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Cancer stem cells in primary liver cancers: pathological concepts and imaging findings.

Joo I, Kim H, Lee JM - Korean J Radiol (2015)

Bottom Line: There is accumulating evidence that cancer stem cells (CSCs) play an integral role in the initiation of hepatocarcinogenesis and the maintaining of tumor growth.Liver CSCs derived from hepatic stem/progenitor cells have the potential to differentiate into either hepatocytes or cholangiocytes.Primary liver cancers originating from CSCs constitute a heterogeneous histopathologic spectrum, including hepatocellular carcinoma, combined hepatocellular-cholangiocarcinoma, and intrahepatic cholangiocarcinoma with various radiologic manifestations.

View Article: PubMed Central - PubMed

Affiliation: Department of Radiology, Seoul National University Hospital, Seoul 110-744, Korea.

ABSTRACT
There is accumulating evidence that cancer stem cells (CSCs) play an integral role in the initiation of hepatocarcinogenesis and the maintaining of tumor growth. Liver CSCs derived from hepatic stem/progenitor cells have the potential to differentiate into either hepatocytes or cholangiocytes. Primary liver cancers originating from CSCs constitute a heterogeneous histopathologic spectrum, including hepatocellular carcinoma, combined hepatocellular-cholangiocarcinoma, and intrahepatic cholangiocarcinoma with various radiologic manifestations. In this article, we reviewed the recent concepts of CSCs in the development of primary liver cancers, focusing on their pathological and radiological findings. Awareness of the pathological concepts and imaging findings of primary liver cancers with features of CSCs is critical for accurate diagnosis, prediction of outcome, and appropriate treatment options for patients.

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Pathologically confirmed classical type of cHCC-CC.A. Portal phase CT image showing ill-defined mass (arrow) in left lobe of liver and dilated intrahepatic duct (arrowhead). B. On gross specimen showing ill-defined infiltrative solid mass (arrows). C-E. Microscopic findings revealing mixture of glandular (CC) and hepatocytic (HCC) differentiation. CC component (D) and HCC component (E) are shown in greater detail on right panel (H&E stain, × 100 (C), × 200 (D, E)). CC = cholangiocarcinoma, cHCC-CC = combined hepatocellular-cholangiocarcinoma, HCC = hepatocellular carcinoma
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Figure 2: Pathologically confirmed classical type of cHCC-CC.A. Portal phase CT image showing ill-defined mass (arrow) in left lobe of liver and dilated intrahepatic duct (arrowhead). B. On gross specimen showing ill-defined infiltrative solid mass (arrows). C-E. Microscopic findings revealing mixture of glandular (CC) and hepatocytic (HCC) differentiation. CC component (D) and HCC component (E) are shown in greater detail on right panel (H&E stain, × 100 (C), × 200 (D, E)). CC = cholangiocarcinoma, cHCC-CC = combined hepatocellular-cholangiocarcinoma, HCC = hepatocellular carcinoma

Mentions: In the 2010 WHO classification (most recent version), cHCC-CC is largely classified into two types: 1) cHCC-CC, the classical type (Fig. 2); 2) cHCC-CC with stem cell features (Figs. 3, 4, 5). The classical type of cHCC-CC is characterized by the presence of typical HCC-like and typical CC-like areas within the same tumor (Fig. 2). Separate HCCs and CCs arising in the same liver are not included in this category. HCC and CC components are also immunohistochemically compatible with hepatocytic and cholangiocytic differentiation, respectively. For example, HCC components may express HepPar1 and alpha-fetoprotein (AFP) showing canalicular patterns on CD10 or polyclonal-carcinoembryonic antigen (CEA) immunostains, whereas CC components may express biliary markers such as K19, K7, and CEA. Interestingly, in the majority of these classical cHCC-CCs, careful microscopic evaluation often reveals transitional areas that are morphologically intermediate between HCCs and CCs. Tumor cells in these areas often have morphological features that are similar to HPCs (small cells with increased nuclear/cytoplasmic ratio and hyperchromatic nuclei) expressing immunohistochemical markers of progenitor cell differentiation, such as K19, neural cell adhesion molecules (CD56), EpCAM, and c-kit (31).


