Imaging of Focal Liver Lesions

Imaging of Focal Liver Lesions

Imaging of Focal Liver Lesions Hyun-Jung Jang, MD, Hojun Yu, MD, and Tae Kyoung Kim, MD With a popular use of cross-sectional imaging, liver masses ar...

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Imaging of Focal Liver Lesions Hyun-Jung Jang, MD, Hojun Yu, MD, and Tae Kyoung Kim, MD With a popular use of cross-sectional imaging, liver masses are often detected incidentally or seen on surveillance scans in high-risk or symptomatic patients. Noninvasive characterization of focal liver lesions is largely based on their enhancement patterns on contrastenhanced imaging. Contrast-enhanced computed tomography (CT) or magnetic resonance (MR) imaging is most commonly used for the characterization of focal hepatic lesions. The recent use of microbubble contrast agents has significantly expanded the role of sonography in the diagnosis of focal liver lesions on the basis of their vascularity and specific enhancement features, with an advantage of a real-time imaging and strictly intravascular contrast agent. This article describes the features of commonly encountered benign and malignant liver lesions on sonography and contrast-enhanced dynamic imaging, including contrast-enhanced ultrasound (CEUS), CT, and MR imaging. Semin Roentgenol 44:266 –282 © 2009 Elsevier Inc. All rights reserved.

Benign Hepatic Neoplasms Cavernous Hemangioma

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avernous hemangiomas are the most common benign tumor of the liver, consisting of multiple vascular channels of varying size supported by fibrous interstitium. On sonography, hemangioma appears as typically homogeneous and hyperechoic because of the numerous interfaces between the walls of the cavernous sinuses and the blood within them.1 Well known atypical feature is a granular or lace-like hypoechoic center with an echogenic rind (Fig. 1).2 Larger lesions are more frequently heterogeneous as a result of thrombosis or fibrosis. It may show hypoechogenicity in a fatty liver and there is also a tendency of hypoechogenicity in rapid-filling hemangiomas.3 A small incidental hyperechoic nodule typical of hemangioma does not necessarily require further confirmation and repeat sonography in 3-6 months to ensure stability would usually suffice. However, metastasis from a colon primary or a neuroendocrine tumor and small hepatocellular carcinoma (HCC) may show homogeneous hyperechogenicity, mimicking a hemangioma.4 Therefore, in a patient with a known malignancy or with a risk factor for HCC, further characterization with contrast-enhanced imaging is recommended. Diagnostic findings on dynamic contrast-enhanced imaging, including CEUS, CT, and MR are peripheral globular Department of Medical Imaging, Toronto General Hospital, University of Toronto, Toronto, ON, Canada. Address reprint requests to Hyun-Jung Jang, MD, Department of Medical Imaging, Toronto General Hospital, 585 University Ave, Toronto, ON, M5G 2N2 Canada. E-mail: [email protected]

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0037-198X/09/$-see front matter © 2009 Elsevier Inc. All rights reserved. doi:10.1053/j.ro.2009.05.008

enhancement with centripetal fill-in pattern or homogeneous flash filling that persists, with the attenuation or signal intensity of enhancing areas similar to that of the blood pool on the same phase scan.5,6 A long T2 relaxation time on MR has been attributed to the presence of slowly flowing blood within vascular spaces of the tumor, and this bright T2 signal is one of the most reliable findings in diagnosing hemangioma.7 The diagnostic accuracy of hemangioma on CEUS is comparable with that of MRI, including those of very small size, thus removing the necessity for further imaging for confirmation of diagnosis when CEUS shows characteristic findings.8,9 The rapidity of enhancement of hemangioma greatly varies. On histopathology, hemangiomas with a slow fill-in pattern had relatively large vascular spaces, and those with rapid enhancement had small vascular spaces and a large interstitium.7 Rapid-filling hemangioma may be seen as homogeneously enhancing nodule on arterial phase CT or MR scans. An arterioportal shunt (APS) is often associated with hemangiomas, especially in a rapid-filling type, at multiphasic CT and dynamic MR images10,11 (Fig. 2). Association with APS is generally considered characteristic of malignant tumors. However, in small tumors ⬍3 cm, APS is actually more frequent in hemangioma than in HCC.12 Slowly enhancing hemangiomas that show persistent hypoattenuation on multiphasic CT could be problematic in oncological patients. Knowledge of the bright dot sign (Fig. 3)7,13⫺ tiny enhancing dots within hemangiomas that do not progress to the classic globular enhancement because of the small size of the lesion and the propensity for very slow fill in – is very helpful, if present, in diagnosing this type of hemangioma. High temporal resolution and the real-time nature of CEUS often enables to depict a very early, or very late nodular enhancement

