—  SHORT COURSE #08  —

Mimics in Gastrointestinal Pathology

Case 3 - Diverticular Colitis Mimicking Ulcerative Colitis

Alyssa Krasinskas, Jeffrey Goldsmith and Susan Abraham


Case Description:
Left colon biopsies were received on a 59 year-old man. The clinical history provided on the requisition stated "painless bright red blood per rectum." Histologically, the colonic mucosa showed foci of crypt architectural distortion with crypt branching and gland foreshortening, a basally oriented lymphoplasmacytic infiltrate that extended into the submucosa, and focal acute cryptitis. Before the diagnosis was rendered, additional history was obtained from the electronic medical record. The patient had been experiencing painless bright red blood per rectum for nine months. He had a colonoscopy upon initial presentation that revealed colitis confined to a 10 cm area within the sigmoid colon. He was unresponsive to therapy with Asacol and prednisone. The colonoscopy was repeated and the current biopsies were obtained. In addition to patchy colitis in the left colon, left-sided diverticulosis was seen endoscopically. Based on the endoscopic and histopathologic findings, the following final diagnosis was made: "Mild chronic active colitis (see comment). Comment: Based on the distribution of the colitis in an area involved by diverticulosis, the histologic features are consistent with diverticular colitis. However, ulcerative colitis cannot be completely excluded on this material."

Background:
If not further specified, the histologic diagnosis of "chronic active colitis" implies the presence of inflammatory bowel disease (IBD), either ulcerative colitis or Crohn's disease. To make a diagnosis of chronic active colitis (IBD), there has to be histologic evidence of chronic mucosal injury and active inflammation. Features of chronic mucosal injury include crypt architectural distortion (crypt branching), basal lymphoplasmacytic inflammation, gland foreshortening and Paneth cell or pyloric gland metaplasia. Acute cryptitis, crypt abscesses and lamina propria neutrophils represent the active component.

Since the features of chronic active colitis can be seen in both ulcerative colitis and Crohn's disease, as well as in other conditions, pathologists should favor the underlying disease process or should formulate a differential diagnosis in their reports. The differential diagnosis of chronic active colitis actually includes several different entities in addition to ulcerative colitis and Crohn's disease, including diverticular colitis, diversion colitis, radiation colitis and drug-induced injury (such as seen with nonsteroidal anti-inflammatory drugs [NSAIDs]). Correlation between the clinical /endoscopic findings and the histologic findings is required for an accurate diagnosis when chronic active colitis is present.

Mimics of Inflammatory Bowel Disease

Diverticular colitis (as demonstrated by this case)
Diverticular colitis is a focal chronic inflammatory process occurring in association with diverticulosis. It does not appear to be related to the presence of diverticulitis. Other terms have been used to describe this entity, including diverticular disease-associated colitis, segmental colitis and sigmoiditis. While asymptomatic left-sided diverticulosis in Western societies is common (it may affect up to 50% of people in by the age of 60-70 years), the prevalence of diverticular colitis appears uncommon (diverticular colitis was noted in 1.4% of colonoscopies / sigmoidoscopies)(Gore et al). However, up to 25% sigmoid colons resected for diverticular disease (symptomatic diverticulitis / peridiverticulitis) demonstrate evidence of luminal mucosal inflammation in the segment involved by diverticulosis (Ludeman et al). Patients with diverticular colitis often present with rectal bleeding, left lower quadrant pain, diarrhea and constipation. In some, the symptoms may persist for months to years.

Gross/Endoscopic Features:
Grossly (endoscopically), diverticular colitis can appear as patchy or confluent areas of mucosal congestion, petechiae, edema, granularity and/or exudates and friability. The inflammation is confined to the segment with diverticulosis and should spare the rectum. The inflammation may spare the orifices of the diverticula.

Histologic Features and Differential Diagnosis:
The histologic features seen in diverticular colitis include:
  • Lamina propria lymphoplasmacytosis +/- eosinophils

  • Crypt architectural distortion

  • Paneth cell metaplasia

  • Acute cryptitis, crypt abscesses

  • Granulomatous inflammation

  • Features of mucosal prolapse
These histopathologic features are nonspecific. The differential diagnosis includes ulcerative colitis, Crohn's disease, diverticulitis, ischemic colitis, infectious colitis and colitis secondary to NSAIDs. This is why correlation with clinical history and the distribution of the colitis is essential. Ischemia, infections and NSAID use can usually be easily excluded clinically. If there is rectal sparing (in the setting of diverticulosis), then diverticular colitis would be favored, but some cases of ulcerative colitis can present with apparent rectal sparing. Conversely, if the rectum is involved, ulcerative colitis should be favored. Diverticulosis and ulcerative colitis are not mutually exclusive: older patients with ulcerative colitis can develop diverticulosis. Also, in a minority of patients with diverticular colitis, the colitis can progress to classic ulcerative colitis.

On resection specimens for diverticular disease, many of the above-mentioned histologic features of "diverticular colitis" can be observed within the diverticula themselves. It is also important to realize that in resection specimens, some cases of diverticular colitis can mimic Crohn's disease, with transmural chronic inflammation, well-formed granulomas and chronic active colitis. If such patients do not have a prior diagnosis of Crohn's disease or evidence of Crohn's disease elsewhere, the Crohn's-like reaction is likely related to diverticular disease.

Pathogenesis:
The pathogenesis of diverticular colitis is not known. Possible factors that may contribute to the development of diverticular colitis include mucosal redundancy or prolapse, "mass effect" of peridiverticulitis, bacterial overgrowth and fecal stasis.

