Intraepithelial lymphocytosis in architecturally preserved proximal small intestinal mucosa: an increasing diagnostic problem with a wide differential diagnosis.

CONTEXT: An increased intraepithelial lymphocyte density in an architecturally normal proximal small intestinal mucosal biopsy is a common finding facing surgical pathologists dealing with gastrointestinal biopsy specimens. Approximately 1% to 2% of all proximal small intestinal biopsies will show this change. It is increasingly recognized by surgical pathologists that gluten-sensitive enteropathy is an important cause of this pattern; however, gluten-sensitive enteropathy accounts for the minority of all cases. A wide variety of immunologic stimuli can raise intraepithelial lymphocyte numbers. Among the other common associations are enteric infection, autoimmune disease, drugs, and gastric Helicobacter infection. OBJECTIVE: To outline the causes of intraepithelial lymphocytosis, to highlight the importance and the difficulties faced in establishing gluten-sensitive enteropathy as the cause, and to aid the surgical pathologist in the routine sign out of these cases. DATA SOURCES: A review of the literature detailing the causes or associations of proximal small intestinal intraepithelial lymphocytosis is presented. CONCLUSIONS: Increased lymphocyte numbers in the epithelium of architecturally preserved proximal small intestinal biopsies is a morphologic feature associated with a broad differential diagnosis.