Malignant Focal Liver Lesions of Hepatocellular Origin

From Regenerative Nodules to Hepatocellular Carcinoma (HCC)

According to the terminology established by an International Working Party in 1994, there are three steps in the development of HCC: regenerative nodule, dysplastic nodule (low-grade; high-grade; with focus of HCC) and small (< 2 cm) HCC.

Regenerative nodules are benign lesions with an exclusive portal venous blood supply. Low-grade dysplastic nodules, on the other hand, show slight cytologic atypia with mainly large cell changes, while high-grade dysplastic nodules are considered pre-malignant lesions. The development of new non-triadal arterial flow to small HCC and dysplastic nodules can result in some enhancement of dysplastic nodules at contrast-enhanced CT and MR and thus simulate HCC. However, this is comparatively rare [11,17]. Small foci of carcinoma can be found in about one third of high-grade dysplastic nodules. When elements of HCC are found in lesions smaller than 2 cm in size, they are termed "small HCC".

Dysplastic nodules are commonly encountered pathologically in severe cirrhosis. However, only about 15% of such nodules are detected at MR imaging. When visualized, dysplastic nodules are typically hyperintense on T1-weighted images and hy-pointense on T2-weighted images [14]. However, since most are not seen, the most common appearance is therefore isointense compared to the surrounding liver parenchyma. Although arterial phase enhancement can increase the sensitivity for characterization of dysplastic nodules, this is at the expense of decreased specificity because of the overlap with the much more commonly seen arterial phase enhancement in HCC.

The nature of nodular regeneration in cirrhosis, and the development of dysplastic nodules may lead to additional false-positive diagnoses of HCC. MR imaging is now widely considered the most successful imaging modality for differentiating regenerative and dysplastic nodules from HCC. Regenerating nodules may have altered SI depending on whether or not they contain hemosiderin. Regenerating nodules without hemosiderin are typically iso- to slightly hyperintense on T1-weighted images and iso- or mildly hypointense on T2-weighted images. Those with hemosiderin are more hypointense on T2-weighted images due to their iron content (Fig. 15, 16). While dysplastic nodules have been reported to have low SI foci on T2-weighted images, and slightly hyperintense foci on T1-weighted images, most dysplastic nodules remain isointense with the cirrhotic liver, and it is generally only large, occasional dysplastic nodules that are identified at MR. The signal changes in dysplastic nodules also reflect the accumulation of iron and hemosiderin products (Fig. 17).

The macroscopic appearance of HCC has been classified as expanding, spreading and multifocal. On the basis of histological differentiation they can be classified as belonging to one of four grades, from I to IV. A frequent occurrence in small HCC is fatty degeneration. However, while this is seen microscopically, it is only rarely appreciated at imaging.

The formation of a pseudocapsule around the lesion (constructed usually from connective fibrous tissue) and of a septum within the tumor is frequently observed in larger HCC. This may derive from an interaction between tumor and host liver and may interfere with the growth and invasion of the HCC [9]. The internal septation process as well as the heterogeneity inherent within larger lesions due to macroscopic fat accumulation, hemorrhage, necrosis, and fibrosis creates a relatively characteristic 'mosaic' appearance (see Chapter 6, Fig. 16,17) [29].

Kupffer cells are usually present in HCC. Although the number of Kupffer cells tends to be lower in cancerous compared to non-cancerous tissue, particularly as the tumor size increases and histologic grade decreases, there are typically few differences in Kupffer cell number in small well-differentiated HCC and non-cancerous tissues.

Many factors affect the visualization of primary HCC during unenhanced and/or contrast-enhanced MR imaging of the liver: the dimensions, composition and degree of vascularization of the lesion, and the functionality of the normal hepatic parenchyma and the residual hepatic function of the neoplastic cells themselves. Unfortunately such factors vary from patient to patient, often making the behavior of a given HCC lesion difficult to predict. Studies aimed at correlating the appearance of HCC on MR imaging with the pathologic characteristics of the lesion reflect the difficulty in drawing firm conclusions on the behavior of such lesions [5].

A large number of usually small HCC are isointense on T1- and T2-weighted imaging. When visualized, HCC typically appear mildly to moderately hyperintense at turbo spin echo (TSE) T2-weighted and/or short TI inversion-recovery (STIR) imaging. On T1-weighted images, increased SI correlates more strongly with a well-differentiated histologic grade than does iso- or hypointen-sity [22]. Hyperintensity on T1-weighted images is related to several factors, such as fatty metamorphosis, glycogen, clear cells and copper.