Treatment:
Diverticular colitis tends to respond to the same therapy as IBD. However, mild cases also respond to therapy aimed at diverticulitis. If a high fiber diet and a short course of antibiotics are ineffective, aminosalicylates are recommended. Corticosteroids, although effective, are not recommended due to their side effects. If patients have persisting symptoms despite medical therapy, a sigmoid resection is indicated.

The histologic diagnosis of diverticular colitis relies on the knowledge that the biopsies are from a segment of colon that is affected by diverticulosis and that the colitis is limited to this segment.

Diversion colitis
Diversion colitis is an inflammatory process occurring in a segment of colon (colitis) excluded from the fecal stream. It can occur following colostomy for any reason (for example, ulcerative colitis, cancer, diverticular disease, etc.) It typically occurs 2-3 months following diversion of the fecal stream. Patients can be asymptomatic, or they may present with mucoid or bloody discharge and abdominal pain. Grossly and endoscopically, the mucosa in diversion colitis can appear erythematous, friable, edematous and nodular, with or without aphthous ulcers. Histologic features include:
  • Large lymphoid aggregates with prominent germinal centers

  • Variable crypt distortion/atrophy

  • Cryptitis/crypt abscesses

  • Aphthous lesions
These histologic features can mimic IBD and, as such, diversion colitis cannot be reliably distinguished from ulcerative colitis or Crohn's disease histologically. The cause of diversion colitis is believed to be a "colonic nutritional deficiency" with a lack of short chain fatty acids. The treatment includes reestablishment of the fecal stream, if possible. The colitis resolves within 2-3 months once the diversion is eliminated. If reanastomosis is not possible, short chain fatty acid enemas have been shown to improve symptoms and resolve the colitis endoscopically and histologically.

The histologic diagnosis of diversion colitis relies on the knowledge that the biopsies are obtained from a diverted segment of colon.

Radiation-induced colitis
Radiation injury to the colon can be acute or chronic. Biopsies are not often obtained during the course of radiation therapy, since the gastrointestinal symptoms are often directly related to the course of radiation. Chronic radiation damage to the colon occurs in a minority of patients receiving pelvic radiation. Those at highest risk include patients receiving radiation for prostate and cervical cancer. Radiation-induced colitis tends to occur 6-24 months following therapy and tends to produce symptoms such as rectal bleeding, diarrhea and abdominal pain. Unlike acute radiation that directly injures the mucosa, chronic radiation injury is secondary to mesenchymal tissue damage. Gross (endoscopic) features include strictures, fistulas, patchy erythema and ulceration. Histologic features include:
  • Mucosal telangiectasia

  • Perivascular hyalinization

  • Atypical "radiation" fibroblasts

  • Architectural distortion

  • Abnormal crypts, crypt dropout, cystica profunda
The histologic diagnosis of radiation-induced colitis relies on the knowledge of prior radiation exposure to the affected segment of colon.

Chronic ischemic injury and non-steroidal anti-inflammatory drugs
Typically, ischemia and NSAIDs induce acute mucosal injury with acute inflammation, acute ulceration and superficial epithelial cell injury without significantly increased chronic inflammation or evidence of chronic mucosal injury. However, mild injury from both entities can persist over time, inducing chronic changes such as crypt branching, pyloric or Paneth cell metaplasia and mucosal atrophy. The amount of inflammation in the chronic phase tends to be mild, but in some instances, increased lamina propria chronic inflammation and acute cryptitis, along with the architectural changes, can mimic IBD. NSAIDs can also contribute to injury related to underlying mucosal diseases such as diverticular disease and ulcerative colitis. Most patients with chronic ischemia are known to have prior episodes of ischemic colitis, but some low-grade vascular diseases, including vasculidities, can present at the chronic phase. The patchy distribution of the mucosal injury can exclude ulcerative colitis. Since NSAID use is rather ubiquitous, keeping this entity in the differential diagnosis of chronic (active) colitis may be helpful to clinicians.

The histologic diagnosis of chronic ischemic colitis relies on the knowledge of prior episodes of ischemic colitis and the distribution of the colitis. It is difficult to make a diagnosis of NSAID-related colitis since the drug history is often unknown to the pathologist, but it should be included in the differential diagnosis of atypical cases of "chronic active colitis."

Take-Home Message
  • Some diseases/inflammatory processes of the colon are histologically indistinguishable from inflammatory bowel disease.

  • A diagnosis of "chronic active colitis" alone is not useful to clinicians.

  • Do not diagnose inflammatory bowel disease unless the entire clinical picture is known.

  • If uncertain, include inflammatory bowel disease as one of several possible etiologies in your differential diagnosis.

References:

General
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Diverticular colitis
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Diversion colitis
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Radiation-induced colitis
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  4. Oya M, Yao T, Tsuneyoshi M. Chronic irradiation enteritis: its correlation with the elapsed time interval and morphological changes. Hum Pathol 1996; 27 (8):774.

Ischemic and NSAID-induced colitis
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  4. Gan SI, Urbanski S, Coderre SP, Panaccione R. Isolated visceral small artery fibromuscular hyperplasia-induced ischemic colitis mimicking inflammatory bowel disease. Am J Gastroenterol 2004; 99 (10): 2058.

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  7. Lee FD. Drug-related pathological lesions of the intestinal tract. Histopathology 1994; 25 (4): 303.

  8. Puspok A, Kiener HP, Oberhuber G. Clinical, endoscopic, and histologic spectrum of nonsteroidal anti-inflammatory drug-induced lesions in the colon. Dis Colon Rectum 2000; 43 (5): 685.

  9. Thiefin G, Beaugerie L. Toxic effects of nonsteroidal antiinflammatory drugs on the small bowel, colon, and rectum. Joint Bone Spine 2005; 72 (4): 286.