21/07/2017
Outline
• Colorectal biopsies Ulcerative colitis versus Crohn’s • Ileal and upper GI biopsies disease: is biopsy useful? • Special situations • New techniques Roger Feakins • Summary
UC vs. Crohn’s? Is it easy? Inflammatory bowel disease (IBD) = chronic idiopathic inflammatory bowel disease 10-15% Crohn’s reclassified as UC after 1 year
Never classified: 1-20% IBD • IBD unclassified (IBDU) • “Indeterminate colitis” in resections
Reclassified even after resection…
UC Crohn’s • 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
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(Imaging) Stool Endoscopy culture
Symptoms, IBD? NEW IBD VS NON-IBD clinical Infection? Histology course Other?
Basic principles of IBD diagnosis
IBD > non-IBD (initial biopsies) Basal plasmacytosis
Basal plasmacytosis Plasma cells at base of mucosa + loss of plasma cell gradient
Architectural changes Significance: • • Crypt distortion Earliest feature of IBD • Crypt atrophy • Best predictor of IBD • Irregular or villiform mucosal surface
Other features (less discriminatory) “Crypts with their feet in pools of plasma cells” • Granulomas • Mucin depletion • Lymphoid aggregates 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
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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
New IBD / suspected new IBD Treated / UC (IBDU) Crohn’s longstanding IBD
Histology less reliable for UC vs Crohn’s
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Clinical features
UC Crohn’s
Blood in stools > 90% < 50% Distribution Continuous Discontinuous
Endoscopic features Erythema, granularity, Longitudinal ulcers, ulceration cobblestoning UC VS CROHN’S Perianal disease Uncommon Fistulas and fissures common
Small bowel strictures Very rare Not uncommon
UC vs Crohn’s: considerations for the Distribution in biopsies pathologist What is Architectural assessed? changes
Chronic inflammation Distribution of changes
Where? Within a biopsy Granulomas Diffuse, patchy, focal Between biopsies Mucin depletion Between Continuous, discontinuous anatomical sites
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
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Crohn’s disease > UC (initial biopsies) Typical Crohn’s disease
In any biopsy Non-diffuse crypt distortion Granuloma
• Granulomas** • Non-diffuse crypt distortion • Non-diffuse chronic inflammation
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 L Paneth cells – Not significant proximal to splenic flexure “…..at least five epithelioid – Distally? 17 % rectal biopsies macrophages” Discriminatory value Not always Crohn’s – Chronicity – TB, parasite, foreign material, – IBD > non-IBD drug, sarcoid, etc. – Seen in GVHD, radiation colitis, collagenous colitis Cryptolytic granulomas – also in UC and other colitides
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?
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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% Absolute rectal sparing 0-5% 15-44% Relative rectal sparing 31% Relative rectal sparing 31% 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% 15-44% Relative rectal sparing 31% 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 Ileal feature UC Crohn’s • Also 17% of UC Granuloma No Yes
Pyloric metaplasia Rare Yes
Villous atrophy Yes Yes
Focal cryptitis / crypt Yes Yes abscesses / erosions Patchy lamina proprial Yes Yes neutrophils UPPER GI
Haskell H et al. 2005; Geboes K et al. 1998
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UC vs CD: Upper GI inflammation UGI granulomas
Exclude other causes Crohn’s UC • Reflux Crohn’s UC • Helicobacter Oesophagus 0-33% 0 • Drugs Oesophagitis 46-72% 15-50% Stomach 6-37% 0
Gastritis 59-81% 58-77% Duodenum 2-11% 0 Duodenitis 40-53% 17-19% Upper GI 19-78% 0
Tobin JM, Sinha B 2001; Bousvaros A 2007 Schmitz-Moormann, Malchow 1985; Wright CL 1998; Tobin JN 2001; Alcantara 1993; Horjus Talabur Horje CS 2016
Focally enhanced gastritis UGI UC
Gastric UC Histology 1. Focal gastritis – Mixed inflammatory infiltrate around 2. Patchy mixed basal inflammation glands and foveolae 3. Superficial plasmacytosis – Epithelial damage
Duodenal UC Diffuse duodenitis • Crohn’s UC Rare • Resembles colonic changes Focally enhanced gastritis 12-54% 21-23%
Oberhuber G 1997; McHugh JB 2013 Lin J. Am J Surg Pathol 2010
Early IBD
% 100 90 Basal plasma 80 cells 70 60 Crypt distortion 50 40 Crypt atrophy 30 20 10 Villous surface SPECIAL SITUATIONS 0 < 16 days 16-30 days 1-4 months > 4 months Duration of symptoms Granulomas – after 25 days Schumacher G 1994
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Paediatric UC UC vs CD post-operatively
Setting Confusing feature UC vs CD
Feature Adults Children Pouch / pre-pouch ileum Fissures, fistulas, granulomas Granulomas do not can occur necessarily indicate Crohn’s Diffuse continuous disease 100% 68% Diversion proctocolitis Histology resembles UC Diffuse crypt abnormalities 58% 32% Granulomas / granulomatous Granulomas do not Severe crypt atrophy 21% 6% vasculitis can occur necessarily indicate Crohn’s
Patchiness of chronic changes 0% 21%
Granulomas in diversion proctocolitis Washington K 2002
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 ACCURACY OF BIOPSY DIAGNOSIS – Usually involves colon Validity of UC/Crohn’s label?
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) DO WE NEED HISTOPATHOLOGISTS? 0 20 40 60 80 100
% accuracy – multiple site biopsies
Bentley E 2002; Cross SS 2002
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New techniques?
• Confocal laser endomicroscopy • Magnification x 1400
UC Crohn’s p value Discontinuous inflammation 5 87 <0.0001 Discontinuouscrypt changes 10 87 <0.0001 Focal cryptitis 13 75 <0.0001 Severe widespread crypt distortion 87 17 <0.0001 Irregular surface ++ 90 17 <0.0001
Scoring system: 93.7 % accurate Disturbed architecture Colonic crypts regularly arranged
Neumann H, Kiesslich R 2013 Tontini GE 2014
Summary: UC vs Crohn’s in colorectal Summary: UC vs Crohn’s in ileal and biopsy UGI biopsy
Category of abnormality Discriminatoryvalue Site Comment
Granulomas (20% Crohn’s biopsies) ++++ Ileal Involvementfavours Crohn’s
Distribution of crypt changes +++ Granulomas discriminate
Distribution of chronic inflammation ++ Upper GI Granulomas discriminate Severity of mucin depletion +
Extent of activity +
Summary: UC vs Crohn’s - special or Histology enhances or completes the difficult situations picture
Special situation Discontinuity in new UC Caecal patch; rectal sparing
Histology Longstanding UC Discontinuity,rectal sparing Imaging
Early IBD Absence of architectural changes
Paediatric UC Discriminatory changes less common Endoscopy Symptoms
PSC-related “IBD” Non-conformism
Pouch, pre-pouch, diversion +/- Crohn’s-like features and granulomas Past history proctocolitisin UC
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THANK YOU
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