CT and MR imaging diagnosis and staging of hepatocellular carcinoma: part I. Development, growth, and spread: key pathologic and imaging aspects

Abstract

Computed tomography (CT) and magnetic resonance (MR) imaging play critical roles in the diagnosis and staging of hepatocellular carcinoma (HCC). The first article of this two-part review discusses key concepts of HCC development, growth, and spread, emphasizing those features with imaging correlates and hence most relevant to radiologists; state-of-the-art CT and MR imaging technique with extracellular and hepatobiliary contrast agents; and the imaging appearance of precursor nodules that eventually may transform into overt HCC.

Figure 1:

Hemodynamic and OATP expression changes during multistep hepatocarcinogenesis. Schematic drawing illustrates typical changes in intranodular hemodynamics and OATP expression during multistep hepatocarcinogenesis. As shown, multistep hepatocarcinogenesis is characterized by successive selection and expansion of less-differentiated subnodules within more well differentiated parent nodules. The subnodules grow and eventually replace (blue arrows) the parent nodules. Progressed HCCs show expansile growth (red arrows) and characteristically are encapsulated with fibrous septa. Earlier nodules lack these structures and show replacing growth. During hepatocarcinogenesis, the density of portal triads diminishes while the density of unpaired arteries increases. The net effect is that intranodular arterial supply diminishes initially and then increases (bottom graph); progressed HCCs typically show arterial hypervascularity compared with background liver, while earlier nodules typically do not. OATP expression usually diminishes progressively (top graph); progressed HCCs, early HCCs, many high-grade dysplastic nodules, and some low-grade dysplastic nodules show OATP underexpression compared with background liver. The shaded area in each graph represents the window of opportunity to detect nodules at different stages of tumor development based on net arterial flow or OATP expression; window of opportunity is larger and begins at earlier stages for OATP expression. Note that illustrations and graphs reflect typical changes in hemodynamics and OATP expression. Not all nodules exhibit the illustrated characteristics. Also note that during tumor development some stages may be skipped and not all HCCs arise from histologically definable precursor lesions. (Illustration by Matt Skalski, MD; copyright 2014, RSNA.)

Figure 2a:

Images in a 51-year-old man with HCC and hepatitis B–related cirrhosis: multiphasic CT technique. (a) There is no discernible lesion on precontrast CT image. (b) Late hepatic arterial phase image shows heterogeneously hyperenhancing mass with mosaic architecture in segment VIII. Notice enhancement of hepatic artery and portal vein branches in late hepatic arterial phase. Hepatic veins are not enhanced. (c, d) Relative to liver, mass de-enhances on (c) portal venous and (d) 3-minute delayed phase images to become isoattenuating with background parenchyma. Mass has capsule appearance in venous phases, shown to best advantage in delayed phase. Notice that hepatic veins are enhanced in portal venous and delayed phases. (e) Gross pathology photograph of resected specimen confirms progressed, encapsulated HCC with expansile growth pattern. Histologic examination showed moderately differentiated tumor (Edmondson grade II). As illustrated in this case, delayed phase may show capsule appearance more clearly than portal venous phase.

Figure 2b:

Images in a 51-year-old man with HCC and hepatitis B–related cirrhosis: multiphasic CT technique. (a) There is no discernible lesion on precontrast CT image. (b) Late hepatic arterial phase image shows heterogeneously hyperenhancing mass with mosaic architecture in segment VIII. Notice enhancement of hepatic artery and portal vein branches in late hepatic arterial phase. Hepatic veins are not enhanced. (c, d) Relative to liver, mass de-enhances on (c) portal venous and (d) 3-minute delayed phase images to become isoattenuating with background parenchyma. Mass has capsule appearance in venous phases, shown to best advantage in delayed phase. Notice that hepatic veins are enhanced in portal venous and delayed phases. (e) Gross pathology photograph of resected specimen confirms progressed, encapsulated HCC with expansile growth pattern. Histologic examination showed moderately differentiated tumor (Edmondson grade II). As illustrated in this case, delayed phase may show capsule appearance more clearly than portal venous phase.

