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Transcript of Inflammatory Bowel Disease - · PDF fileInflammatory Bowel Disease: ... • Infectious...

1

Inflammatory Bowel Disease:Frequent Diagnostic Pitfalls

James Michael Mitchell, MD

Problems encountered

Pathologist blinded or does not understand reason(s) for biopsies

Lack of clinical information

Signs and symptoms

Abdominal pain, diarrhea

Bloody versus non-bloody diarrhea

Temporality of disease

Laboratory findings (microbiology, serology)

Endoscopy findings

Spatial distribution

Imaging

Pathologist cannot answer question if there is not one

Pathologist is unaware of criteria to make diagnosis

Endoscopist lacks clinical information to answer question

Problems encountered

Distribution or focality of disease not demonstrated by bx sample(s)

Limited biopsy sample

Assessing and diagnosing disease/disease activity

All biopsy samples submitted in one container

Random colon

Limits assessment of chronicity

Granulomata

Treatment effect

Other medication effect

Question being asked cannot be answered

Pathologist cannot differentiate between CD and UC on biopsy

Histopathologic mimicry

Normal histology

Right-sided biopsy Left-sided biopsy

Rectal biopsy

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1. Classify colitis

Acute

Chronic

Active

Inactive

2. Grade activity

Mild

Moderate

Severe

3. Clinico-pathologic correlation

Pattern-based approach to colitis

Microscopic features of acute vs. chronic colitis

Acute colitis

Generally preserved crypt architectureAcute cryptitis and abscessesChronic inflammatory infiltrate

Pitfall: lymphoid aggregates

Acute cryptitis limited to one or few crypts

Associated with epithelial injury

+/- increased chronic inflammatory infiltrate

Focal active colitis (FAC)

Previously thought to have strong correlation with CD (Greenson, et al.)

Acute self-limited colitisNSAIDs, sodium phosphate

Irritable bowel syndromeCrohns diseaseIschemic colitis

Presenting symptoms

Sudden-onset diarrheaAbdominal tenderness

Fever

Focal active colitis (FAC)

163 adult patients (F>M)

31 pediatric patients (F=M)

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Chronic colitis

Crypt architectural distortion

Basally located lymphoid aggregates

Basal plasmacytosis

Chronic inflammatory infiltrate

Paneth cell metaplasia/hyperplasia

Lamina propria fibrosis

Granulomata

Necrotizing (Ix) Non-necrotizing (CD) Crypt-rupture (mucin)

Microscopic features of untreated IBD

Pitfall: colorectal fissure in IBD (CD vs UC)

Rectal biopsy prior to therapy withchronic active colitis

Pitfall: discontinuous disease in UC

Rectal biopsy after 6 months ofmesalamine therapy with

complete resolution of disease

Infectious agents

Infectious colitis: Salmonella, E. coli, Yersinia, C. jejuni, Shigella, E. histolytica, Tuberculosis

STD-associated proctitis: Syphilis, N. gonorrhea, C. trachomatis (LGV)

Drug induced colitis

NSAIDs

Mycophenolate

Biologics: Ipilimumab, Rituximab, Bevacizumab

Systemic conditions involving the GI tract

Vasculitis: Behet's disease, Henoch Schnlein purpura

Chronic granulomatous disease

Hermansky-Pudlak syndrome

Common variable immunodeficiency syndrome

Systemic mastocytosis

Langerhans cell histiocytosis

Idiopathic hypereosinophilic syndrome

Diverticular colitis

Crohn's-like colitis

Ulcerative colitis-like

Histologic Mimics of IBD

*Crohn-like disease

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Infectious mimics of IBD

Mycobacterium aviumintracellulare colitis

Acute self-limited colitis

Shigella

Campylobacter

Non-typhoid Salmonella

Aeromonas

Ischemic colitis w/ or w/o pseudomembranes

Shigella

STEC

Granulomatous inflammation

Yersinia

Lymphohistiocytic inflammation

S. typhi

Architectural distortion

S. typhi

Shigella

Aeromonas (occasionally)

Histologic pattern of injury bacterial pathogens

Salmonella infection

Acute self-limited colitis

Minimal crypt architecture distortion

Yersinia infection

Neutrophil-rich granuloma

Generally preserved crypt architecture

Biopsy: Virtually indistinguishable from CC

Erosions/ulcerationsChronic lymphocytic inflammation in lamina propria

Villous architectural abnormalitiesPseudopyloric gland metaplasia

Isolated ulcers of the TI (Yersinia infection)

