We previously reported the clinicopathologic features of 116 patients with 126 oxyntic gland adenoma or GA-FG lesions and concluded that endoscopic resection is a suitable initial treatment strategy for these neoplasms [8]. In the current study, we added 49 patients with 54 oxyntic gland adenoma and GA-FG lesions to the previous study population, resulting in the largest number of lesions investigated to date.
A small, elevated lesion with a subepithelial tumor-like appearance occurring in the upper third of the stomach is a representative endoscopic feature of oxyntic gland adenoma or GA-FG [3, 4, 11–21]. Benedict et al. reviewed 111 previously reported cases and described that most tumors (89 cases, 80.2%) occurred in the upper third of the stomach [2]. Ueyama et al. reported a similar proportion of lesions in the upper third of the stomach (79/100, 79.0%) [6]. They also reported that 62 of the 100 lesions (62.0%) showed a protruded morphology. In the current study, the H. pylori-uninfected group showed the following typical features of oxyntic gland adenoma or GA-FG: (i) frequent occurrence in the gastric fornix or cardia; (ii) elevated, subepithelial lesion-like morphology; and (iii) a color similar to that of the peripheral mucosa. Conversely, in patients with current or past H. pylori infection, oxyntic gland adenoma and GA-FG appeared as flat lesions in atypical locations, rather than in the upper third of the stomach. To our knowledge, this is the first study to investigate the difference in the endoscopic features of oxyntic gland adenoma and GA-FG between patients with and without H. pylori infection.
H. pylori infection is a major causative factor in the development of conventional gastric cancer through chronic inflammation, in addition to environmental, dietary, and genetic factors [22]. In contrast, oxyntic gland adenoma and GA-FG are believed to develop independently of H. pylori infection, as most of these neoplasms arise in areas with no apparent atrophy endoscopically or pathologically [23]. In the present study, atrophic changes were not identified endoscopically in the surrounding mucosa in 150 of the 180 lesions (83.3%). Ueyama et al. investigated the clinicopathologic and molecular biological features of 100 lesions and found no significant differences between H. pylori infection-negative and H. pylori infection-positive or -eradicated groups, except for patient age and Ki-67 MIB-1 labeling index [6]. These results suggest that oxyntic gland adenoma and GA-FG have similar carcinogenesis and biological properties, regardless of the H. pylori infection status. However, we observed that the location and morphology were different between the Hp and uninfected groups. In addition, multiple tumors were more frequently found in the atrophy group than in the non-atrophy group (20.0% vs. 5.0%) in the present study.
On pathologic examination, the surface of these lesions is generally covered by normal-appearing foveolar-type epithelium [1, 2]. We speculate that oxyntic gland adenoma and GA-FG occurring in the gastric body, particularly flat lesions, are less detectable in patients without H. pylori infection owing to the non-atrophic, thick mucosa that covers the lesions. In contrast, during esophagogastroduodenoscopy in patients with H. pylori infection, these lesions may be more noticeable in the mucosa, which shows atrophic change, inflammation, or metaplasia due to the infection. Another hypothesis is that oxyntic gland adenoma and GA-FG may be misinterpreted as fundic gland polyps and may be underdiagnosed in H. pylori-uninfected patients. These hypotheses might explain why the location, morphology, color, and number of lesions differed between patients with and without H. pylori infection. However, further investigation is required to elucidate the nature of oxyntic gland adenoma and GA-FG in relation to H. pylori infection status.
As previously described, although an elevated, subepithelial lesion-like morphology is a representative endoscopic feature of oxyntic gland adenoma and GA-FG, tumors often present as flat lesions [23–30]. Ueyama et al. reported that 62 of 100 lesions (62.0%) showed a protruded morphology, whereas the remaining 38 lesions (38.0) presented as flat or depressed lesions [6]. In the present study, we observed that the flat or depressed type of oxyntic gland adenoma and GA-FG predominantly occurred in the gastric body in the Hp group (Fig. 1). As these lesions can show a whitish color (Fig. 2E,F), endoscopists may need to differentiate them from conventional gastric cancer and extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue. Meanwhile, from the standpoint of pathologists, oxyntic gland adenoma and GA-FG may be mistaken for a neuroendocrine tumor or even non-neoplastic polyps on pathologic analysis [1]. Thus, endoscopists should be aware of the occurrence of oxyntic gland adenoma and GA-FG with a flat or depressed morphology in the gastric body of patients with current or past H. pylori infection. In addition, endoscopists and pathologists should have a similar index of suspicion for oxyntic gland adenoma and GA-FG to make an appropriate diagnosis.
This study had several limitations. First, researchers at various institutions subjectively investigated the presence or absence of atrophy in the surrounding mucosa using endoscopic images. Interobserver variations and differences in methodologies between the participating endoscopists may have resulted in interpretation bias during the analysis of the atrophy and non-atrophy groups. Thus, pathologic evaluation of mucosal atrophy should be incorporated in the analysis of these cases. Second, immunohistochemical studies were not performed for all patients. Although a diagnosis can essentially be made according to the WHO classification criteria [1], confirmation by positive immunohistochemical staining for both pepsinogen I and MUC6, as well as cell differentiation markers such as H+/K+-ATPase (parietal cell) and MUC5AC (foveolar epithelium), is preferable [5–7].