Figure 2c:

Images in a 51-year-old man with HCC and hepatitis B–related cirrhosis: multiphasic CT technique. (a) There is no discernible lesion on precontrast CT image. (b) Late hepatic arterial phase image shows heterogeneously hyperenhancing mass with mosaic architecture in segment VIII. Notice enhancement of hepatic artery and portal vein branches in late hepatic arterial phase. Hepatic veins are not enhanced. (c, d) Relative to liver, mass de-enhances on (c) portal venous and (d) 3-minute delayed phase images to become isoattenuating with background parenchyma. Mass has capsule appearance in venous phases, shown to best advantage in delayed phase. Notice that hepatic veins are enhanced in portal venous and delayed phases. (e) Gross pathology photograph of resected specimen confirms progressed, encapsulated HCC with expansile growth pattern. Histologic examination showed moderately differentiated tumor (Edmondson grade II). As illustrated in this case, delayed phase may show capsule appearance more clearly than portal venous phase.

Figure 2d:

Images in a 51-year-old man with HCC and hepatitis B–related cirrhosis: multiphasic CT technique. (a) There is no discernible lesion on precontrast CT image. (b) Late hepatic arterial phase image shows heterogeneously hyperenhancing mass with mosaic architecture in segment VIII. Notice enhancement of hepatic artery and portal vein branches in late hepatic arterial phase. Hepatic veins are not enhanced. (c, d) Relative to liver, mass de-enhances on (c) portal venous and (d) 3-minute delayed phase images to become isoattenuating with background parenchyma. Mass has capsule appearance in venous phases, shown to best advantage in delayed phase. Notice that hepatic veins are enhanced in portal venous and delayed phases. (e) Gross pathology photograph of resected specimen confirms progressed, encapsulated HCC with expansile growth pattern. Histologic examination showed moderately differentiated tumor (Edmondson grade II). As illustrated in this case, delayed phase may show capsule appearance more clearly than portal venous phase.

Figure 2e:

Images in a 51-year-old man with HCC and hepatitis B–related cirrhosis: multiphasic CT technique. (a) There is no discernible lesion on precontrast CT image. (b) Late hepatic arterial phase image shows heterogeneously hyperenhancing mass with mosaic architecture in segment VIII. Notice enhancement of hepatic artery and portal vein branches in late hepatic arterial phase. Hepatic veins are not enhanced. (c, d) Relative to liver, mass de-enhances on (c) portal venous and (d) 3-minute delayed phase images to become isoattenuating with background parenchyma. Mass has capsule appearance in venous phases, shown to best advantage in delayed phase. Notice that hepatic veins are enhanced in portal venous and delayed phases. (e) Gross pathology photograph of resected specimen confirms progressed, encapsulated HCC with expansile growth pattern. Histologic examination showed moderately differentiated tumor (Edmondson grade II). As illustrated in this case, delayed phase may show capsule appearance more clearly than portal venous phase.

Figure 3a:

Images in 64-year-old man with HCC and hepatitis B–related cirrhosis: multiphasic MR technique with extracellular contrast agent. (a–d) Gadolinium-enhanced T1-weighted three-dimensional (3D) gradient-echo (GRE) images (repetition time msec/echo time msec, 6.3/1.9; flip angle, 15°) show large hypointense mass on (a) precontrast image with (b) hyperenhancement in late hepatic arterial phase. Notice enhancement of portal vein branches but not of hepatic vein branches in late hepatic arterial phase. (c) Portal venous and (d) 3-minute delayed phase images show persistent enhancement of tumor relative to liver. Persistent enhancement is atypical of large progressed HCCs, which characteristically appear to washout on venous phase images. Notice capsule appearance (arrow) on delayed phase image. Capsule appearance is seen to better advantage on delayed compared with portal venous phase image and permits confident diagnosis of HCC despite lack of washout appearance.

Figure 3b:

Images in 64-year-old man with HCC and hepatitis B–related cirrhosis: multiphasic MR technique with extracellular contrast agent. (a–d) Gadolinium-enhanced T1-weighted three-dimensional (3D) gradient-echo (GRE) images (repetition time msec/echo time msec, 6.3/1.9; flip angle, 15°) show large hypointense mass on (a) precontrast image with (b) hyperenhancement in late hepatic arterial phase. Notice enhancement of portal vein branches but not of hepatic vein branches in late hepatic arterial phase. (c) Portal venous and (d) 3-minute delayed phase images show persistent enhancement of tumor relative to liver. Persistent enhancement is atypical of large progressed HCCs, which characteristically appear to washout on venous phase images. Notice capsule appearance (arrow) on delayed phase image. Capsule appearance is seen to better advantage on delayed compared with portal venous phase image and permits confident diagnosis of HCC despite lack of washout appearance.

