Feng Jiliang, Zhu Ruidong, Yin Yu, Wang Shanshan, Zhou Lei, Lv Fudong, Zhao Dawei
Clinical-Pathology Center, Beijing You-An Hospital, Capital Medical University, Beijing, 100069, People's Republic of China.
General Surgical Center, Beijing You-An Hospital, Capital Medical University, Beijing, 100069, People's Republic of China.
J Hepatocell Carcinoma. 2021 Dec 7;8:1537-1563. doi: 10.2147/JHC.S334935. eCollection 2021.
The primary epithelial tumors of the liver (PETL) are composed of a series of heterogeneous tumors. Although the classification of PETLs has been updated several times by the World Health Organization, the cellular origins of some tumors in this family remain to be precisely depicted. In addition, certain tumors in different categories have similar histology, molecular phenotypes and biological characteristics, suggesting that they may have the same cellular origin. In this work, a narrative review method was adopted to review the relevant papers. By comparing the expression profiles of biomarkers of liver epithelium at different lineages and stages of differentiation, the cells-of-origin of some major members of the PETL family were reassessed. We propose that 1) hepatic adenomas, hepatocellular carcinomas (HCCs) and pure fetal hepatoblastomas (HBs) share the same spectrum in their cellular origin including the hepatocytic-committed progenitors (HCP) and their differentiated descendants. 2) Bile duct adenomas, peribiliary cysts and intrahepatic cholangiocellular carcinomas (ICCs) can share the same spectrum in their cellular origin including the cholangiocytic-committed progenitors (CCP) and their differentiated descendants. 3) The cells-of-origin of embryonal HBs include liver stem cells (LSCs), hepatoblasts, and transitional cells between them. Embryonal HB with small cell element, small cell undifferentiated HB and small cell neuroendocrine carcinoma of the liver can have the same or similar cells-of-origin from LSC. Embryonal HB lacking the small cell component of the LSC phenotype and presenting both hepatocytic and bile duct/ductule components may originate from actual hepatoblasts/hepatic progenitor cells (HPCs) as the combined HCC-ICC does. 4) Teratoid hepatoblastoma and mixed epithelial/mesenchymal HBs can be derived from the LSCs or even less committed extrahepatic pluripotent stem cell. 5) Many members of the PETLs family, including those derived from LSCs, hepatoblasts/HPCs, early HCPs and CCPs, have neuroendocrine potentiality. Except for those primary hepatic neuroendocrine tumor (PHNET) exhibit hepatocytic and/or cholangiocytic phenotypes, other PHNETs subtype may be derived from the descendants of LSC that differentiate towards the upper digestive tract, pancreas or other lineages.
肝脏原发性上皮性肿瘤（PETL）由一系列异质性肿瘤组成。尽管世界卫生组织已多次更新PETL的分类，但该家族中某些肿瘤的细胞起源仍有待精确描述。此外，不同类别中的某些肿瘤具有相似的组织学、分子表型和生物学特征，这表明它们可能具有相同的细胞起源。在这项工作中，采用叙述性综述方法回顾相关论文。通过比较肝脏上皮生物标志物在不同谱系和分化阶段的表达谱，对PETL家族一些主要成员的起源细胞进行了重新评估。我们提出：1）肝腺瘤、肝细胞癌（HCC）和纯胎儿型肝母细胞瘤（HB）在细胞起源方面具有相同的谱系，包括肝祖细胞（HCP）及其分化后代。2）胆管腺瘤、胆管周围囊肿和肝内胆管细胞癌（ICC）在细胞起源方面可具有相同的谱系，包括胆管祖细胞（CCP）及其分化后代。3）胚胎型HB的起源细胞包括肝干细胞（LSC）、肝母细胞以及它们之间的过渡细胞。具有小细胞成分的胚胎型HB、小细胞未分化型HB和肝脏小细胞神经内分泌癌可具有相同或相似的起源于LSC的细胞。缺乏LSC表型小细胞成分且同时具有肝细胞和胆管/胆小管成分的胚胎型HB可能起源于实际的肝母细胞/肝祖细胞（HPC），如同混合性HCC-ICC一样。4）畸胎样肝母细胞瘤和混合性上皮/间叶性HB可源自LSC，甚至是分化程度更低的肝外多能干细胞。5）PETL家族的许多成员，包括那些源自LSC、肝母细胞/HPC、早期HCP和CCP的成员，具有神经内分泌潜能。除了那些表现出肝细胞和/或胆管细胞表型的原发性肝脏神经内分泌肿瘤（PHNET）外，其他PHNET亚型可能源自向消化道上段、胰腺或其他谱系分化的LSC后代。
