Histomorphologic and Molecular Features of Pouch and Peripouch Adenocarcinoma

Abstract

The occurrence of adenocarcinoma after ileal pouch-anal anastomosis for ulcerative colitis (UC) is an infrequent but potentially lethal complication. Neither histomorphologic nor molecular features of pouch adenocarcinoma after ileal pouch-anal anastomosis have been fully investigated. We report the largest series of 12 pouch and peripouch adenocarcinomas and compared them with 58 randomly selected UC-associated adenocarcinomas. The mean age of patients with pouch/peripouch adenocarcinoma was 55.2 years (SD 14.8), which was not significantly different from that of controls (P=0.52). Pouch/peripouch adenocarcinoma and UC-associated adenocarcinoma had a comparable frequency of tumor-infiltrating lymphocytes, lack of dirty necrosis, mucin differentiation, signet ring cell differentiation, heterogeneity, and well differentiation (P>0.05 for all). Pouch/peripouch adenocarcinoma was more likely to show Crohn-like reaction compared with UC-associated adenocarcinoma (P=0.047). Loss of at least 1 mismatch repair protein was noted in 9% of pouch/peripouch adenocarcinomas and 9.6% of UC-related adenocarcinomas (P=1.0). There was no significant difference in the frequency of p53 overexpression (36.4% vs. 61.1%, P=0.184) or nuclear immunoreactivity for β-catenin (9% vs. 7.4%, P=0.99) in pouch/peripouch versus UC-associated adenocarcinomas, respectively. Pouch/peripouch and UC-associated adenocarcinoma had a comparable positive rate for CK7 (54.5% vs. 55.5%, P=0.99), CK20 (100% vs. 98.1%, P=0.99), and CDX2 (72.8% vs. 72.2%, P=0.99) by immunohistochemistry. In summary, pouch and peripouch adenocarcinoma can occur in patients without colorectal neoplasia and in those with idiopathic inflammatory bowel disease, can be potentially lethal, and has histomorphologic and molecular features similar to those of UC-associated adenocarcinoma.

Diagnostic utility of TP53 and cytokeratin 7 immunohistochemistry in idiopathic inflammatory bowel disease-associated neoplasia

“…CK7 immunoreactivity has been routinely used in pathology practice to determine the possible origin of metastatic adenocarcinoma. It has been recently described in small bowel adenocarcinoma, 16 pouch and peri-pouch adenocarcinoma, 5 and inflammatory bowel disease-associated neoplasia in small series. [6][7][8] However, CK7 immunoreactivity in inflammatory bowel disease-associated neoplasia has not been well investigated in a cohort with reasonable size.…”

“…3 This was demonstrated by the distinct histomorphology of colitis-associated colorectal adenocarcinoma. 4 In addition, our previous study on ileal pouch and peri-pouch adenocarcinomas developed in inflammatory bowel disease patients showed that approximately 60% of these tumors expressed CK7, rarely had nuclear b-catenin accumulation, 5 in contrast to the pattern seen in sporadic colorectal adenocarcinoma. 6 Therefore, CK7 expression may be associated with tumorigenesis in inflammatory bowel disease.…”

Novel specific microRNA biomarkers in idiopathic inflammatory bowel disease unrelated to disease activity

“…21,22 Aberrant expression of miRNA-31 has been briefly mentioned in inflammatory bowel disease patients in a prior study of inflammatory bowel disease-associated colon cancer, but it has not been recognized as a specific marker in inflammatory bowel disease. 13 In this study, we emphasize the role of miR-31 as a universal biomarker of idiopathic inflammatory bowel 23 while the non-inflammatory bowel disease patients are largely free of the risk and are spared from difficult and costly cancer surveillance. This study brings several advances, as (1) the first report assessing miR-31 expression in inflammatory bowel disease in formalin-fixed, paraffin-embedded tissue; (2) the first report to identify aberrant expression of miR-31 in inflammatory bowel disease independent of inflammatory activity; and (3) an addition to small but growing knowledge of miRNA analysis by next-generation sequencing in colonic mucosa of inflammatory bowel disease patients.…”

Ileal Pouch Morphology and Microbiology in Ulcerative Colitis Patients

“…Only a limited number of cases of adenocarcinoma in an intestinal pouch have been described so far [24][25][26], while dysplasia of different degrees can be seen in 4.4% of intestinal pouches [6]. In the present study no cases of dysplasia were diagnosed.…”

“…Some authors suggest that a malignancy developing in an intestinal pouch may in fact be cancer of ileal-anal anastomosis originating from the remaining "cuff" of rectal mucosa [28,29]. Jiang et al describe the features of 12 cases of pouch and peripouch adenocarcinoma, and there was just 1 in the pouch only; 8 in the anal transitional zone (ATZ, defined as the part of the rectum between the dentate line and anastomosis); 2 in the ATZ and pouch; and 1 in a nonspecific peripouch region [26] In the present study, in addition to the clinical, endoscopic and histological evaluation of intestinal pouches, a microbiological assessment of material collected from pouch lumen was performed. The main components of the bacterial flora of the intestinal pouches were aerobic species.…”