College of American Pathologists

2013 — February Case of the Month

Posted February 18, 2013


CAP Foundation Online Case of the Month

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After reading the summary, try answering the three related multiple-choice questions below.

A 25-year-old woman with history of abdominal pain and diarrhea presents with bowel obstruction. She undergoes a partial colectomy. The colectomy specimen shows a stricture and areas of cobble stone appearing mucosa with intervening normal looking mucosa. The serosa shows creeping fat.

Archive Case and Diagnosis:
This case first appeared as Performance Improvement Program in Surgical Pathology (PIP) 2010, case 05, and is Crohn disease.

Criteria for Diagnosis and Comments:
The sections show architectural distortion, cryptitis, crypt abscess and inflammatory infiltrate that is transmural or at least going beyond the muscularis mucosa. Few of the sections also show epithelioid granulomas. These histological features combined with history and gross features favor the diagnosis of Crohn disease.

Crohn disease is one of two major inflammatory bowel diseases, the other is ulcerative colitis. Clinically, Crohn disease has a bimodal age distribution with one peak in the 2nd and 3rd decades and a second peak in the 5th, 6th and 7th decades of life. In the United States Crohn disease is more prevalent among Caucasians than non-Caucasians, and this follows the worldwide pattern with lower incidence in Asian, Mediterranean, African and Middle Eastern countries and higher incidence in European countries, Australia, New Zealand, Canada and United States. The etiology of Crohn disease is largely unknown. However, recent studies point to abnormal innate and acquired immune responses to normal flora of gut in individuals who are genetically predisposed to the disease. A few candidate genes involved in inflammatory and immune responses have been implicated in the pathogenesis of Crohn disease. These genes (and the implicated pathways) include NOD2 (NF-κB), CCR5, CCR9 (chemokine receptors), MLH1 (mis-match repair), CSF-2 (cytokines and CASP9 (protease).

Crohn disease can occur anywhere in the gastrointestinal mucosa from the oral cavity to ano-rectal verge. One of the most common sites is the ileocecal area. Grossly, the serosa is reddened, hyperemic and shows creeping fat which is the encircling of antimesenteric serosal surface by fat. The mucosa can show cobblestoning, aphthous ulcers, fistulas, fissures and abscesses. Aphthous ulcers (which may also occur in infectious enterocolitis) are the characteristic ulcers which are formed over lymphoid tissue. As they enlarge, they develop a hemorrhagic rim. The small stellate aphthous ulcers develop into discontinuous linear or serpiginous ulcers and finally to wide based ulcers. A second type of ulcer that can be seen is the knife-like longitudinal fissures that can extend through the bowel wall and can result in fistulas, abscesses and peri-intestinal pseudotumors. In contradistinction to ulcerative colitis, the mucosal involvement in Crohn disease tends to be discontinuous; in ulcerative colitis, the colitis should extend in a continuous fashion from distal to proximal. Another diagnostic hallmark of Crohn disease is transmural chronic inflammation often noted as lymphoid aggregates on both sides of the muscularis propria and within the pericolonic fat. Other features of Crohn disease include cryptitis, crypt abscess, architectural distortion with deep crypt branching, increased lamina propria chronic inflammation, hypertrophy of the muscularis mucosa and neuronal hyperplasia. Epithelioid granulomas can be seen in 60–90% of resection specimens and 30% of mucosal biopsy specimens. They should be differentiated from small mucosal granulomas related to crypt rupture, which can be seen in conditions other than Crohn disease. These are oriented around the crypts and may have mucin-containing macrophages (muciphages) and foreign body giant cells. Mucin stains have been used to identify them but are often not helpful.. The epithelioid granulomas of Crohn disease can be found in any layer of bowel and their diagnostic value increases if they are found away from the ulceration. Patients with Crohn disease are at a much higher 1 risk of developing small intestinal and colorectal adenocarcinoma. Approximately 5% of patients with Crohn disease develop adenocarcinoma, and there is a positive correlation with the duration as well as the anatomical extent of the disease.

The main entity in the differential diagnosis of Crohn disease is ulcerative colitis. Ulcerative colitis involves the colon in a continuous fashion with involvement of rectum. However, peri-anal involvement is characteristic of Crohn disease. The mucosa shows numerous pseudopolyps which are islands of intact mucosa in ulcerated areas. Microscopically inflammation is limited to mucosa and submucosa. As in Crohn disease cryptitis, crypt abscesses and features of architectural distortion are seen however epithelioid granulomas are absent. Small mucosal granulomas related to crypt rupture can be seen, but well-formed epithelioid granulomas are not present. Upper GI involvement is more characteristic of Crohn disease, but diffuse chronic inflammation in the stomach and duodenum can be seen in ulcerative colitis. Both forms of inflammatory bowel disease can be associated with primary sclerosing cholangitis. Patients with ulcerative colitis have a higher incidence of developing colorectal carcinoma than Crohn disease.

Patients with radiation induced colitis will have a history of exposure to radiation 6–24 months prior to the onset and may show a similar clinical picture; however, mucosal telangiectasia, perivascular hyalinization and atypical fibroblasts in the lamina propria clinch the diagnosis of radiation induced colitis.

Various infectious agents can mimic Crohn disease, the common being infections due to Yersinia and Mycobacterium tuberculosis. Yersinia infections very closely mimic Crohn disease: both diseases can show ileo-colonic involvement, fissures, granulomas and transmural inflammation. Similarly granulomatous infection with mycobacteria can closely mimic Crohn disease with granulomas. However, granulomas in Mycobacterial infections are also seen in draining lymph nodes, as opposed to Crohn where they are restricted mostly to the intestine. Transverse ulcers are more characteristic of mycobacterial infection as opposed to longitudinal ulcers and cobblestoning in Crohn disease. Infectious colitis may show diffuse colonic involvement, increased chronic inflammatory cells and neutrophils. In contrast to Crohn disease, neutrophils are often more prominent in the lamina propria compared to the crypts. The architecture is generally preserved.

Ischemic colitis can clinically mimic Crohn disease. Characteristic features of acute ischemic injury like hyalinization of the lamina propria and small atrophic crypts are not seen in Crohn disease. Dense chronic inflammation with cryptitis and crypt abscesses are not a feature of ischemic colitis.

Supplementary Questions:

Question Diagnostic Set
1. Which of the following features strongly favors Crohn colitis over ulcerative colitis? A. Chronic inflammation in biopsies from upper
     gastrointestinal tract

B. Diffuse colonic involvement
C. Perianal disease
D. Presence of primary sclerosing cholangitis
2. Which of the following infections can closely mimic Crohn disease by showing ileocolonic involvement, fissuring ulcers, granulomas and transmural inflammation? A. Campylobacter
B. Cytomegalovirus
C. Entamoeba
D. Spirochetosis
E. Yersinia
3. Which of the following features favors Crohn disease over Mycobacterium tuberculosis infection? A. Granulomas in draining lymph nodes
B. Ileocolic involvement
C. Large and confluent granulomas
D. Longitudinal ulcers and cobblestoning
E. Prominent necrosis


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Talat Mehmood Nazir, MBBS, DO
Surgical Pathology Committee
Houston, TX