Dynamic T1-weighted imaging during the arte-

Dynamic Liver Mri

Fig. 15a-g. Regenerative nodule after Gd-BOPTA. The pre-contrast T2-weighted image (a) reveals a small, round hypointense nodule (arrows). The lesion is slightly hyperintense on the pre-contrast GRE T1-weighted "in-phase" image (b) and homogeneously markedly hyperintense on the corresponding GRE Tl-weighted "out-of-phase" image (c). Significant enhancement is not seen during the dynamic Tl-weighted series (d-f) after Gd-BOPTA administration. On the Tl-weighted fat-suppressed image (g) acquired during the hepatobiliary phase, the regenerative nodule appears isointense, due to the uptake of Gd-BOPTA

Liver Lesions Mri

Fig. 16a-f. Regenerative nodule after SH U 555 A. On the pre-contrast HASTE T2-weighted image (a) a round, well-defined slightly hyperintense nodule (arrows) with a thin hypointense rim is visible. On the pre-contrast GRE Tl-weighted "in-phase" image (b) the lesion appears homogeneously hyperintense, while on the corresponding GRE Tl-weighted "out-of-phase" image (c) it appears slightly hypointense. On the pre-contrast VIBE image (d) the lesion appears isointense compared to the surrounding normal liver parenchyma. During the arterial phase after SH U 555 A injection (e) the nodule does not show enhancement, while in the reticuloendothelial phase (f) the lesion shows significant signal drop, which indicates a benign lesion containing Kupffer cells

Fig. 16a-f. Regenerative nodule after SH U 555 A. On the pre-contrast HASTE T2-weighted image (a) a round, well-defined slightly hyperintense nodule (arrows) with a thin hypointense rim is visible. On the pre-contrast GRE Tl-weighted "in-phase" image (b) the lesion appears homogeneously hyperintense, while on the corresponding GRE Tl-weighted "out-of-phase" image (c) it appears slightly hypointense. On the pre-contrast VIBE image (d) the lesion appears isointense compared to the surrounding normal liver parenchyma. During the arterial phase after SH U 555 A injection (e) the nodule does not show enhancement, while in the reticuloendothelial phase (f) the lesion shows significant signal drop, which indicates a benign lesion containing Kupffer cells

Fig. 17a-h. Dysplastic nodule after Gd-EOB-DTPA and Gd-BOPTA. The pre-contrast T2-weighted image (a) reveals a slightly hypointense lesion (arrows) located in segment VIII of the liver. On the pre-contrast GRE Tl-weighted image (b) the nodule appears hyperintense, while on the pre-contrast VIBE image (c) it appears slightly hyperintense, coexisting with a round, vascular malformation near the right branch of the portal vein (asterisk in b). The solid lesion does not show evident enhancement on the arterial phase image (d) acquired during the dynamic study after Gd-EOB-DTPA administration. During the portal venous (e) and equilibrium (f) phases the lesion appears heteroge-neously hypointense. In the hepatobiliary phase after Gd-EOB-DTPA (g), the nodule is slightly hypointense compared to the normal liver parenchyma. On the hepatobiliary phase image (h) acquired after Gd-BOPTA administration the nodule is isointense with respect to the surrounding liver parenchyma

Fig. 17a-h. Dysplastic nodule after Gd-EOB-DTPA and Gd-BOPTA. The pre-contrast T2-weighted image (a) reveals a slightly hypointense lesion (arrows) located in segment VIII of the liver. On the pre-contrast GRE Tl-weighted image (b) the nodule appears hyperintense, while on the pre-contrast VIBE image (c) it appears slightly hyperintense, coexisting with a round, vascular malformation near the right branch of the portal vein (asterisk in b). The solid lesion does not show evident enhancement on the arterial phase image (d) acquired during the dynamic study after Gd-EOB-DTPA administration. During the portal venous (e) and equilibrium (f) phases the lesion appears heteroge-neously hypointense. In the hepatobiliary phase after Gd-EOB-DTPA (g), the nodule is slightly hypointense compared to the normal liver parenchyma. On the hepatobiliary phase image (h) acquired after Gd-BOPTA administration the nodule is isointense with respect to the surrounding liver parenchyma rial phase is important for the detection of small HCC, because these may be occult at other pulse sequences and on portal venous and equilibrium phase images (Fig. 18). As HCC is a hypervascular lesion, characterized by abundant neoangiogene-sis, these lesions typically demonstrate arterial enhancement at dynamic imaging. The enhancement is mainly intense and homogeneous in small non-necrotic lesions, while it may appear heterogeneous and less intense in large necrotic or hemor-rhagic nodules. In about 10% of cases HCC may appear hypointense (Figs. 19, 20). Contrast agent wash-out during the portal venous phase is also typical of HCC.

