REVIEW The pathology of malabsorption: current concepts S R Owens & J K Greenson 1 Departments of Pathology, University of Pittsburgh Medical Center, Pittsburgh, PA and 1 University of Michigan Health System, Ann Arbor, MI, USA Owens S R & Greenson J K (2007) Histopathology 50, 64–82 The pathology of malabsorption: current concepts Intestinal malabsorption results from a wide variety of causes, which can most easily be organized into three groups. Maldigestion arises from problems with mix- ing or with digestive mediators, and includes post- gastrectomy patients and those with deficiencies of pancreatic or intestinal enzymes, or of bile salts. Mucosal and mural causes of malabsorption are abundant, and include gluten-sensitive enteropathy, tropical sprue, autoimmune enteropathy, and HIV/ AIDS-related enteropathy, as well as mural conditions such as systemic sclerosis. Finally, microbial causes of malabsorption include bacterial overgrowth, Whipple’s disease, and numerous infections or infestations that are most frequently seen in immunocompromised patients. An overview of the most common and interesting entities in each of these categories follows, along with a discussion of current concepts. Mucosal conditions and microbial causes of malabsorption are given special attention. Keywords: autoimmune enteropathy, bacterial overgrowth, coeliac disease, giardiasis, gluten-sensitive enteropathy, malabsorption, sprue, Whipple’s disease Abbreviations: AE, autoimmune enteropathy; CD, Crohn’s disease; DH, dermatitis herpetiformis; EATCL, enteropathy associated T-cell lymphoma; ELISA, enzyme-linked immunosorbent assay; EM, electron microscopy; GFD, gluten-free diet; GSE, gluten-sensitive enteropathy; H&E, haematoxylin and eosin; HIV/AIDS, human immunodeficiency virus/acquired immunodeficiency syndrome; IBD, inflammatory bowel disease; IEL, intra- epithelial lymphocyte(s); NSAIDS, non-steroidal anti-inflammatory drugs; PIL, primary lymphangectasia; SI, small intestine; TPN, total parenteral nutrition; TS, tropical sprue; TTG, tissue transglutaminase; UC, ulcerative colitis; WD, Whipple’s disease Introduction The human gastrointestinal (GI) tract is the site of absorption of a wide variety of ingested nutrients, including vitamins, proteins, carbohydrates and fats. Much of this absorption occurs in the small intestine (SI), where the high surface area provided by the villous and microvillous architecture optimizes uptake of dietary substances. The specialized SI mucosa contains numerous digestive enzymes on its surface, as well as an intricate network of lymphatics and blood vessels providing access to the bloodstream. Adequate digestion and absorption depend on a multitude of factors, including mechanical mixing, enzyme produc- tion and activity, proper mucosal function, adequate blood supply, intestinal motility and even normal microbial ecology. Accordingly, malfunctions in any of these compo- nents can lead to failure to absorb nutrients from the diet, often resulting in some combination of diarrhoea, steatorrhoea, malnutrition, weight loss and anae- mia. The resultant symptoms are known as the mal- absorption syndrome(s), which can be grouped by Address for correspondence: Joel K Greenson MD, Professor of Pathology, University of Michigan Medical School, Rm 2G332, Box 0054, 1500 E. Medical Center Drive, Ann Arbor, MI 48109–0054, USA. e-mail: facjkgmd@umich.edu Ó 2007 The Authors. Journal compilation Ó 2007 Blackwell Publishing Limited. Histopathology 2007, 50, 64–82. DOI: 10.1111/j.1365-2559.2006.02547.x