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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 combined hepatocellular-cholangiocarcinoma with stem cell features of cholangiolocellular subtype in 58-year-old male patient with chronic hepatitis B.A. Fat-suppressed T2-weighted image revealing lobulated mass (arrow) in right posterior segment of liver with moderately high signal intensity in peripheral portion of mass. On arterial phase (B) and portal phase (C) of gadoxetic acid-enhanced MR T1-weighted images, mass demonstrates strong arterial enhancement in peripheral portion and delayed concentric enhancement without washout (arrows). D. Hepatobiliary phase T1-weighted image showing mass as clear hypointense lesion. Note hepatic surface retraction (arrowhead). E. Solid lobulated on gross examination.
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Figure 8: Pathologically confirmed combined hepatocellular-cholangiocarcinoma with stem cell features of cholangiolocellular subtype in 58-year-old male patient with chronic hepatitis B.A. Fat-suppressed T2-weighted image revealing lobulated mass (arrow) in right posterior segment of liver with moderately high signal intensity in peripheral portion of mass. On arterial phase (B) and portal phase (C) of gadoxetic acid-enhanced MR T1-weighted images, mass demonstrates strong arterial enhancement in peripheral portion and delayed concentric enhancement without washout (arrows). D. Hepatobiliary phase T1-weighted image showing mass as clear hypointense lesion. Note hepatic surface retraction (arrowhead). E. Solid lobulated on gross examination.

Mentions: Another subtype of interest is cholangiolocellular carcinoma (CLC), an extremely rare primary liver cancer. CLC was previously classified as a subtype of intrahepatic CC. The latest WHO classification has reclassified CLC as one of the stem-cell subtype of cHCC-CC (28). Although few characteristic imaging findings of each subtype of cHCC-CCs have been reported, imaging features of CLCs have been relatively more investigated than other subtypes of cHCC-CCs because CLCs resembles HCCs, particularly in patients with chronic liver disease or liver cirrhosis, or as a subtype of CCs showing atypical imaging features based on previous classification schemes (49, 50). Most CLCs are found in the peripheral portion of the liver which could be explained by the location of its cells of origin (HPCs are located in cholangioles or the canals of Hering) (20). On contrast-enhanced imaging or angiographic studies, considering that CLCs have histologically intermediate characteristics between HCCs and CCs, various dynamic enhancement patterns are expected depending on the pattern of tumor cell proliferation and the degree of fibrous stroma (50). Asayama et al. (50) reported that CLCs can show a variety of imaging features that resemble HCC and/or CC, i.e., they are either homogeneous, mosaic, or peripheral enhancement on arterial phase image of dynamic CT or MRI; they have delayed washout or concentric delayed filling; they have hypervascularity on CT hepatic angiography; they have portal perfusion defects on CT arterioportography. Motosugi et al. (49) have demonstrated that CLCs show HCC-like complete enhancement or CC-like peripheral enhancement on arterial phase and CC-like persistent enhancement on delayed phase of dynamic CT and MRI. Fukukura et al. (51) reported two cases of CLCs with obvious contrast enhancement in the peripheral portion of the tumor on the arterial and portal venous phases with concentric filling on the delayed phase. In summary, although imaging findings is not specific for the diagnosis of CLCs yet, a tumor located in the peripheral portion of the liver with HCC-like early enhancement and CC-like persistent delayed enhancement may suggest the possibility of CLCs (Figs. 5, 8). Sasaki et al. (52) recently reported that a proportion of subtypes with stem cell features of cHCC-CCs may affect clinicopathological factors. According to their study results, the CLC component in cHCC-CC was significantly correlated with the degree of fibrosis and inversely correlated with tumor size (52). Further studies on the correlation of histopathologic findings with corresponding imaging features of the different subtypes of cHCC-CCs are warranted.


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

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

Pathologically confirmed combined hepatocellular-cholangiocarcinoma with stem cell features of cholangiolocellular subtype in 58-year-old male patient with chronic hepatitis B.A. Fat-suppressed T2-weighted image revealing lobulated mass (arrow) in right posterior segment of liver with moderately high signal intensity in peripheral portion of mass. On arterial phase (B) and portal phase (C) of gadoxetic acid-enhanced MR T1-weighted images, mass demonstrates strong arterial enhancement in peripheral portion and delayed concentric enhancement without washout (arrows). D. Hepatobiliary phase T1-weighted image showing mass as clear hypointense lesion. Note hepatic surface retraction (arrowhead). E. Solid lobulated on gross examination.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 8: Pathologically confirmed combined hepatocellular-cholangiocarcinoma with stem cell features of cholangiolocellular subtype in 58-year-old male patient with chronic hepatitis B.A. Fat-suppressed T2-weighted image revealing lobulated mass (arrow) in right posterior segment of liver with moderately high signal intensity in peripheral portion of mass. On arterial phase (B) and portal phase (C) of gadoxetic acid-enhanced MR T1-weighted images, mass demonstrates strong arterial enhancement in peripheral portion and delayed concentric enhancement without washout (arrows). D. Hepatobiliary phase T1-weighted image showing mass as clear hypointense lesion. Note hepatic surface retraction (arrowhead). E. Solid lobulated on gross examination.
Mentions: Another subtype of interest is cholangiolocellular carcinoma (CLC), an extremely rare primary liver cancer. CLC was previously classified as a subtype of intrahepatic CC. The latest WHO classification has reclassified CLC as one of the stem-cell subtype of cHCC-CC (28). Although few characteristic imaging findings of each subtype of cHCC-CCs have been reported, imaging features of CLCs have been relatively more investigated than other subtypes of cHCC-CCs because CLCs resembles HCCs, particularly in patients with chronic liver disease or liver cirrhosis, or as a subtype of CCs showing atypical imaging features based on previous classification schemes (49, 50). Most CLCs are found in the peripheral portion of the liver which could be explained by the location of its cells of origin (HPCs are located in cholangioles or the canals of Hering) (20). On contrast-enhanced imaging or angiographic studies, considering that CLCs have histologically intermediate characteristics between HCCs and CCs, various dynamic enhancement patterns are expected depending on the pattern of tumor cell proliferation and the degree of fibrous stroma (50). Asayama et al. (50) reported that CLCs can show a variety of imaging features that resemble HCC and/or CC, i.e., they are either homogeneous, mosaic, or peripheral enhancement on arterial phase image of dynamic CT or MRI; they have delayed washout or concentric delayed filling; they have hypervascularity on CT hepatic angiography; they have portal perfusion defects on CT arterioportography. Motosugi et al. (49) have demonstrated that CLCs show HCC-like complete enhancement or CC-like peripheral enhancement on arterial phase and CC-like persistent enhancement on delayed phase of dynamic CT and MRI. Fukukura et al. (51) reported two cases of CLCs with obvious contrast enhancement in the peripheral portion of the tumor on the arterial and portal venous phases with concentric filling on the delayed phase. In summary, although imaging findings is not specific for the diagnosis of CLCs yet, a tumor located in the peripheral portion of the liver with HCC-like early enhancement and CC-like persistent delayed enhancement may suggest the possibility of CLCs (Figs. 5, 8). Sasaki et al. (52) recently reported that a proportion of subtypes with stem cell features of cHCC-CCs may affect clinicopathological factors. According to their study results, the CLC component in cHCC-CC was significantly correlated with the degree of fibrosis and inversely correlated with tumor size (52). Further studies on the correlation of histopathologic findings with corresponding imaging features of the different subtypes of cHCC-CCs are warranted.

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