P754 Beyond Paneth cell metaplasia: Small intestinal metaplasia of the sigmoid colon in patients with Inflammatory Bowel Disease

Abstract

Abstract Background Paneth cells are normally found in the small intestine, and when found in the left colon, they represent Paneth cell metaplasia (PCM). This finding indicates a chronic inflammatory state and is seen in some patients with inflammatory bowel disease (IBD). However, small intestinal differentiation beyond PCM has not been reported. We report a broader range of small intestinal metaplasia in the sigmoid colon in patients with IBD, including loss of expression of the colonic marker SATB2, presence of a brush border and villous architecture, and gain of expression of the small intestinal markers CD10 and HepPar1. We perform a pilot study to investigate the frequency, staining patterns, and clinical correlates of this metaplastic phenomenon. Methods A database search for sigmoid biopsies for the words “Paneth cell metaplasia” from 2010-2018 returned 862 cases. The 100 most recent consecutive cases with a history of IBD were reviewed and confirmed to have PCM in non-neoplastic sigmoid biopsies in 96 cases. Of these, 94 blocks from 91 patients (age range 7-88, median age 43, 53% male, 74% ulcerative colitis (UC), 23% Crohn’s disease, 3% IBD) were on file. IHC staining for HepPar1, CD10, and SATB2 was performed on each case. Results Of the 94 cases, 13 (13.8%) had HepPar1 positivity, 5 (5.3%) had CD10 positivity, 2 (2.1%) had SATB2 loss, 1 (1.1%) had reduced SATB2 expression, and 2 showed villous architectural features. Extensive positivity for CD10 was seen in 3 (3.2%) cases, and one case showed all 3 IHC markers of small intestinal metaplasia. Of the CD10+ cases, there were 3 UC, 1 Crohn's, and 1 IBD (Table 1). The index case (sigmoid colon) showed a brush border (Figure 1) and intermixed small (Figure 2, red arrows) and large bowel (Figure 2, black arrows) differentiation. Conclusion A range of small intestinal differentiation may be seen in the left colon in IBD patients, including PCM, the presence of brush border, villous architecture, CD10 and HepPar1 positivity, and reduced or lost SATB2 expression. Since the frequency of HepPar1+>CD10+>SATB2 loss, there may be a sequence of small intestinal metaplasia, with PCM occurring first, and loss of SATB2 reflecting more advanced metaplasia. Previous studies suggest that SATB2 and HepPar1 are helpful in distinguishing between inflamed ileal pouch vs rectal cuff in patients with IBD, and that CD10 could be used to distinguish between ileum and colon in anastomoses, but our data refute these claims. SATB2 loss has been described in dysplastic lesions in patients with IBD, and thus these markers could serve as biomarkers of progression to dysplasia.