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Pathology Jürg Vosbeck
Patho Basic Chronic Inflammatory Bowel Diseases
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General
• Group of chronic relapsing diseases with chronic bloody or watery diarrhea
• Usually ulcerative colitis (UC) or Crohn’s disease (CD)
• Some cases of «indeterminate colitis»
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Ulcerative colitis
• IBD of the large intestine
• Almost always begins in rectum
• May stay limited to rectum (ulcerative proctitis) or may extend to the entire colon in continuous fashion
• Maximum activity usually in distal colon
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Ulcerative colitis
• Clinical course characterized by periods of exacerbation and remission («UC flares»)
• Rarely continuous low grade activity or initial single attack
• Involvement of terminal Ileum may occur in patients with pancolitis («backwash ileitis»), 5 – 25 cm, 10% total colectomies
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Ulcerative colitis
• Primarily inflammation of mucosa (DD Crohn’s), but may involve deep layers in severe disease
• Classically diffuse distribution, however: false segmental distribution possible esp. in treated patients
• Cecal or periappendiceal patch
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Ulcerative colitis
• Aetiology unknown
• One or more genetic factors in association with external factors and altered host immunology (failure to downregulate normal immune reaction?)
• Interplay microbes <–> immune system
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Ulcerative colitis
• Appendectomy may be protective of UC (mechanism?)
• Smoking seems to be preventive!
• Abnormality of colonic mucus?
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Ulcerative colitis
• Peak in 3rd decade, range all ages
• M<F
• Anglo-Saxon origin (N Europe, N America), Jews
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UC Macro
• Frail erythematous mucosa, hemorrhagic bowel content (F: rectocolite ulcérohémorrhagique, RCUH)
• Relative rectal sparing in treated patients
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UC Macro
• Relatively little fibrosis, mostly of rectal submucosa
• Inflammatory polyps/mucosal tags and mucosal islands common
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UC Histo
• Histology:
– Active, resolving, in remission
• Active:
– Neutrophils, cryptitis, crypt abscesses
– «basal plasmocytosis», sometimes very large numbers of Eos or Mast cells
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UC Histo
– Granulomas possible! But:
– Mucin-granulomas, reaction to damaged crypts («cryptolytic granulomas»).
– Location important; genuine sarcoid-type basally oriented granulomas don’t occur in UC.
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UC Histo
• Resolving:
– Changes in crypt architecture
– Submucosal fibrosis
– Duplication of muscularis mucosae
– May occur in different rates depending on site -> false impression of segmental disease
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Ulcerative colitis
• Extraintestinal manifestations:
– Primary sclerosing cholangitis (5% of all UC patients; 70% of PSC patients have UC)
– Arthritis, ankylosing spondylitis, Erythema nodosum, Uveitis...
