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We studied small bowel biopsy specimens with architecturally normal villi from 78 adult patients with potential gluten sensitivity (GS) and correlated them with outcome to characterize morphologic features that would allow a pathologist to suggest GS. No patient had a previous GS diagnosis. Twelve study patients had GS. The mean number of intraepithelial lymphocytes (IELs) per 20 enterocytes from the tips of 5 random villi was significantly greater in GS than non-GS biopsy samples, but the groups overlapped significantly, making the number diagnostically useful only when markedly increased. Crypt mitoses counts had similar relationships. Twelve patients had an even distribution of IELs along villus sides and over tips (3/66 [5%] non-GS patients, 9/12 [75%] GS patients). Non-GS patients had a decrescendo pattern of IELs along the sides of villi. Architecturally normal small bowel biopsy specimens with an appreciable, continuous, even distribution of IELs along the sides and tips of villi and a mean of 12 or more IELs in the tips of several villi are suggestive of GS. Pathologists should be watchful for these morphologic features in small bowel biopsy specimens to suggest GS.

Morphologic Features Suggestive of Gluten Sensitivity in Architecturally Normal Duodenal Biopsy Specimens