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Surgical Pathology Criteria

Crohn Disease


  • Idiopathic chronic inflammatory bowel disease characterized by transmural inflammation and patchy involvement

Alternate/Historical Names

  • (Idiopathic) Inflammatory bowel disease encompasses both ulcerative colitis and Crohn disease and implies that other specific causes and diseases have been ruled out
  • Regional enteritis

Diagnostic Criteria

  • The diagnosis of Crohn disease requires clinicopathologic correlation
  • Inflammation is transmural, from mucosa to serosa
    • Lymphoid aggregates present at all levels
    • Infiltrate in some cases is more prominent in submucosa and serosa, with relative sparing of muscularis propria
      • Especially in early cases
    • Serosal involvement leads to fat wrapping around the bowel
    • Ulceration and fissures may extend into and through the muscularis propria
      • Fistulas to other bowel loops, skin and other organs may form
  • Intramural inflammatory infiltrate is largely lympho-histiocytic
    • Neutrophils may be focally present
    • Crypt abscesses may be present
  • Granulomas are present in about 15-36% of biopsied cases
    • Present in over half of colectomy specimens
    • Compact aggregates of epithelioid histiocytes
      • Non-necrotic
      • Multinucleated giant cells may be present
    • May be seen at all levels and in draining lymph nodes
    • More common in children
    • If present, acid fast and fungal stains should be performed to rule out infection
    • Presence of granulomas does not indicate active disease
  • Aphthous ulcers may be present in the intestine
    • Erosion or ulcer abutting a mucosal or submucosal lymphoid aggregate
      • Acute inflammation may be present in adjacent crypt lumens
  • Architectural changes characterized by crypt distortion are present in both active and inactive (quiescent) disease
    • Irregular, horizontal, dilated crypts
    • Gland dropout is frequent
    • Bifid, forked glands
    • Shortened glands that fail to reach the muscularis mucosae
    • Lamina propria fibrosis may be present
    • Thickening of muscularis mucosae
    • These findings are important as they demonstrate the chronic nature of the process
    • Minimal architectural distortion may be seen in pediatric cases at initial presentation
    • Complete resolution of architectural changes after a long period of disease inactivity is unusual but may be seen
  • Process is usually discontinuous with patchy involvement and skip lesions
    • It is important to biopsy normal appearing areas to rule out a contiguous segment of bowel that includes an area of quiescent colitis
  • Process may involve the entire gastrointestinal tract
    • Small intestine only - 30-50%
    • Large intestine only – 25-30%
    • Both small and large intestine – 30-50%
    • Stomach or duodenum – 50% (typically mild)
    • Anal fissures, fistulas and skin tags common, especially in children
    • Esophagus and oral cavity - rare
  • Paneth cell metaplasia may be prominent
    • Paneth cells are rare in the normal left colon
  • Neural hyperplasia may be present
    • In submucosa and muscularis propria
    • May contain ganglion cells
  • Vascular changes are occasionally seen
    • Non-inflammatory
      • Intimal proliferation
      • Fibrosis may occur at any level of the vessel wall
    • Inflammatory
      • Perivascular and intramural lymphoplasmacytic infiltrate
      • Occasionally may include granulomas
      • Distinguished from primary systemic vasculitis by the lack of extraintestinal involvement
  • Clinically and histopathologically intractable disease should prompt close inspection and immunohistologic staining for cytomegalovirus
  • Extensively ulcerated cases may develop toxic megacolon
  • The presence of dysplasia predicts the development of colorectal carcinoma in Crohn disease
  • Indeterminate colitis
    • Diagnosis used for cases in which a definitive separation of ulcerative colitis and Crohn disease cannot be made
    • May constitute up to 15% of cases
    • Most are cases of fulminant colitis
    • With long term follow-up, 80% of such cases are found to be ulcerative colitis
    • This diagnosis should be reserved for resection specimens
    • Endoscopic biopsy specimens that are not definitive may be designated as “Inflammatory Bowel Disease, Unclassified"
Robert V Rouse MD
Department of Pathology
Stanford University School of Medicine
Stanford CA 94305-5342

