Idiopathic inflammatory bowel diseases include the chronic crypt destructive colitides, chronic ulcerative colitis, and Crohn’s disease. Ulcerative colitis and Crohn’s disease differ in natural history, clinical and pathologic associations, effective therapies, and response to treatment. These differences, particularly with regard to recommended surveillance strategies and treatment options, underscore the importance of distinguishing between them. While classic cases can be separated, there may be gross, clinical, and histologic overlap of features not only between ulcerative colitis and Crohn’s disease but also with other inflammatory conditions of the colon, resulting in an initial diagnosis of indeterminate colitis initially in up to 20% of cases of idiopathic inflammatory bowel disease.
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Ulcerative colitis
Ulcerative colitis is a chronic crypt destructive inflammatory process of unknown cause characterized by a predominantly mucosal-based disease and clinically associated with exacerbations and remissions of bloody diarrhea.
Clinical features
Ulcerative colitis has a slightly higher incidence in males, and occurs at all ages, with the major peak incidence in the age range of 15 to 25 years and a minor peak in the seventh decade of life. There is a familial association, with up to 25% of the patients having another affected family member.
Clinically, ulcerative colitis is characterized by recurrent episodes of bloody diarrhea that can undergo spontaneous or therapy-induced remission. The initial presentation may be indolent in onset or may be severe and acute, presenting with toxic hemorrhagic colitis. The clinical diagnosis is rendered following the exclusion of infectious colitis.
Definition
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Chronic idiopathic inflammatory bowel disease with episodes of bloody diarrhea
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Histologically characterized by mucosal-based chronic crypt destructive colitis with continuous involvement from the rectum extending proximally
Incidence and location
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Uncommon (4 to 20 per 100,000 population annually)
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Higher incidence in North America, Western Europe, South Africa
Gender, race, and age distribution
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Incidence slightly higher in males than females
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Whites higher incidence than other ethnic groups
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Jews higher incidence than other religious groups
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Rare in first decade of life
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Major peak at 15 to 25 years of age
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Minor peak at 60 to 70 years of age
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Familial association: up to 25% have affected relative
Clinical features
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Recurrent episodes of bloody diarrhea
Endoscopic features
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Active phase: mucosa erythematous, bloody, friable, and granular
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Quiescent phase: mucosa granular with punctuate erythema; loss of haustral folds (tubelike appearance)
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Polyps: pseudopolyps (mucosal remnants) and inflammatory polyps in active disease and postinflammatory polyps in active or quiescent disease
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All phases: normal submucosal vascular network is lost
Prognosis and therapy
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Cure: none
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Low mortality, high morbidity
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Treatment: anti-inflammatory and immunosuppressive drugs; surgery if not responsive
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Increased risk for dysplasia and adenocarcinoma
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Surveillance for dysplasia annually after 8 years
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Colectomy for fulminant disease (toxic colitis), high-grade dysplasia, DALM, and adenocarcinoma
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Ileal pouch anal anastomosis recommended
Radiologic features
Endoscopy has virtually replaced radiology in the diagnosis of inflammatory bowel disease. Features that may be seen radiographically in ulcerative colitis include continuous involvement of the colon with ulcers or polyps, no strictures, and the occasional finding of megacolon. Fistulas, “thumbprinting,” and skip areas are not seen.
Endoscopic features
The gross endoscopic appearance of ulcerative colitis varies with the degree of activity, duration of disease, and response to therapy. It is characterized by diffuse disease, with rectal involvement extending proximally. In the more active phases the mucosa is typically erythematous, bloody, and friable, with a granular appearance ( Fig. 10-1 ). Quiescent disease may appear granular with areas of punctuate erythema ( Fig. 10-2 ). Pseudopolyps (mucosal remnants) and inflammatory polyps may be seen in active disease and postinflammatory polyps in active or quiescent disease ( Fig. 10-3 ). In all cases, the normal submucosal vascular network is lost and is an important clue to the endoscopist that there is chronic colitis. In patients who have had repeated bouts of colitis, the normal haustral folds may be lost, giving the lumen a tubelike appearance. The transition between normal and abnormal mucosa is generally gradual but may be abrupt. Except for the occasional presence of focal cecal and appendiceal involvement, there is no loss of disease continuity and no skip lesions in ulcerative colitis.
Pathologic features
Gross findings
The serosa is typically unremarkable. Longitudinal opening usually reveals a bowel wall that is of normal thickness, which opens with ease in the fresh state. Strictures are unusual. The mucosa may be flattened, bloody, and friable ( Fig. 10-4 ) or may be granular with numerous polyps. The process grossly extends in a continuous manner from the rectum proximally and may involve the entire colon and appendix and even the terminal ileum (backwash ileitis). If the mucosal involvement extends proximally beyond the splenic flexure, it is designated as pancolitis; if it is confined to the colon distal to the splenic flexure, it is termed left-sided disease. Discontinuity is not a feature of ulcerative colitis except for focal cecal or appendiceal involvement.
Microscopic findings
Biopsy findings
Crypt architectural distortion and increased mucosal chronic inflammation are the two characteristic histologic findings ( Fig. 10-5 ). The architectural distortion is the result of prior mucosal destruction and imperfect repair resulting in decreased numbers of crypts and branched malformed regenerated crypts. (“Crypt destructive colitis” refers to the distortion of regenerated crypts rather than active destruction of crypts resulting from cryptitis.) The chronic inflammatory cells consist of variable numbers of plasma cells, eosinophils, and lymphocytes, which expand the lamina propria and extend into the muscularis mucosae (basal plasmacytosis). Eosinophils may predominate. Lymphoid aggregates are commonly seen at the mucosal-submucosal interface. Neutrophils, the hallmark of active disease, are located within crypt epithelium (cryptitis) and crypt lumens (crypt abscesses), and fewer are seen within the lamina propria around the crypts ( Fig. 10-6 ). The regenerating epithelium is immature and as such does not contain mucin, typical of a mature goblet cell (mucin depletion). Biopsy fragments from the same topographic area typically show similar findings. Inflammation is usually more severe distally.
