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Critical Evaluation Critical Evaluation of colonoscopic of colonoscopic biopsies in Crohn’s biopsies in Crohn’s Disease 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.

Critical Evaluation of colonoscopic biopsies in Crohn’s Disease Najib Haboubi MB Ch B,D Path, FRCPath Professor of Health Science, Liver and Gastrointestinal

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Page 1: Critical Evaluation of colonoscopic biopsies in Crohn’s Disease Najib Haboubi MB Ch B,D Path, FRCPath Professor of Health Science, Liver and Gastrointestinal

Critical Evaluation of Critical Evaluation of colonoscopic biopsies in colonoscopic biopsies in

Crohn’s DiseaseCrohn’s Disease

Najib Haboubi MB Ch B ,D Path, FRCPathProfessor of Health Science, Liver and

Gastrointestinal and Pathology, Universities of John Moors, Liverpool and Salford, Manchester.

Page 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

Crohn, Ginzburg and Crohn, Ginzburg and Oppenhiemer 1932 JAMAOppenhiemer 1932 JAMA

‘A disease of the terminal ileum, affecting mainly young adults and characterised by……

Page 3: Critical Evaluation of colonoscopic biopsies in Crohn’s Disease Najib Haboubi MB Ch B,D Path, FRCPath Professor of Health Science, Liver and Gastrointestinal

Things have changedThings have changed

Young and old All GIT ( mostly small and large intestine)

Page 4: Critical Evaluation of colonoscopic biopsies in Crohn’s Disease Najib Haboubi MB Ch B,D Path, FRCPath Professor of Health Science, Liver and Gastrointestinal

Distinction between UC and Distinction between UC and CDCD

From a single mucosal biopsy.

Not easy!

Page 5: Critical Evaluation of colonoscopic biopsies in Crohn’s Disease Najib Haboubi MB Ch B,D Path, FRCPath Professor of Health Science, Liver and Gastrointestinal

CD Classical featuresCD Classical features

Focality Rectal sparingGranulomas.Transmural inflammation

Page 6: Critical Evaluation of colonoscopic biopsies in Crohn’s Disease Najib Haboubi MB Ch B,D Path, FRCPath Professor of Health Science, Liver and Gastrointestinal

DistalDistal UCUC is mostly is mostly

accompanied by inflammatory accompanied by inflammatory lesions of the lesions of the caecumcaecum

Geboes et al Gastroenterology 1987

Page 7: Critical Evaluation of colonoscopic biopsies in Crohn’s Disease Najib Haboubi MB Ch B,D Path, FRCPath Professor of Health Science, Liver and Gastrointestinal

Patchy Patchy CoecalCoecal Inflammation Inflammation

Associated with Associated with DistalDistal UCUC: : A Prospective Endoscopic A Prospective Endoscopic

StudyStudy D’Haens,Geboes,Peeters,Baert,Ectors, Rutgeerts. Am.J.Gasroenterol. 1997

Page 8: Critical Evaluation of colonoscopic biopsies in Crohn’s Disease Najib Haboubi MB Ch B,D Path, FRCPath Professor of Health Science, Liver and Gastrointestinal

Patchiness of mucosal Patchiness of mucosal inflammation in treated inflammation in treated

UCUC

Bernstein , Shanahan , Anton , Weinstein.

Gastrointestinal Endoscopy. 1995.

Page 9: Critical Evaluation of colonoscopic biopsies in Crohn’s Disease Najib Haboubi MB Ch B,D Path, FRCPath Professor of Health Science, Liver and Gastrointestinal

Ulcerative ColitisUlcerative Colitis

Patterns of Involvement in Colorectal Biopsies and Changes With Time.

Celina Kleer and Henry Appelman

Am.J.Surg.Path.

Page 10: Critical Evaluation of colonoscopic biopsies in Crohn’s Disease Najib Haboubi MB Ch B,D Path, FRCPath Professor of Health Science, Liver and Gastrointestinal

Material and MethodMaterial and Method

41 patients with proven chronic UC.

Sequential sets of colonic biopsies.

Page 11: Critical Evaluation of colonoscopic biopsies in Crohn’s Disease Najib Haboubi MB Ch B,D Path, FRCPath Professor of Health Science, Liver and Gastrointestinal

ResultsResultsHistologically normal

appearing mucosal biopsies do occur in established cases of CUC.

This finding is enhanced with treatment with 5 ASA.

Page 12: Critical Evaluation of colonoscopic biopsies in Crohn’s Disease Najib Haboubi MB Ch B,D Path, FRCPath Professor of Health Science, Liver and Gastrointestinal

Summary Summary In In CUCCUC

Mucosa can revert to normal with or without treatment.

