Preface

Due to recent advancements in endoscopic and radiologic techniques, pathologists and clinicians are increasingly exposed to early neoplastic precursor lesions of the gastrointestinal (GI) tract, liver, biliary tract and pancreas. This has led to a better understanding of the molecular pathogenesis of cancer development in these organs, and in disorders such as Barrett's esophagus and inflammatory bowel disease, has contributed to the development of models of tumor progression that may be applicable to other organ systems in humans. Scientific advancements with regard to the biological characteristics of neoplastic precursor lesions have also translated into early detection and improved patient survival as a result of use of screening and surveillance programs.

In this issue of Gastroenterology Clinics of North America, internationally recognized pathologists have contributed timely reviews focused on the pathologic features, molecular pathogenesis, natural history, clinical relevance, and treatment of neoplastic precursor lesions of the GI tract, liver, biliary tract and pancreas. A cancer precursor lesion is defined as neoplastic epithelium that is confined to the basement membrane of the mucosal compartment in which it is normally located or has not invaded the surrounding tissues. In some diseases, such as Barrett's esophagus and chronic gastritis, the dysplasia–carcinoma sequence is preceded by epithelial metaplasia. As discussed in some of the review articles in this issue, however, it is now increasingly apparent that even some types of metaplastic epithelium possess genetic, proliferation, and differentiation abnormalities that occur prior to the onset of morphologic dysplasia.

In general, GI pathologists have converted to a two-tiered grading system of neoplastic precursor lesions, termed low or high grade, that define progressive stages of neoplastic development prior to tissue invasion. This grading system has proved to be clinically useful and is used by the authors in this issue. In addition, in most, if not all, precursor grading systems, the term “carcinoma in situ” has been abandoned by pathologists and is now incorporated into the high-grade category because it has an equivalent degree of clinical relevance. As you read through this comprehensive review about neoplastic precursor lesions, it is important to realize that, regardless of the anatomic site, progression of tumor development represents a continuous/linear spectrum of advancing degrees of epithelia neoplasia, which in some instances, is difficult to compartmentalize into discrete grades. Thus, there is interobserver variability regarding interpretation of neoplastic precursor lesions by pathologists, which is important to keep in mind when evaluating pathology reports and translating the information in those reports toward patient care.

It is my hope that after reading this issue of Gastroenterology Clinics of North America you will recognize several important take-home points. First is the critical role of pathologists in the diagnosis and management of patients who have neoplastic precursor lesions of the GI tract, liver, biliary tract or pancreas. However, it is also important to recognize the limitations of pathology in this regard. For a number of reasons, such as the low prevalence rate of dysplastic lesions in the general population, the relative inexperience with dysplastic lesions by most non-tertiary care–affiliated general pathologists, the difficulties in morphologic interpretation, and sampling limitations, it is highly recommended (if not mandatory) that at least two experienced, preferably GI, pathologists evaluate and agree on a specific grade of neoplastic precursor lesion before institution of patient management. The value of close cooperation, and/or face-to-face interaction, between clinicians and pathologists cannot be overemphasized with regard to the care of patients who have neoplastic precursor lesions.

Second, because of inherent limitations of pathologic assessment of neoplastic precursor lesions, there is a need for better, more reliable, and reproducible biomarkers to assess risk of malignancy in affected patients. In some organs, understanding the biological characteristics and natural history of these lesions is limited by various factors, such as poor accessibility of tissue, low prevalence rate in the general population, and the relatively long period of time necessary for progression of pre-neoplasia to invasive neoplasia, and this makes the study of these lesions difficult. In some instances, such as in Barrett's esophagus and inflammatory bowel disease, there has been much headway with regard to screening and surveillance guidelines, but in other disorders, such as chronic gastritis, precursor lesions of the liver and endocrine system, and hyperplastic/serrated precursors in the colon, surveillance guidelines are still evolving and there is need for more research in this area.

Finally, although screening and surveillance for precursor lesions is both logical and scientifically valid, there is an ongoing need for prospective randomized controlled trials to determine the actual costs and benefits of surveillance programs.

I would like to thank all of the authors who contributed to this issue of Gastroenterology Clinics of North America for their patience with the editorial process, for supplying their manuscripts in a timely fashion, and most importantly, for providing remarkably concise and comprehensive reviews of the key morphologic, biological, and clinically relevant aspects of pre-neoplastic lesions of the GI tract, liver, biliary tract and pancreas. As a result, much of the information provided in this issue can be used to better serve our patients directly and identify areas in need of further research.