Approach to Gastric Subepithelial Lesions: From Differential Diagnosis to Histologic Confirmation

The detection of gastric subepithelial lesions (SELs) has increased with the widespread use of endoscopic screening. While most SELs are benign, some, such as gastrointestinal stromal tumors, have malignant potential, underscoring the importance of accurate diagnosis. Histological confirmation is often challenging due to the submucosal location of these lesions, which limits the effectiveness of conventional biopsy techniques. Endoscopic ultrasonography (EUS) plays a central role in lesion characterization, providing information on the layer of origin, echogenicity, and internal features. When tissue sampling is required, techniques such as mucosal incision-assisted biopsy (MIAB) and EUS-guided fine-needle biopsy (FNB) offer complementary advantages. MIAB has demonstrated a diagnostic yield of approximately 89%, particularly for lesions <20 mm, whereas FNB provides sufficient tissue for immunohistochemical analysis. As international guidelines differ regarding indications and methods of tissue acquisition for SELs, tailored management based on EUS findings, patient-specific factors, and institutional capacity is essential for optimal diagnostic outcomes. This review aims to summarize the current understanding of gastric SELs based on evidence-based guidelines and recent studies and offer practical guidance for clinicians diagnosing these lesions in routine practice.