Neoplasia without dysplasia: Lessons from Barrett esophagus and other tubal gut neoplasms

Context.-Classic pathology teaching emphasizes that neoplastic lesions of the gastrointestinal tract are characterized by architectural and cytologic abnormalities that distinguish it from normal tissue. Recent studies suggest that many important-and in some cases clonal-molecular abnormalities that lead to dysregulation of cell proliferation and differentiation (neoplasia) occur before morphologic expression of dysplasia. Objective.-To summarize the biologic and pathologic features of preneoplastic conditions of the tubal gut that reveal evidence of neoplastic alteration, but without the traditional morphologic features of dysplasia, in order to provide guidance on how to identify these lesions. Particular attention is given to Barrett esophagus, a chronic inflammatory condition in which early molecular and morphologic events that drive carcinogenesis are best understood. Data Sources.-Selected references and abstracts were obtained by a PubMed (US National Library of Medicine) search by using the search headings neoplasia, preneoplasia, dysplasia, adenoma, serrated polyps, and Barrett's esophagus between the years 1980 and 2009. Conclusions.-Many types of lesions throughout the tubal gut fulfill the most basic and classic principles of a neoplastic precursor lesion but lack conventional morphologic evidence of dysplasia and/or maintain the capacity for cell differentiation and maturation. All of these lesions, such as squamous dysplasia of the esophagus, dysplasia in Barrett esopahagus, and hyperplastic/serrated polyps of the colon, represent early neoplastic precursor lesions but without conventional histologic features of dysplasia. It is important for pathologists to be aware of these lesions, both for diagnostic and prognostic purposes, but also so that future studies can be performed with regard to risk stratification of patients.