Epithelioid Cell Granulomas in Crohn’s Disease Are Differentially Associated With Blood Vessels and Lymphatic Vessels: A Sequential Double Immunostaining Study

Crohn’s disease (CD) is a gastrointestinal disorder of unknown etiology. CD-specific longitudinal ulcers show an association between disease pathogenesis and vasculature dysfunction. Granulomatous lymphangitis may also contribute to CD pathogenesis; meanwhile, vasculitis is the primary CD lesion. We investigated the association between granulomas and lymphatic and blood vessels to assess the role of vasculature in CD pathogenesis. Two small and large intestine specimens were obtained from four CD patients. From each specimen, 160 sequential sections were obtained and double immunohistochemical stained to label lymphatic and blood vessels in association with granulomas. We found that 289 of 342 granulomas (85%) were associated with a lymphatic vessel and 313 of 364 granulomas (86%) were associated with a blood vessel. Although intrablood vessel granulomas were not detected, intralymphatic vessel granulomas were. In the internal region of the granuloma, we found more blood vessels than lymphatic vessels. Hence, these results cumulatively demonstrate that CD epithelioid cell granulomas are differentially associated with lymphatic and blood vessels, suggesting both as essential for the formation and maintenance of these granulomas. Moreover, both lymphatic and blood vessels may participate in granulomatous inflammation in the primary CD lesions; however, additional studies with larger numbers of participants are required to validate our findings.