Small (<2 cm), asymptomatic gastric subepithelial lesions (SELs) arising from the muscularis propria are frequently managed conservatively through follow-up, since most represent gastrointestinal stromal tumors (GISTs) with a favorable prognosis or benign lesions. This study aimed to evaluate the role of endoscopic ultrasound (EUS) in the long-term surveillance of such lesions.

We conducted a retrospective multicenter study including patients with incidentally detected, asymptomatic, gastric SELs ≤20 mm arising from the muscularis propria who underwent EUS-based surveillance. Clinical outcomes (iron deficiency anemia, epigastric pain, weight loss) and EUS changes (mucosal ulceration, enlargement ≥25% of the initial main diameter as suggested by previously published studies, change in the EUS pattern of the lesions) were analyzed together with risk factors for size increase and diagnosis of GISTs.

A total of 150 patients (38.7% male; median age 62 [IQR 55-68] years) were followed for a median of 49 (IQR 22–96) months. No patient developed lesion-related symptoms. Thirty-five lesions (23.3%) demonstrated a ≥25% increase in size, which was significantly associated with age (P = 0.02), a ≥5% size increase at 1 year (P <0.001) and histologically confirmed GIST (P = 0.001). Histological diagnosis was obtained in 42 cases, with 22 confirmed GISTs. On multivariate analysis predictors of GIST included location in the gastric fundus or cardia (OR 0.94 (0.86 – 0.98); P = 0.05), baseline diameter for each mm (OR 1.17 (1.03 – 1.38); P = 0.01), ≥5% enlargement at 1 year (OR 4.7 (1.1 – 20.5); P = 0.04), and size increase during follow-up for each % (OR 1.02 (1.01 – 1.04); P = 0.02). A resulting composite model was developed to predict the risk of having a GIST according to SEL location (fundus = 0 points; body or antrum = 1 point), basal SEL size (≥10 mm = 1 point), 5% increase at 1-year (2 points). The prevalence of GIST was 0%, 4.4%, 6.3%, 34.8%, 43.8% in case of scores = 0, 1, 2, 3, 4 respectively; patients with a composite score >2 showed an Odd ratio 13.3 (95% confidence interval 4.39 - 39.9; P value <0.001) for a diagnosis of GIST.

Our multicenter study confirms that EUS-based surveillance is a safe and effective strategy for small, asymptomatic gastric SELs of the muscularis propria. Most lesions remain stable over time, but younger age, baseline size >1 cm, location in the fundus and early growth identify patients at higher risk of clinically relevant progression or GIST diagnosis. In such cases, closer EUS follow-up and tissue acquisition should be prioritized, while resection may be considered. Emerging techniques such as contrast-enhanced EUS, elastography and the incorporation of artificial intelligence in EUS image interpretation may further refine the risk stratification, but histology remains essential to guide management.