title: An S100P-positive biliary epithelial field is a preinvasive intraepithelial neoplasm in nodular-sclerosing cholangiocarcinoma.
abstract: Nodular-sclerosing cholangiocarcinoma (NS-CCA) is a common CCA of the intrahepatic large, perihilar, and distal bile ducts. Intraepithelial biliary neoplasms, such as the mucosal extension of carcinoma and preinvasive neoplastic lesions (ie, biliary intraepithelial neoplasia) reportedly occur in the bile ducts around CCA. In the present study, we collectively refer to these intraepithelial lesions as "intraepithelial neoplasms of the bile duct (IENBs)". We examined the IENBs in 57 surgically resected cases of NS-CCA. S100P immunostaining was used to help detect IENBs. The IENBs formed field(s) of continuous neoplastic biliary epithelial cells and showed a flat, micropapillary, or papillotubular configuration. IENBs could be classified into 3 categories based on their atypia: group A (neoplastic but not enough for malignancy), B (neoplastic and sufficiently well differentiated for high-grade dysplasia), and C (overtly malignant and variably differentiated). IENB was found in 31 of 57 cases, with group C the most common (26 cases) followed by group B (22 cases) and group A (16 cases). The expression of cancer-related molecules and MIB-1 index of groups A and B differed from those of invasive CCA, whereas these features of group C were relatively similar to those of invasive CCA. In conclusion, IENB was not infrequently found in NS-CCA and could be classified into 3 grades. Preinvasive lesions (biliary intraepithelial neoplasias) are likely to be found in groups A and B, whereas cancerization would be included in group C. The classification of IENB may be useful for future studies of the preinvasive intraepithelial neoplastic lesions of NS-CCAs.
authors.affiliation: Department of Diagnostic Pathology, Shizuoka Cancer Center, Shizuoka, 411-8777, Japan. Electronic address: nakanuma@staff.kanazawa-u.ac.jp.
authors.forename: Yasuni
authors.initials: Y
authors.lastname: Nakanuma
authors.affiliation: Department of Diagnostic Pathology, Shizuoka Cancer Center, Shizuoka, 411-8777, Japan; Department of Hepatobiliary Pancreatic Surgery, Shizuoka Cancer Center, Shizuoka, 411-8777, Japan.
authors.forename: Tsuneyuki
authors.initials: T
authors.lastname: Uchida
authors.affiliation: Department of Human Pathology, Kanazawa University Graduate School of Medicine, Kanazawa, 920-8640, Japan.
authors.forename: Yasunori
authors.initials: Y
authors.lastname: Sato
authors.affiliation: Department of Hepatobiliary Pancreatic Surgery, Shizuoka Cancer Center, Shizuoka, 411-8777, Japan.
authors.forename: Katsuhiko
authors.initials: K
authors.lastname: Uesaka
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D001650:Bile Duct Neoplasms / Q000737:chemistry* / Q000473:pathology / Q000601:surgery; D014408:Biomarkers, Tumor / Q000032:analysis*; D001706:Biopsy; D002135:Calcium-Binding Proteins / Q000032:analysis*; D002278:Carcinoma in Situ / Q000737:chemistry* / Q000473:pathology / Q000601:surgery; D002454:Cell Differentiation; D018281:Cholangiocarcinoma / Q000737:chemistry* / Q000473:pathology / Q000601:surgery; D018450:Disease Progression; D004847:Epithelial Cells / Q000737:chemistry* / Q000473:pathology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D009361:Neoplasm Invasiveness; D009363:Neoplasm Proteins / Q000032:analysis*; D011237:Predictive Value of Tests; D012598:Sclerosis; D009626:Terminology as Topic
chemical_list: D014408:Biomarkers, Tumor; D002135:Calcium-Binding Proteins; D009363:Neoplasm Proteins; C103003:S100P protein, human
keywords: Biliary tree; Cancerization; Intraepithelial neoplasm preinvasive lesion; Invasion; Nodular-sclerosing cholangiocarcinoma