases was similar to that of a fundic gland polyp (FGP) . Since edema-like FGP may occur with long-term PPI use, it has been pointed out that there may be a relationship between the development of oxyntic gland neoplasm and oral administration of PPI [16, 26]. Chan et al. reported that in a 12-case series, seven patients received acid suppressive therapy (six PPI and one H2 blocker) . In our study, 37% (10/27) of patients were taking antacids (nine PPI and one H2 blocker) (median duration of administration 646 days (35-5381 days)) 【Table 1】. However, of the 9 patients who took antacids, FGP was found with oxyntic gland neoplasm in only three patients, and it was not clear whether FGP was related to the pathogenesis of OGNs.
Initially, OGNs were reported to be found only in stomachs uninfected by H. pylori, but later reports revealed that they were also discovered in stomachs that had already been infected with H. pylori [24, 25]. Of the 27 patients in whom we found lesions, 18 patients with 20 lesions had a history of H. pylori infection and atrophic gastritis 【Table 1】. Of the 20 lesions, 17 lesions were found in the non-atrophic region. Similar to the reports by Chiba et al. and Tohda et al., our research results suggest that the oxyntic gland neoplasm is a tumor that is easily detected in endoscopic non-atrophic regions, with or without a history of H. pylori infection. [24, 25].
For the two lesions without any cancer-specific histopathological findings after endoscopy, we concluded that they were completely resected at the time of biopsy because of their small size. Of the 19 lesions that underwent endoscopic treatment, 9 had remnant tumors in the mucosa; the remaining eight lesions had infiltrated the submucosa. The median pathological tumor size (width) of the eight submucosal infiltrating lesions was as small as 5 mm (2–8); this confirms that OGNs infiltrate the submucosa while still quite small. Chiba et al. reported that of the 10 lesions in nine patients who underwent ESD (median tumor diameter: 7 mm, width 2 to 20 mm), 80% of the lesions were SM infiltrated . In this study, no desmoplastic reaction was observed at the advanced part of the tumor in all eight cases with submucosal infiltration 【Figure 2】. Therefore, we ascertained SM infiltration as a tumor prolapse. In WHO classification (on page 83, oxyntic adenoma part), the description says that “a morphological continuum exists from OGA to GA-FG. However, there is ongoing discussion as to whether OGA should be regarded as an intramucosal component of GA-FG”. Considering our results, GA-FG without stromal reaction could be regarded as the prolapse-type changes of OGA into the submucosa.
In this study, all the oxyntic gland neoplasm with SM infiltration were endoscopically diagnosed as intramucosal cancer, preoperatively. We believe it is difficult to endoscopically diagnose SM infiltration of OGNs before endoscopic treatment. OGNs infiltrate SM frequently at a very early stage and should be resected endoscopically as soon as they are discovered. Alternatively, since previous reports have reported that the malignant potential is low, it is necessary to wait for future case accumulation to determine whether follow-up is a good practice [2, 13]. In this study, eight patients with pathological diagnosis of SM infiltration were followed up without additional surgical resection in all patients. No recurrence was observed in all patients. However, in five of the eight cases, the period from the endoscopic treatment date to the final CT examination date was less than 1 year, and we believe that careful follow-up is required in the future.