Is random biopsy necessary for normal esophageal mucosa during chromoendoscopy? Evidence from a population-based...

Esophageal squamous intraepithelial neoplasia could be detected in normally stained mucosa under Lugol's chromoendoscopy. We aim to determine whether an active biopsy should be performed on such mucosa.

This study was based on a population-based screening cohort where participants underwent Lugol's chromoendoscopy with biopsies taken from abnormal-unstaining areas and normally stained standard site. A total of 641 participants with esophageal squamous intraepithelial neoplasia or more severe lesions were included in the analysis. The cumulative incidence of high-grade intraepithelial neoplasia/esophageal squamous cell carcinoma (HGIN/ESCC) and ESCC-specific mortality were compared between participants biopsied from iodine unstained and stained areas. Additionally, paired eligible tissues were utilized for comparative genomic analysis.

For participants diagnosed with low-grade intraepithelial neoplasia (LGIN), HGIN, and ESCC, 292 (54.8%), 11 (14.9%), and 1 (2.9%) cases, respectively, were biopsied from normal-staining mucosa. Over a median 9.5-year follow-up, no incident HGIN/ESCC cases were identified among individuals with LGIN diagnosed from normal-staining esophageal mucosa. In contrast, LGIN cases detected in unstained lesions exhibited a cumulative incidence of HGIN/ESCC of 15.8 (95% CI, 11.4-21.0) per 100 persons. No ESCC-related deaths occurred in patients having normal-staining lesions, irrespective of pathological grade. Contrastingly, cumulative ESCC-specific mortality per 100 persons for LGIN, HGIN, and ESCC patients of unstained lesions were 2.1 (95% CI, 0.7-4.8), 14.3 (95% CI, 6.7-25.4), and 36.4 (95% CI, 20.4-54.9), respectively. Genomic analysis revealed minimal copy number variants in normally stained lesions compared to substantial alterations in unstained lesions.

Random biopsies of normally stained esophageal mucosa under Lugol's chromoendoscopy should be unnecessary for population-level ESCC screening.