Stem Cells, Pre-neoplasia, and Early Cancer of the Upper Gastrointestinal Tract

Myrtle J. van der Wel M.D., Marnix Jansen M.D., Ph.D., M.Sc., Michael Vieth, Sybren L. Meijer M.D., Ph.D., Myrtle J. van der Wel, Marnix Jansen, Sybren L. Meijer

Marnix Jansen, Nicholas A. Wright

Clonal evolution to esophageal adenocarcinoma in Barrett's esophagus (BO) is characterized by relentless clonal competition. Developing markers that capture the dynamics of clonal competition in BO patients for risk stratification purposes is a key goal of translational research. Dysplastic epithelial changes in patients who progress to neoplasia can be viewed as a proxy marker of the clonal dynamics in BO progression. However, this marker is relatively insensitive because it does not pick up on clonal expansions that are not accompanied by morphologic changes. Moreover, interobserver variability between histopathologists hampers the specificity of this marker in predicting disease progression. International guidelines now stipulate that dysplasia should be confirmed by a second gastrointestinal histopathologist. This recommendation emphasizes the importance of special expertise in Barrett's histopathology. Currently, though there are no criteria that lay down "what makes an expert Barrett's histopathologist?" Here we review the histopathology of Barrett's dysplasia with an emphasis on the collaborative role of the histopathologist in the management of BO patients who progress to dysplasia, while the accompanying paper by Shepherd and colleagues discusses the histopathology of nondysplastic BO. We evaluate factors that may contribute to interobserver variability and provide details on adjunct tests (such as p53 immunohistochemistry) and standardized handling and reporting of risk factors in endoscopic resection specimens. Strict application of diagnostic criteria fosters diagnostic uniformity and facilitates tailored care of patients with early stage esophageal adenocarcinoma and its precursor lesions.