Barrett's esophagus, dysplasia, and adenocarcinoma

Haggitt, Rodger C.

doi:10.1016/0046-8177(94)90057-4

Cited by 582 publications

(370 citation statements)

References 86 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%

“…Necrotic or apoptotic debris in dilated glandular lumina was considered highly abnormal and indicative of at least high-grade dysplasia. [5][6][7][8] Observer Variability…”

Section: Histologymentioning

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%

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

et al. 2015

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“…[6][7][8][9] The latter, is identified by the presence of goblet-shaped cells, the metaplastic element regarded as the hallmark of Barrett's esophagus due to its association with cancer risk. 9,10 Nevertheless, the prevalent cellular elements of Barrett's esophagus are the columnar nongoblet cells, which exhibit gastric and intestinal characteristics as goblet cells do. 11 Gastric and intestinal mucosas are protected by a mucus layer of high molecular weight glycoproteins synthesized by normal epithelial cells in a cell-and tissue-specific pattern.…”

mentioning

confidence: 99%

“…10 This pathway to malignancy is the morphologic counterpart of a progressive accumulation of genetic events (gross chromosomal and/or subtle DNA sequence abnormalities) that lead to genomic instability. [14][15][16][17] Aneuploidy and increased G2/tetraploid fraction, signs of gross DNA chromosomal abnormalities, have been related to Barrett's tumorigenesis.…”

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confidence: 99%

Chromosomal analysis of Barrett's cells: demonstration of instability and detection of the metaplastic lineage involved

et al. 2007

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Barrett's esophagus is lined by columnar and goblets cells with gastric and intestinal characteristics. Despite the association between goblet elements and malignancy, it was not demonstrated that other columnar cells lineages are not related to neoplasia. Chromosomal abnormalities were described in metaplasia adjacent to Barrett's neoplasia, but it is unknown which metaplastic lineages are involved. This work assessed the frequency and the type of chromosomal abnormalities in Barrett's esophagus without neoplasia and performed the identification of the metaplastic cells carrying chromosomal gains. Barrett's esophagus biopsies were collected and processed for short-term cell culture and cytogenetic analysis. Combined immunofluorescence/ fluorescence in situ hybridization was performed in cases exhibiting chromosomal gains by using antisera against intestinal (MUC2) and gastric (MUC5AC and MUC6) apomucins and chromosome pericentromeric alpha satellite DNA probes for the chromosomes involved. Each case was scored for the number of spots (0, 1, 2, 42) in 200 nonoverlapping nuclei. Columnar and goblet cells were separately assessed. Short-term cell cultures were achieved in 40/60 cases (67%). There were clonal abnormalities in 27/40 cases (68%) and tetraploid (4n) clones in 10/40 (25%). Structural alterations were detected in 14/40 (35%) with recurrent breakpoints at 1q21, 15q15 and 15q22. Numerical changes (trisomies 7 and 18 and loss of Y) occurred in 16/40 (40%). Gains of chromosomes 7 and 18 were more frequent in columnar than in goblet cells (9.8% vs 0.7% (Po0.05)) and (7.9 vs 1.9% (Po0.05)) respectively. These alterations were detected in cells exhibiting gastric as well as intestinal features and were more frequent in cells without apomucin production. Conclusions: (1) chromosomal instability is a common finding in Barrett's esophagus without neoplasia. (2) The two metaplastic populations are committed, chromosomal gains being more frequent in columnar nongoblet than in goblet cells. (3) The two metaplastic phenotypes, gastric and intestinal, are equally involved.

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