A 44-year-old male presented with an asymptomatic gastric subepithelial lesion (SEL), detected incidentally during a screening endoscopy. The lesion was a round mass measuring approximately 1.5 cm, located on the greater curvature of the fundus of the stomach. Although the overlying mucosa mainly appeared intact, the center of the lesion showed hyperemic and erosive changes (Fig. 1). A biopsy of the overlying mucosa revealed Helicobacter pylori-associated gastritis; however, it was non-diagnostic because the submucosal layer was not included. Follow-up evaluations at 4 and 12 months showed no change in the lesion size; however, erosion in the surface mucosa progressed further, resulting in ulcerative changes (Fig. 2). Additional diagnostic workup and surgical resection were planned, considering the patient’s age and persistent erosive changes in the overlying mucosa. A computed tomography scan confirmed a 1.5 cm SEL in the fundus of the stomach (Fig. 3), with no evidence of invasion into adjacent organs or lymph node metastasis. As surgical resection had already been decided, endoscopic ultrasonography was not performed. What was the most likely diagnosis?

The lesion was removed via laparoscopic gastric wedge resection, and final histopathological examination revealed early gastric cancer (EGC; tubular adenocarcinoma, well-differentiated, stage pT1a, with invasion confined to the muscularis mucosa) occurring against a background of gastritis cystica profunda (Fig. 4). The lesion, measuring 2×2×1 mm, was observed within the mucosal layer at a site separate from the surface mucosal defect. The lesion, including both gastritis cystica profunda and adenocarcinoma, was completely resected surgically, and the patient is currently under follow-up without the need for additional treatment.

Gastritis cystica profunda is a relatively rare condition characterized by cystic dilatation of benign gastric glands with submucosal extension [1]. It was previously known as a relatively rare lesion that typically develops in patients with a history of gastroenterostomy, especially for treating benign conditions such as gastric ulcers. However, more recent reports have described its occurrence in the stomachs of patients without any history of gastric surgery [2]. Gastritis cystica profunda is often presented as a polyp or SEL incidentally found on endoscopy, and diagnosis is challenging based on endoscopic appearance and biopsy. Therefore, it is typically diagnosed after endoscopic submucosal dissection or surgical resection [3]. Endoscopically, gastritis cystica profunda is known to be highly variable. It most commonly presents as a polypoid or SEL; however, rare cases of giant gastric folds have been reported. The most characteristic endoscopic ultrasound finding is the presence of multiple anechoic cystic lesions in the submucosal layer [4].

In the present case, surgical resection was performed based on the gross endoscopic appearance, specifically, the erosive changes of the overlying mucosa, raising suspicion of an SEL with size increment and malignant potential [5], such as a gastrointestinal stromal tumor. However, contrary to the initial impression, the lesion was diagnosed as EGC arising from gastritis cystica profunda. Although gastritis cystica profunda is generally considered a benign condition, there are cases of malignancy near or arising from the overlying mucosa of such lesions [2,6-8]. Furthermore, recent studies have suggested the possibility of underlying molecular genetic alterations associated with the development of gastritis cystica profunda [9]. Therefore, when encountering a SEL with atypical features, clinicians should be mindful of the possibility of gastritis cystica profunda and associated mucosal neoplasia.