Skip lesions and rectal sparing .

Page 13: Critical Evaluation of colonoscopic biopsies in Crohn’s Disease Najib Haboubi MB Ch B,D Path, FRCPath Professor of Health Science, Liver and Gastrointestinal

Classical featuresClassical features

Multi focality and Rectal sparing

Granulomas. Transmural inflammation

Page 14: Critical Evaluation of colonoscopic biopsies in Crohn’s Disease Najib Haboubi MB Ch B,D Path, FRCPath Professor of Health Science, Liver and Gastrointestinal

GranulomasGranulomas

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.

Page 15: Critical Evaluation of colonoscopic biopsies in Crohn’s Disease Najib Haboubi MB Ch B,D Path, FRCPath Professor of Health Science, Liver and Gastrointestinal
Page 16: Critical Evaluation of colonoscopic biopsies in Crohn’s Disease Najib Haboubi MB Ch B,D Path, FRCPath Professor of Health Science, Liver and Gastrointestinal

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

Page 17: Critical Evaluation of colonoscopic biopsies in Crohn’s Disease Najib Haboubi MB Ch B,D Path, FRCPath Professor of Health Science, Liver and Gastrointestinal

Infective GranulomasInfective Granulomas

TBFungal infection.Viral infection.

Page 18: Critical Evaluation of colonoscopic biopsies in Crohn’s Disease Najib Haboubi MB Ch B,D Path, FRCPath Professor of Health Science, Liver and Gastrointestinal

UCUC

Classic ViewsNever patchy No granuloma

Current viewsCan be .Pericryptal

granuloma

Page 19: Critical Evaluation of colonoscopic biopsies in Crohn’s Disease Najib Haboubi MB Ch B,D Path, FRCPath Professor of Health Science, Liver and Gastrointestinal

In practiceIn practice

The distinction between UC and CD is not always easy .

Even in the hands of the experts?

Page 20: Critical Evaluation of colonoscopic biopsies in Crohn’s Disease Najib Haboubi MB Ch B,D Path, FRCPath Professor of Health Science, Liver and Gastrointestinal

How could pathologists How could pathologists improve the initial diagnosis of improve the initial diagnosis of

colitis? colitis?

Bentley et al J Clin Path 2002,55;955-960

Page 21: Critical Evaluation of colonoscopic biopsies in Crohn’s Disease Najib Haboubi MB Ch B,D Path, FRCPath Professor of Health Science, Liver and Gastrointestinal

AimAim

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.

Page 22: Critical Evaluation of colonoscopic biopsies in Crohn’s Disease Najib Haboubi MB Ch B,D Path, FRCPath Professor of Health Science, Liver and Gastrointestinal

MethodsMethods

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.

Page 23: Critical Evaluation of colonoscopic biopsies in Crohn’s Disease Najib Haboubi MB Ch B,D Path, FRCPath Professor of Health Science, Liver and Gastrointestinal

Diagnosing CDDiagnosing CD

Experts Rectal 24% Full colonoscopy 64%

Non experts Rectal 12% Full colonoscopy 60%

Page 24: Critical Evaluation of colonoscopic biopsies in Crohn’s Disease Najib Haboubi MB Ch B,D Path, FRCPath Professor of Health Science, Liver and Gastrointestinal

Diagnosing UCDiagnosing UC

Experts Rectal 64% Full colonoscopy 74%

Non experts Rectal 62% Full colonoscopy 72%

Page 25: Critical Evaluation of colonoscopic biopsies in Crohn’s Disease Najib Haboubi MB Ch B,D Path, FRCPath Professor of Health Science, Liver and Gastrointestinal

ConclusionConclusion

Full colonoscopic series are more accurate in diagnosing CD and UC

No difference between the experts and the non experts in blinded biopsies

Page 26: Critical Evaluation of colonoscopic biopsies in Crohn’s Disease Najib Haboubi MB Ch B,D Path, FRCPath Professor of Health Science, Liver and Gastrointestinal

Trafford / Manchester Trafford / Manchester approachapproach

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

Page 27: Critical Evaluation of colonoscopic biopsies in Crohn’s Disease Najib Haboubi MB Ch B,D Path, FRCPath Professor of Health Science, Liver and Gastrointestinal

Thanks for the invitationThanks for the invitation

Page 28: Critical Evaluation of colonoscopic biopsies in Crohn’s Disease Najib Haboubi MB Ch B,D Path, FRCPath Professor of Health Science, Liver and Gastrointestinal
Page 29: Critical Evaluation of colonoscopic biopsies in Crohn’s Disease Najib Haboubi MB Ch B,D Path, FRCPath Professor of Health Science, Liver and Gastrointestinal
Page 30: Critical Evaluation of colonoscopic biopsies in Crohn’s Disease Najib Haboubi MB Ch B,D Path, FRCPath Professor of Health Science, Liver and Gastrointestinal

