The significance of "indefinite for dysplasia" grading in Barrett metaplasia

Context.-For a confident diagnosis of dysplasia in Barrett metaplasia, the epithelial atypia should also involve the surface epithelium. However, pathologists are often faced with biopsies where the crypts show dysplasia, but the surface epithelium is either uninvolved or unevaluable. We previously grouped these cases with indefinite for dysplasia (IND). Objective.-To determine the clinical significance of IND grading in Barrett metaplasia. Design.-All biopsies from 276 prospectively followed patients with Barrett metaplasia, who did not have highgrade dysplasia (HGD) or esophageal adenocarcinoma (EAC) on initial biopsy, were graded as negative for dysplasia, IND, low-grade dysplasia (LGD), HGD, and EAC. Biopsies with multifocal IND or LGD were graded as INDM or LGDM, respectively. Results.-Only 3 of 193 patients (2%) with an initial diagnosis of negative for dysplasia and only 1 of 48 patients (2%) diagnosed with IND progressed to HGD or EAC. By contrast, 1 of 7 patients (14%) with INDM, 2 of 21 (10%) with LGD, and 1 of 7 (14%) with LGDM progressed to HGD or EAC. There was no significant difference in progression rate between patients with an initial diagnosis of negative for dysplasia and those diagnosed IND nor were there significant differences among patients with initial diagnoses of INDM, LGD, or LGDM. Kaplan-Meier analysis showed that patients with INDM, LGD, or LGDM on initial biopsy (group 1 ) were more likely to progress to HGD or EAC than were those patients who were diagnosed negative for dysplasia or IND (group 2; log-rank test, P < .001). Conclusions.-Multifocal IND in an esophageal biopsy from a patient with Barrett metaplasia has the same clinical implication as LGD.