PITFALLS OF THE MORPHOLOGICAL EVALUATION

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1 MASTERING THE COELIAC CONDITION FROM MEDICINE TO SOCIAL SCIENCES AND FOOD TECHNOLOGY FIRENZE MARCH 2012 PITFALLS OF THE MORPHOLOGICAL EVALUATION THE POINT OF VIEW OF THE PATHOLOGIST

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4 METHODOLOGY NUMBER OF BIOPSIES AND ORIENTATION CLASSIFICATIONS DIAGNOSTIC VARIABILITY

5 METHODOLOGY NUMBER OF BIOPSIES AND ORIENTATION

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7 ORIENTATION LOCATION OF THE BIOPSIES TO CORRECTLY EVIDENCE THE DIFFERENT LAYERS OF THE BOWEL WALL

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10 CLASSIFICATIONS

11 Type 1 Infiltrative Type 2 Hyperplastic Type 3 Destructive

12 CORAZZA VILLANACCI TYPE 1 TYPE2 GRADE A NON ATROPHIC TYPE 3 A TYPE 3 B GRADE B 1 PARTIAL ATROPHY TYPE 3 C GRADE B 2 TOTAL ATROPHY

13 DIAGNOSTIC VARIABILITY

14 A major pitfall in the diagnosis of coeliac disease is in pathological interpretation of intestinal biopsies. An adequate number of biopsies needs to be taken. A poorly oriented biopsy, as shown by crypts cut tangentially, will falsely reduce the crypt to villous ratio. Green P., Jabri B. THE LANCET 2003

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17 Ecoendoscopy Enteroscopy N.B.I Video capsule Magnification Endomicroscopy

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22 ESPGHAN (Coordinator: S. Husby; D. Branski, C. Catassi, S. Koletzko, I. Korponay Szabo, M. Maki, M.L. Mearin, R. Shamir, R. Troncone, A. Ventura, K.P. Zimmer) REVISION OF THE CRITERIA FOR THE DIAGNOSIS OF CD PROPOSAL: TO AVOID BIOPSY IN SYMPTOMATIC CHILDREN WITH HIGH VALUES OF TtG (>10 normal value) AND POSITIVITY FOR DQ2

23 AND NOW WE ARE.. WE WERE THE GOLD STANDARD

24 HOW TO CHANGE? TIME TO CHANGE! YOU ARE RIGHT!

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26 The diagnosis and management of CD is a team process. High quality reporting of CD histology is very important as the whole team relies upon the skill of the pathologist. Failure to report key features can lead to undertreatment or overtreatment of the disease.

27 PATHOLOGIST GASTROENTEROLOGIST LABORATORIST ENDOSCOPIST GENETIST

28 Celiac disease: changing dogma on historical diagnosis V. Villanacci, C. Catassi, K. Rostami and U. Volta, 13 January 2010

29 WHERE AND HOW TO TAKE BIOPSIES

30 DUODENUM STOMACH 2 PART BULB PAPILLA OF VATER

31 BIOPSY HANDLING AND ORIENTATION

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33 NOT ORIENTED ORIENTED

34 NORMAL MUCOSA VILLOUS / CRYPT RATIO = 3/1

35 Intraepithelial Lymphocytes Quantitation of intraepithelial lymphocytes in human duodenum:what is normal? M.Hayat, A. Cairns, M.F. Dixon, S.O Mahony J. Clin. Pathol 2002 Duodenal intraepithelial Lymphocyte. Count revisited Veress B, Franzen L,Bodin & Kork K Scand J Gastroenterol IELs/100 epithelial cells should be taken as the upper limit of the normal range for duodenal mucosa when counting profile densities in standard histological sections 40 IELs/100 epithelial cells is used as the upper limit of the normal range, a figure derived from jejunal biopsies over 30 years ago

36 Normal T LYMPHOCYTES < 25/100

37 Pathological T LYMPHOCYTES > 25/100

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40 Intraepithelial Most european lymphocytosis pathologists do not in an otherwise routinely Increased count normal the intraepithelial small bowel biopsy lymphocytes is somewhat ( IEL) in ( I.E.L. duodenal nonspecific, is the first and most sensitive marker biopsies. of the Minor intestinal but in nearly 10% changes of cases compatible can be the initial effects of gluten on the small bowel mucosa; with CD are, therefore, overlooked presentation thus it is the major histological in many of GS. feature symptomatic Therefore of CD WHAT IS THE PROBLEM? cases Celiac and subsequently all patients with this Disease: A Progress Report labelled finding should IBS or be investigated functional for GS Donald A. Antonioli Kakar Rostami S. et K. Digestive and Liver Disease The American Journal of Modern2003 Gastroenterology Pathology

41 Counting of IELs is recommended in borderline cases where the histology is difficult to interpret. An increase, especially, in gamma delta positive cells strengthens the probability of CD Jarvinen T.T. et al. The American Journal of Gastroenterology 2003

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43 Prof. Gino Roberto Corazza

44 Some considerations on the histological diagnosis of coeliac disease Gino Roberto Corazza and Vincenzo Villanacci Journal of Clinical Pathology CORAZZA VILLANACCI vol. 58 issue

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46 Intraepithelial lymphocytosis in architecturally preserved small intestinal mucosa. An increasing diagnostic problem with a wide differential diagnosis Brown I, Mino Kenudson M, Deshande V, Lauwers GY Arch Pathol Lab Med 2006

47 Helicobacter pylori infection in patients with coeliac disease Villanacci V., Bassotti G., Liserre B., Lanzini A., Lanzarotto F., Genta R. The American Journal of Gastroenterology 2006

48 Whole variation at second biopsy 11% 1% 3% Improvement No variation Restitutio ad integrum Worsening 85%

49 GIARDIA LAMBLIA

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52 CD 3

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55 CMV

56 APOPTOTIC BODIES APOPTOTIC BODIES

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59 Treated celiac patients who do not respond clinically and histologically to treatment with a gluten free diet CD 3 CD 8

60 CD3 CD8 CD 3 CD 8

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62 Ulcerative Jejunitis

63 THE PAST CD REFRACTORY CD ULCERATIVE JEJUNITIS LYMPHOMA THE PRESENT CD REFRACTORY CD ULCERATIVE JEJUNITIS LYMPHOMA CD 3

64 INTESTINAL BIOPSY: Is it yet the diagnostic essential Gold Standard? NO! but certainly still an important support to reach a correct diagnosis.

65 GASTROENTEROLOGIST MULTIDISCIPLINARY TEAM GOLD STANDARD

66 THANKS FOR COMPREHENSION!