Number Number

Page 31: Critical Evaluation of colonoscopic biopsies in Crohn’s Disease Najib Haboubi MB Ch B,D Path, FRCPath Professor of Health Science, Liver and Gastrointestinal
Page 32: Critical Evaluation of colonoscopic biopsies in Crohn’s Disease Najib Haboubi MB Ch B,D Path, FRCPath Professor of Health Science, Liver and Gastrointestinal

Classically UCClassically UC

A mucosal disease.The histology does not come back

to normal.In Distal disease it is Never patchy

(continuous).

Page 33: Critical Evaluation of colonoscopic biopsies in Crohn’s Disease Najib Haboubi MB Ch B,D Path, FRCPath Professor of Health Science, Liver and Gastrointestinal

UCUCMucosal. May extend into the

submucosa in acute cases and ulceration.

This is not Transmural inflammation.

Page 34: Critical Evaluation of colonoscopic biopsies in Crohn’s Disease Najib Haboubi MB Ch B,D Path, FRCPath Professor of Health Science, Liver and Gastrointestinal

Is time a good Is time a good healer?healer?

Page 35: Critical Evaluation of colonoscopic biopsies in Crohn’s Disease Najib Haboubi MB Ch B,D Path, FRCPath Professor of Health Science, Liver and Gastrointestinal

UCUC

Mucosal.

Never patchy Never come back to

normal.

May extend into the submucosa.

Yes it could .Yes it could.

Page 36: Critical Evaluation of colonoscopic biopsies in Crohn’s Disease Najib Haboubi MB Ch B,D Path, FRCPath Professor of Health Science, Liver and Gastrointestinal

Diagnostic DifficultiesDiagnostic Difficulties

There is no specific histological feature that distinguishes CUC from many other colitides.

The diagnosis has to be a team responsibility .

Page 37: Critical Evaluation of colonoscopic biopsies in Crohn’s Disease Najib Haboubi MB Ch B,D Path, FRCPath Professor of Health Science, Liver and Gastrointestinal

SystemSystemPattern based provisional report

with a working differential diagnosis.

The final diagnosis is in the CPC.No place for Non Specific Colitis

Page 38: Critical Evaluation of colonoscopic biopsies in Crohn’s Disease Najib Haboubi MB Ch B,D Path, FRCPath Professor of Health Science, Liver and Gastrointestinal

Causes of DifficultyCauses 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.

Page 39: Critical Evaluation of colonoscopic biopsies in Crohn’s Disease Najib Haboubi MB Ch B,D Path, FRCPath Professor of Health Science, Liver and Gastrointestinal

Colitis with no Colitis with no distinguishing distinguishing

histological histological featuresfeatures

Page 40: Critical Evaluation of colonoscopic biopsies in Crohn’s Disease Najib Haboubi MB Ch B,D Path, FRCPath Professor of Health Science, Liver and Gastrointestinal

Despite the legitimate Despite the legitimate pressure we cannot tell pressure we cannot tell

the differencethe difference

Page 41: Critical Evaluation of colonoscopic biopsies in Crohn’s Disease Najib Haboubi MB Ch B,D Path, FRCPath Professor of Health Science, Liver and Gastrointestinal

DilemmaDilemma

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

Page 42: Critical Evaluation of colonoscopic biopsies in Crohn’s Disease Najib Haboubi MB Ch B,D Path, FRCPath Professor of Health Science, Liver and Gastrointestinal

ResultsResults

Page 43: Critical Evaluation of colonoscopic biopsies in Crohn’s Disease Najib Haboubi MB Ch B,D Path, FRCPath Professor of Health Science, Liver and Gastrointestinal

Infective GranulomasInfective Granulomas

Campylobacter colitis.Salmonella colitis.TBYersinia

Page 44: Critical Evaluation of colonoscopic biopsies in Crohn’s Disease Najib Haboubi MB Ch B,D Path, FRCPath Professor of Health Science, Liver and Gastrointestinal

Vienna ClassificationVienna Classification

InflammatoryStricturing , non penetrating ( stenosing)Fistulating( penetrating)

Page 45: Critical Evaluation of colonoscopic biopsies in Crohn’s Disease Najib Haboubi MB Ch B,D Path, FRCPath Professor of Health Science, Liver and Gastrointestinal

Size is not every thingSize is not every thing

Page 46: Critical Evaluation of colonoscopic biopsies in Crohn’s Disease Najib Haboubi MB Ch B,D Path, FRCPath Professor of Health Science, Liver and Gastrointestinal

Accurate reportingAccurate reporting

Full clinical storey

Page 47: Critical Evaluation of colonoscopic biopsies in Crohn’s Disease Najib Haboubi MB Ch B,D Path, FRCPath Professor of Health Science, Liver and Gastrointestinal

Classical featuresClassical features

Sarcoid type granulomas.FocalDiscontinuous.Rectal sparing.