Cancer stem cells in primary liver cancers: pathological concepts and imaging findings.

Joo I, Kim H, Lee JM - Korean J Radiol (2015)

Pathologically confirmed classical type of cHCC-CC.A. Portal phase CT image showing ill-defined mass (arrow) in left lobe of liver and dilated intrahepatic duct (arrowhead). B. On gross specimen showing ill-defined infiltrative solid mass (arrows). C-E. Microscopic findings revealing mixture of glandular (CC) and hepatocytic (HCC) differentiation. CC component (D) and HCC component (E) are shown in greater detail on right panel (H&E stain, × 100 (C), × 200 (D, E)). CC = cholangiocarcinoma, cHCC-CC = combined hepatocellular-cholangiocarcinoma, HCC = hepatocellular carcinoma
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4296278&req=5

Figure 2: Pathologically confirmed classical type of cHCC-CC.A. Portal phase CT image showing ill-defined mass (arrow) in left lobe of liver and dilated intrahepatic duct (arrowhead). B. On gross specimen showing ill-defined infiltrative solid mass (arrows). C-E. Microscopic findings revealing mixture of glandular (CC) and hepatocytic (HCC) differentiation. CC component (D) and HCC component (E) are shown in greater detail on right panel (H&E stain, × 100 (C), × 200 (D, E)). CC = cholangiocarcinoma, cHCC-CC = combined hepatocellular-cholangiocarcinoma, HCC = hepatocellular carcinoma
Mentions: In the 2010 WHO classification (most recent version), cHCC-CC is largely classified into two types: 1) cHCC-CC, the classical type (Fig. 2); 2) cHCC-CC with stem cell features (Figs. 3, 4, 5). The classical type of cHCC-CC is characterized by the presence of typical HCC-like and typical CC-like areas within the same tumor (Fig. 2). Separate HCCs and CCs arising in the same liver are not included in this category. HCC and CC components are also immunohistochemically compatible with hepatocytic and cholangiocytic differentiation, respectively. For example, HCC components may express HepPar1 and alpha-fetoprotein (AFP) showing canalicular patterns on CD10 or polyclonal-carcinoembryonic antigen (CEA) immunostains, whereas CC components may express biliary markers such as K19, K7, and CEA. Interestingly, in the majority of these classical cHCC-CCs, careful microscopic evaluation often reveals transitional areas that are morphologically intermediate between HCCs and CCs. Tumor cells in these areas often have morphological features that are similar to HPCs (small cells with increased nuclear/cytoplasmic ratio and hyperchromatic nuclei) expressing immunohistochemical markers of progenitor cell differentiation, such as K19, neural cell adhesion molecules (CD56), EpCAM, and c-kit (31).

Bottom Line: There is accumulating evidence that cancer stem cells (CSCs) play an integral role in the initiation of hepatocarcinogenesis and the maintaining of tumor growth.Liver CSCs derived from hepatic stem/progenitor cells have the potential to differentiate into either hepatocytes or cholangiocytes.Primary liver cancers originating from CSCs constitute a heterogeneous histopathologic spectrum, including hepatocellular carcinoma, combined hepatocellular-cholangiocarcinoma, and intrahepatic cholangiocarcinoma with various radiologic manifestations.

View Article: PubMed Central - PubMed

Affiliation: Department of Radiology, Seoul National University Hospital, Seoul 110-744, Korea.

ABSTRACT
There is accumulating evidence that cancer stem cells (CSCs) play an integral role in the initiation of hepatocarcinogenesis and the maintaining of tumor growth. Liver CSCs derived from hepatic stem/progenitor cells have the potential to differentiate into either hepatocytes or cholangiocytes. Primary liver cancers originating from CSCs constitute a heterogeneous histopathologic spectrum, including hepatocellular carcinoma, combined hepatocellular-cholangiocarcinoma, and intrahepatic cholangiocarcinoma with various radiologic manifestations. In this article, we reviewed the recent concepts of CSCs in the development of primary liver cancers, focusing on their pathological and radiological findings. Awareness of the pathological concepts and imaging findings of primary liver cancers with features of CSCs is critical for accurate diagnosis, prediction of outcome, and appropriate treatment options for patients.

Show MeSH
Related in: MedlinePlus