Overdiagnosis of High-grade Dysplasia in Barrett's Esophagus: A Multicenter, International Study

Nikhil A Sangle; Shari L Taylor; Mary J Emond; Michelle Depot; Bergein F Overholt; Mary P Bronner On behalf of the International Photodynamic Group for High-Grade Dysplasia in Barrett's Esophagus


Mod Pathol. 2015;28(6):758-765. 

In This Article

Abstract and Introduction


Numerous histological mimics of high-grade dysplasia in Barrett's esophagus predispose to overdiagnosis and potential serious mismanagement, including unnecessary esophagectomy. This study investigates the prevalence and sources of this problem. Biopsies from 485 patients diagnosed with Barrett's high-grade dysplasia were screened for a multi-institutional, international Barrett's endoscopic ablation trial. Screening included review of the original diagnostic slides and an additional protocol endoscopy with an extensive biopsy sampling. Observer variability by the study pathologists was assessed through two blinded diagnostic rounds on 437 biopsies from 26 random study endoscopies. Study diagnostic reassessments revealed significantly lower rates of high-grade dysplasia. Only 248 patients (51%) were confirmed to have high-grade dysplasia. The remaining patients had inflamed gastric cardia without Barrett's (n=18; 7%), Barrett's without dysplasia (n=35; 15%), indefinite change (n=61; 26%), low-grade dysplasia (n=79; 33%), adenocarcinoma (n=43; 18%), and other (n=1; <1%), yielding an alarming total of 194 or 40% of patients who were overdiagnosed with Barrett's high-grade dysplasia. Study pathologists achieved a high-level agreement (90% three-way inter-observer agreement per biopsy, Kappa value 0.77) for high-grade dysplasia. Confounding factors promoting overdiagnosis included Barrett's inflammatory atypia (n=182), atypia limited to the basal metaplastic glands (n=147), imprecise criteria for low grade neoplasia (n=102), tangential sectioning artifact (n=59), and reactive gastric cardiac mucosa (n=38). A total of 194 patients (40%) were overdiagnosed with Barrett's high-grade dysplasia, as affirmed by the extensive screening process and high-level study pathologist agreement. The multiple diagnostic pitfalls uncovered should help raise pathologists' awareness of this problem and improve diagnostic accuracy.


The pathological and clinical criteria, as well as the management of Barrett's esophagus have undergone a considerable change since the condition was first described in 1957 by the influential British surgeon, Dr Norman Barrett.[1] Neoplastic change, including both dysplasia and carcinoma in Barrett's esophagus is prone to overdiagnosis because of the prominent histological overlap between metaplastic, inflammatory, regenerative, and neoplastic pathology in this challenging condition. Overdiagnosis of high-grade dysplasia is especially unfortunate considering its aggressive management consequences, including esophagectomy or endoscopic treatment modalities.[2]

The magnitude of the overdiagnosis problem has not been systematically evaluated. We sought to examine the prevalence and sources of this problem, based on patients undergoing screening for an endoscopic ablation trial of Barrett's esophagus with high-grade dysplasia.[3,4] To help determine the validity of the trial diagnoses, the three study pathologists (SLT, MPB and late Dr Rodger C Haggitt) were evaluated for observer variability on a per endoscopy and per biopsy basis. The patients also underwent an additional protocol screening endoscopy with intensive biopsy sampling (four-quadrant jumbo biopsies every 2 cm throughout the Barrett's segment with additional biopsies of any visible lesions). Finally, the diagnostic pitfalls leading to overdiagnosis of Barrett's high-grade dysplasia were cataloged from this series to explain the sources of error and increase pathologists' awareness in this difficult area of diagnostic pathology.