Original posting : November 11, 2009


Differential Diagnosis

  • Fungal, mycobacterial, amebic and other parasitic diseases must all be ruled out by close inspection and by laboratory tests
    • Necrotic granulomas strongly suggest infection
  • In cases of colitis refractory to treatment, cytomegalovirus must be ruled out immunohistochemically
  • Quiescent colitis may be histologically indistinguishable from the effects of radiation or chemotherapy or chronic ischemia
    • Clinical correlation is necessary
  • Segmental colitis associated with sigmoid diverticular disease may be histologically identical to Crohn disease
    • Clinical correlation is necessary
Ulcerative Colitis Crohn Disease
Inflammation limited to mucosa and superficial submucosa Transmural inflammation
Contiguous disease, no skip lesions Discontinuous, patchy disease with skip lesions
Limited to colon May involve entire GI tract
No granulomas Granulomas may be present
Predominantly neutrophilic infiltrate with crypt abscesses Predominantly lympho-histiocytic infiltrate
Perinuclear anti-neutrophilic cytoplasmic antibody (pANCA) favors ulcerative colitis Anti-Saccharomyces cerevisiae antibody (ASCA) favors Crohn disease
  • The distinction may be impossible on biopsies and always requires clinical correlation
  • Rare cases deviate from some of these criteria
  • Up to 15% of cases may be indeterminate even after full evaluation
  • pANCA and ASCA have considerable overlap and are felt by some to lack clinical utility


Mucosal Prolapse / Cloacogenic Polyp (Solitary Rectal Ulcer) Crohn Disease
Shallow ulceration Deep ulcers and fissures
Restricted to rectum (rarely in sigmoid) May involve any part of GI tract
Not concentric, usually localized to anterior rectal wall Usually concentric
Frequently forms a polyp that appears hamartomatous with muscularis mucosae extension into lamina propria No polyp formation or muscularis mucosae extension into lamina propria


Crohn Disease Common Variable Immunodeficiency – GI Involvement
Skip lesions predominate Usually diffuse
Transmural inflammation Mild lamina propria infiltrate with nodular lymphoid hyperplasia
Numerous plasma cells Plasma cells frequently markedly decreased
Deep fissures frequent No fissures or deep ulcers


Incidental Chronic Colitis Crohn Disease
Isolated disease Usually multifocal
Virtually restricted to cecum/right colon May involve entire GI tract
No granulomas Granulomas may be present
Incidental, asymptomatic Nearly always symptomatic
  • Histologically indistinguishable



  • The risk of carcinoma is elevated in both ulcerative colitis and Crohn disease
  • A diagnosis of high grade dysplasia frequently leads to colectomy
  • A diagnosis of low grade dysplasia may result in a variety of clinical responses
    • Some merely increase the frequency of follow up screening
    • Some recommend colectomy, especially if the dysplasia is identified in multiple sites or on subsequent endoscopy
  • A diagnosis of indefinite for dysplasia typically leads to medical therapy and rebiopsy after inflammation is reduced
  • A diagnosis of no dysplasia usually results in routine follow up endoscopy in 3 to 5 years


Dysplasia in Inflammatory Bowel Disease

  • The presence of dysplasia predicts the development of colorectal carcinoma in ulcerative colitis and Crohn disease
    • Dysplasia is best evaluated in areas without significant acute inflammation
      • If acute inflammation is present, dysplasia should be diagnosed only if the dysplastic findings are clearly disproportionate to the degree of inflammation
    • Dysplastic features should be present on the luminal bowel surface
      • Reactive atypia rarely extends to the luminal surface
    • Dysplasia may be focal, requiring adequate sampling
      • Recommended sampling is 4 biopsies every 10 cm of colorectum
    • A diagnosis of dysplasia should be confirmed by an experienced gastrointestinal pathologist
  • Low grade dysplasia demonstrates cytologic features identical to those of colorectal adenomas
    • Densely packed, enlarged, elongated nuclei
    • Mucin depletion is common
  • High grade dysplasia demonstrates markedly atypical features
    • Marked cytologic atypia
    • Complete loss of polarity
    • Cribriform gland formations
  • Indefinite for dysplasia should be used if the lesion is suggestive of but not diagnostic of dysplasia
    • Frequently used if acute inflammation is present
  • Sporadic adenomas can be confused with dysplasia
    • Polypoid growths that resemble sporadic tubular adenomas both endoscopically and microscopically and can be completely removed endoscopically can be considered sporadic adenomas rather than dysplasia
    • Sessile lesions in areas involved by inflammatory bowel disease should be considered dysplasia
    • Both sessile and polypoid lesions in areas not involved by the inflammatory bowel disease should be considered adenomas



  • Noffsinger A, Fenoglio-Preiser CM, Maru D, Gilinisky N.  Gastrointestinal Diseases, AFIP Atlas of Nontumor Pathology, First Series, Fascicle 5, 2007.
  • Odze RD. Pathology of indeterminate colitis. J Clin Gastroenterol. 2004 May-Jun;38(5 Suppl):S36 40.
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