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Pathol Int. 2005 Apr;55(4):180-8.

Proposal of histological criteria for intraepithelial atypical/proliferative biliary epithelial lesions of the bile duct in hepatolithiasis with respect to cholangiocarcinoma: preliminary report based on interobserver agreement.

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  • 1Department of Human Pathology, Kanazawa University Graduate School of Medicine, Kanazawa, Japan.


Biliary lining epithelia of the bile ducts in biliary diseases are known to have intraepithelial atypical/proliferative lesions related to the development of cholangiocarcinoma. The purpose of the present study was to determine the histological criteria for these lesions based on interobserver agreement. Digital images of 30 intraepithelial atypical/proliferative lesions in the stone-containing intrahepatic bile ducts of hepatolithiasis (30 cases) were sent to 10 pathologists. At first, 10 pathologists made a diagnosis (either of reactive/regenerative change, low-grade or high-grade biliary intraepithelial neoplasia (BilIN-1 and BilIN-2), or in situ carcinoma (BilIN-3)) based on their own criteria. The histological criteria for these four lesions were then determined, and the digital images of the same lesions with proposed criteria were re-distributed. Interobserver agreement on these four lesions was slightly improved (kappa = 0.44, first diagnosis; 0.49, second diagnosis) and intraobserver agreement was 'almost perfect' (kappa = 0.82 at both first and second diagnosis). Interobserver agreement between BilIN-1 and BilIN-2 and that between BilIN-2 and BilIN-3 were 'moderate', although the agreement between regenerative/reactive change and BilIN-1 was 'fair'. In this report, we propose histological criteria for reactive/regenerative change, BilIN-1, BilIN-2 and BilIN-3. Improvement of interobserver agreement suggests their applicability in diagnostic and research fields.

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