Crohn Disease

Definition

• 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"

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

• 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

• Histologically indistinguishable

Clinical

• 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

Bibliography

• 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.