Background & Aims:Gastric subepithelial lesions (SELs) represent a heterogeneous group of benign and malignant entities, including gastrointestinal stromal tumors (GISTs), leiomyomas, lipomas, and schwannomas. Although endoscopic ultrasound (EUS) with fine-needle biopsy (FNB) plays a central role in diagnostic work-up, histological yield remains variable due to sampling limitations. Endoscopic full-thickness resection (EFTR) has emerged as both a diagnostic and therapeutic tool when tissue diagnosis is inconclusive and the malignant potential of an SEL cannot be confidently excluded. We report a case that highlights challenges in obtaining a definitive diagnosis and underscores the value of EFTR combined with immunohistochemical evaluation and follow-up.

Methods / Case Description:A 46-year-old woman with recent diagnosis of an ulcerated gastric lesion was referred for further evaluation due to persistent physical asthenia and upper abdominal pain. Laboratory findings revealed mild microcytic hypochromic anemia. EUS demonstrated a well-defined, heterogeneous hypoechoic submucosal lesion located along the greater curvature toward the gastric fundus, with a mixed elastography pattern. EUS-FNB was performed with differential diagnosis including neuroendocrine tumor, ectopic pancreas, fibrinoid polyp, and lymphoma; histopathology was negative for malignancy and excluded ectopic pancreas, but remained non-diagnostic.

Due to diagnostic uncertainty and symptomatic context, the patient underwent therapeutic endoscopic re-evaluation. A centrally ulcerated, polypoid, subepithelial lesion measuring approximately 3 × 2 × 2 cm was confirmed during upper endoscopy, and EFTR was performed with complete en-bloc resection and closure using an over-the-scope Padlock clip. The immediate post-procedural course was uneventful. Histopathology of the resected specimen suggested a submucosal lipoma without atypia.

At 6-month surveillance endoscopy, a residual submucosal lesion was noted at the previous resection site, with the Padlock clip still in situ, suggesting partial resection or persistent lesion tissue. Multiple biopsies were obtained. Final pathology revealed a gastric schwannoma, positive for S-100 protein and negative for CD117/DOG-1, with a low proliferative index (Ki-67 = 1%), confirming a benign, low-risk neoplasm.

Results:Despite negative FNB and initial lipoma diagnosis, final immunohistochemistry on targeted control biopsies established a definitive diagnosis of schwannoma. No complications or recurrence were detected on follow-up.

Conclusions:This case illustrates that EUS-FNB may yield false-negative or misleading results in SELs, and that EFTR represents a valuable approach for both therapeutic management and diagnostic confirmation. Immunohistochemistry and systematic surveillance remain essential when histology does not correlate with endoscopic and imaging characteristics.