The diagnosis of low-grade dysplasia in Barrett's esophagus and its implications for disease progression

OBJECTIVE:The reported risk of progression from low-grade dysplasia (LGD) to high-grade dysplasia (HGD) or carcinoma (CA) in Barrett's esophagus varies. However, the validity of a diagnosis of LGD may be questioned because of interobserver variability.METHODS:A search of the Cleveland Clinic Foundation surgical pathology files between 1986 and 1997 yielded biopsy specimens from 43 patients with Barrett's esophagus diagnosed and coded as LGD. Patients with concurrent or prior diagnoses of HGD or carcinoma were excluded. The LGD cases were randomized and blindly reviewed by three gastrointestinal (GI) pathologists along with cases originally diagnosed as Barrett's esophagus without dysplasia (ND; n = 28), indefinite for dysplasia (IND; n = 14), or HGD (n = 15). Each pathologist classified every biopsy specimen as ND, IND, LGD, or HGD, and interobserver agreements were determined by kappa statistics (K). Follow-up data were available on 25 patients originally diagnosed with LGD. Progression was defined as a subsequent diagnosis of HGD or CA on esophageal biopsy or resection specimens.RESULTS:Agreement between two GI pathologists for a diagnosis of LGD was fair (K = 0.28) and poor (K = 0.21 and −0.04). Individual GI pathologists agreed with the original diagnosis of LGD in 70%, 56%, and 16% of cases. The 25 patients with follow-up included 21 men and four women (mean age, 67 yr) with a mean follow-up of 26 months (range: 2–84 months). Seven patients (28%) with follow-up developed HGD (five patients) or CA (two patients), 2–43 months (median: 11 months) after a diagnosis of LGD. The individual GI pathologists’ diagnosis did not correlate with progression. However, when at least two GI pathologists agreed on LGD, there was a significant association with progression (seven of 17 patients, 41%, p= 0.04). When all three GI pathologists agreed on a diagnosis of LGD, four of five patients progressed (p= 0.012). In contrast, of the eight patients with follow-up and no agreement among GI pathologists for a diagnosis of LGD, none progressed.CONCLUSIONS:A high degree of interobserver variability is seen in the histological diagnosis of Barrett's esophagus–related LGD. Although the number of observations is low, a consensus diagnosis of LGD among GI pathologists suggests an increased risk of progression from LGD to HGD or carcinoma.