PATHOLOGY OF CROHN’S DISEASE

Posted by Alex

CD involves any segment or combination of segments of the alimentary tract from the mouth to the anus. Unlike UC, microscopic changes often are identified distant from sites of macroscopic disease. These focal changes and the tendency of CD to recur after segmental resection suggest that subtle changes of CD exist throughout the alimentary tract. Most commonly the distal ileum and right colon are macroscopically inflamed (ileocolitis). The colon is involved, exclusively, in about 20% of patients (Crohn’s colitis or granulomatous colitis); approximately 15 to 20% have gross disease limited to the small bowel (ileitis or regional enteritis). The stomach or duodenum is involved in < 10% of patients and usually in association with more distal disease. Disease of the anal canal, including deep fissures, fistulas, and prominent “hemorrhoidal” skin tags, are common and distinguish CD confined to the colon from UC. Unlike UC, the mucosa in CD is involved in a focal, discontinuous manner, both microscopically and macroscopically. Rarely, lesions indistinguishable from those of CD occur in the skin or urogenital mucosal surfaces (miliary CD).

The earliest macroscopic lesion of CD is the minute aphthoid ulcer, invariably occurring over a lymphoid aggregate. These ulcerations extend linearly, often isolating normal islands of mucosa to produce a “cobblestone appearance”, or extend deep throughout the layers of the bowel wall, producing a fissure that can become a fistula into the mesentery or a contiguous organ. Inflammatory changes in CD are typically transmural, accounting for the thickening of the bowel wall and narrowing of the lumen. As CD heals, fibrotic changes replace acute inflammation, creating permanent focal strictures. In gross specimens, changes include thickened, sausage-shaped bowel with serosal hyperemia, “creeping fat” along the antimesenteric border, and thickening and lymphoid hyperplasia of the adjacent mesentery. The inflammatory process is focal in all layers of the bowel. Acute and chronic inflammatory cells invade isolated or contiguous single crypts (including the production of crypt abscesses) with normal adjacent glands. Lymphoid aggregates are common throughout all layers of the mucosa, submucosa, and serosa, with characteristic aggregations of histiocytes forming noncaseating granulomas in up to 50% of resected specimens. Mucosal biopsies, however, reveal granuloma formation in < 20% of patients. The presence of granulomas differentiates CD from UC, but they are not necessary to distinguish the two diseases. Rather, the focal, transmural involvement of CD associated with aphthoid or linear ulcers, fissures, fistulas, perianal disease, or small intestinal involvement morphologically distinguishes CD from UC. In approximately 20% of patients with colitis, “indeterminate” features do not allow classification between UC and CD. Response to therapy and repeated observations over the course usually allow eventual classification.