Carl E. I. Janssen
Department of Imaging & Pathology, Belgium
Title: The presence of granuloma-in-follicles in Crohn’s disease appendectomy is an independent prognostic factor to predict lymph node involvement
Biography
Biography: Carl E. I. Janssen
Abstract
Granulomas are one of the diagnostic features of Crohn’s disease(CD). Genetic variants in nucleotide oligomerisation domain 2(NOD2) are linked with CD. We reported granulomas-in-follicles (GIF) are linked to increased IFNγ/IL1β/IL17/IL23R/RIP2 expression, polycyclic granulomas and extended disease to anus, appendix, lymph nodes or mouth in paediatric CD(pCD). We selected 10pCD cases with granulomatous appendicitis (pCD-A) and screened all available tissue for granulomas in intestinal lymph nodes. We studied granulomas by a standardized set of morphological features and immunohistochemistry; CD68 to detect microgranulomas, CD20 to visualize GIF, cytokines TNFα and IL17, and determined NOD2 variants p.R702W(rs2066844), p.G908R(rs2066845) and p.Leu1007fsX1008(rs2066847). At least one variant was present in 60% of pCD-A. Lymphocyte emperipolesis was observed in 60% of pCD-A and found in polycyclic granulomas irrespective of NOD2 variants, GIF or lymph node involvement. rs2066847 (30%), was not associated with GIF or lymph node involvement. rs2066845 was found in a single case with GIF, but without lymph node granulomas. rs2066844 (20%) was associated with GIF and lymph node involvement. All except one case exhibited tissue sclerosis. Polycyclic granulomas and eosinophils were common in NOD2+, but virtually absent in NOD2- cases. Coronary CD68+ granulomas, CD20+ GIF and lymph node involvement were prominent in NOD2-, but rare in NOD2+ cases. No significant difference in TNFα or IL17 staining was related to NOD2 variants, GIF or lymph node granulomas. This is the first pathological study of pCD-A granulomas. Although NOD2 variants were present in the majority of cases, they were independent of GIF, a novel feature linked to intestinal lymph node involvement.