Low-grade dysplasia in Barrett’s esophagus - an innocent bystander? Pro

Introduction

Barrett’s esophagus, a complication of chronic gastroesophageal reflux disease, is well-established as a premalignant condition for esophageal adenocarcinoma. Esophageal carcinogenesis is a multistep process in which patients progress from intestinal metaplasia with no dysplasia through increasing grades of dysplasia to invasive cancer, a progression that occurs in a probabilistic rather than a deterministic manner [1] [2].

Despite its several imperfections, the conventional histologic classification of dysplasia based on endoscopic biopsies is the single most predictive ”biomarker“ for progression to cancer in patients with Barrett’s esophagus. The degree of dysplasia has been shown to correlate with the risk of developing cancer, and high-grade dysplasia (HGD) is associated with the greatest risk [3]. In contrast, data regarding the association of esophageal adenocarcinoma risk and the identification of low-grade dysplasia (LGD) is confusing at best. LGD is characterized by crypts with relatively well-preserved architecture and stratified, atypical, pencil-shaped nuclei, limited for the most part to the basal portion of the cell cytoplasm. The nuclei are typically elongated and hyperchromatic, with an irregular contour and a dense chromatin pattern. The dysplastic cells are mucin-depleted and there is a decrease in the number of goblet cells. Other features include increased mitoses, preservation (or only slight loss) of cell polarity, increased nuclear/cytoplasmic ratio, and lack of surface maturation [4].

References

• 1 van Sandick J W, van Lanschot J J, Kuiken B W. et al . Impact of endoscopic biopsy surveillance of Barrett’s oesophagus on pathological stage and clinical outcome of Barrett’s carcinoma.  Gut. 1998;  43 216-222
• 2 Haggitt R C. Barrett’s esophagus, dysplasia, and adenocarcinoma.  Human Pathol. 1994;  25 982-993
• 3 Reid B J, Levine D S, Longton G. et al . Predictors of progression to cancer in Barrett’s esophagus: baseline histology and flow cytometry identify low- and high-risk patient subsets.  Am J Gastroenterol. 2000;  95 1669-1676
• 4 Odze R D. Diagnosis and grading of dysplasia in Barrett’s oesophagus.  J Clin Pathol. 2006;  59 1029-1038
• 5 Reid B J, Haggitt R C, Rubin C E. et al . Observer variation in the diagnosis of dysplasia in Barrett’s esophagus.  Human Pathol. 1988;  19 166-178
• 6 Montgomery E, Bronner M P, Goldblum J R. et al . Reproducibility of the diagnosis of dysplasia in Barrett esophagus: a reaffirmation.  Human Pathol. 2001;  32 368-378
• 7 Alikhan M, Rex D, Khan A. et al . Variable pathologic interpretation of columnar-lined esophagus by general pathologists in community practice.  Gastrointest Endosc. 1999;  50 23-26
• 8 Baak J P, ten Kate F J, Offerhaus G J. et al . Routine morphometrical analysis can improve reproducibility of dysplasia grade in Barrett’s oesophagus surveillance biopsies.  J Clin Pathol. 2002;  55 910-916
• 9 Skacel M, Petras R E, Gramlich T L. et al . The diagnosis of low-grade dysplasia in Barrett’s esophagus and its implications for disease progression.  Am J Gastroenterol. 2000;  95 3383-3387
• 10 Montgomery E, Goldblum J R, Greenson J K. et al . Dysplasia as a predictive marker for invasive carcinoma in Barrett esophagus: a follow-up study based on 138 cases from a diagnostic variability study.  Human Pathol. 2001;  32 379-388
• 11 Schnell T G, Sontag S J, Chejfec G. et al . Long-term nonsurgical management of Barrett’s esophagus with high-grade dysplasia.  Gastroenterology. 2001;  120 1607-1619
• 12 Weston A P, Banerjee S K, Sharma P. et al . p53 protein overexpression in low-grade dysplasia (LGD) in Barrett’s esophagus: immunohistochemical marker predictive of progression.  Am J Gastroenterol. 2001;  96 1355-1362
• 13 Conio M, Blanchi S, Lapertosa G. et al . Long-term endoscopic surveillance of patients with Barrett’s esophagus. Incidence of dysplasia and adenocarcinoma: a prospective study.  Am J Gastroenterol. 2003;  98 1931-1939
• 14 Dulai G S, Shekelle P G, Jensen D M. et al . Dysplasia and risk of further neoplastic progression in a regional Veterans Administration Barrett’s cohort.  Am J Gastroenterol. 2005;  100 775-783
• 15 Sharma P, Falk G W, Weston A P. et al . Dysplasia and cancer in a large multicenter cohort of patients with Barrett’s esophagus.  Clin Gastroenterol Hepatol. 2006;  4 566-572
• 16 Srivastava A, Hornick J L, Li X. et al . Extent of low-grade dysplasia is a risk factor for the development of esophageal adenocarcinoma in Barrett’s esophagus.  Am J Gastroenterol. 2007;  102 483-493; quiz, 694
• 17 Lim C H, Treanor D, Dixon M F, Axon A TR. Low-grade dysplasia in Barrett’s esophagus has a high risk of progression.  Endoscopy. 2007;  39 581-587
• 18 Shaheen N J, Crosby M A, Bozymski E M, Sandler R S. Is there publication bias in the reporting of cancer risk in Barrett’s esophagus?.  Gastroenterology. 2000;  119 333-338
• 19 Ofman J J, Lewin K, Ramers C. et al . The economic impact of the diagnosis of dysplasia in Barrett’s esophagus.  Am J Gastroenterol. 2000;  95 2946-2952
• 20 Shaheen N J. Should we worry about the length of Barrett’s esophagus?.  Gastrointest Endosc. 2005;  62 682-685
• 21 Sharma P. Low-grade dysplasia in Barrett’s esophagus.  Gastroenterology. 2004;  127 1233-1238
• 22 Dorer R, Odze R D. AMACR immunostaining is useful in detecting dysplastic epithelium in Barrett’s esophagus, ulcerative colitis, and Crohn’s disease.  Am J Surg Pathol. 2006;  30 871-877
• 23 Buttar N S, Wang K K, Sebo T J. et al . Extent of high-grade dysplasia in Barrett’s esophagus correlates with risk of adenocarcinoma.  Gastroenterology. 2001;  120 1630-1639
• 24 Skacel M, Petras R E, Rybicki L A. et al . p53 expression in low-grade dysplasia in Barrett’s esophagus: correlation with interobserver agreement and disease progression.  Am J Gastroenterol. 2002;  97 2508-2513
• 25 Kara M A, Peters F P, Rosmolen W D. et al . High-resolution endoscopy plus chromoendoscopy or narrow-band imaging in Barrett’s esophagus: a prospective randomized crossover study.  Endoscopy. 2005;  37 929-936
• 26 Sharma P, Bansal A, Mathur S. et al . The utility of a novel narrow-band imaging endoscopy system in patients with Barrett’s esophagus.  Gastrointest Endosc. 2006;  64 167-175
• 27 Kara M A, Peters F P, Fockens P. et al . Endoscopic video-autofluorescence imaging followed by narrow-band imaging for detecting early neoplasia in Barrett’s esophagus.  Gastrointest Endosc. 2006;  64 176-185
• 28 Kiesslich R, Gossner L, Goetz M. et al . In vivo histology of Barrett’s esophagus and associated neoplasia by confocal laser endomicroscopy.  Clin Gastroenterol Hepatol. 2006;  4 979-987