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  • Title: Two distinct pathways of carcinogenesis in primary sclerosing cholangitis.
    Author: Zen Y, Quaglia A, Heaton N, Rela M, Portmann B.
    Journal: Histopathology; 2011 Dec; 59(6):1100-10. PubMed ID: 22175890.
    Abstract:
    AIMS: To identify clinicopathological characteristics of cholangiocarcinoma and premalignant lesions arising in patients with primary sclerosing cholangitis (PSC). METHODS AND RESULTS: This study consisted of 25 patients with PSC and bile duct neoplasia [16 with cholangiocarcinoma and nine with biliary intra-epithelial neoplasia (BilIN) equivalent to biliary dysplasia]. Tumour cell morphology, growth patterns, history of inflammatory bowel disease and postoperative survival were recorded. Immunohistochemistry for CK7, CK20, MUC1, MUC2, MUC5AC, MUC6 and CDX2 was performed to characterize cell phenotypes. Cholangiocarcinoma and BilIN were classified into intestinal (n = 14) and non-intestinal classical (n = 11) types. Intestinal-type lesions showed histological features resembling intestinal dysplasia or adenocarcinoma. Intestinal-type cholangiocarcinoma commonly showed intraductal papillary proliferation and mucinous nodule formation. Intestinal-type lesions often had an intestinal immunophenotype that was not detected in classical-type lesions: CK20, 50% versus 0% (P = 0.007); MUC2, 86% versus 0% (P < 0.001); CDX2, 54% versus 0% (P = 0.003). Less commonly, intestinal-type cholangiocarcinoma showed perineural invasion (P = 0.003). Patients with intestinal-type cholangiocarcinoma had a more favourable cancer-specific prognosis than those with classical-type cholangiocarcinoma (P = 0.043). CONCLUSIONS: Bile ducts in PSC show two distinct dysplasia-carcinoma sequences as evidenced by differences in cell morphology, growth patterns, immunophenotypes and grade of malignancy.
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