Refining Diagnostic Criteria for High-Grade Dysplasia in Barrett Esophagus

Abstract

In many respects, the medical community has failed patients with esophageal carcinoma miserably. Even with contemporary treatment, the overall 5-year survival for esophageal cancer in the United States is an abysmal 13%. 1 A number of studies suggest that surveillance is effective in capturing the early lesions for which survival is excellent, but current data indicate that only a small fraction (<5%) of patients in whom gastric cardiac and esophageal carcinomas develop are actually targeted by surveillance programs 2 ; most patients seek care too late in the disease course to benefit from even the most aggressive treatment. Unfortunately, because esophageal cancer is relatively uncommon (there were 16,470 estimated new cases of esophageal cancer in the United States in 2008 compared with 148,419 colon cancers and 215,020 lung cancers), 3 it is not likely, given economic factors, that there will be a push for intensified screening and early detection of esophagus cancers. It is well-known that Barrett esophagus is a precursor lesion for esophageal adenocarcinomas. In the United States, Barrett esophagus has been defined as change of the distal esophageal epithelium of any length that can be recognized as columnar epithelium at endoscopy and that has intestinal metaplasia revealed by biopsy, 4 whereas documentation of goblet cells is not required in the United Kingdom, some of continental Europe (excluding Germany), or Japan. As such, Barrett esophagus is thus often an endoscopic rather than a histologic diagnosis outside the United States. The reasoning for the US definition is the belief that intestinal metaplasia is a marker for a higher likelihood over that of gastric-type mucosa for progression to adenocarcinoma. 5 However, regardless of where the patient resides, most endoscopists biopsy columnar epithelium in the esophagus to assess for neoplasia. Whether definitions will gradually be modified in the United States to transform Barrett esophagus from a histologic diagnosis to an endoscopic one remains a subject of debate (some of which relates to economic issues), but some studies indicate that, in fact, high-grade columnar epithelial dysplasia and early esophageal adenocarcinomas are more likely to be accompanied by gastric cardiac-type mucosa than by metaplastic mucosa with goblet cells. 6 Those of us in the pathology community will be part of any changes that come in the endoscopy community. In the interim, however, we should strive to best serve the lucky minority of at-risk patients who are screened and whose precursor lesions and early cancers are likely to be biopsied. Since the progression from Barrett esophagus to dysplasia to adenocarcinoma is a continuum and presumably the reflection of accumulating genetic events, it is not surprising that pathologists do not always agree in classifying the stages of this progression. This disagreement is present for grading dysplasia 7 and for distinguishing between high-grade