Moving beyond the horizon of inflammatory bowel … · Chronic colitis Moving beyond the horizon of inflammatory bowel disease Sanjay Kakar, MD UCSF

Chronic colitisMoving beyond the horizon of inflammatory

bowel disease

Sanjay Kakar, MDUCSF

Chronic colitisMoving beyond the horizon of inflammatory

bowel disease

Chronic colitis• Clinical

Acute: symptoms < 1 month Subacute/chronic 1-6 monthsChronic >6 months

• HistologicalArchitectural distortionIncreased lamina propria inflammationPaneth cell metaplasia

Chronic colitis

• NONCRYPT DESTRUCTIVE

• CRYPT DESTRUCTIVE

Colitis: patterns

NONCRYPT DESTRUCTIVELymphocytic/collagenous colitis Nonspecific ulcer GranulomatousEosinophilic colitis

Colitis: patterns• NONCRYPT DESTRUCTIVE• CRYPT DESTRUCTIVE

Inflammatory bowel diseaseDiverticular diseaseDiversion colitisPouchitisCertain infectionsDrugs, chronic ischemia/radiation

Approach to diagnosis

• Pattern-crypt destructive/nondestructive-histological categories based onadditional features

• Etiologic diagnosis-clinical and endoscopic findings-suggested work-up to establish etiology



Diverticular disease-associated colitis

• Mild inflammatory changes around ostia• Mucosal prolapse• IBD-like changes

Mimic Crohn disease and ulcerative colitis

Diverticular disease-associated colitis mimicking UC

Diverticular disease-associated colitis mimicking UC

Diverticular disease-associated colitis: fissuring ulcers

Diverticular disease-associated colitis: epithelioid granulomas


Distinction from ulcerative colitis• Segmental disease limited to sigmoid

colon• Rectal involvement favors UC


Distinction from Crohn disease• Ileocecal disease or anal fissures/fistulae

favor Crohn disease • Segmental disease limited to sigmoid

colon


Distinction from Crohn diseaseGoldstein, AJCP 1997

• 25 patients with diverticulosis and histological features of Crohn disease limited to sigmoid colon

• 23/25 patients did not develop Crohndisease on follow-up



Diversion colitis

• Obstructive disease of sigmoid or rectum: carcinoma, diverticulitis, Crohn disease

• Defunctioned rectum in UC during 3-stage pouch procedure

Diversion colitis

• Florid lymphoid hyperplasia• IBD-like features: architectural distortion,

ulceration, crypt inflammation• Diverted segments in Crohn disease

resemble ulcerative colitis• Diverted segments in ulcerative colitis

resemble Crohn disease

Diversion colitis: marked lymphoid hyperplasia

Diversion colitis: ulceration over lymphoid follicle

Diversion colitis: fissuring ulcers in diverted rectum in UC

Diversion colitis: granulomas, giant cells

Diversion colitis in CD: architectural distortion and crypt abscesses mimicking UC

Diversion colitis

Role of the pathologist• Clinical information necessary for

distinction from IBD• Diagnosis of Crohn or UC should never

be changed based on findings in diverted segment alone



Ileoanal pouch

Adaptive changes• Mild inflammation, variable villous

atrophy : 50%• Intermittent increase in inflammation with

recovery: 30-40%• Complete atrophy with active

inflammation: 10-20%

Chronic pouchitis

• Clinical, endoscopic and pathologic features

• Clinical: Diarrhea, pain, urgency, discharge

• Endoscopic: Diffuse process with contact bleeding, ulcers

Chronic pouchitis

Pathologic features• Active chronic inflammation• Villous atrophy• Superficial ulcers• Fissures and fistulae uncommon• Granulomas

Ileoanal pouch: villous blunting and inflammation

Pouchitis: chronic active inflammation, ulceration, villous atrophy

Chronic pouchitis

Role of the pathologist• Diagnosis of pouchitis

-integration of clinical and endoscopic data -diffuse process -localized: ischemia, mucosal prolapse, inflammatory polyps

• Is it Crohn disease?

