[772] Crohn's-Associated Small Bowel Adenocarcinomas Exhibit Gastric Differentiation

Emma Whitcomb, Xiuli Liu, Shu-Yuan Xiao. University of Chicago, Chicago, IL; Cleveland Clinic, Cleveland, OH

Background: Long-term Crohn's enteritis increases the risk of small bowel adenocarcinoma (SBA), which, when compared to de novo SBA, usually occurs at a younger age, is frequently located in the ileum, and is more often poorly differentiated. In addition, we have observed that some cases of SBA in Crohn's disease exhibit gastric-type morphology, which may be related to pyloric gland metaplasia (PGM), a common finding in Crohn's disease. To investigate if this feature is unique to Crohn's SBA, a retrospective study (compared with non-Crohn's, de novo SBA) is performed.
Design: Cases of Crohn's-associated and de novo SBA were identified from the surgical pathology archives. H&E sections were examined for PGM. IHC was performed for CK20, CDX2, MUC2, CK7, MUC5AC and MUC6. Staining was scored on the invasive component as follows: 0 = entirely negative, 1+ = focally positive, and 2+ = diffusely positive. The two groups were then compared for their IHC expression frequencies.
Results: Seven cases of SBA in Crohn's disease were found and had adequate material for IHC evaluation and 7 de novo SBA cases were used as controls. Five of 7 Crohn's cases had PGM, which was absent in all de novo cases. By IHC, all de novo SBAs were positive for intestinal markers (CK20, CDX2, and MUC2) and 6 out of 7 were negative for gastric markers (CK7, MUC5AC, and MUC6). In contrast, all cases of Crohn's SBA were positive for a mixture of both intestinal and gastric markers. See Table 1.

Table 1. Expression of Intestinal and Gastric Markers in de novo and Crohn's-associated SBA
 De Novo SBA (n = 7)Crohns SBA (n = 7)
Intestinal Markers (% positive)  
CK20100% (n = 7)86% (n = 6)
CDX2100% (n = 7)86% (n = 6)
MUC2100% (n = 7)71% (n = 5)
Gastric Markers (% positive)  
CK714% (n = 1)71% (n = 5)
MUC5AC0% (n = 0)71% (n = 5)
MUC60% (n = 0)71% (n = 5)

Conclusions: These findings suggest that gastric differentiation and aberrant expression of gastric mucin markers is a common occurrence in Crohn's SBA while a rare occurrence in de novo SBA. Given that PGM is a well-known change in Crohn's disease, it is conceivable these cancers may arise out of gastric metaplasia (similar to adenocarcinoma arising from intestinal metaplasia in Barrett's esophagus), and thus, the presence of PGM may contribute to risk for development of adenocarcinoma in Crohn's enteritis. Further investigation may shed new light on the pathogenesis of this disease. In addition, the frequent aberrancy of staining should be considered when evaluating an unknown primary in a patient with Crohn's enteritis.
Category: Gastrointestinal

Monday, March 4, 2013 9:30 AM

Poster Session I Stowell-Orbison/Surgical Pathology/Autopsy Awards Poster Session # 120, Monday Morning


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