Figure 3c:

Images in 64-year-old man with HCC and hepatitis B–related cirrhosis: multiphasic MR technique with extracellular contrast agent. (a–d) Gadolinium-enhanced T1-weighted three-dimensional (3D) gradient-echo (GRE) images (repetition time msec/echo time msec, 6.3/1.9; flip angle, 15°) show large hypointense mass on (a) precontrast image with (b) hyperenhancement in late hepatic arterial phase. Notice enhancement of portal vein branches but not of hepatic vein branches in late hepatic arterial phase. (c) Portal venous and (d) 3-minute delayed phase images show persistent enhancement of tumor relative to liver. Persistent enhancement is atypical of large progressed HCCs, which characteristically appear to washout on venous phase images. Notice capsule appearance (arrow) on delayed phase image. Capsule appearance is seen to better advantage on delayed compared with portal venous phase image and permits confident diagnosis of HCC despite lack of washout appearance.

Figure 3d:

Images in 64-year-old man with HCC and hepatitis B–related cirrhosis: multiphasic MR technique with extracellular contrast agent. (a–d) Gadolinium-enhanced T1-weighted three-dimensional (3D) gradient-echo (GRE) images (repetition time msec/echo time msec, 6.3/1.9; flip angle, 15°) show large hypointense mass on (a) precontrast image with (b) hyperenhancement in late hepatic arterial phase. Notice enhancement of portal vein branches but not of hepatic vein branches in late hepatic arterial phase. (c) Portal venous and (d) 3-minute delayed phase images show persistent enhancement of tumor relative to liver. Persistent enhancement is atypical of large progressed HCCs, which characteristically appear to washout on venous phase images. Notice capsule appearance (arrow) on delayed phase image. Capsule appearance is seen to better advantage on delayed compared with portal venous phase image and permits confident diagnosis of HCC despite lack of washout appearance.

Figure 4a:

Images in 42-year-old man with HCC and hepatitis B–related cirrhosis: multiphasic MR technique with gadoxetate disodium. (a, b) Gadoxetate disodium–enhanced T1-weighted 3D GRE images (2.5/0.9; flip angle, 11°) show large hypointense mass on (a) precontrast image with (b) hyperenhancement in late hepatic arterial phase. (c) Portal venous and (d) transitional phase images show apparent washout of contrast material from tumor. (e) Mass is hypointense relative to strongly enhanced liver parenchyma on hepatobiliary phase image obtained at 20 minutes after injection. Surgical specimen confirmed progressed HCC with perilesional satellite metastases. Metastases were visible on other MR sections (not shown). Histologically, tumor was poorly differentiated (Edmondson grade III).

Figure 4b:

Images in 42-year-old man with HCC and hepatitis B–related cirrhosis: multiphasic MR technique with gadoxetate disodium. (a, b) Gadoxetate disodium–enhanced T1-weighted 3D GRE images (2.5/0.9; flip angle, 11°) show large hypointense mass on (a) precontrast image with (b) hyperenhancement in late hepatic arterial phase. (c) Portal venous and (d) transitional phase images show apparent washout of contrast material from tumor. (e) Mass is hypointense relative to strongly enhanced liver parenchyma on hepatobiliary phase image obtained at 20 minutes after injection. Surgical specimen confirmed progressed HCC with perilesional satellite metastases. Metastases were visible on other MR sections (not shown). Histologically, tumor was poorly differentiated (Edmondson grade III).

