Mimics in Gastrointestinal Pathology
Case 3 -
Diverticular Colitis Mimicking Ulcerative Colitis
Alyssa Krasinskas, Jeffrey Goldsmith and Susan Abraham
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."
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
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
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:
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.
- Lamina propria lymphoplasmacytosis +/- eosinophils
- Crypt architectural distortion
- Paneth cell metaplasia
- Acute cryptitis, crypt abscesses
- Granulomatous inflammation
- Features of mucosal prolapse
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.
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.
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
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 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:
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.
- Large lymphoid aggregates with prominent germinal centers
- Variable crypt distortion/atrophy
- Cryptitis/crypt abscesses
- Aphthous lesions
The histologic diagnosis of diversion colitis
relies on the knowledge that the biopsies are obtained from a diverted segment of colon.
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:
The histologic diagnosis of radiation-induced colitis relies
on the knowledge of prior radiation exposure to the affected segment of colon.
- Mucosal telangiectasia
- Perivascular hyalinization
- Atypical "radiation" fibroblasts
- Architectural distortion
- Abnormal crypts, crypt dropout, cystica profunda
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
- 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.
- Carpenter HA, Talley NJ. The importance of clinicopathological correlation in the diagnosis of inflammatory conditions of the colon: histological patterns with clinical implications. Am J Gastroenterol 2000; 95 (4): 878.
- Maxson CJ, Klein HD, Rubin W. Atypical forms of inflammatory bowel disease. Med Clin North Am 1994; 78 (6): 1259.
- Tanaka M, Riddell RH, Saito H, Soma Y, Hidaka H, Kudo H. Morphologic criteria applicable to biopsy specimens for effective distinction of inflammatory bowel disease from other forms of colitis and of Crohn's disease from ulcerative colitis. Scand J Gastroenterol 1999; 34 (1): 55.
- Goldstein NS, Leon-Armin C, Mani A. Crohn's colitis-like changes in sigmoid diverticulitis specimens is usually an idiosyncratic inflammatory response to the diverticulosis rather than Crohn's colitis. Am J Surg Pathol 2000; 24 (5): 668.
- Gore S, Shepherd NA, Wilkinson SP. Endoscopic crescentic fold disease of the sigmoid colon: the clinical and histopathological spectrum of a distinctive endoscopic appearance. Int J Colorectal Dis 1992; 7(2):76.
- Hokama A, Kinjo F, Tomiyama R, Maeda K, Saito A, Matayoshi M. Progression of diverticular colitis to ulcerative colitis. Inflamm Bowel Dis 2005; 11 (6): 618.
- Ludeman L, Shepherd NA. What is diverticular colitis? Pathology 2002; 34 (6): 568.
- Nair S, Peppercorn M, Floch MH, West AB. Diverticulitis and IBD. J Clin Gastroenterol 2004; 38 (5 Suppl): S17.
- Makapugay LM, Dean PJ. Diverticular disease-associated chronic colitis. Am J Surg Pathol 1996; 20 (1):94.
- Peppercorn MA. The overlap of inflammatory bowel disease and diverticular disease. J Clin Gastroenterol 2004; 38 (5 Suppl): S8.
- Rampton DS. Diverticular colitis: diagnosis and management. Colorectal Dis 2001; 3 (3): 149.
- West AB, Losada M. The pathology of diverticulosis coli. J Clin Gastroenterol 2004; 38 (5 Suppl): S11.
- Dixon MF. Diversion colitis: new light through old windows. Histopathology 1999; 35 (1): 86.
- Edwards CM, George B, Warren B. Diversion colitis--new light through old windows. Histopathology 1999; 34 (1): 1.
- Eggenberger JC, Farid A. Diversion Colitis. Curr Treat Options Gastroenterol 2001; 4 (3): 255.
- Giardiello FM, Lazenby AJ, Bayless TM. The new colitides, Collagenous, lymphocytic, and diversion colitis. Gastroenterol Clin North Am 1995; 24 (3): 717.
- Glotzer DJ, Glick ME, Goldman H. Proctitis and colitis following diversion of the fecal stream. Gastroenterology 1981; 80 (3): 438.
- Haque S, Eisen RN, West AB. The morphologic features of diversion colitis: studies of a pediatric population with no other disease of the intestinal mucosa. Hum Pathol 1993; 24 (2): 211.
- Komorowski RA. Histologic spectrum of diversion colitis. Am J Surg Pathol 1990; 14 (6): 548.
- Warren BF, Shepherd NA, Bartolo DC, Bradfield JW. Pathology of the defunctioned rectum in ulcerative colitis. Gut 1993; 34 (4): 514.
- Bismar MM, Sinicrope FA. Radiation enteritis. Curr Gastroenterol Rep 2002; 4 (5): 361.
- Fajardo LF. The pathology of ionizing radiation as defined by morphologic patterns. Acta Oncol 2005; 44 (1): 13.
- Leupin N, Curschmann J, Kranzbuhler H, Maurer CA, Laissue JA, Mazzucchelli L. Acute radiation colitis in patients treated with short-term preoperative radiotherapy for rectal cancer. Am J Surg Pathol 2002; 26 (4): 498.
- 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
- Eisenberg RL, Montgomery CK, Margulis AR. Colitis in the elderly: ischemic colitis mimicking ulcerative and granulomatous colitis. AJR Am J Roentgenol 1979; 133 (6): 1113.
- Fajardo LF. The pathology of ionizing radiation as defined by morphologic patterns. Acta Oncol 2005; 44 (1): 13.
- Faucheron JL. Toxicity of non-steroidal anti-inflammatory drugs in the large bowel. Eur J Gastroenterol Hepatol 1999; 11 (4): 389.
- 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.
- Gandhi SK, Hanson MM, Vernava AM, Kaminski DL, Longo WE. Ischemic colitis. Dis Colon Rectum 1996; 39 (1): 88.
- Iwashita A, Yao T, Schlemper RJ, Kuwano Y, Yao T, Iida M, Matsumoto T, Kikuchi M. Mesenteric phlebosclerosis: a new disease entity causing ischemic colitis. Dis Colon Rectum 2003; 46 (2): 209.
- Lee FD. Drug-related pathological lesions of the intestinal tract. Histopathology 1994; 25 (4): 303.
- 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.
- Thiefin G, Beaugerie L. Toxic effects of nonsteroidal antiinflammatory drugs on the small bowel, colon, and rectum. Joint Bone Spine 2005; 72 (4): 286.