Dysplasia as a predictive marker for invasive carcinoma in Barrett esophagus: A follow-up study based on 138 cases from a diagnostic variability study

The objective of endoscopic surveillance in Barrett esophagus (BE) is to assess the risk of subsequent development of invasive carcinoma. Criteria for morphologic evaluation of dysplasia, the presumed precursor lesion, have been established, although there are surprisingly few data in the literature correlating biopsy diagnosis of dysplasia with outcome. We collected follow-up information on 138 patients with BE whose initial endoscopic biopsy specimens had been selected for submission in an interobserver variability study performed by 12 pathologists with special interest in gastrointestinal pathology and reviewed blindly twice each by all the participants. Cases were scored as BE with no dysplasia, atypia indefinite for dysplasia (IND), low-grade dysplasia (LGD) high-grade dysplasia (HGD), intramucosal carcinoma, and frankly invasive carcinoma, thus generating 24 scores on each biopsy specimen. Clinical follow-up was obtained and correlated with both the submitting diagnoses and majority diagnoses. Kaplan-Meier statistics were used to compare both the submitting and majority diagnoses with outcome using detection or documentation of invasive carcinoma as the endpoint. Using the submitting diagnoses, no invasive carcinomas were detected in 44 Eases diagnosed as BE (median follow-up, 38.5 months). Carcinomas were detected in 4 of 22 (18%) cases submitted as IND (median progression-free survival of 62 months), in 4 of 25 (15%) cases of LGD (median progression-free survival of 60 months), in 20 of 33 cases of HGD (median progression-free survival, 8 months), and all 13 (100%) cases submitted as adenocarcinoma. Grade on initial biopsy correlated significantly with progression to invasive carcinoma (log-rank P =.0001). Majority diagnosis was achieved in 99 of the cases. Using the majority diagnoses, no invasive carcinomas were found in 50 cases of BE (median follow-up, 48 months), and carcinomas were detected in 1 of 7 (14%) IND cases (80% progression-free survival at 2 months), 3 of 15 (20%) LGD (median progression-free survival, 60 months), 9 of 15 (60%) HGD (median progression-free survival, 7 months), and all 12 (100%) carcinoma. Initial grading again correlated significantly with progression to invasive carcinoma (log-rank P =.0001). However, there were 39 cases without a majority diagnosis. Among these, no carcinomas developed in 8 cases with an average score between BE and IND. Carcinomas were detected in 9 of 21 (43%) cases with an average score between IND and LGD, and 7 of 10 (70%) cases with an average score between LGD and HGD. There were ulcers in 8 of 39 cases (20%) of the "no-majority" group and in 13 of 99 (13%) of the majority cases. Of 21 total ulcerated cases, cancer was demonstrated in 15 (71%) of these on follow-up. These data support combining the IND and LGD categories for surveillance purposes. Cases without dysplasia may be followed up conservatively. The data obtained from submitted diagnoses as opposed to those from blind review suggest that knowledge of the clinical findings aids in diagnosis. The data also support the assertion that HGD is strongly associated with invasive carcinoma. Rebiopsy of ulcerated areas should be considered because they may harbor malignancy. Histologic grading of dysplasia using established criteria is a powerful prognosticator in BE.