Approach to upper gastrointestinal subepithelial lesions

Subepithelial lesions (SELs) of the upper gastrointestinal tract are commonly encountered during endoscopic evaluations and pose a diagnostic challenge due to their origin from deeper layers of the gastrointestinal wall. Accurate diagnosis is essential, as some SELs have malignant potential. This review presents a comprehensive, structured approach to the evaluation and management of upper gastrointestinal SELs. Key features of common SELs – including gastrointestinal stromal tumors (GISTs), neuroendocrine tumors (NETs), and benign lesions like lipomas and leiomyomas – are discussed. Emphasis is placed on the utility of endoscopic ultrasound (EUS) for lesion characterization and tissue acquisition. Literature was identified through a MEDLINE search up to December 2024, with inclusion of major society guidelines and studies relevant to diagnostic methods and clinical features. EUS, particularly with tissue sampling, has revolutionized SEL evaluation, allowing earlier diagnosis and risk stratification. Future advancements, including artificial intelligence, molecular diagnostics, and improved resection and biopsy techniques, are poised to enhance precision, accessibility, and outcomes in SEL management.