Submucosal tunneling biopsy for histological diagnosis of refractory esophageal strictures following negative conventional biopsy

Accurate diagnosis of esophageal strictures is critical but challenging when lesions are located deep in the submucosa. Conventional forceps biopsies often yield false-negative results due to limited sampling depth, while severe luminal stenosis precludes endoscopic access, thereby rendering Endoscopic Ultrasound-guided Fine-Needle Aspiration (EUS-FNA) unfeasible. This study evaluates the feasibility, safety, and diagnostic yield of a novel technique, Submucosal Tunneling Endoscopic Biopsy (STEB), as a salvage strategy for these difficult cases. We analyzed 14 consecutive patients with esophageal strictures and suspected deep submucosal lesions who underwent STEB between January 2019 and December 2025. All patients had undergone at least two negative conventional biopsies. The STEB procedure involved creating a submucosal tunnel to access the stricture site for deep tissue acquisition. Technical success, procedure time, adverse events, and final pathological diagnoses were recorded. STEB was technically successful in all 14 patients (100%), with a mean procedure time of 39.3 ± 7.0 min. The final diagnoses included esophageal adenocarcinoma ( n = 6), squamous cell carcinoma ( n = 5), metastatic lung cancer ( n = 1), metastatic breast cancer ( n = 1), and esophageal tuberculosis ( n = 1). No major adverse events such as perforation, significant bleeding, or mediastinal infection occurred. STEB is a feasible, safe, and highly effective diagnostic technique for patients with esophageal strictures and suspected deep submucosal lesions when repeated conventional biopsies are negative and EUS-FNA is not feasible. It enables the acquisition of adequate tissue samples with preserved histological architecture, facilitating definitive diagnosis and guiding subsequent management. Large-scale prospective studies are needed to further validate these findings.