Shimonishi Tomonori, Zen Yoh, Chen Tse-Ching, Chen Miin-Fu, Jan Yi-Yin, Yeh Ta-Sen, Nimura Yuji, Nakanuma Yasuni
Department of Pathology (II), Kanazawa University School of Medicine, Japan.
Hum Pathol. 2002 May;33(5):503-11. doi: 10.1053/hupa.2002.124030.
Intraductal papillary neoplasia of the liver (IPN-L) was recently proposed as the name for intraductal papillary proliferation of neoplastic biliary epithelium with a fine fibrovascular stalk resembling intraductal papillary mucinous neoplasm of the pancreas. We histochemically and immunohistochemically examined IPN-L alone or associated with hepatolithiasis, with an emphasis on the gastrointestinal metaplasia, nuclear p53 expression, and histologic progression. A total of 66 cases of IPN-L were divided into 4 groups: group 1, IPN-L with low-grade dysplasia (13 cases); group 2, IPN-L with high-grade dysplasia (20 cases); group 3, IPN-L lined with carcinoma in situ and no or microinvasion (19 cases); and group 4, group 3 with distinct invasive carcinoma (14 cases). It is suggested that IPN-L progresses from group 1 to group 4. As controls, 20 cases of nonneoplastic intrahepatic large bile ducts and 17 cases of nonpapillary invasive intrahepatic cholangiocarcinoma (ICC) were used. Biliary epithelial hypersecretion of sialomucin rather than sulfomucin was prevalent in IPN-L, and this was associated with the progression of INP-L. Immunohistochemically, cytokeratin (CK) 20 and MUC2, a gastrointestinal marker, were expressed more frequently in IPN-L than in nonneoplastic bile ducts and nonpapillary ICC (P <0.01), and their incidence were significantly increased in parallel with the progression of IPN-L (P < 0.01). In contrast, expression of CK 7, a biliary marker, was decreased in IPN-L compared with nonpapillary ICC. Nuclear p53 immunostaining was detected in 30% of IPN-L as a whole and increased in tandem with the progression of IPN-L (P < 0.01). It is suggested that IPN-L forms a spectrum of biliary epithelial neoplasia with frequent gastrointestinal metaplasia, different from the usual nonpapillary ICC, and shows stepwise progression from the perspective of mucin profile, gastrointestinal metaplasia, and p53 nuclear expression.
肝内导管内乳头状瘤变（IPN-L）最近被提议作为具有纤细纤维血管蒂的肿瘤性胆管上皮导管内乳头状增生的名称，其类似于胰腺导管内乳头状黏液性肿瘤。我们对单纯的IPN-L或与肝内胆管结石相关的IPN-L进行了组织化学和免疫组织化学检查，重点关注胃肠化生、核p53表达和组织学进展。总共66例IPN-L病例被分为4组：第1组，低级别异型增生的IPN-L（13例）；第2组，高级别异型增生的IPN-L（20例）；第3组，原位癌且无或微浸润的IPN-L（19例）；第4组，伴有明显浸润性癌的第3组病例（14例）。提示IPN-L从第1组进展至第4组。作为对照，使用了20例非肿瘤性肝内大胆管病例和17例非乳头状浸润性肝内胆管癌（ICC）病例。在IPN-L中，涎黏蛋白而非硫黏蛋白的胆管上皮高分泌较为普遍，且这与IPN-L的进展相关。免疫组织化学显示，细胞角蛋白（CK）20和胃肠标志物MUC2在IPN-L中的表达频率高于非肿瘤性胆管和非乳头状ICC（P<0.01），且它们的发生率随IPN-L的进展而显著增加（P<0.01）。相反，与非乳头状ICC相比，胆管标志物CK 7在IPN-L中的表达降低。总体上30%的IPN-L检测到核p53免疫染色，且其随IPN-L的进展而增加（P<0.01）。提示IPN-L形成了一种具有频繁胃肠化生的胆管上皮肿瘤谱，不同于常见的非乳头状ICC，并且从黏蛋白谱、胃肠化生和p53核表达的角度显示出逐步进展。
