Sub-threshold Colonic Intraepithelial Lymphocytosis Is Predictive of the Development of Lymphocytic and Collagenous Colitis

Introduction: Microscopic colitis is primarily composed of two entities; lymphocytic colitis (LC), defined by >20 intraepithelial lymphocytes per 100 enterocytes, and collagenous colitis (CC) defined by increased intraepithelial lymphocytes and thickened irregular subepithelial collagen deposition. Some biopsies contain sub-threshold intraepithelial lymphocytosis (STIEL) (> 5 and <20 per 100 enterocytes) and no thickened collagen. These cases have been termed “incomplete microscopic colitis” by various authors who suggest it represents a separate entity. The aim of our study is to compare the prevalence of LC or CC in follow-up biopsies of patients with STIEL versus patients without LC, CC, or STIEL on their initial colonoscopy. Methods: From a large computerized pathology database, all patients with multiple colonoscopies from 1/1/2008 - 12/31/2014 were extracted. Patients with LC or CC on their initial colonoscopy were excluded. The remainder were divided into two groups based on initial colonoscopy diagnosis: a study group with STIEL and a control group without STIEL. Differences between these two groups were analyzed by the Mann-Whitney Rank Sum Test and unadjusted Odds ratios. Results: There were 140,250 patients with more than one colonoscopy. Of these 3,688 had LC or CC on their initial colonoscopy and were excluded. The remainder comprised those with STIEL (188) and a control group without STIEL on initial colonoscopy (136,562). Analysis of subsequent colonoscopies revealed 8.5% [16; OR 23.89 (14.21 - 40.15) P<0.0001] patients with LC and 6.9% [13; OR 12.48 (7.07 - 22.12) P<0.0001] patients with CC among the STIEL group compared with 0.4% (529) patients with LC and 0.6% (807) patients with CC in the control group. Conclusion: Our study shows that a significant (15.4%) proportion of patients with STIEL are subsequently found to have LC or CC, which is significantly higher than the 1% who develop either LC or CC in the control group. These finding indicate that there is a subset of patients with STIEL that have or will develop LC or CC. As such, STIEL could represent either incipient LC or CC, sampling from an area of the colon with sub-threshold findings in a patient with LC or CC, or incompletely treated LC or CC. Clinical studies are needed to further evaluate the clinical significance of this microscopic finding.