Chronic pouchitis

Is it Crohn disease?• Granulomas, pseudopyloric metaplasia

can occur in pouchitis• Deep ulcers uncommon in pouchitis• Diagnosis never changed to Crohn

disease based on findings in pouch mucosa alone



Infectious colitis

• Pattern of acute colitis• Self-limited/ infectious-type/

nonrelapsing colitis• Some infections:

Histological picture of chronic colitis that can mimic IBD

Infectious colitis with IBD-pattern

• Bacterial: Salmonella, ShigellaAeromonasYersinia, MycobacteriaActinomyces

• Viral: Cytomegalovirus• Parasitic: Entameba

Yersiniosis

• Granulomatous enterocolitisresembling Crohn disease

Fissuring ulcers, transmuralinflammation, granulomas

• DiagnosisCultures, serological studiesPCR from paraffin-embedded tissue

Ileocolic disease with crypt disarray and crypt abscesses

Fissuring ulcers

Ill-defined epithelioid granulomas

Yersiniosis vs Crohn disease

Favor Yersinia• Short duration of symptoms• Suppurative granulomasFavor Crohn disease• Prominent architectural distortion• Duplication of MM, neural hyperplasia

Ileocecal tuberculosis

• Ileocecal granulomatous disease• Ulcers and strictures• Clinical data (pulmonary disease)

AFB stain/culture/PCR assay

TB vs. Crohn diseaseFavor tuberculosis• Larger, confluent, necrotizing granulomas• Transverse ulcers• Ulcers lined by histiocytes, prominent

submucosal inflammationFavor Crohn disease• Longitudinal ulcers, fissuring ulcers, fistulae• Transmural lymphoid aggregates

Necrotizing granulomas in TB




Actinomycosis

• Suppurative and granulomatous disease • Ileocecal and perianal regions• Fistulae mimicking Crohn disease

Sinuses mimicking abscessMass lesion mimicking carcinoma

Actinomyces colonies (‘sulfur granules’)

Splendore-Hoeppli phenomenon




CMV colitis

• Segmental colitis• Linear ulcers; necrosis and exuberant

granulation tissue• Diagnosis:

Viral inclusionsCMV antigen testSerology, cultures

CMV colitis: ulceration

CMV colitis: dense chronic inflammation

CMV colitis: viral inclusions




Amebic colitis

• Cecum-most common• Rectosigmoid and diffuse colonic disease• Diagnosis:

History of travel Right-sided diseaseIdentification of trophozoites

Amebic colitis

• Ulcers• Spread laterally:

Flask shaped ulcers

• Trophozoites at edge of ulcers



Drugs: chronic colitis

• Mycophenolate mofetilApoptosis resembling GVHDArchitectural distortion resembling IBD

• NSAIDs, potassium chlorideUlcers and segmental inflammation Architectural distortion typically absent

Colitis: patternsCRYPT DESTRUCTIVE

Inflammatory bowel diseaseDiversion colitisPouchitisDiverticular diseaseCertain infectionsChronic ischemia/radiation

Chronic ischemic colitis: crypt disarray mimics IBD

Colitis: patterns

NONCRYPT DESTRUCTIVENonspecific ulcerGranulomatous colitisEosinophilic colitis Lymphocytic/collagenous colitis

Nonspecific (“idiopathic”) ulcer

Typical features are absent• Crohn disease (fissuring, granulomas,

pseudopyloric metaplasia)• CMV: inclusions• Ischemia, pseudomembranous colitis

Nonspecific (“idiopathic”) ulcer: shallow base

Nonspecific (“idiopathic”) ulcer: adjacent normal mucosa

Nonspecific ulcer: architectural disarray

Idiopathic ulcer: nonspecific inflammation and reactive epithelium

Nonspecific ulcer

Role of the pathologist• Recognizable patterns of colitis:

ischemic, pseudomembranous, CMV, Crohn

• Guidance to establish the etiology

Nonspecific (“idiopathic”) ulcer• Iatrogenic

Drugs like NSAIDs, KClRadiation

• Infections• Obstructive colitis/ Stercoral ulcers• Systemic disorders

Vasculitis: Behcet syndromeRenal failure

NSAID-related colitis

• 10% of new colitis cases • Nonspecific ulcers: circumferential

pauci-inflammatory• Perforation and hemorrhage


• StricturesCircumferential, right colonSubmucosal fibrosis

• Endoscopy‘Diaphragm-like’ or membranous

strictures in R colon


• Segmental involvement with acute or focal active colitis

• Acute ischemic colitis• Exacerbation of pre-existing disease:

diverticulitis, IBD• Lymphocytic/collagenous colitis


Role of the pathologist• Raise the possibility of NSAIDs with

different histological patterns• Most resolve on discontinuation of the

drug



• InfectionsYersinia, Campylobacter

• Obstructive colitis/ Stercoral ulcers• Systemic disorders

Vasculitis: Behcet syndromeRenal failure

Obstructive colitis

• Ulceration proximal to site of obstruction• More active inflammation than NSAIDs• Stercoral ulcers:

