International Journal of Celiac Disease, 2017, Vol. 5, No. 1, 40-42 Available online at http://pubs.sciepub.com/ijcd/5/1/6 ©Science and Education Publishing DOI:10.12691/ijcd-5-1-6 Intra-epithelial Lymphocytosis of the Ileum: A Pathological Clue to Clinically Occult Adult Celiac Disease Hugh J. Freeman 1,* , Doug Webber 2 1 Departments of Medicine (Gastroenterology), University of British Columbia, Vancouver, BC, Canada 2 Department of Pathology, University of British Columbia, Vancouver, BC, Canada *Corresponding author: hugfree@shaw.ca Abstract A 39-yr-old male presented with diarrhea, weight loss and rectal bleeding. Hemorrhoids were present but the colon and distal ileum were macroscopically normal. Random mucosal biopsies of the ileum and multiple sites in the colon revealed extensive ileal and focal cecal intra-epithelial lymphocytosis. Subsequent duodenal mucosal biopsies confirmed the suspicion of adult celiac disease. Later endoscopic biopies done after gluten-free diet treatment were normal. This report demonstrates that intra-epithelial lymphocytosis in the ileum may be an important pathological clue to underlying clinically occult adult celiac disease. Keywords: celiac disease, intra-epithelial lymphocytosis, ileal biopsy, colonic biopsy, lymphocytic colitis, microscopic enteritis, lymphocytic ileitis Cite This Article: Hugh J. Freeman, and Doug Webber, “Intra-epithelial Lymphocytosis of the Ileum: A Pathological Clue to Clinically Occult Adult Celiac Disease.” International Journal of Celiac Disease, vol. 5, no. 1 (2017): 40-42. doi: 10.12691/ijcd-5-1-6. 1. Introduction Adult celiac disease is an immune-mediated disorder usually causing diarrhea and weight loss along with characteristic small intestinal biopsy changes that include variable degrees of architectural disturbance and increased numbers of intra-epithelial lymphocytes [1]. Treatment with a strict gluten-free diet usually results in resolution of symptoms, the inflammatory mucosal process and altered architecture. Most severe changes, typical of untreated celiac disease, may be detected in the duodenum and upper endoscopic biopsies are usually employed for diagnostic evaluation [2]. Characteristic architectural changes of adult celiac disease include hyperplastic and elongated crypts with flattened or atrophic villi, sometimes associated with changes elsewhere in the gastrointestinal tract, including intra-epithelial lymphocytosis in gastric [3], ileal [4,5] and colonic biopsies [6]. The case reported here further illustrates that these pathological changes, specifically increased numbers of intra-epithelial lymphocytes, not only may be detected in the ileum but, from a practical clinical perspective, emphasizes their relevance as a presenting pathological clue to subsequent clinical detection of unrecognized adult celiac disease that completely resolves with a gluten-free diet. 2. Case History A 39-yr-old male was referred in 1996 for evaluation of diarrhea and a 10 kg weight loss. Blood studies, including a haemoglobin and iron studies, were normal and fecal studies for infectious causes of diarrhea were negative. Endoscopic evaluation of the lower intestinal tract revealed macroscopically normal mucosa of the distal ileum and colon. Biopsies of the ileum and multiple sites within the colon were done to exclude a microscopic cause for diarrhea. These showed increased numbers of intra-epithelial lymphocytes in the ileum (Figure 1 and Figure 2) along with focal collections of intra-epithelial lymphocytes in the cecum alone (Figure 3), while biopsies distally in the rest of the colon were normal. Because of continued diarrhea with these ileal biopsy findings showing increased numbers of intra-epithelial lymphocytes, the possibility of occult celiac disease was considered. At that time, serological studies were not available in our hospital, so upper endoscopic biopsies were done. These revealed typical features of untreated celiac disease in the duodenal mucosa with severe “flat” biopsy lesion (i.e., crypt hyperplastic villous atrophy, Marsh 3) (Figure 4 and Figure 5). A strict gluten-free diet was initiated. In 1997, he was reviewed. He was compliant with his gluten-free diet. Diarrhea had resolved and his weight had returned to his prior pre-illness level. In 2001, he was reviewed. Blood studies were normal along with serological studies, including immunoglobulin A quantitation and anti-IGA tissue transglutaminase (tTG) antibodies of 8 units (normal, less than 20 units). Endoscopic studies were normal and biopsies of the stomach and duodenum were normal. He continued on a strict gluten-free diet. In 2008, his tTG was 4.7 units. In 2010, he developed vague left lower quadrant abdominal pain. A colonoscopy showed a small adenoma that was resected. Added biopsies of the