Poor Interobserver Agreement in the Distinction of High-Grade Dysplasia and Adenocarcinoma in Pretreatment Barrett's Esophagus Biopsies

Downs‐Kelly, Erinn; Mendelin, Joel E.; Bennett, Ana E.; Castilla, Elias A.; Henricks, Walter H.; Schoenfield, Lynn; Skacel, Marek; Yerian, Lisa; Rice, Thomas W.; Rybicki, Lisa; Bronner, Mary P.; Goldblum, John R.

doi:10.1111/j.1572-0241.2008.02020.x

Cited by 181 publications

(105 citation statements)

References 32 publications

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“…With pronounced inflammation and particularly erosion/ulceration, the best criterion to exclude dysplasia is maturation of atypia as the epithelium extends onto the mucosal surface. [5][6][7][8][11][12][13][14][15] Surface maturation, however, may be lacking altogether in marked inflammatory injury. The cytological features of inflammatory change can be indistinguishable from those of high-grade dysplasia.…”

Section: Discussionmentioning

confidence: 99%

“…[5][6][7][8][11][12][13][14][15] Caution should be exercised in the setting of prominent inflammation by diagnosing indefinite changes for dysplasia. [5][6][7][8][11][12][13][14][15] If concern for high-grade dysplasia exists, a cautionary disclaimer indicating that high-grade dysplasia cannot be excluded is appropriate. This exact diagnosis achieved univariate and multivariate significance for predicting disagreement among the study pathologists, with a relative risk of 2.9 (95% confidence interval 1.3, 6.5; P ¼ 0.009), emphasizing the magnitude of the difficulty imposed by inflammatory change.…”

Section: Discussionmentioning

confidence: 99%

“…[5][6][7][8]11,12 Surface maturation of basal atypia, in which the nuclei become smaller, normochromatic, uniform, and nonstratified as the epithelium extends onto the biopsy surface, is again the most important criterion available for excluding dysplasia, similar to its importance in inflammatory change. [5][6][7][8][11][12][13][14][15] The proposed concept of crypt-limited dysplasia contradicts that surface maturation excludes dysplasia. [13][14][15] Only 15 such crypt-limited cases have been reported in the literature in relation to the patients' corresponding Barrett's segments.…”

Section: Discussionmentioning

confidence: 99%

“…[5][6][7][8][11][12][13][14][15] This factor contributed to 102 of the over diagnosed cases in this study. Maintenance of nuclear polarity in low-grade dysplasia is the most reliable criterion for this distinction, whereby the long axes of the nuclei remain parallel to one another and perpendicular to the basal lamina.…”

Section: Discussionmentioning

confidence: 99%

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Overdiagnosis of high-grade dysplasia in Barrett's esophagus: a multicenter, international study

et al. 2015

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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 ¼ 18; 7%), Barrett's without dysplasia (n ¼ 35; 15%), indefinite change (n ¼ 61; 26%), low-grade dysplasia (n ¼ 79; 33%), adenocarcinoma (n ¼ 43; 18%), and other (n ¼ 1; o1%), yielding an alarming total of 194 or 40% of patients who were overdiagnosed with Barrett's highgrade 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 ¼ 182), atypia limited to the basal metaplastic glands (n ¼ 147), imprecise criteria for low grade neoplasia (n ¼ 102), tangential sectioning artifact (n ¼ 59), and reactive gastric cardiac mucosa (n ¼ 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.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Overdiagnosis of high-grade dysplasia in Barrett's esophagus: a multicenter, international study

et al. 2015

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“…The categories of neoplasia, including negative for dysplasia, indefinite for dysplasia, low-grade dysplasia, high-grade dysplasia, intramucosal carcinoma, and adenocarcinoma with at least submucosal invasion, were defined according to the published criteria of Montgomery et al 6 and Downs-Kelly et al 9 These criteria refer only to the intestinal variant of dysplasia in Barrett's esophagus.…”

Section: Histological Evaluationmentioning

confidence: 99%

Grading of gastric foveolar-type dysplasia in Barrett's esophagus

et al. 2010

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Dysplasia is the gold standard biomarker of cancer risk in Barrett's esophagus, but its diagnosis remains difficult. This is due in part to its multitude of histological appearances. One aspect receiving little attention concerns gastric-type Barrett's dysplasia, which is distinctly different from the well-established intestinal variant. Recognition of gastric-type dysplasia and development of separate grading criteria are required. The prevalence, diagnostic criteria, and natural history of gastric-type Barrett's dysplasia were systematically evaluated in 1854 endoscopic biopsies from a cohort of 200 consecutive Barrett's dysplasia patients. Goblet cells were present in all cases, confirming the utility of this defining feature of Barrett's esophagus. The prevalence of Barrett's gastric-type dysplasia was 15% at the patient level (30 of 200 patients) and 20% at the biopsy level (166 of 852 dysplastic biopsies). Gastric-type dysplasia uniformly showed non-stratified, basally oriented nuclei as the major criterion for distinguishing it from intestinal-type Barrett's dysplasia. As such, loss of nuclear polarity, as the most objective criterion to distinguish intestinal-type low-and high-grade dysplasia, cannot be applied to gastric-type dysplasia. Rather, discriminatory features included increased nuclear size with a high-grade dysplasia cutoff by receiver operating characteristic (ROC) analysis approximating 3-4 times the size of a mature lymphocyte, providing an optimal sensitivity, specificity, and area under the curve of 0.78, 0.90, and 0.90 (95% CI: (0.87, 0.93)), respectively. Crowded, irregular glandular architecture (Po0.001) was more common in high-grade lesions (Po0.001), as was eosinophilic and oncocytic cytoplasm relative to the mucinous cytoplasm (Po0.001), prominent nucleoli (Po0.001), mild nuclear pleomorphism (Po0.001), and villiform architecture (Po0.001). During follow-up, 64% (7 of 11) of patients with pure gastric and 26% (5 of 19) with mixed gastric and intestinal dysplasia underwent neoplastic progression. The recognition of Barrett's gastric-type dysplasia and use of the proposed grading criteria should promote better diagnostic classification of the Barrett's neoplastic spectrum.

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Radiofrequency Ablation for Barrett Esophagus With Confirmed Low-Grade Dysplasia

Mönkemüller

2014

JAMA

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Poor Interobserver Agreement in the Distinction of High-Grade Dysplasia and Adenocarcinoma in Pretreatment Barrett's Esophagus Biopsies

Cited by 181 publications

References 32 publications

Overdiagnosis of high-grade dysplasia in Barrett's esophagus: a multicenter, international study

Overdiagnosis of high-grade dysplasia in Barrett's esophagus: a multicenter, international study

Grading of gastric foveolar-type dysplasia in Barrett's esophagus

Radiofrequency Ablation for Barrett Esophagus With Confirmed Low-Grade Dysplasia

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