Pressure effects on colonic mucosa by inspissated feces



• Infections• Obstructive colitis/ Stercoral ulcers• Systemic disorders

Renal failure Vasculitis: Behcet syndrome

Behcet syndrome

• Ileocecal and anorectal ulcers• Typical features of Crohn disease absent • Triad of oral ulcers, genital ulcers and

uveitis• Cutaneous involvement, arthritis

Colitis: patterns

NONCRYPT DESTRUCTIVENonspecific ulcer Granulomatous colitisEosinophilic colitis Lymphocytic/collagenous colitis

Granulomas in Crohn disease

• Small mucosal granulomas are nonspecific• Well-formed granulomas away from

inflammation, basal mucosa or submucosa• Young patients, early phase, distal

locations

Granulomatous colitis

• Crohn disease• Infections: yersiniosis, tuberculosis,

fungal infections• Diversion colitis, diverticular disease-

associated colitis, pouchitis

History

• 40/M HIV positive with diarrhea• Endoscopy revealed yellowish nodular

plaques in the colon

Prominent histiocytic infiltrate

Prominent histiocytic infiltrate

Histiocytic infiltrate• Infections

Atypical mycobacteriaFungal infectionsRhodococcus equiWhipple disease

• Xanthelasma• Storage disorders

PAS-D stain

Malakoplakia

• Abnormal phagocytic response to bacterial infections

• Immunodeficiency statesChronic diseases (SLE)Malignant neoplasms (colorectal cancer)

SummaryChronic colitis

• Crypt destructive (IBD-like)• Non-crypt destructive

Nonspecific ulcerCollagenous/lymphocytic colitisGranulomatousEosinophilic

Summary

Approach to diagnosis• Pattern

histological features• Etiologic diagnosis

clinical and endoscopic features

Tufas in Mono Lake, CA

Are eosinophils increased??• Seasonal variation• Site variationsFavor pathologic states:• Eosinophilic cryptitis/crypt abscesses• Clusters in deeper mucosa/submucosa• Extracellular granules• Eosinophils predominate

Eosinophilic colitis

• PrimaryAllergic (Cow’s milk, soy protein) Idiopathic (eosinophilic gastroenteritis)

• Secondary

Eosinophilic colitis• Parasites• Iatrogenic

Drugs, radiation• Inflammatory bowel disease• Collagen vascular diseases

Rheumatoid arthritis, Churg-Strauss syndrome

• Tumor or tumor-like conditionsLeukemia/lymphoma Hypereosinophilic syndrome

Allergic colitis

• Infancy: most common cause of bloody diarrhea

• Peripheral eosinophilia often present• Eo >60/HPF has been suggested• Favorable outcome; can tolerate food by

1-3 years of age

Hypereosinophilic syndrome

• Eosinophilia (>1500/mm2) >6 months• No discernible cause• Organ system involvement

Heart, GI tract, lung

Prominent apoptosis“Apoptotic colopathy”

• Bowel preparation (oral sodium phosphate)

• Graft vs. host disease• Drugs• Nonspecific feature in inflammatory

colonic involvement by infections or other colitides

Increased apoptosis in deeper crypts

Focal active colitis

• Infections/self-limited colitis• Drugs, especially NSAIDs• Crohn disease• Effects of bowel preparation

Lymphoid folliclesFew cryptsNo chronic inflammation


• Adults5% have or develop Crohn disease

• Pediatric20% Crohn disease

Raise possibility only if clinically relevant

Pseudopyloric metaplasia


J pouch donuts

Dysplasia

Anal sphincter

Chronic pouchitis

• Risk highest in first 2 years• Antibiotics, steroids• Severe refractory disease rare ~1%• Neoplastic changes rare

Pouch: focal inflammation due to ischemia

Actinomyces: PAS-D stain

Moving beyond the horizon of inflammatory bowel … · Chronic colitis Moving beyond the horizon of inflammatory bowel disease Sanjay Kakar, MD UCSF

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