Lymphocytic disorders of the gastrointestinal tract: a review for the practicing pathologist

Increased numbers of intraepithelial lymphocytes (lymphocytosis) can be found in the esophagus, stomach, small intestine, and colon in a variety of clinical circumstances. This review, directed at practicing pathologists, portrays the normal resident lymphocyte population in the mucosa of each segment of the digestive tract and discusses the different situations that may result in quantitative or qualitative alterations of intraepithelial lymphocytes. Esophageal lymphocytosis has not been fully characterized and its clinical significance, if any, awaits definition. Thus, this diagnosis is presently discouraged. In the stomach, it is particularly important to exclude Helicobacter pylori infection and celiac sprue before diagnosing lymphocytic gastritis. Duodenal lymphocytic infiltrates, inextricably tied with alterations of the villous architecture of the mucosa, are often caused by gluten sensitivity. However, similar morphologic changes may be caused by a vast array of other conditions that must be carefully considered and excluded. Lymphocytic and collagenous colitis are most often unexplained, but their frequent association with autoimmune conditions or certain medications deserve a thorough investigation in each case. Using a combination of histologic and clinical clues, a cause for the intraepithelial lymphocytic infiltration can be identified in many instances. As some of the associated conditions are amenable to effective treatment, the importance of diligently seeking such associations before resorting to a diagnosis of primary lymphocytosis is emphasized.