IBD. Crohn s. Outline. Ulcerative colitis versus Crohn s disease: is biopsy useful? UC vs. Crohn s? Is it easy? Biopsy settings 21/07/2017 IBD

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1 Outline Ulcerative colitis versus Crohn s disease: is biopsy useful? Roger Feakins Colorectal biopsies Ileal and upper GI biopsies Special situations New techniques Summary Inflammatory bowel disease (IBD) = chronic idiopathic inflammatory bowel disease UC vs. Crohn s? Is it easy? 10-15% Crohn s reclassified as UC after 1 year IBD Never classified: 1-20% IBD unclassified (IBDU) Indeterminate colitis in resections UC Crohn s Reclassified even after resection UC colectomy: 24% re-diagnosed as Crohn's Stange EF et al (ECCO) 2008; Odze R 2015; Silverberg MS 2005; Jones I 2017 Biopsy settings IBD UC (IBDU) Crohn s New IBD / suspected new IBD Treated / longstanding IBD 1

2 (Imaging) Stool culture Endoscopy NEW IBD VS NON-IBD Symptoms, clinical course IBD? Infection? Other? Histology Basic principles of IBD diagnosis IBD > non-ibd (initial biopsies) Basal plasmacytosis Basal plasmacytosis Architectural changes Crypt distortion Crypt atrophy Irregular or villiform mucosal surface Plasma cells at base of mucosa + loss of plasma cell gradient Significance: Earliest feature of IBD Best predictor of IBD Other features (less discriminatory) Granulomas Mucin depletion Lymphoid aggregates Crypts with their feet in pools of plasma cells Schumacher G. 1994; Stange EF, Travis SPL 2008 Architectural changes: crypt distortion and atrophy IBD CANNOT BE CLASSIFIED IF IT S NOT IBD Dilatation Branching Loss of parallelism Variation in size and shape 2

3 IBD? IBD? Diverticular colitis Architectural changes Basal plasmacytosis Crohn s disease on endoscopy? Lymphogranuloma venereum (LGV) Histology Chronic inflammation No/minimal basal plasmacytosis No/minimal crypt distortion Rectal biopsy Rectal biopsy Biopsy settings IBD Not IBD UC (IBDU) Crohn s New IBD / suspected new IBD Treated / longstanding IBD Histology less reliable for UC vs Crohn s 3

4 Clinical features UC Crohn s Blood in stools > 90% < 50% Distribution Continuous Discontinuous UC VS CROHN S Endoscopic features Erythema, granularity, ulceration Longitudinal ulcers, cobblestoning Perianal disease Uncommon Fistulas and fissures common Small bowel strictures Very rare Not uncommon UC vs Crohn s: considerations for the pathologist Distribution of changes What is assessed? Architectural changes Chronic inflammation Distribution in biopsies Granulomas Where? Within a biopsy Diffuse, patchy, focal Mucin depletion Between biopsies Between anatomical sites Continuous, discontinuous Basic principles of IBD diagnosis UC > Crohn s (initial biopsies) Typical UC In any biopsy Diffuse crypt changes Diffuse chronic inflammation Severe mucin depletion (Extensive activity) (Presence of crypt changes) In biopsies from multiple sites Continuous crypt changes Absence of ileitis Distal > proximal Diffuse changes within a biopsy Diffuse changes between biopsies 4

5 Crohn s disease > UC (initial biopsies) Typical Crohn s disease In any biopsy Granulomas** Non-diffuse crypt distortion Non-diffuse chronic inflammation Non-diffuse crypt distortion Granuloma In biopsies from multiple sites Anatomical discontinuity Ileal inflammation Proximal > distal; rectal sparing Non-diffuse chronic inflammation Granuloma Paneth cell metaplasia 20% of Crohn s biopsies..at least five epithelioid macrophages Not always Crohn s TB, parasite, foreign material, drug, sarcoid, etc. Cryptolytic granulomas also in UC and other colitides Paneth cells Not significant proximal to splenic flexure Distally? 17 % rectal biopsies Discriminatory value Chronicity IBD > non-ibd Seen in GVHD, radiation colitis, collagenous colitis Pezhouh MK 2016; Simmonds N 2014; Ayata 2002 Paneth cells No single feature is diagnostic Multiple features increase accuracy DISCONTINUOUS UC IBD diagnosis: is biopsy best? 5

