2. Critical Evaluation of colonoscopic biopsies in Crohn’s Disease Najib Haboubi MB Ch B,D Path, FRCPath Professor of Health Science, Liver and Gastrointestinal and Pathology, Universities of John Moors, Liverpool and Salford, Manchester.

3. Crohn, Ginzburg and Oppenhiemer 1932 JAMA ‘A disease of the terminal ileum, affecting mainly young adults and characterised by……

4. Things have changed Young and old All GIT ( mostly small and large intestine)

5. Distinction between UC and CD From a single mucosal biopsy. Not easy!

6. CD Classical features Focality Rectal sparing Granulomas. Transmural inflammation

7. Distal UC is mostly accompanied by inflammatory lesions of the caecum Geboes et al Gastroenterology 1987

8. Patchy Coecal Inflammation Associated with Distal UC : A Prospective Endoscopic Study D’Haens,Geboes,Peeters,Baert,Ectors, Rutgeerts. Am.J.Gasroenterol. 1997

9. Patchiness of mucosal inflammation in treated UC Bernstein, Shanahan, Anton, Weinstein. Gastrointestinal Endoscopy. 1995.

10. Ulcerative Colitis Patterns of Involvement in Colorectal Biopsies and Changes With Time. Celina Kleer and Henry Appelman Am.J.Surg.Path.

11. Material and Method 41 patients with proven chronic UC. Sequential sets of colonic biopsies.

12. Results Histologically normal appearing mucosal biopsies do occur in established cases of CUC. This finding is enhanced with treatment with 5 ASA.

13. Summary In CUC Mucosa can revert to normal with or without treatment. Skip lesions and rectal sparing.

14. Classical features Multi focality and Rectal sparing Granulomas. Transmural inflammation

15. Granulomas 25-90% of cases (site, specimen type,no. of slides). Seen more in early disease. Younger age group Increase yield as we travel throughout the colon. Usually related to active inflammation and ulceration/disputed! May indicate aggressive disease (Heresbach et al Gut 2005) Specific to CD only in the setting of IBD and when they are Sarcoid type.

17. Non Infective Granulomas Non Infective Granulomas Pericryptal position can be seen in UC Diversion colitis. Diverticular disease. Sarcoidosis Chronic granulomatous disease of childhood Foreign body Pericryptal in infective colitis. Vasculitis

18. Infective Granulomas Infective Granulomas TB Fungal infection. Viral infection.

19. UC Classic Views Never patchy No granuloma Current views Can be. Pericryptal granuloma

20. In practice The distinction between UC and CD is not always easy. Even in the hands of the experts?

21. How could pathologists improve the initial diagnosis of colitis? Bentley et al J Clin Path 2002,55;955-960

22. Aim 1. Determine the effect of a single versus multiple biopsies on the accuracy of diagnosis. 2. Study the accuracy and reproducibility of different criteria used in the diagnosis of multiple biopsies by the experts and the non experts pathologists.

23. Methods 13 experts and 12 non experts examined 60 well followed up cases of CD and UC, totally blinded and in 2 rounds. Diagnoses were made initially on rectal then full colonoscopic biopsies.

24. Diagnosing CD Experts Rectal 24% Full colonoscopy 64% Non experts Rectal 12% Full colonoscopy 60%

25. Diagnosing UC Experts Rectal 64% Full colonoscopy 74% Non experts Rectal 62% Full colonoscopy 72%

26. Conclusion Full colonoscopic series are more accurate in diagnosing CD and UC No difference between the experts and the non experts in blinded biopsies

27. Trafford / Manchester approach CD is by and large a clinicopathological diagnosis. A preliminary working pattern based report with a differential diagnosis. The final diagnosis is made in the CPC when all the data become available. The mutual responsibility of the clinician and the pathologist

28. Thanks for the invitation

31. Number

33. Classically UC A mucosal disease. The histology does not come back to normal. In Distal disease it is Never patchy (continuous).

34. UC Mucosal. May extend into the submucosa in acute cases and ulceration. This is not Transmural inflammation.

35. Is time a good healer?

36. UC Mucosal. Never patchy Never come back to normal. May extend into the submucosa. Yes it could.

37. Diagnostic Difficulties There is no specific histological feature that distinguishes CUC from many other colitides. The diagnosis has to be a team responsibility.

38. System Pattern based provisional report with a working differential diagnosis. The final diagnosis is in the CPC. No place for Non Specific Colitis

39. Causes of Difficulty 1.Limited morphological response of the colonic mucosa to various injuries. 2.Incomplete morphological expression of IBD. 3. Overlap of some features. 4. Clinical and histological mimicry of IBD.

40. Colitis with no distinguishing histological features

41. Despite the legitimate pressure we cannot tell the difference

42. Dilemma Absence of a histological parameter that is invariably present in one disease and invariably absent from the other.

43. Results

44. Infective Granulomas Campylobacter colitis. Salmonella colitis. TB Yersinia

45. Vienna Classification Inflammatory Stricturing, non penetrating ( stenosing) Fistulating( penetrating)

46. Size is not every thing

47. Accurate reporting Full clinical storey

48. Classical features Sarcoid type granulomas. Focal Discontinuous. Rectal sparing.

49. Patchiness of mucosal inflammation in treated UC Bernstein, Shanahan, Anton, Weinstein. Gastrointestinal Endoscopy. 1995.

50. Conclusion In patients with treated UC, the finding of rectal sparing or patchiness should not necessarily indicate a change in the diagnosis to CD.

51. Ulcerative Colitis Patterns of Involvement in Colorectal Biopsies and Changes With Time. Celina Kleer and Henry Appelman Am.J.Surg.Path.

52. Material and Method 41 patients with proven chronic UC. Sequential sets of colonic biopsies.

53. Results Histologically normal appearing mucosal biopsies do occur in established cases of Chronic UC. This finding is enhanced with treatment with 5 ASA.

54. Summary Skip lesions do occur in CUC. Mucosa can revert to normal with or without treatment.

56. Granuloma specific to CD Well formed Isolated Away from areas of inflammation. Basally or submucosally situated

58. Frequency and significance of granulomas in a cohort of incidence cases of CD Heresbach et al Gut 2005;54: 215222

59. Aim Evaluate epitheloid granulomas occurence in incident CD. Association between epitheloid granuloma and outcome of CD

60. M&M 188 cases of endoscopic (upper and lower) and surgical (intestinal or colonic) procedures. Follow up for at least 5 years.

61. Results Epitheloid granulomas are associated with higher rate of surgical resections.