Sasaki Motoko, Sato Yasunori
Department of Human Pathology, Kanazawa University Graduate School of Medical Sciences, Kanazawa 920-8640, Japan.
Department of Human Pathology, Kanazawa University Graduate School of Medical Sciences, Kanazawa 920-8640, Japan.
Hum Pathol. 2017 Apr;62:152-159. doi: 10.1016/j.humpath.2016.12.028. Epub 2017 Jan 13.
Biliary tumors showing intraductal papillary growth (Pap-BTs) include intraductal papillary neoplasm of the bile duct (IPNB) and papillary cholangiocarcinoma (CC). A differential diagnosis between IPNB and papillary CC currently remains challenging. The aim of the present study is to identify histological features and immunohistochemical markers of malignant potential such as tumor invasion in Pap-BTs. Subjects comprised 37 patients with Pap-BT (intrahepatic and perihilar [proximal], 27: 17 noninvasive and 10 invasive; distal, 10: all invasive). We examined histological features and the expression of p53, enhancer of zeste homolog 2, insulin-like growth factor II mRNA-binding protein 3 (IMP3), and DNA methyltransferase-1 in the intraductal area in Pap-BTs. Noninvasive Pap-BT was characterized by the presence of a low-grade dysplastic area, edematous stroma, and the absence of necrosis. The expression of p53, enhancer of zeste homolog 2, IMP3, and DNA methyltransferase-1 was significantly weaker in noninvasive Pap-BTs than in invasive Pap-BTs (P<.01). Diffuse cytoplasmic IMP3 expression was absent in noninvasive Pap-BTs. IMP3 showed the greatest specificity to predict a presence of invasion. A heatmap demonstrated that proximal noninvasive Pap-BTs and distal Pap-BTs may be completely different. In bile duct biopsies, the expression of IMP3 was the most precise predictor of invasion in Pap-BTs. In conclusion, Pap-BTs may be separated into 3 subgroups: (1) proximal noninvasive Pap-BT, corresponding to IPNB; (2) distal invasive Pap-BT, corresponding to papillary CC; and (3) the remaining Pap-BT including IPNB with associated adenocarcinomas, based on histological and immunohistochemical features. IMP3 may be a useful marker for predicting invasion in Pap-BT.
表现为导管内乳头状生长的胆管肿瘤（Pap-BTs）包括胆管内乳头状肿瘤（IPNB）和乳头状胆管癌（CC）。目前，IPNB和乳头状CC之间的鉴别诊断仍然具有挑战性。本研究的目的是确定Pap-BTs中肿瘤侵袭等恶性潜能的组织学特征和免疫组化标志物。研究对象包括37例Pap-BT患者（肝内和肝门周围[近端]，27例：17例非侵袭性和10例侵袭性；远端，10例：均为侵袭性）。我们检查了Pap-BTs导管内区域的组织学特征以及p53、zeste同源物2增强子、胰岛素样生长因子II mRNA结合蛋白3（IMP3）和DNA甲基转移酶-1的表达。非侵袭性Pap-BT的特征是存在低度发育异常区域、水肿性间质且无坏死。非侵袭性Pap-BTs中p53、zeste同源物2增强子、IMP3和DNA甲基转移酶-1的表达明显弱于侵袭性Pap-BTs（P<0.01）。非侵袭性Pap-BTs中不存在弥漫性细胞质IMP3表达。IMP3对预测侵袭的存在具有最高的特异性。热图显示近端非侵袭性Pap-BTs和远端Pap-BTs可能完全不同。在胆管活检中，IMP3的表达是Pap-BTs侵袭的最准确预测指标。总之，基于组织学和免疫组化特征，Pap-BTs可分为3个亚组：（1）近端非侵袭性Pap-BT，对应于IPNB；（2）远端侵袭性Pap-BT，对应于乳头状CC；（3）其余的Pap-BT，包括伴有相关腺癌的IPNB。IMP3可能是预测Pap-BT侵袭的有用标志物。
