Theise N D, Yao J L, Harada K, Hytiroglou P, Portmann B, Thung S N, Tsui W, Ohta H, Nakanuma Y
Department of Pathology, New York University Medical Center, New York, NY, USA.
Histopathology. 2003 Sep;43(3):263-71. doi: 10.1046/j.1365-2559.2003.01707.x.
Combined hepatocellular/cholangiocarcinomas have been explained by some investigators as bidirectional differentiation of neoplastic progenitor cell populations. The presence of hepatic progenitor cells has now been confirmed in humans, though whether they can give rise to malignant tumours has not been confirmed. We report four cases of small tumours identified in livers with features of chronic hepatitis which may suggest a role for malignant transformation of hepatic stem cells in hepatic malignancies.
Tumour samples were studied from four patients by histochemistry and immunohistochemistry.
Two patients had chronic hepatitis B, one had chronic hepatitis C and chronic alcoholic liver injury, and one had non-B non-C chronic hepatitis. Stages of disease ranged from portal fibrosis to cirrhosis. All tumours contained undifferentiated cells with morphological and immunohistochemical features that would be expected of hepatic progenitor cells. These cells merged with both hepatocellular carcinoma and cholangiocarcinoma components as well as with mature appearing hepatocytes within the tumours.
We suggest that these tumours are of hepatic progenitor cell origin, supporting the concepts that human hepatocarcinogenesis can be based on transformation of progenitor cells and that such a process may underlie development of some mixed hepatocellular/cholangiocarcinomas and dysplastic nodules.
一些研究者认为，肝细胞癌/胆管癌混合性肿瘤是肿瘤祖细胞群双向分化的结果。目前，人类肝脏中已证实存在肝祖细胞，但其是否会引发恶性肿瘤尚未得到证实。我们报告了4例在具有慢性肝炎特征的肝脏中发现的小肿瘤，这些肿瘤可能提示肝干细胞恶性转化在肝脏恶性肿瘤中的作用。
对4例患者的肿瘤样本进行组织化学和免疫组织化学研究。
2例患者患有慢性乙型肝炎，1例患有慢性丙型肝炎和慢性酒精性肝损伤，1例患有非乙非丙型慢性肝炎。疾病阶段从门脉纤维化到肝硬化不等。所有肿瘤均含有未分化细胞，其形态和免疫组织化学特征符合肝祖细胞的预期。这些细胞与肝细胞癌和胆管癌成分以及肿瘤内成熟的肝细胞融合。
我们认为这些肿瘤起源于肝祖细胞，这支持了人类肝癌发生可能基于祖细胞转化的观点，并且这一过程可能是一些肝细胞癌/胆管癌混合性肿瘤和发育异常结节发生的基础。
