Original Article
Copyright ©2012 Baishideng Publishing Group Co., Limited. All rights reserved.
World J Gastroenterol. Jul 28, 2012; 18(28): 3673-3680
Published online Jul 28, 2012. doi: 10.3748/wjg.v18.i28.3673
Intraductal neoplasm of the intrahepatic bile duct: Clinicopathological study of 24 cases
Yoshiki Naito, Hironori Kusano, Osamu Nakashima, Eiji Sadashima, Satoshi Hattori, Tomoki Taira, Akihiko Kawahara, Yoshinobu Okabe, Kazuhide Shimamatsu, Jun Taguchi, Seiya Momosaki, Koji Irie, Rin Yamaguchi, Hiroshi Yokomizo, Michiko Nagamine, Seiji Fukuda, Shinichi Sugiyama, Naoyo Nishida, Koichi Higaki, Munehiro Yoshitomi, Masafumi Yasunaga, Koji Okuda, Hisafumi Kinoshita, Masamichi Nakayama, Makiko Yasumoto, Jun Akiba, Masayoshi Kage, Hirohisa Yano
Yoshiki Naito, Hironori Kusano, Osamu Nakashima, Masamichi Nakayama, Makiko Yasumoto, Jun Akiba, Hirohisa Yano, Departments of Pathology, Kurume University School of Medicine, Kurume 830-0011, Japan
Eiji Sadashima, Satoshi Hattori, Biostatistics Center, Kurume University, Kurume 830-0011, Japan
Tomoki Taira, Akihiko Kawahara, Masayoshi Kage, Department of Diagnostic Pathology, Kurume University Hospital, Kurume 830-0011, Japan
Yoshinobu Okabe, Division of Gastroenterology, Department of Medicine, Kurume University School of Medicine, Kurume 830-0011, Japan
Kazuhide Shimamatsu, Department of Pathology, Omuta City General Hospital, Omuta 836-8567, Japan
Jun Taguchi, Department of Pathology, Asakura Medical Association Hospital, Fukuoka 838-0069, Japan
Seiya Momosaki, Department of Pathology, National Hospital Organization Kyushu Medical Center, Fukuoka 810-8563, Japan
Koji Irie, Department of Pathology, Shin-Koga Hospital, Tenjin-kai, 120 Tenjincho, Kurume 830-0033, Japan
Rin Yamaguchi, Department of Pathology, Kurume University Medical Center, 155-1 Kokubumachi, Kurume 839-0863, Japan
Hiroshi Yokomizo, Department of Surgery, Japanese Red Cross Kumamoto Hospital, Kumamoto 861-8520, Japan
Michiko Nagamine, Seiji Fukuda, Department of Pathology, Japanese Red Cross Kumamoto Hospital, Kumamoto 861-8520, Japan
Shinichi Sugiyama, Division of Surgery, Saiseikai Kumamoto Hospital, Kumamoto 861-4193, Japan
Naoyo Nishida, Koichi Higaki, Department of Pathology, St Mary’s Hospital, Kurume 830-8543, Japan
Munehiro Yoshitomi, Masafumi Yasunaga, Koji Okuda, Hisafumi Kinoshita, Department of Surgery, Kurume University School of Medicine, Kurume 830-0011, Japan
Author contributions: Naito Y, Nakashima O and Kusano H performed the majority of the experiments; Yano H was involved in editing the manuscript; all authors provided the collection of all the human material and advised for the manuscript.
Correspondence to: Yoshiki Naito, MD, PhD, Department of Pathology, Kurume University School of Medicine, 67 Asahimachi, Kurume 830-0011, Japan. nyoshiki@med.kurume-u.ac.jp
Telephone: +81-942-317546 Fax: +81-942-320905
Received: November 14, 2011
Revised: March 27, 2012
Accepted: March 29, 2012
Published online: July 28, 2012
Abstract

AIM: 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.

CONCLUSION: 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.

Keywords: Intraductal biliary neoplasm; Intraductal papillary neoplasm of the bile duct; Intraductal tubular neoplasm of the bile duct; Intraductal tubulopapillary neoplasm of the bile duct; Mucin expression