Smooth Muscle Hyperplasia/Hypertrophy is the Most Prominent Histological Change in Crohn’s Fibrostenosing Bowel Strictures: A Semiquantitative Analysis by Using a Novel Histological Grading Scheme

Abstract

Background: The simplistically and ambiguously termed “fibrostenosis” of bowel is a hallmark of severe Crohn's disease (CD) and a major contributor to medical treatment failure. Noninvasive imaging assessment and novel medical therapy targeting this condition are under investigation, which particularly requires a better understanding of the underlying histologic basis. Methods: We analyzed 48 patients with stricturing Crohn’s ileitis or/and colitis that required surgical resection. The most representative sections of the fibrostenotic, non-stenotic, and uninvolved regions were reviewed for histologic analysis. For each layer of bowel wall [mucosa including muscularis mucosae (MU), submucosa (SM), muscularis propria (MP), subserosal adventitia (SS)], histologic abnormalities were evaluated individually, including active and chronic inflammation, fibrosis, smooth muscle hyperplasia or hypertrophy, neuronal hypertrophy, and adipocyte proliferation. A novel semiquantitative histological grading scheme was created. Results: The most significant histopathologic features characterizing the stricturing intestines were smooth muscle hyperplasia of SM, hypertrophy of MP, and chronic inflammation. The muscular alteration was predominant in all layers. The overall muscular hyperplasia/hypertrophy was positively correlated with chronic inflammation and negatively correlated with fibrosis, while SM muscular hyperplasia was also associated with MU active inflammation. Similar changes, to a less extent, occurred in the adjacent non-stenotic inflamed bowel as well. Conclusions: In CD-associated ‘fibrostenosis’, it is the smooth muscle hyperplasia/hypertrophy that contributes most to the stricturing phenotype, whereas fibrosis is less significant. The ‘inflammation-smooth muscle hyperplasia axis’ may be the most important in the pathogenesis of Crohn’s strictures.