Figure 4c:

Images in 42-year-old man with HCC and hepatitis B–related cirrhosis: multiphasic MR technique with gadoxetate disodium. (a, b) Gadoxetate disodium–enhanced T1-weighted 3D GRE images (2.5/0.9; flip angle, 11°) show large hypointense mass on (a) precontrast image with (b) hyperenhancement in late hepatic arterial phase. (c) Portal venous and (d) transitional phase images show apparent washout of contrast material from tumor. (e) Mass is hypointense relative to strongly enhanced liver parenchyma on hepatobiliary phase image obtained at 20 minutes after injection. Surgical specimen confirmed progressed HCC with perilesional satellite metastases. Metastases were visible on other MR sections (not shown). Histologically, tumor was poorly differentiated (Edmondson grade III).

Figure 4d:

Images in 42-year-old man with HCC and hepatitis B–related cirrhosis: multiphasic MR technique with gadoxetate disodium. (a, b) Gadoxetate disodium–enhanced T1-weighted 3D GRE images (2.5/0.9; flip angle, 11°) show large hypointense mass on (a) precontrast image with (b) hyperenhancement in late hepatic arterial phase. (c) Portal venous and (d) transitional phase images show apparent washout of contrast material from tumor. (e) Mass is hypointense relative to strongly enhanced liver parenchyma on hepatobiliary phase image obtained at 20 minutes after injection. Surgical specimen confirmed progressed HCC with perilesional satellite metastases. Metastases were visible on other MR sections (not shown). Histologically, tumor was poorly differentiated (Edmondson grade III).

Figure 4e:

Images in 42-year-old man with HCC and hepatitis B–related cirrhosis: multiphasic MR technique with gadoxetate disodium. (a, b) Gadoxetate disodium–enhanced T1-weighted 3D GRE images (2.5/0.9; flip angle, 11°) show large hypointense mass on (a) precontrast image with (b) hyperenhancement in late hepatic arterial phase. (c) Portal venous and (d) transitional phase images show apparent washout of contrast material from tumor. (e) Mass is hypointense relative to strongly enhanced liver parenchyma on hepatobiliary phase image obtained at 20 minutes after injection. Surgical specimen confirmed progressed HCC with perilesional satellite metastases. Metastases were visible on other MR sections (not shown). Histologically, tumor was poorly differentiated (Edmondson grade III).

Figure 5a:

MR Images in 39-year-old man with liver cirrhosis and multiple cirrhotic nodules, some of which resemble dysplastic nodules at imaging. (a) Transverse T1-weighted 3D GRE in-phase image (6.6/4.4; flip angle, 12°) and (b) opposed-phase image (6.6/2.1; flip angle, 12°) show multiple iso- or hyperintense nodules in both lobes of liver. (c) Nodules are iso- or hypointense on fat-suppressed T2-weighted fast spin-echo image (3500/101). Some of the T1-hyperintense/T2-hypointense nodules are distinctive compared with background liver at MR imaging, suggesting the possibility of dysplastic nodules, but no dysplastic nodules were identified in the pathologic specimen (not shown). This case illustrates the difficulty in differentiating cirrhotic nodules and dysplastic nodules at imaging.

Figure 5b:

MR Images in 39-year-old man with liver cirrhosis and multiple cirrhotic nodules, some of which resemble dysplastic nodules at imaging. (a) Transverse T1-weighted 3D GRE in-phase image (6.6/4.4; flip angle, 12°) and (b) opposed-phase image (6.6/2.1; flip angle, 12°) show multiple iso- or hyperintense nodules in both lobes of liver. (c) Nodules are iso- or hypointense on fat-suppressed T2-weighted fast spin-echo image (3500/101). Some of the T1-hyperintense/T2-hypointense nodules are distinctive compared with background liver at MR imaging, suggesting the possibility of dysplastic nodules, but no dysplastic nodules were identified in the pathologic specimen (not shown). This case illustrates the difficulty in differentiating cirrhotic nodules and dysplastic nodules at imaging.

Figure 5c:

MR Images in 39-year-old man with liver cirrhosis and multiple cirrhotic nodules, some of which resemble dysplastic nodules at imaging. (a) Transverse T1-weighted 3D GRE in-phase image (6.6/4.4; flip angle, 12°) and (b) opposed-phase image (6.6/2.1; flip angle, 12°) show multiple iso- or hyperintense nodules in both lobes of liver. (c) Nodules are iso- or hypointense on fat-suppressed T2-weighted fast spin-echo image (3500/101). Some of the T1-hyperintense/T2-hypointense nodules are distinctive compared with background liver at MR imaging, suggesting the possibility of dysplastic nodules, but no dysplastic nodules were identified in the pathologic specimen (not shown). This case illustrates the difficulty in differentiating cirrhotic nodules and dysplastic nodules at imaging.

