Background: Specialized columnar epithelium in Barrett's esophagus res
embles gastric intestinal metaplasia, wh ich selectively stains with m
ethylene blue. Methods: We prospectively evaluated the safety, accurac
y, reproducibility, cost, and diagnostic yield of methylene blue-direc
ted biopsy in detecting specialized columnar epithelium and dysplasia
in Barrett's esophagus. We performed upper endoscopy with methylene bl
ue-directed biopsy and obtained 236 large cup biopsy specimens (145 st
ained, 91 unstained) from 14 patients with Barrett's esophagus of any
length (Group 1) and 12 control patients. Biopsy specimens were indepe
ndently examined by two pathologists unaware of the endoscopic results
.Results: Methylene blue stained specialized columnar epithelium in 18
of the 26 patients, including those with intramucosal carcinoma (1),
high-grade dysplasia (1), and indefinite/low-grade dysplasia (6). Meth
ylene blue staining pattern, which was focal in 72% and diffuse in 28%
of patients, was reproduced in 8 patients who had repeat staining wit
hin 4 weeks. The overall accuracy of methylene blue staining for detec
ting specialized columnar epithelium was 95%. The diagnostic yield of
methylene blue staining for specialized columnar epithelium in ''contr
ol'' patients was 42%. The risk for dysplasia in stained biopsy specim
ens was greater than in unstained ones (odds ratio 17.7, p = .0004). C
onclusions: Methylene blue mucosal staining is a safe, inexpensive, re
producible, and highly accurate method of diagnosing specialized colum
nar epithelium in Barrett's esophagus.