Diagnosis by PCR

Acute self-limited colitis

Minimal crypt architecture distortion

C. jejuni infection

Shigella infection

Acute cryptitisAcute crypt abscess

Mucin granuloma

Minimal crypt architectural distortionReactive epithelial features

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Entamoeba histolytica colitis

Trophozoites

Round to oval

25-40 nm

Luminal

Entamoeba histolytica colitis

Mycobacterial infection

Crypt architectural distortionDense chronic inflammatory infiltrate

in lamina propriaNon-necrotizing and necrotizing

granulomata

IC > ISPreferentially affects TI and cecum

Pseudomembranes inchronic active UC

UlcerationCrypt architectural distortion

Acute cryptitisCrypt abscesses

Basal lymphoplasmacytosis

C. difficile-induced pseudomembranous colitis

Concomitant CMV infection

Intense lymphohistiocytic infiltrate with prominent plasma cells

Lymphoid aggregatesMild to moderate acute

inflammation

Minimal basal plasmacytosisMinimal crypt distortion

Rare granulomata Paneth cell metaplasia

STI-associated proctitis

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Treponema pallidum infection

Lymphogranuloma venereum infection

ErosionPatchy acute cryptitis

Crypt abscessesChronic inflammatory infiltrate

UlcerationCrypt architectural distortion

Dense chronic inflammatory infiltrate in lamina propria

Infectious agents

Infectious colitis: Salmonella, E. coli, Yersinia, C. jejuni, Shigella, E. histolytica, Tuberculosis

STD-associated proctitis: Syphilis, N. gonorrhea, C. trachomatis (LGV)

Drug induced colitis

NSAIDs

Mycophenolate

Biologics: Ipilimumab, Rituximab, Bevacizumab

Systemic conditions involving the GI tract

Vasculitis: Behet's disease, Henoch Schnlein purpura

Chronic granulomatous disease

Hermansky-Pudlak syndrome

Common variable immunodeficiency syndrome

Systemic mastocytosis

Langerhans cell histiocytosis

Idiopathic hypereosinophilic syndrome

Diverticular colitis

Crohn's-like colitis

Ulcerative colitis-like

Histologic Mimics of IBD

Biopsy: Virtually indistinguishable from CC

Erosions/ulcerationsChronic lymphocytic inflammation in lamina propria

Villous architectural abnormalitiesPseudopyloric gland metaplasia

Isolated ulcers of the terminal ileum (NSAIDs)

NON-STEROIDALANTI-INFLAMMATORIES

Variable mucosal injury

Subepithelial fibrosis

MYCOPHENOLATE INJURY

Scattered epithelial apoptotic bodies

Increased plasma cells and eosinophils in lamina propria

Robust lymphoplasmacytic infiltrate extending in submucosa

Crypt abscesses

Epithelial cell apoptosis

Ipilimumab colitis

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Infectious agents

Infectious colitis: Salmonella, E. coli, Yersinia, C. jejuni, Shigella, E. histolytica, Tuberculosis

STD-associated proctitis: Syphilis, N. gonorrhea, C. trachomatis (LGV)

Drug induced colitis

NSAIDs

Mycophenolate

Biologics: Ipilimumab, Rituximab, Bevacizumab

Systemic conditions involving the GI tract

Vasculitis: Behet's disease, Henoch Schnlein purpura

Chronic granulomatous disease

Hermansky-Pudlak syndrome

Common variable immunodeficiency syndrome

Systemic mastocytosis

Langerhans cell histiocytosis

Idiopathic hypereosinophilic syndrome

Diverticular colitis

Crohn's-like colitis

Ulcerative colitis-like

Histologic Mimics of IBD

Behcets disease

Diffuse, severe colitis

Numerous inflammatory polyps and erosions

Crypt architectural distortion

Basal lymphoplasmacytosis

Leukocytoclastic vasculitisin lamina propria

PAUCITY of neutrophils in lamina propria and crypts

Henoch-Schnlein purpura

Majority with normal crypt architectureNo significant chronic inflammatory infiltrate in lamina propria

Plasma cells absent or drastically diminishedProminent crypt cell apoptosis

Common variable immunodeficiency

Marked crypt architectural distortionPaucity of plasma cellsConcomitant pathology

Common variable immunodeficiency

Expansion of lamina propria by chronic inflammatory infiltrate

with eosinophilia

+/- crypt architectural distortion

Clusters/aggregates of CD117+/tryptase mast cells

Systemic mastocytosis

GI involvement: ~75% of pts

Endoscopy: Normal or non-specific changes (G or D ulcers)

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Bimodal: Childhood & middle age

GI involvement: Rare

Pediatric: Disseminated diseaseAdults: