Small intestinal adenocarcinoma is an uncommon neoplasm morphologically similar to or indistinguishable from colorectal adenocarcinoma. Although much has been learned about genetic pathways critical to colorectal tumorigenesis, little is known about molecular alterations involved in the development of small intestinal adenocarcinoma. In this study, we immunohistochemically compared non-ampullary small intestinal adenocarcinomas with sporadic colorectal adenocarcinomas for the expression of several proteins known to serve pivotal roles in colorectal tumorigenesis. These included adenomatous polyposis coli and b-catenin involved in the Wnt signaling pathway, and DNA mismatch repair enzymes hMLH1, hMSH2 and hMSH6 involved in the microsatellite instability pathway. The expression of two important tumor suppressors, p53 and RB, was also examined. The results show that complete loss of adenomatous polyposis coli immunoreactivity, presumably resulting from its gene mutations, was observed in eight of 26 (31%) small intestinal adenocarcinomas and 36 of 51 (71%) colorectal adenocarcinomas (P ¼ 0.0008). Nuclear localization of b-catenin, an indirect evidence of deregulated Wnt signaling pathway, was observed in 5 (19%) small intestinal adenocarcinomas and 36 (71%) colorectal adenocarcinomas (Po0.0001). Total lack of nuclear staining for one or more of the DNA mismatch repair enzymes occurred in a similar low frequency in both small intestinal and colorectal adenocarcinomas, seen in two of 25 (8%) and 10 of 47 (21%) cases, respectively (P ¼ 0.1958). The frequencies of aberrant p53 and RB expression were also similar between small intestinal and colorectal adenocarcinomas. These observations indicate that defects in the Wnt and microsatellite instability pathways occur in over 90% of colorectal adenocarcinomas, but in only 40% of small intestinal adenocarcinomas. Small intestinal tumorigenesis appears to follow a distinct, yet unidentified, molecular pathway(s) from its colorectal counterpart despite their morphologic similarity.

Expression of gastrointestinal biomarkers MUC1, MUC2, MUC5AC, small-intestinal mucin antigen (SIMA), villin, and CDX2 has been studied in colorectal adenocarcinoma (CRC). Little is known, however, about their expression in small-intestinal adenocarcinoma (SIA). We immunohistochemically compared 30 SIAs with 48 CRCs for the expression of these biomarkers. The results showed that all 6 proteins were variably expressed in SIA, but the frequencies of expression were significantly lower than those for CRC with the exception of MUC1. Specifically, positive staining for MUC1, MUC2, MUC5AC, SIMA, villin, and CDX2 was observed in 16 (53%), 17 (57%), 12 (40%), 15 (50%), 20 (67%), and 18 (60%) of SIAs and 25 (52%), 43 (90%), 39 (81%), 45 (94%), 47 (98%), and 47 (98%) of CRCs, respectively. In addition, SIAs more frequently exhibited a focal staining pattern for MUC2, MUC5AC, SIMA, and villin, whereas more diffuse immunoreactivity was evident in CRCs. Focal staining for MUC1 and diffuse staining for CDX2 were common for SIAs and CRCs. Furthermore, poorly differentiated SIAs tended to express MUC1 more frequently when compared with well- and moderately differentiated SIAs. These observations further support the notion that SIA is immunophenotypically distinct from CRC despite their morphologic similarity.

A 74-year-old woman with a clinical history of invasive ductal carcinoma of the breast was found to have a splenic mass during a routine radiographic survey. Splenectomy revealed a 3-cm well-demarcated lesion, which on histopathologic examination consisted of heterogeneous inflammatory cells. A striking feature of the lesion was the presence of innumerable well-formed non-necrotizing granulomas. Immunohistochemical studies confirmed the lesion to be composed mainly of mixed T and B lymphocytes, histiocytes, and plasma cells. No spindle cell component was evident on light microscopic examination or by immunohistochemical staining for smooth muscle actin, anaplastic lymphoma kinase, or follicular dendritic cell markers CD21 and CD35. Interestingly, Epstein-Barr virus-encoded RNA and latent membrane protein were detected by in situ hybridization and immunohistochemistry in numerous lymphohistiocytic cells within the lesion, but not in surrounding uninvolved splenic tissue. To our knowledge, this case represents a rare example of splenic inflammatory pseudotumor with exuberant granulomatous reaction in association with Epstein-Barr viral infection.