Histological characteristics of biliary intraepithelial neoplasia-3 and intraepithelial spread of cholangiocarcinoma
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ORIGINAL ARTICLE
Histological characteristics of biliary intraepithelial neoplasia-3 and intraepithelial spread of cholangiocarcinoma Yasunori Sato & Kenichi Harada & Motoko Sasaki & Yasuni Nakanuma
Received: 17 July 2012 / Revised: 13 December 2012 / Accepted: 11 February 2013 / Published online: 28 February 2013 # Springer-Verlag Berlin Heidelberg 2013
Abstract The increasing grades of biliary intraepithelial neoplasia (BilIN) reflect multistep carcinogenesis of cholangiocarcinoma, BilIN-3 representing the carcinoma in situ stage. A different form of in situ growth form of cancer cells is the intraepithelial spreading of cholangiocarcinoma cells. We examined the histological characteristics of carcinoma in situ in the biliary tract on 64 partial hepatectomy specimens with a diagnosis of hepatolithiasis. We distinguished two forms of carcinoma in situ: BilIN-3 and intraepithelial spread of carcinoma (IES). BilIN-3 is defined by epithelial atypia gradually decreasing towards the transition to adjacent normal biliary epithelium. In IES, the lesion shows an abrupt transition to normal biliary epithelium, in which the intraepithelial carcinoma then tends to spread. BilIN-3 and IES were observed in 17 (94 %) and seven (39 %), respectively, in cases of invasive cholangiocarcinoma (n=18), and neither of them was observed in cases without invasive cholangiocarcinoma (n= 46). Most lesions of BilIN-3 and IES microscopically showed a flat or pseudopapillary pattern. The less frequent micropapillary configuration was noted more often in BilIN-3. BilIN-3 was not observed in septal and small intrahepatic bile ducts, while IES was regularly observed in such bile ducts. Immunohistochemical analysis showed p53 to be expressed significantly more frequently in IES (29 %) than in BilIN-3 (8 %). In conclusion, carcinoma in situ in the biliary tract is morphologically heterogeneous, and it is important to distinguish BilIN-3 and intraepithelial carcinoma spreading as distinct lesions, to better understand their biology.
Y. Sato : K. Harada : M. Sasaki : Y. Nakanuma (*) Department of Human Pathology, Kanazawa University Graduate School of Medicine, 13-1 Takara-machi, Kanazawa 920-8640, Japan e-mail: [email protected]
Keywords Cholangiocarcinoma . Intraepithelial carcinoma . Biliary intraepithelial neoplasia . Intraepithelial spread Abbreviations BilIN Biliary intraepithelial neoplasia CK Cytokeratin IES Intraepithelial spread of carcinoma PanIN Pancreatic intraepithelial neoplasia
Introduction Cholangiocarcinoma arising in the large bile ducts develops through multistep carcinogenesis, and biliary intraepithelial neoplasia (BilIN) has been recognized as its precursor lesion [1–3]. BilIN occurs in large intraand extrahepatic bile ducts and is not infrequently encountered in the large intrahepatic bile ducts in chronic biliary diseases such as hepatolithiasis. It is usually observed by histological examination in biliary epithelium around invasive cholangiocarcinoma and, also incidentally, in large intrahepatic bile duct
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