6 Discontinuity in UC Discontinuity in UC New UC New UC Longstanding UC Caecal patch Up to 75% Caecal patch Up to 75% Common Absolute rectal sparing 0-5% Relative rectal sparing 31% Absolute rectal sparing 0-5% Relative rectal sparing 31% 15-44% Focal or patchy changes Uncommon Focal or patchy changes Uncommon 30-38% Caecal patch D'Haens G 1997 Odze 1993; Bernstein 1995; Kleer 1998; Kim 1999; D'Haens G 1997 Discontinuity in UC New UC Longstanding UC Caecal patch Up to 75% Common Absolute rectal sparing 0-5% Relative rectal sparing 31% 15-44% Focal or patchy changes Uncommon 30-38% Normalisation 10% ILEAL BIOPSY Odze 1993; Bernstein 1995; Kleer 1998; Kim 1999; D'Haens G 1997; Christensen B 2017 UC vs CD: ileal inflammation Favours Crohn s Also 17% of UC Ileal feature UC Crohn s Granuloma No Yes Pyloric metaplasia Rare Yes Villous atrophy Yes Yes Focal cryptitis / crypt abscesses / erosions Yes Yes Patchy laminaproprial neutrophils Yes Yes UPPER GI Haskell H et al. 2005; Geboes K et al

7 21/07/2017 UC vs CD: Upper GI inflammation Exclude other causes Reflux Helicobacter Drugs Crohn s UC Oesophagitis 46-72% 15-50% Gastritis 59-81% 58-77% Duodenitis 40-53% 17-19% Tobin JM, Sinha B 2001; Bousvaros A 2007 UGI granulomas Crohn s UC Oesophagus 0-33% 0 Stomach 6-37% 0 Duodenum 2-11% 0 Upper GI 19-78% 0 Schmitz-Moormann, Malchow 1985; Wright CL 1998; Tobin JN 2001; Alcantara 1993; Horjus Talabur Horje CS 2016 UGI UC Focally enhanced gastritis Histology Mixed inflammatory infiltrate around glands and foveolae Epithelial damage Crohn s Focally enhanced gastritis 12-54% UC 21-23% Oberhuber G 1997; McHugh JB 2013 Gastric UC 1. Focal gastritis 2. Patchy mixed basal inflammation 3. Superficial plasmacytosis Duodenal UC Diffuse duodenitis Rare Resembles colonic changes Lin J. Am J Surg Pathol 2010 Early IBD SPECIAL SITUATIONS % Basal plasma cells Crypt distortion Crypt atrophy Villous surface < 16 days days 1-4 months > 4 months Duration of symptoms Granulomas after 25 days Schumacher G

8 Paediatric UC UC vs CD post-operatively Setting Confusing feature UC vs CD Feature Adults Children Diffuse continuous disease 100% 68% Pouch / pre-pouch ileum Diversion proctocolitis Fissures, fistulas, granulomas can occur Histology resembles UC Granulomas do not necessarily indicate Crohn s Diffuse crypt abnormalities 58% 32% Severe crypt atrophy 21% 6% Granulomas / granulomatous vasculitis can occur Granulomas do not necessarily indicate Crohn s Patchiness of chronic changes 0% 21% Washington K 2002 Granulomas in diversion proctocolitis Primary sclerosing cholangitis (PSC) Prevalence Most PSC develop IBD 2% IBD develop PSC Type of IBD 80-90% UC Pancolitis (if IBD precedes PSC) Right-sided UC (if PSC precedes IBD) 10% Crohn s Usually involves colon Validity of UC/Crohn s label? ACCURACY OF BIOPSY DIAGNOSIS de Vries 2015; Joo M 2009; Boonstra K 2012; Schaeffer DF 2013 Accuracy of colorectal biopsy Better at confirming IBD than classifying it Rectal biopsy predicts 70% UC and 40% Crohn s Crohn's (non-experts) Crohn's (experts) UC (non-experts) UC (experts) % accuracy multiple site biopsies DO WE NEED HISTOPATHOLOGISTS? Bentley E 2002; Cross SS

9 Confocal laser endomicroscopy Magnification x 1400 New techniques? UC Crohn s p value Discontinuous inflammation 5 87 < Discontinuouscrypt changes < Focal cryptitis < Severe widespread crypt distortion < Irregular surface < Disturbed architecture Colonic crypts regularly arranged Scoring system: 93.7 % accurate Neumann H, Kiesslich R 2013 Tontini GE 2014 Summary: UC vs Crohn s in colorectal biopsy Summary: UC vs Crohn s in ileal and UGI biopsy Category of abnormality Discriminatoryvalue Site Comment Granulomas (20% Crohn s biopsies) ++++ Distribution of crypt changes +++ Distribution of chronic inflammation ++ Severity of mucin depletion + Ileal Upper GI Involvement favours Crohn s Granulomas discriminate Granulomas discriminate Extent of activity + Summary: UC vs Crohn s - special or difficult situations Histology enhances or completes the picture Special situation Discontinuity in new UC Caecal patch; rectal sparing Longstanding UC Discontinuity, rectal sparing Imaging Histology Early IBD Absence of architectural changes Paediatric UC Discriminatory changes less common Endoscopy Symptoms PSC-related IBD Non-conformism Pouch, pre-pouch, diversion proctocolitisin UC +/- Crohn s-like features and granulomas Past history 9

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