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UC Treatment
• Drugs:
– 1st line:
• 5-ASA (aminosalicylic acid), Steroids
– Refractory disease:
• Azathioprine, 6-Mercaptopurine, Tacrolimus, MTX…
– Novel therapies:
• Probiotics (alter bacterial flora); «stool transplantation»
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UC Treatment
• Surgery:
– Colectomy
• Urgent in fulminant colitis, toxic megacolon, intractable bleeding
• Elective in refractory disease
– Ileoanal pouch
– Potentially curative
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UC Prognosis
• Chronic, usually unrelenting
• Colonic adenocarcinoma in 3-5% of patients
– Risk: total colitis +/- backwash ileitis, early onset disease, > 8 years duration (some suggest > 5 yrs), PSC, family history
• Extensive disease: 19 fold risk compared to no
• Left sided disease: 4 fold risk
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IBD Dysplasia
• Adenomas just like in healthy colon
• DALM concept outdated (dysplasia associated lesion or mass ->
colectomy)
• Adenoma resected endoscopically + biopsies taken around the base
– Biopsies w/o dysplasia -> no further actions
– Biopsies with dysplasia -> EMR, ESD, colectomy
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Crohn’s Disease
• 1932, «regional enteritis» (terminal Ileitis)
• Involves any part of the gut, mouth to anus
• Restricted to colon in 15-30% of patients
• Rectum macroscopically normal in 50% of cases
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Crohn’s Disease
• Incidence continues to increase (UC has reached plateau in 1990s)
• Peak 3rd decade, wide range • Aetiology remains mystery
– Genetic – Immunological
• Deficiency of innate intestinal mucosal barrier? • No autoimmunity involved
– Environmental: • Smoking is strong risk factor (<-> UC) • Appendectomy < 20 yrs. is a risk factor (<-> UC) • Microbes (sustained alterations of gut flora through dietary habits,
increased use of antibiotics)
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Crohn’s Disease Macro
• Segmental disease
• Ulceration, strictures, thickening of gut wall
• Small aphthous lesions to complete loss of mucosa in extensive disease
• Cobblestone appearance as result of intercommunicating fissures
• Transmural extension, expansion to neighboring organs (abscesses, fistulae)
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Crohn’s Disease Macro
• Esophageal: rare (<1%)
• Gastric: typically antral
• Duodenal: usually concomitant distal ileal or colonic disease
• Oral: 20-50%! Vesicles, aphthous ulcers
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Crohn’s Disease Macro
• Nonalimentary tract: 25%
– Arthritis, sacroileitis, ankylos. spondylitis
– Erythema nodosum, vasculitis
– Uveitis, conjunctivitis
– Rarely PSC
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Crohn’s Disease Histo
• Biopsy:
– Discontinuity of inflammation
– Granulomas
– Architectural abnormalities
• Terminal ileoscopic biopsies:
– Focal active inflammation, sometimes granulomas
– DD: NSAIDs, Yersiniosis, Behçet, UC...
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Crohn’s Disease
• Surgical specimen:
– Focal ulceration, transmural inflammation with lymphoid aggregates, granulomas
– Hyperplasia of nerve fibers (submucosal and myenteric plexus)
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• DD «diverticular colitis»
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Crohn’s Disease Treatment
• Drugs:
– Aminosalicylates (…-salazines)
– Cyclosporin, steroids
– Azathioprine, Mercaptopurine
– Metronidazol, Ciprofloxacin
• Surgery:
– >60% repeated OPs, risk of short bowel syndrome
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Crohn’s Disease Prognosis
• Recurrences in 95%
• Less prone to pre-cancerous and malignant changes in colon thank UC
• Risk of carcinoma in small bowel 10-20x compared to normal
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Indeterminate colitis
• Term widely used with variety of definitions
• Aetiology and type of colitis can’t be identified properly
• Confusion:
– «Uncertainty whether or not IBD»
– «Patients with IBD but unsure if UC or Crohn’s»
-> clinical diagnosis of indeterminate colitis doesn’t necessarily mean that the patient has an IBD!
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Indeterminate colitis
• Strict definition (Montreal classification):
– Colectomy has been performed and pathologists are unable to make a definitive diagnosis of either UC or Crohn’s
• In practice, distinction only of major importance if ileal pouch is considered (Crohn’s -> no ileal pouch)
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Indeterminate colitis
• Temporary «diagnosis»
• Most cases will behave like UC (80-90%) -> ileal pouch not contraindicated
• Never use term on biopsy (inflammatory bowel disease of undetermined aetiology, IBDU, instead)
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Summary
• Chronic inflammatory disease of colon (and small bowel) with many overlapping clinical and histological features
• -> interdisciplinary approach to correct patient handling
– Context, context, context!
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Picture credits:
Thank you
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Thank you
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Indeterminate colitis
• Colectomy:
– UC
– Crohn’s
– «severe fulminant colitis without features of ulcerative colitis or Crohn’s disease» = indeterminate colitis
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Indeterminate colitis
• Overlapping histological features of UC and Crohn’s
• Relative rectal sparing in UC