Figure 6a:

MR Images in 55-year-old man with low-grade dysplastic nodule and hepatitis B–related cirrhosis. A 1-cm nodule (arrow) near the hepatic capsule in segment V is minimally hyperintense relative to adjacent parenchyma on T1-weighted (a) in-phase image (7.8/5.2) and (b) opposed-phase image (7.8/2.3). (c) Nodule (arrow) is hypointense on T2-weighted fast-recovery fast spin-echo image (3500/101) and (d) isointense (arrow) on precontrast T1-weighted 3D GRE (4.5/2.2; 12° flip angle) image. (e) At gross pathologic examination, nodule (arrow) differs in size and color from background nodules, the gross pathologic definition of a dysplastic nodule. Histologically, cellular atypia was absent, and a diagnosis of low-grade dysplastic nodule was made.

Figure 6b:

MR Images in 55-year-old man with low-grade dysplastic nodule and hepatitis B–related cirrhosis. A 1-cm nodule (arrow) near the hepatic capsule in segment V is minimally hyperintense relative to adjacent parenchyma on T1-weighted (a) in-phase image (7.8/5.2) and (b) opposed-phase image (7.8/2.3). (c) Nodule (arrow) is hypointense on T2-weighted fast-recovery fast spin-echo image (3500/101) and (d) isointense (arrow) on precontrast T1-weighted 3D GRE (4.5/2.2; 12° flip angle) image. (e) At gross pathologic examination, nodule (arrow) differs in size and color from background nodules, the gross pathologic definition of a dysplastic nodule. Histologically, cellular atypia was absent, and a diagnosis of low-grade dysplastic nodule was made.

Figure 6c:

MR Images in 55-year-old man with low-grade dysplastic nodule and hepatitis B–related cirrhosis. A 1-cm nodule (arrow) near the hepatic capsule in segment V is minimally hyperintense relative to adjacent parenchyma on T1-weighted (a) in-phase image (7.8/5.2) and (b) opposed-phase image (7.8/2.3). (c) Nodule (arrow) is hypointense on T2-weighted fast-recovery fast spin-echo image (3500/101) and (d) isointense (arrow) on precontrast T1-weighted 3D GRE (4.5/2.2; 12° flip angle) image. (e) At gross pathologic examination, nodule (arrow) differs in size and color from background nodules, the gross pathologic definition of a dysplastic nodule. Histologically, cellular atypia was absent, and a diagnosis of low-grade dysplastic nodule was made.

Figure 6d:

MR Images in 55-year-old man with low-grade dysplastic nodule and hepatitis B–related cirrhosis. A 1-cm nodule (arrow) near the hepatic capsule in segment V is minimally hyperintense relative to adjacent parenchyma on T1-weighted (a) in-phase image (7.8/5.2) and (b) opposed-phase image (7.8/2.3). (c) Nodule (arrow) is hypointense on T2-weighted fast-recovery fast spin-echo image (3500/101) and (d) isointense (arrow) on precontrast T1-weighted 3D GRE (4.5/2.2; 12° flip angle) image. (e) At gross pathologic examination, nodule (arrow) differs in size and color from background nodules, the gross pathologic definition of a dysplastic nodule. Histologically, cellular atypia was absent, and a diagnosis of low-grade dysplastic nodule was made.

Figure 6e:

MR Images in 55-year-old man with low-grade dysplastic nodule and hepatitis B–related cirrhosis. A 1-cm nodule (arrow) near the hepatic capsule in segment V is minimally hyperintense relative to adjacent parenchyma on T1-weighted (a) in-phase image (7.8/5.2) and (b) opposed-phase image (7.8/2.3). (c) Nodule (arrow) is hypointense on T2-weighted fast-recovery fast spin-echo image (3500/101) and (d) isointense (arrow) on precontrast T1-weighted 3D GRE (4.5/2.2; 12° flip angle) image. (e) At gross pathologic examination, nodule (arrow) differs in size and color from background nodules, the gross pathologic definition of a dysplastic nodule. Histologically, cellular atypia was absent, and a diagnosis of low-grade dysplastic nodule was made.

