Primary Motility  Disorders of the  Esophagus
 The Esophageal
 Esophagogastric  Junction

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Volume: Barrett's Esophagus
Chapter: Dysplasia

What is the long-term significance of low-grade dysplasia?

J.E. Richter (Cleveland)

Barrett's esophagus is a premalignant condition. Once the diagnosis is established, patients are followed by periodic endoscopy with biopsy, the goal being to detect carcinoma at a curable stage or before it has a chance to develop. As of now, the histopathologic identification of dysplasia remains the best marker of increased cancer risk. Although morphologic criteria for dysplasia have been established, the risk of progression in patients who have a biopsy diagnosis of low-grade dysplasia (LGD) is difficult to determine, in part because of the high degree of inter-observer variability known to exist in establishing this diagnosis [1]

There are very limited data in the literature, mostly in abstract form, correlating biopsy diagnosis of LGD with clinical outcome. Preliminary data reported by Weston et al. found that 5 of 62 patients (8%) with a diagnosis of Barrett's esophagus related LGD progressed to cancer (4 patients) or high-grade dysplasia (HGD) (1 patient) at 3, 14, 16, 17 and 41 months following the diagnosis of LGD, respecttively [2]. Nine patients (16.4%) had persistent LGD during a mean follow-up of nearly 30 months. The others reported that 41 patients (75%) eventually "regressed" to no dysplasia during a mean follow-up of 22 months. In the other available study by Sontag et al. [3], 33 of 848 patients (3.9%) with LGD progressed to HGD and 18 patients (2.1%) progressed to carcinoma. The vast majority of patients (94%) continued to have LGD documented on subsequent surveillance biopsies. In both of these studies, it is unknown how many pathologists were involved in reading the biopsies and the effect of interobserver variability.

Goldblum et al. at the Cleveland Clinic Foundation reviewed their experience with 43 patients with Barrett’s esophagus diagnosed and coded as LGD. Patients with concurrent or prior diagnosis of HGD or cancer were excluded. The LGD cases were randomized and blinded read by three gastrointestinal pathologists along with cases originally diagnosed as Barrett's esophagus without dysplasia, indefinite for dysplasia or HGD. The follow-up data was available on 25 patients originally diagnosed with LGD.

The individual gastrointestinal pathologists agreed with the original diagnosis of lowgrade in 70%, 56% and 16% of cases, respectively. Agreement between the three combinations of two gastrointestinal pathologists for a diagnosis of LGD was fair (Kappa score = 0.28) and poor (Kappa score = 0.20). Among the 25 patients with several biopsies, a mean follow-up of 26 months (ranged 2 to 84 months) was obtained. Seven patients (28%) went on to develop HGD (5) or cancer (2), 2 to 43 months (median: 11 months) following the diagnosis of LGD. The individual gastrointestinal pathologist diagnozes did not correlate with progression. However, when at least two gastrointestinal pathologists agreed on LGD, there was a significant association with progression (7 of 17 patients, 41%, p = 0.04). When all three pathologists agreed on a diagnosis of LGD, 4 of 5 patients progressed (Table I). In contrast, of the 8 patients with follow-up and no agreement of gastrointestinal pathologists for a diagnosis of LGD, none progressed.

Table I. Cleveland Clinic Foundation experience with low grade dysplasia (LGD).

These studies confirm that the vast minority of patients with LGD (6% to 25%) go onto develop HGD or cancer. Our preliminary data suggest an increased risk of progression for LGD if a consensus diagnosis of LGD is made among several gastrointestinal pathologists. Thus, it may be advisable that biopsy specimens with suspected LGD be reviewed by at least two pathologists experienced with these specimens.


1. Reid BJ, Haggitt RC, Rubin CE, et al. Observer variation in the diagnosis of dysplasia in Barrett's esophagus. Hum Pathol 1988;19:166-178.

2. Weston AP, Sharma P, Topaloski M, et al. Low-grade dysplasia in Barrett's esophagus: variable fate during long-term prospective follow-up. Gastroenterology 1999;116:1349A.

3. Sontag SJ, Schnell T, Chejfec G, et al. Barrett's, low-grade dysplasia and fear; yearly endoscopy is not justified: surveillance every 2 to 3 years detects all cancers early. Gastroenterology 1999;116:1381A.

Publication date: August 2003 OESO©2015