The pseudocapsule of HCC usually appears hypointense on unenhanced T1- and T2-weighted images. On enhanced MR imaging with Gd-based contrast agents, enhancement of the pseudocapsule is seen principally on portal venous phase images although initial enhancement may be seen in the late arterial phase. As is typical of fibrous tissues, the enhancement usually persists into the equilibrium phase. Contrast agent wash-out from the lesion parenchyma means that the capsule is usually more prominent in the equilibrium phase [9].

Whereas dynamic phase imaging of HCC with Gd-BOPTA and Gd-EOB-DTPA gives similar results to that seen with conventional Gd agents, delayed phase imaging reveals a number of different enhancement patterns, with both iso-, hypo- and hyperintense patterns possible (Figs. 19, 20, and see Chap. 6, Fig. 16). Generally, moderately-differentiated lesions tend to enhance to a greater extent on delayed images than well-or poorly-differentiated lesions [5]. In a recent retrospective analysis of 94 HCC evaluated with Gd-BOPTA, 89.4% were hypointense in the delayed phase, compared with only 3.2% and 7.4% that were hyper- and isointense, respectively [5] (Figs. 21, 22). Elsewhere it has been shown that well- and moderately-differentiated HCC demonstrate superior signal enhancement ratios to poorly-differentiated HCC on images acquired at 0.5 Tesla at 60-120 min after Gd-BOPTA administration [18]. This finding reflects the retention of sufficient hepatocytic activity in these lesions to allow take-up of Gd-BOPTA. In this regard, a significant correlation has been observed between the presence of intra-lesional bile and the degree of lesion enhancement after Gd-BOPTA administration [5,18].

HCC typically show heterogeneous enhancement with the hepatobiliary agent mangafodipir trisodium [21]. Well-differentiated HCC enhance to a greater extent than poorly-differentiated HCC. A rim-like enhancement on mangafodipir trisodi-um-enhanced MR images may be indicative of peritumoral infiltration of malignant cells into neighboring normal liver parenchyma resulting in intermingling of malignant cells with normal functioning hepatocytes in the peripheral region. However, such a finding has also been reported for CCC and metastases and may be due to compression of the surrounding normal liver tissue.

Post-mangafodipir trisodium MR imaging has been shown to result in a more accurate differentiation between benign (FNH) and malignant (HCC) hepatocellular tumors than unenhanced MR imaging alone, although overlapping enhancement behavior is more common with this agent than with Gd-based hepatobiliary agents [3]. On delayed images after mangafodipir trisodium infusion, most moderate and well-differentiated lesions are hypointense (Fig. 23).

HCC lesions generally do not show a significant decrease in SI after administration of SPIO contrast agents, although SI loss has been seen in some individual HCC [12].

The conspicuity of HCC after SPIO depends on differences in the number of Kupffer cells between the lesion and the surrounding liver. Typically, moderately- or poorly-differentiated HCC show large differences in the number of Kupffer cells compared to the surrounding liver and thus demonstrate a high contrast-to-noise ratio at SPIO-enhanced MR imaging, particularly in cir-rhotic livers (see Chap. 6, Figs. 21a, 21f). Dysplastic nodules and most well-differentiated HCC, on the other hand, contain nearly the same number of Kupffer cells as the surrounding cirrhotic hepatic parenchyma and therefore are not well-depicted on T2-weighted MR images [12]. Focal HCC degeneration within dysplastic nodules can be detected with SPIO agents as areas of hyperintensity which do not show significant signal drop in comparison with the surrounding dysplastic non-neo-plastic portion. This results in a typical "nodule in nodule" appearance (Fig. 24).

As regards the detection of HCC, there are conflicting reports as to whether dynamic Gd-en-hanced MR imaging or SPIO-enhanced imaging is preferable. Tang et al. [30] found significantly more lesions on Gd-enhanced MR images than on SPIO-enhanced MR images in 53 patients (97 of 103 versus 80 of 103, P < 0.01) (see Chapter 6, Fig.15) whereas Vogl et al. [32] detected more HCC lesions with SPIO-enhanced MR imaging than with dynamic Gd-enhanced MR imaging. Pauleit et al. [23] found that unenhanced and Gd-enhanced MR imaging was significantly more sensitive and accurate than SPIO-enhanced imaging for the detection of small HCC but that SPIO-enhanced imaging was superior for the detection of large HCC, albeit non-significantly. Analysis of all HCC revealed no significant differences for Gd- and SPIO-enhanced imaging.

