title: Intraductal neoplasm of the intrahepatic bile duct: clinicopathological study of 24 cases.
abstract: OBJECTIVE
  To investigate the clinicopathological features of intraductal neoplasm of the intrahepatic bile duct (INihB).
  
  
  METHODS
  Clinicopathological features of 24 cases of INihB, which were previously diagnosed as biliary papillomatosis or intraductal growth of intrahepatic biliary neoplasm, were reviewed. Mucin immunohistochemistry was performed for mucin (MUC)1, MUC2, MUC5AC and MUC6. Ki-67, P53 and β-catenin immunoreactivity were also examined. We categorized each tumor as adenoma (low grade), borderline (intermediate grade), and malignant (carcinoma in situ, high grade including tumors with microinvasion).
  
  
  RESULTS
  Among 24 cases of INihB, we identified 24 tumors. Twenty of 24 tumors (83%) were composed of a papillary structure; the same feature observed in intraductal papillary neoplasm of the bile duct (IPNB). In contrast, the remaining four tumors (17%) showed both tubular and papillary structures. In three of the four tumors (75%), macroscopic mucin secretion was limited but microscopic intracellular mucin was evident. Histologically, 16 tumors (67%) were malignant, three (12%) were borderline, and five (21%) were adenoma. Microinvasion was found in four cases (17%). Immunohistochemical analysis revealed that MUC1 was not expressed in the borderline/adenoma group but was expressed only in malignant lesions (P = 0.0095). Ki-67 labeling index (LI) was significantly higher in the malignant group than in the borderline/adenoma group (22.2 ± 15.5 vs 7.5 ± 6.3, P < 0.01). In the 16 malignant cases, expression of MUC5AC showed borderline significant association with high Ki-67 LI (P = 0.0622). Nuclear expression of β-catenin was observed in two (8%) of the 24 tumors, and these two tumors also showed MUC1 expression. P53 was negative in all tumors.
  
  
  CONCLUSIONS
  Some cases of INihB have a tubular structure, and are subcategorized as IPNB with tubular structure. MUC1 expression in INihB correlates positively with degree of malignancy.
authors.affiliation: Departments of Pathology, Kurume University School of Medicine, Kurume 830-0011, Japan. nyoshiki@med.kurume-u.ac.jp
authors.forename: Yoshiki
authors.initials: Y
authors.lastname: Naito
authors.forename: Hironori
authors.initials: H
authors.lastname: Kusano
authors.forename: Osamu
authors.initials: O
authors.lastname: Nakashima
authors.forename: Eiji
authors.initials: E
authors.lastname: Sadashima
authors.forename: Satoshi
authors.initials: S
authors.lastname: Hattori
authors.forename: Tomoki
authors.initials: T
authors.lastname: Taira
authors.forename: Akihiko
authors.initials: A
authors.lastname: Kawahara
authors.forename: Yoshinobu
authors.initials: Y
authors.lastname: Okabe
authors.forename: Kazuhide
authors.initials: K
authors.lastname: Shimamatsu
authors.forename: Jun
authors.initials: J
authors.lastname: Taguchi
authors.forename: Seiya
authors.initials: S
authors.lastname: Momosaki
authors.forename: Koji
authors.initials: K
authors.lastname: Irie
authors.forename: Rin
authors.initials: R
authors.lastname: Yamaguchi
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Yokomizo
authors.forename: Michiko
authors.initials: M
authors.lastname: Nagamine
authors.forename: Seiji
authors.initials: S
authors.lastname: Fukuda
authors.forename: Shinichi
authors.initials: S
authors.lastname: Sugiyama
authors.forename: Naoyo
authors.initials: N
authors.lastname: Nishida
authors.forename: Koichi
authors.initials: K
authors.lastname: Higaki
authors.forename: Munehiro
authors.initials: M
authors.lastname: Yoshitomi
authors.forename: Masafumi
authors.initials: M
authors.lastname: Yasunaga
authors.forename: Koji
authors.initials: K
authors.lastname: Okuda
authors.forename: Hisafumi
authors.initials: H
authors.lastname: Kinoshita
authors.forename: Masamichi
authors.initials: M
authors.lastname: Nakayama
authors.forename: Makiko
authors.initials: M
authors.lastname: Yasumoto
authors.forename: Jun
authors.initials: J
authors.lastname: Akiba
authors.forename: Masayoshi
authors.initials: M
authors.lastname: Kage
authors.forename: Hirohisa
authors.initials: H
authors.lastname: Yano
mesh_terms: D000368:Aged; D001650:Bile Duct Neoplasms / Q000175:diagnosis* / Q000503:physiopathology*; D001653:Bile Ducts, Intrahepatic / Q000503:physiopathology*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D008297:Male; D008875:Middle Aged; D055271:Mucin 5AC / Q000096:biosynthesis; D018396:Mucin-1 / Q000096:biosynthesis; D055262:Mucin-2 / Q000096:biosynthesis; D055272:Mucin-6 / Q000096:biosynthesis; D009361:Neoplasm Invasiveness; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis; D051176:beta Catenin / Q000096:biosynthesis
chemical_list: C524678:MUC5AC protein, human; D055271:Mucin 5AC; D018396:Mucin-1; D055262:Mucin-2; D055272:Mucin-6; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D051176:beta Catenin