Figure 7a:

MR images in a 58-year-old man with fat-containing high-grade dysplastic nodule and hepatitis B–related cirrhosis. (a, b) Axial dual-echo GRE images show a nodule in segment VII of liver. Nodule loses signal intensity on (b) out-of-phase (7.8/2.3) image compared with (a) in-phase (7.8/5.1) image, indicating intralesional fat. (c) Nodule is isointense on T2-weighted fast-recovery fast spin-echo (3500/101) image. (d) Nodule is hypointense on hepatobiliary phase image, which favors a diagnosis of high-grade dysplastic nodule or early HCC over low-grade dysplastic nodule or cirrhotic nodule. Notice nodule-in-nodule architecture on hepatobiliary phase image, which raises concern for an incipient HCC subnodule developing within a parent dysplastic nodule. Percutaneous needle biopsy with histologic analysis was consistent with high-grade dysplastic nodule with fatty change. Sampling errors may occur with biopsy, and it is possible that an HCC subnodule was missed.

Figure 7b:

MR images in a 58-year-old man with fat-containing high-grade dysplastic nodule and hepatitis B–related cirrhosis. (a, b) Axial dual-echo GRE images show a nodule in segment VII of liver. Nodule loses signal intensity on (b) out-of-phase (7.8/2.3) image compared with (a) in-phase (7.8/5.1) image, indicating intralesional fat. (c) Nodule is isointense on T2-weighted fast-recovery fast spin-echo (3500/101) image. (d) Nodule is hypointense on hepatobiliary phase image, which favors a diagnosis of high-grade dysplastic nodule or early HCC over low-grade dysplastic nodule or cirrhotic nodule. Notice nodule-in-nodule architecture on hepatobiliary phase image, which raises concern for an incipient HCC subnodule developing within a parent dysplastic nodule. Percutaneous needle biopsy with histologic analysis was consistent with high-grade dysplastic nodule with fatty change. Sampling errors may occur with biopsy, and it is possible that an HCC subnodule was missed.

Figure 7c:

MR images in a 58-year-old man with fat-containing high-grade dysplastic nodule and hepatitis B–related cirrhosis. (a, b) Axial dual-echo GRE images show a nodule in segment VII of liver. Nodule loses signal intensity on (b) out-of-phase (7.8/2.3) image compared with (a) in-phase (7.8/5.1) image, indicating intralesional fat. (c) Nodule is isointense on T2-weighted fast-recovery fast spin-echo (3500/101) image. (d) Nodule is hypointense on hepatobiliary phase image, which favors a diagnosis of high-grade dysplastic nodule or early HCC over low-grade dysplastic nodule or cirrhotic nodule. Notice nodule-in-nodule architecture on hepatobiliary phase image, which raises concern for an incipient HCC subnodule developing within a parent dysplastic nodule. Percutaneous needle biopsy with histologic analysis was consistent with high-grade dysplastic nodule with fatty change. Sampling errors may occur with biopsy, and it is possible that an HCC subnodule was missed.

Figure 7d:

MR images in a 58-year-old man with fat-containing high-grade dysplastic nodule and hepatitis B–related cirrhosis. (a, b) Axial dual-echo GRE images show a nodule in segment VII of liver. Nodule loses signal intensity on (b) out-of-phase (7.8/2.3) image compared with (a) in-phase (7.8/5.1) image, indicating intralesional fat. (c) Nodule is isointense on T2-weighted fast-recovery fast spin-echo (3500/101) image. (d) Nodule is hypointense on hepatobiliary phase image, which favors a diagnosis of high-grade dysplastic nodule or early HCC over low-grade dysplastic nodule or cirrhotic nodule. Notice nodule-in-nodule architecture on hepatobiliary phase image, which raises concern for an incipient HCC subnodule developing within a parent dysplastic nodule. Percutaneous needle biopsy with histologic analysis was consistent with high-grade dysplastic nodule with fatty change. Sampling errors may occur with biopsy, and it is possible that an HCC subnodule was missed.