Fig. 18a-e. Small HCC on unenhanced and dynamic imaging after Gd-BOPTA. On the pre-contrast T2-weighted (a) and T1-weighted (b) images, no focal lesions are visible. During the arterial phase (c) after Gd-BOPTA administration, a well-defined hyperintense nodule (arrows) can be seen. Rapid contrast agent wash-out from the lesion occurs during the portal venous phase (d), resulting in the lesion appearing slightly hyperintense to isointense in the equilibrium phase (e). A thin hyperintense pseudocapsule (arrowhead) can be seen in the equilibrium phase

Liver Lesions Mri

Fig. 19a-f. Hypovascular HCC and cavernous hemangioma after Gd-BOPTA. On the pre-contrast T2-weighted image (a) a round heterogeneous, slightly hyperintense nodule (arrows) and a heterogeneously hyperintense lesion (arrowheads) can be seen. The corresponding pre-contrast GRE Tl-weighted image (b) reveals a well-defined heterogeneous, slightly hypointense nodule (arrows), and a homogeneously hypointense lesion (arrowheads) (b). On the arterial phase image (c) of the dynamic series after Gd-BOPTA injection, the round nodule (arrow) shows weak and irregular enhancement, while an initial nodular peripheral enhancement (arrowheads) can be observed in the other lesion. This latter behavior is suggestive of hemangioma. On the portal venous (d) and equilibrium (e) phase images the cavernous hemangioma shows progressive centripetal enhancement, while the round nodule appears consistently hypointense with a thin hyperintense pseudocapsule (arrowhead in d). This enhancement pattern is suggestive for HCC. Both lesions are heterogeneously hypointense on the delayed hepatobiliary phase image (f)

Fig. 19a-f. Hypovascular HCC and cavernous hemangioma after Gd-BOPTA. On the pre-contrast T2-weighted image (a) a round heterogeneous, slightly hyperintense nodule (arrows) and a heterogeneously hyperintense lesion (arrowheads) can be seen. The corresponding pre-contrast GRE Tl-weighted image (b) reveals a well-defined heterogeneous, slightly hypointense nodule (arrows), and a homogeneously hypointense lesion (arrowheads) (b). On the arterial phase image (c) of the dynamic series after Gd-BOPTA injection, the round nodule (arrow) shows weak and irregular enhancement, while an initial nodular peripheral enhancement (arrowheads) can be observed in the other lesion. This latter behavior is suggestive of hemangioma. On the portal venous (d) and equilibrium (e) phase images the cavernous hemangioma shows progressive centripetal enhancement, while the round nodule appears consistently hypointense with a thin hyperintense pseudocapsule (arrowhead in d). This enhancement pattern is suggestive for HCC. Both lesions are heterogeneously hypointense on the delayed hepatobiliary phase image (f)

Nodular Enhancement Mri

Fig. 20a-d. Hypovascular HCC and cavernous hemangioma after Gd-EOB-DTPA. Same case as shown in Fig. 19. The pre-contrast GRE Tl-weighted image (a) reveals a well-defined heterogeneous, slightly hypointense nodule (arrows) and a homogeneously hypointense lesion (arrowheads). During the dynamic study after Gd-EOB-DTPA administration (b, c), the enhancement behavior is similar to that observed after Gd-BOPTA administration. Likewise, both lesions appear hypointense compared to the normal liver during the hepatobiliary phase (d) after Gd-EOB-DTPA administration

Fig. 20a-d. Hypovascular HCC and cavernous hemangioma after Gd-EOB-DTPA. Same case as shown in Fig. 19. The pre-contrast GRE Tl-weighted image (a) reveals a well-defined heterogeneous, slightly hypointense nodule (arrows) and a homogeneously hypointense lesion (arrowheads). During the dynamic study after Gd-EOB-DTPA administration (b, c), the enhancement behavior is similar to that observed after Gd-BOPTA administration. Likewise, both lesions appear hypointense compared to the normal liver during the hepatobiliary phase (d) after Gd-EOB-DTPA administration

Desgarro Muscular Cuadriceps Resonancia

Fig. 21a, b. Well-differentiated HCC after Gd-BOPTA. The pre-contrast GRE T1-weighted image (a) reveals an isointense nodule (arrows) with a thin peripheral hypointense rim. In the hepatobiliary phase after Gd-BOPTA administration (b), the nodule is slightly hyperintense compared to the normal liver parenchyma. The malignant cells in the well-differentiated HCC retain the ability to take up Gd-BOPTA

