摘要目的：探讨混合型肝癌伴干细胞特征（细胆管癌型）的临床病理特征及其与肝脏祖细胞（ HPC）的关系。方法收集26例混合型肝癌伴干细胞特征（细胆管癌型）病例的临床资料，通过光镜、黏液组织化学染色及免疫组织化学EnVision法分析其临床病理学特征，进一步探讨其与HPC之间的关系。结果26例混合型肝癌伴干细胞特征（细胆管癌型）患者年龄51～82岁，中位年龄64岁。所有肿瘤标本均包括细胆管癌和肝细胞癌结构，其中细胆管癌比例占大部分，其特征为肿瘤腺体呈狭小的腔隙状或“鹿角样”排列，彼此之间吻合，纤维间质丰富；在肿瘤的边缘可见小梁样结构的肝细胞癌，这些癌细胞的异型性较小，嗜酸性胞质丰富。21例（80.8％）具有典型的肝内胆管癌结构，肿瘤细胞排列成明显的腺腔结构，纤维间质丰富，伴有黏液产生。细胆管癌、肝细胞癌样梁索状结构、肝内胆管癌在肿瘤中共存，三种组织结构之间彼此移行过渡。肿瘤周围肝组织均有慢性肝病背景，并可见反应性增生的胆小管。免疫组织化学结果显示细胆管癌区域中胆管上皮／HPC标志物（ CK7、CK9、上皮细胞膜抗原、上皮细胞黏附分子、神经细胞黏附分子、CKIT）几乎均为阳性，与反应性增生的胆小管相似；肝细胞癌样肿瘤区域， CK7和CK19均表达上皮细胞膜抗原和上皮细胞黏附分子，其阳性率分别为80.8％（21／26）和88.5％（23／26），甲胎蛋白和Hep Par-1阳性率分别为46.2％（12／26）和53.8％（14／26），神经细胞黏附分子和CKIT的阳性率分别为84.6％（22／26）和88.5％（23／26），表现出中间状态肝细胞的特点。在肝内胆管癌区域，肿瘤细胞CK7、CK19、上皮细胞膜抗原和上皮细胞黏附分子均呈弥漫强阳性，神经细胞黏附分子、CKIT、Hep Par-1和甲胎蛋白均为阴性。结论混合型肝癌伴干细胞特征（细胆管癌型）具有细胆管癌、肝细胞癌样梁索状结构、肝内胆管癌三种主要成分，结合临床病理特征及免疫组织化学标志物，提示其可能起源于HPC。

abstractsObjective To study the clinicopathologic features of combined hepatocellular-cholangiocarcinoma ( cholangiolocellular type, CLC type ) with stem cell features and its relationship to hepatic progenitor cells ( HPCs ).Methods Clinical and histologic features of 26 cases of combined hepatocellular-cholangiocarcinoma ( CLC type) were reviewed.Histochemistry was performed to confirm the type of mucin and immunohistochemical study was carried out for hepatocytic markers ( Hep Par-1 and AFP) and biliary/HPCs markers ( CK7, CK9, EMA, EpCAM, NCAM, CKIT).Results The age of patients ranged from 51 to 82 years ( mean 64 years ).All 26 cases contained CLC and hepatocellular carcinoma components.CLC area was composed of mixtures of small monotonous glands with abundant fibrous stroma and lymphocytic infiltrate.Tumor cells were cuboidal, smaller in size than normal hepatocytes, with basophilic cytoplasm and round nuclei.All cases, especially at the tumor boundary, showed HCC-like trabecular areas characterized by mildly atypical tumor cells with abundant eosinophilic cytoplasm and little stroma.Out of 26 cases, 21 showed definite glandular formation with mucin production, representing intrahepatic cholangiocarcinoma areas.The three distinct areas showed transitional zones merging with each other.The surrounding liver tissue showed cirrhosis and chronic hepatitis with varying degrees of fibrosis and periportal ductular reaction.Immunohistochemistry showed that biliary/HPC markers ( CK7, CK9, EMA, EpCAM, NCAM and CKIT) were strongly positive in CLC area in almost all cases, similar to the staining pattern of ductular reaction.In HCC-like areas, CK7 and CK19 were positive in all cases and the expression rates of EMA, EpCAM, NCAM, CKIT, AFP, Hep Par-1 were 80.8%(21/26), 88.5%(23/26), 84.6%(22/26), 88.5%(23/26), 46.2%(12/26) and 53.8%(14/26) respectively, similar to the staining pattern of intermediate hepatocytes.In ICC areas, CK7, CK9, EMA and EpCAM were positive in all cases without the expression of NCAM and CKIT. Conclusion The clinicopathologic findings and immunohistochemical results in this study highly suggest a hepatic progenitor cell origin of combined hepatocellular-cholangiocarcinoma ( CLC type).