Gastrointestinal subepithelial lesions (SELs) have been increasingly reported [1]. This rise in detection is likely attributable to endoscopists’ heightened awareness of SELs and the widespread adoption of endoscopic ultrasound (EUS) [2-4]. However, recent studies indicate that the incidence is not negligible [5-7], and given that tumors with malignant potential—such as gastrointestinal stromal tumors (GISTs), neuroendocrine tumors, lymphomas, and glomerular tumors—may be present, accurate identification is clinically significant.

While endoscopic observation, EUS, and computed tomography (CT) aid in characterization, histological confirmation is often definitive and necessary. Although standard biopsy may yield diagnostic tissue in rare cases, pathological confirmation typically requires bite-on-bite biopsy, incision biopsy, or fine-needle aspiration/biopsy (FNA/B), as these lesions originate from the subepithelium [8,9].

Generally, tissue biopsy is not required for lesions smaller than 1 cm or for stable tumors that have shown no size progression over a prolonged period. However, definitive characterization is necessary for tumors that are indeterminate or demonstrate growth. Lesions measuring between 1 and 2 cm often fall into this indeterminate category. Although guidelines for SELs larger than 2 cm are well-established [10], clear consensus is lacking for those measuring 1–2 cm. Furthermore, ambiguity remains regarding the suitability of observation alone for SELs in this size range. Therefore, we conducted this study to characterize SELs measuring 1–2 cm, a group that represents a clinical “gray zone.”

The prevalence of gastrointestinal SELs is increasing due to advancements in modalities such as EUS and increased endoscopist awareness [11]. Active intervention is usually recommended for SELs exceeding 2 cm, consensus is lacking for lesions smaller than this threshold. Consequently, the absence of clear guidelines often leads to anxiety among both patients and physicians [10,12,13]. This study focused exclusively on SELs measuring 1–2 cm, with histological confirmation obtained in the majority of cases. Contrary to expectations, we observed a high prevalence of GISTs; notably, some were classified as highrisk despite measuring approximately 1 cm. This finding challenges the reliance on a strict 2 cm threshold for clinical decision-making.

This study has several strengths. First, literature specifically addressing SELs in the 1–2 cm range is scarce. Although a large-scale multicenter study reported an average incidental SEL size of 1.6 cm [7], specific research focusing on the 1–2 cm range remains limited [14]. Second, the high biopsy rate in our cohort enabled the validation of EGD diagnostic accuracy. EUS alone is often insufficient to clearly determine malignancy [15-17]. Although recent advancements in artificial intelligence show promise in predictive modeling, histological analysis remains the diagnostic gold standard [18]. Third, the single-center design ensured data homogeneity and minimized the risk of error by limiting examinations to four gastroenterologists.

Despite these strengths, this study has limitations. First, the single-center design limited the sample size. However, this design facilitated consistent data recording and allowed for the retrospective review of endoscopic images. Furthermore, longitudinal surveillance of this cohort is ongoing. Second, this study was retrospective. However, we mitigated this by ensuring the rigor of histological examination and surveillance data. This distinguishes our work from prior studies, which lack sufficient histological confirmation. Third, reliance on endoscopic estimation of lesion size represents a limitation. Post-resection dimensions of GISTs exceeded pre-operative endoscopic estimates by an average of 1 cm. Although size estimation was standardized using open biopsy forceps, significant discrepancies are likely, especially for lesions 1 to 2 cm in size. This suggests that endoscopic measurement is inherently difficult to obtain and inaccurate for predicting actual tumor size.

Despite the fact that histological confirmation remains the gold standard, imaging modalities such as EUS and CT are crucial for initial evaluation. Previous studies have demonstrated the limited accuracy of EUS in identifying true GISTs [13]. This underscores the inability of EUS alone to reliably differentiate GISTs from leiomyomas, particularly in the 1–2 cm range. Although CT is less effective for mass characterization, it is valuable for assessing extraluminal extension, lymphadenopathy, and distant metastases. The difference in lesion size measured by the two modalities was not statistically significant; however, CT measurements were slightly larger, likely reflecting the lesion’s full extent. Therefore, a comprehensive evaluation integrating EUS and CT findings is necessary; in equivocal cases, tissue acquisition is essential. Various tissue acquisition methods, including bite-on-bite biopsy, incision biopsy, and unroofing, demonstrate high diagnostic yields. In this study, the difference in diagnostic yields between methods was not statistically significant. However, incision biopsy and unroofing demonstrated high success rates and align with European Society of Gastrointestinal Endoscopy guidelines, which recommend mucosal incision-assisted biopsy as a firstline procedure [13].

GISTs were most frequently located in the upper stomach (fundus and proximal corpus). This anatomical location presents technical challenges for EGD and EUS, supporting the need for a more aggressive surveillance protocol for upper gastric SELs. In conclusion, approximately half of the gastric SELs measuring 1–2 cm in this study were diagnosed as GISTs, a subset of which were stratified as moderate-to-high risk. For SELs located in the upper stomach, even those smaller than 2 cm, we recommend close monitoring with short-term surveillance and aggressive efforts to obtain histological confirmation.