Dysplasia arising in barrett's esophagus: diagnostic pitfalls and natural history

Barrett's esophagus is a complication of chronic gastroesophageal reflux disease and is defined as a change in the esophageal epithelium of any length that can be recognized at endoscopy and is confirmed to have intestinal metaplasia by biopsy. Esophageal ulcerations and stricture are rarely seen, and the major complications of this disease are epithelial dysplasia and esophageal adenocarcinoma. Dysplasia is felt to represent the best currently available marker of increased cancer risk in these patients. However, there are many pitfalls in the histologic recognition of dysplasia, a particularly difficult problem in the face of active inflammation in patients with ongoing reflux disease. The recognition and grading of dysplasia is subject to significant interobserver variability, particularly at the lower end of the histologic spectrum (negative v indefinite for dysplasia v low-grade dysplasia). High-grade dysplasia and to a lesser degree low-grade dysplasia are markers of increased cancer risk, although their natural history are difficult to determine. Up to 40% of patients with a preoperative diagnosis of high-grade dysplasia have an adenocarcinoma in their esophagectomy specimen. Despite this observation, there is still debate as to whether esophagectomy or close endoscopic surveillance with biopsy is the most appropriate and cost-effective way to manage these patients. The search for more objective surrogate biomarkers that recognize patients who are truly at risk of progressing along the dysplasia-carcinoma sequence is underway. However, no biomarker has yet proven to be superior to the histologic recognition of dysplasia in identifying these high-risk patients.