Quiescent, or inactive, ulcerative colitis is characterized by the absence of neutrophils, slight architectural distortion, and mildly increased lymphoplasmacytic infiltrate ( Fig. 10-7 ), sometimes associated with the presence of Paneth cells. Paneth cells are normal in the ascending colon but are considered an indicator of prior mucosal injury and repair in the distal colon.
Ileal involvement by ulcerative colitis (“backwash ileitis”) occurs in patients who have severe pancolitis. Inflammation in the ileum is often mild, characterized by mild acute inflammation in the lamina propria and the crypt and villous epithelium. Chronic changes such as villus destruction and repair and pyloric metaplasia, reminiscent of Crohn’s disease, may be seen but are uncommon.
Resection findings
The inflammatory process is confined predominantly to the mucosal surface and has an abrupt interface with the submucosa ( Fig. 10-8 ). The mucosa is, on low power, cellular, often congested, and has decreased numbers of crypts and loss of the normal perpendicular, or “test tube,” arrangement of crypts. There may be lymphoid aggregates at the mucosal interface, which can be numerous. In areas of significant activity, ulcers can be adjacent to preserved mucosa. These mounds of residual mucosa surrounded by ulcer are termed pseudopolyps. With time, as the adjacent mucosa regenerates, the mound may protrude, forming a postinflammatory polyp, sometimes bizarre in shape ( Fig. 10-9 ). The submucosa, while often edematous and congested, is typically without significant inflammation and lacks fibrosis. Transmural chronic inflammation and lymphoid aggregates are not present except in areas of deep ulceration, as seen when toxic colitis (toxic megacolon) occurs.
Gross findings
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Unremarkable serosa
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Bowel wall of normal thickness
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Mucosa flattened, bloody, friable, and granular with variable numbers of polyps
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Continuous involvement from rectum proximally
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May progressively extend to involve entire colon and terminal ileum
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Focal cecal involvement may be present with distal disease
Microscopic findings
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Biopsy
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Crypt architectural distortion
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Increased mucosal chronic inflammation
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Neutrophils, the hallmark of active disease, are located within crypt epithelium (cryptitis) and crypt lumens (crypt abscesses)
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Eosinophils may predominate
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Lymphoid aggregates commonly seen at mucosal–submucosal interface
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Regenerating epithelium is immature and does not contain mucin (mucin depletion)
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Biopsy fragments from the same topographic area typically show similar findings
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Inflammation usually more severe distally
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Resection
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Inflammatory process is confined predominantly to mucosal surface with abrupt interface with submucosa; no fissures
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Mucosa often congested
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Decreased numbers of crypts
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Crypts malformed: loss of the normal perpendicular, or “test tube” arrangement of crypts
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Pseudopolyps and postinflammatory polyps, sometimes bizarre in shape
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Submucosa without significant inflammation and lacks fibrosis
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Transmural chronic inflammation and lymphoid aggregates not present except in areas of deep ulceration (in toxic colitis)
Differential diagnosis
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Infectious colitis
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Medication-induced colitis
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Ischemic colitis
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Crohn’s disease
Ancillary studies
No specific tests for ulcerative colitis are available. Initially, patients should be tested for infectious causes that are associated with long-standing and toxic colitis, particularly to exclude Shigella, Salmonella, and Campylobacter jejuni. Patients who have a flare-up of ulcerative colitis while being treated with immunosuppressives may also benefit from testing for cytomegalovirus infection, which can present with deep ulcers in the background of ulcerative colitis. Results of serologic tests for perinuclear antineutrophil cytoplasmic antibody (P-ANCA) are often positive in ulcerative colitis.
Dysplasia in ulcerative colitis/dalm (dysplasia-associated lesion or mass)
Long-standing ulcerative colitis is associated with an increased risk for dysplasia and adenocarcinoma, even in patients with well-controlled, quiescent disease. Periodic colonoscopic examinations are used to survey for dysplasia and adenocarcinoma. Routine surveillance with biopsies is recommended annually for patients with extensive disease of more than 8 years’ duration because there is an increasing annual incidence of adenocarcinoma. Biopsies are generally taken from the cecum, ascending colon, hepatic flexure, transverse colon, splenic flexure, descending colon, sigmoid colon, and rectum. The pathologist records evidence of colitis, activity, and the presence or absence of dysplasia.
Gross findings
Dysplasia can be found in both flat, grossly undetectable, and raised mucosa, termed DALM (dysplasia-associated lesion or mass). There are no specific features grossly to distinguish between an inflammatory polyp and DALM.
Microscopic findings
Dysplasia in ulcerative colitis is characterized by both cytologic and architectural changes of dysplasia including nuclear hyperchromatism, enlargement, and irregularity. The cytoplasm of dysplastic epithelium is often eosinophilic while regenerative epithelium often has a basophilic “blush.” Architecturally, there is crypt budding and crowding. Interestingly, dysplasia in ulcerative colitis may appear at the crypt base, in contrast to dysplasia in colonic adenomas, which begins at the surface. Cytologically, low-grade dysplasia is characterized by mild nuclear enlargement and hyperchromasia and small nucleoli. The cells maintain polarity and show mild nuclear overlap and irregularities ( Fig. 10-10 ). High-grade dysplasia is characterized by more pronounced nuclear changes including nuclear pleomorphism, hyperchromasia, and overlap. Architecturally, there is loss of polarity, more crypt crowding complex glands, and glandular distortion ( Fig. 10-11 ).