Fig. 21a, b. Well-differentiated HCC after Gd-BOPTA. The pre-contrast GRE T1-weighted image (a) reveals an isointense nodule (arrows) with a thin peripheral hypointense rim. In the hepatobiliary phase after Gd-BOPTA administration (b), the nodule is slightly hyperintense compared to the normal liver parenchyma. The malignant cells in the well-differentiated HCC retain the ability to take up Gd-BOPTA

Micronodular Cirrhosis Mri

Fig. 22a, b. Poorly-differentiated HCC in liver cirrhosis after Gd-BOPTA. The pre-contrast GRE T1-weighted image (a) reveals a homogeneously isointense nodule (arrows) with a thin peripheral hypointense rim. Note the micronodular transformation of the liver by advanced cirrhosis. In the hepatobiliary phase after Gd-BOPTA administration (b), the nodule appears homogeneously hypointense compared to the normal liver parenchyma. In poorly-differentiated HCC the malignant cells are not able to take up Gd-BOPTA

Fig. 22a, b. Poorly-differentiated HCC in liver cirrhosis after Gd-BOPTA. The pre-contrast GRE T1-weighted image (a) reveals a homogeneously isointense nodule (arrows) with a thin peripheral hypointense rim. Note the micronodular transformation of the liver by advanced cirrhosis. In the hepatobiliary phase after Gd-BOPTA administration (b), the nodule appears homogeneously hypointense compared to the normal liver parenchyma. In poorly-differentiated HCC the malignant cells are not able to take up Gd-BOPTA

Mri Images Liver Cancer

Fig. 23a-h. Moderately-differentiated HCC after Gd-BOPTA and Mn-DPDP. The pre-contrast HASTE T2-weighted image (a) reveals a round, heterogeneously hyperintense nodule (arrows). On the pre-contrast GRE Tl-weighted "in-phase" (b) and "out-of-phase" (c) images the lesion appears hyper- and hypointense, respectively, compared to the normal liver parenchyma. On the arterial phase image (d) of the dynamic series after Gd-BOPTA injection, the nodule demonstrates marked and heterogeneous enhancement. Rapid wash-out of contrast agent is noted in the subsequent portal venous (e) and equilibrium (f) phases. In the hepatobiliary phase after Gd-BOPTA (g) and Mn-DPDP (h) administration the lesion is hypointense due to the lack of contrast agent uptake by the malignant hepatocytes

Fig. 23a-h. Moderately-differentiated HCC after Gd-BOPTA and Mn-DPDP. The pre-contrast HASTE T2-weighted image (a) reveals a round, heterogeneously hyperintense nodule (arrows). On the pre-contrast GRE Tl-weighted "in-phase" (b) and "out-of-phase" (c) images the lesion appears hyper- and hypointense, respectively, compared to the normal liver parenchyma. On the arterial phase image (d) of the dynamic series after Gd-BOPTA injection, the nodule demonstrates marked and heterogeneous enhancement. Rapid wash-out of contrast agent is noted in the subsequent portal venous (e) and equilibrium (f) phases. In the hepatobiliary phase after Gd-BOPTA (g) and Mn-DPDP (h) administration the lesion is hypointense due to the lack of contrast agent uptake by the malignant hepatocytes

Fig. 24a-i. Dysplastic nodule and focal HCC degeneration after SH U 555 A. The pre-contrast HASTE T2-weighted image (a) reveals a round, well-defined slightly hypointense nodule (arrows). On the pre-contrast GRE Tl-weighted "in-phase" (b), "out-of-phase" (c), and VIBE (d) images, the lesion appears hyperintense, most likely due to glycogen content. Only minimal enhancement is seen on images acquired during the dynamic series after SH U 555 A administration (e-g) although a thin and complete hyperintense peripheral rim is clearly visible. The VIBE image (h) acquired during the delayed phase reveals an intra-lesional round, slightly hyperintense nodule (arrowhead). A corresponding delayed GRE Tl-weighted image (i) reveals a marked hyperintensity of the intranodular lesion (arrowhead, giving it the "nodule within a nodule" aspect suggestive of focal HCC in a dysplastic nodule

10 Ways To Fight Off Cancer

10 Ways To Fight Off Cancer

Learning About 10 Ways Fight Off Cancer Can Have Amazing Benefits For Your Life The Best Tips On How To Keep This Killer At Bay Discovering that you or a loved one has cancer can be utterly terrifying. All the same, once you comprehend the causes of cancer and learn how to reverse those causes, you or your loved one may have more than a fighting chance of beating out cancer.

Get My Free Ebook


Post a comment