Barrett’s esophagus with indefinite dysplasia(GIE, Jan-2026)

Barrett’s esophagus with indefinite dysplasia (IND) represents a challenging diagnostic category, characterized by histologic uncertainty between nondysplastic Barrett’s esophagus and low-grade dysplasia. This ambiguity often arises due to overlapping features and confounding factors such as inflammation or technical issues during biopsy interpretation. IND is considered a "gray zone" diagnosis with significant variability in pathologic interpretation among different pathologists, leading to inconsistent clinical management.

Patients with IND are at risk of harboring undetected dysplasia, underscoring the importance of early re-evaluation through repeat endoscopy after optimizing acid suppression. Persistent IND over time signals a meaningful risk of progression to higher-grade dysplasia or esophageal adenocarcinoma, necessitating careful surveillance and potentially more aggressive management strategies. High-quality endoscopic techniques, systematic biopsy protocols, and improved training for endoscopists are critical to reducing missed dysplasia and ensuring accurate diagnosis.

Emerging technologies, such as artificial intelligence-based computer-aided detection systems, show promise in enhancing the recognition of Barrett’s-related neoplasia. Additionally, risk stratification beyond histology, incorporating clinical factors and biomarkers, may help identify IND patients at highest risk for progression. Given the progression risk comparable to low-grade dysplasia, closer surveillance and selective therapeutic interventions are increasingly justified for patients with IND to mitigate the risk of advanced disease.