Lymphatics, tertiary lymphoid organs and the granulomas of Crohn’s disease: an immunohistochemical study

Aliment Pharmacol Ther 2011; 33: 930–939 Summary Background Case studies in the past repeatedly suggested that the fundamental alteration in Crohn's disease occurs in the regional lymphatics of the intestine. Aim To evaluate the lymphatic inflammation in Crohn's disease, and to characterise lymphoid aggregates and granulomas in and surrounding lymphatics and blood vasculature. Methods Forty-eight tissue blocks from 24 Crohn's disease patients and 23 tissue blocks from 23 control patients were selected. Tissue sections were immunostained with a lymphatic endothelial cell marker (D2-40), a marker for blood vasculature (FVIII), and markers for T cells (CD3), B cells (CD20) and macrophages (CD68). Results Lymphangiectasia and lymphocytic perilymphangitis were demonstrated in all 24 patients, lymphocyte-obstructed lymphatics in seven patients, granuloma-obstructed lymphatics in nine patients and inflammatory lymphoid follicles in all 24 patients. Free-standing granulomas occurred in 19 patients, and in three further patients granulomas were in or attached to blood vascular units. Conclusions This study, employing immunohistochemistry, revealed, better than standard microscopy, the association of inflammation, granulomas and tertiary lymphoid follicles or organs with the lymphatic vasculature in Crohn's disease. Disease in some patients was characterised by perilymphangitis and lymphoid follicular inflammation and in others by granulomas, some of which totally obstructed lymphatics. These findings have aetiological, therapeutic and prognostic implications.