Page 48: Critical Evaluation of colonoscopic biopsies in Crohn’s Disease Najib Haboubi MB Ch B,D Path, FRCPath Professor of Health Science, Liver and Gastrointestinal

Patchiness of mucosal Patchiness of mucosal inflammation in treated inflammation in treated

UCUC

Bernstein , Shanahan , Anton , Weinstein.

Gastrointestinal Endoscopy. 1995.

Page 49: Critical Evaluation of colonoscopic biopsies in Crohn’s Disease Najib Haboubi MB Ch B,D Path, FRCPath Professor of Health Science, Liver and Gastrointestinal

ConclusionConclusion

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

Page 50: Critical Evaluation of colonoscopic biopsies in Crohn’s Disease Najib Haboubi MB Ch B,D Path, FRCPath Professor of Health Science, Liver and Gastrointestinal

Ulcerative ColitisUlcerative Colitis

Patterns of Involvement in Colorectal Biopsies and Changes With Time.

Celina Kleer and Henry Appelman

Am.J.Surg.Path.

Page 51: Critical Evaluation of colonoscopic biopsies in Crohn’s Disease Najib Haboubi MB Ch B,D Path, FRCPath Professor of Health Science, Liver and Gastrointestinal

Material and MethodMaterial and Method

41 patients with proven chronic UC.

Sequential sets of colonic biopsies.

Page 52: Critical Evaluation of colonoscopic biopsies in Crohn’s Disease Najib Haboubi MB Ch B,D Path, FRCPath Professor of Health Science, Liver and Gastrointestinal

ResultsResultsHistologically normal

appearing mucosal biopsies do occur in established cases of Chronic UC.

This finding is enhanced with treatment with 5 ASA.

Page 53: Critical Evaluation of colonoscopic biopsies in Crohn’s Disease Najib Haboubi MB Ch B,D Path, FRCPath Professor of Health Science, Liver and Gastrointestinal

SummarySummary

Skip lesions do occur in CUC.Mucosa can revert to normal

with or without treatment.

Page 54: Critical Evaluation of colonoscopic biopsies in Crohn’s Disease Najib Haboubi MB Ch B,D Path, FRCPath Professor of Health Science, Liver and Gastrointestinal
Page 55: Critical Evaluation of colonoscopic biopsies in Crohn’s Disease Najib Haboubi MB Ch B,D Path, FRCPath Professor of Health Science, Liver and Gastrointestinal

Granuloma specific to CDGranuloma specific to CD

Well formedIsolatedAway from areas of inflammation.Basally or submucosally situated

Page 56: Critical Evaluation of colonoscopic biopsies in Crohn’s Disease Najib Haboubi MB Ch B,D Path, FRCPath Professor of Health Science, Liver and Gastrointestinal
Page 57: Critical Evaluation of colonoscopic biopsies in Crohn’s Disease Najib Haboubi MB Ch B,D Path, FRCPath Professor of Health Science, Liver and Gastrointestinal

Frequency and significance of Frequency and significance of granulomas in a cohort of granulomas in a cohort of

incidence cases of CDincidence cases of CD

Heresbach et al Gut 2005;54: 215222

Page 58: Critical Evaluation of colonoscopic biopsies in Crohn’s Disease Najib Haboubi MB Ch B,D Path, FRCPath Professor of Health Science, Liver and Gastrointestinal

AimAim

Evaluate epitheloid granulomas occurence in incident CD.

Association between epitheloid granuloma and outcome of CD

Page 59: Critical Evaluation of colonoscopic biopsies in Crohn’s Disease Najib Haboubi MB Ch B,D Path, FRCPath Professor of Health Science, Liver and Gastrointestinal

M&MM&M

188 cases of endoscopic (upper and lower) and surgical (intestinal or colonic) procedures.

Follow up for at least 5 years.

Page 60: Critical Evaluation of colonoscopic biopsies in Crohn’s Disease Najib Haboubi MB Ch B,D Path, FRCPath Professor of Health Science, Liver and Gastrointestinal

ResultsResults

Epitheloid granulomas are associated with higher rate of surgical resections.