The most important pathologic feature of Crohn's disease is the involvement of all the layers of the bowel and extension into mesenteric lymph nodes. In addition, the disease is discontinuous, with normal areas of bowel ("skip areas") located between one or more involved areas. On gross inspection, the bowel wall is thickened; subsequent luminal narrowing results in stenosis and obstruction of the intestine. The mesenteric fat often extends over the bowel wall ("creeping" fat). The appearance of the mucosa varies with the extent and severity of the disease. Longitudinal, deep ulcerations are characteristic. These often penetrate the bowel wall, resulting in fissures, fistulas, and abscesses. Late in the disease, a "cobblestone" appearance of the mucosa results from the criss-crossing of these ulcers with intervening normal mucosa.

Microscopically, there is an inflammatory reaction that extends through all layers of the intestine but is most marked in the submucosa. This inflammatory response consists of infiltration by mononuclear cells, lymphocytes, plasma cells, and histiocytes. Fissure ulcers frequently penetrate the muscle layer. Unlike the situation in ulcerative colitis, crypt abscesses are infrequent. Discrete granulomas consisting of epithelioid cells, giant cells, and lymphocytes are seen in 50 to 75 percent of the surgical specimens from Crohn's disease patients. Granulomas are seen uncommonly in mucosal biopsies. Although the finding of granulomas is suggestive, it is not essential for the diagnosis.

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