Imaging of focal liver lesions

Figure 1 Atypical hemangioma in a 66-year-old man. Transverse sonogram shows a mass with a lace-like hypoechoic center and an echogenic rind (arrows) in the left lobe of the liver.

initiating from the periphery regardless of its rapidity, providing a confident diagnosis (Fig. 4).6

Focal Nodular Hyperplasia Focal nodular hyperplasia (FNH) is a proliferation of nonneoplastic hepatocytes that are abnormally arranged, as a hyperplastic response to an area of vascular malformation or venous thrombosis, and frequently associated with a central fibrous scar and anomalous arteries.14 FNH commonly occurs in young, asymptomatic female patients. Differentiation from hepatic adenoma and hypervascular malignancies, such as HCC or fibrolamellar carcinoma is important. In contrast to other differential diagnoses, conservative management can be performed safely in FNH, irrespective of their size as FNH does not undergo malignant degeneration, nor is it likely to bleed or rupture.15 Recent advances of new imaging techniques and contrast agents enable us to characterize typical

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Figure 3 Small slowly enhancing hemangioma with a bright dot sign in a 42-year-old man. Portal phase CT scan shows a hypoattenuating mass (arrow). A tiny enhancing dot (arrowhead) is seen in the left aspect of the tumor.

cases of FNH confidently. However, biopsy may be required in the minority of patients with FNH. The role of percutaneous needle biopsy for differentiation of FNH and adenoma is, however, often debated. A confident diagnosis of FNH can be made with a core biopsy only if the sample contains benignappearing hepatocytes and prominent arteries, lacks portal veins, and shows bile ductules at the interface between hepatocytes and fibrous regions from the center,16 which is not always possible. On sonography, FNH is most commonly seen as a subtle isoechoic liver mass, but its echogenicity may vary. The central scar may be seen as a hypoechoic linear or stellate area.17 On color Doppler, anomalous artery can be seen to course within the central scar, with either a linear or stellate configuration.18 FNH is consistently diagnosed on CEUS (Fig. 5) by demonstrating 2 highly suggestive morphologies; arterial-

Figure 2 Rapid filling hemangioma with APS in a 57-year-old man. (A) Arterial phase CT scan shows a mass (short arrows) showing strong homogeneous enhancement with faint wedge-shaped enhancement (long arrows) caused by APS. (B) On portal phase, the mass shows persistent enhancement (arrows). The area of shunt seen on (A) becomes isoattenuating.

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Figure 4 Small fast filling hemangioma in a 52-year-old man. (A-C) Serial contrast-enhanced sonograms at 12- (A), 12(B), and 13 seconds (C) delay clear depict peripheral nodular enhancement with rapid filling-in of a nodule (arrows).

Figure 5 FNH in a 51-year-old woman. (A) Contrast-enhanced sonogram at 7-second delay shows a mass (short arrows) with central stellate arteries (long arrow). (B) At 9-second delay, centrifugal progression of enhancement of the mass (arrows) is noted.

Imaging of focal liver lesions phase centrifugal filling and stellate vascularity.19,20 Maximum intensity processing technique is useful to visualize such typical vascular patterns of FNH.21 Portal venous enhancement is sustained with a nonenhancing scar. CEUS alone should be able to suggest the presence of these insignificant lesions without the necessity of referral for further imaging. FNH typically shows strong hypervascularity in the arterial phase of CT or MR scan with central nonenhancing scar. The

269 enhancement fades over time, and the lesion becomes isodense to the liver parenchyma in the portal and delayed phases. However, mild negative enhancement (washout) can be seen infrequently (Fig. 6). A central fibrous scar shows a positive enhancement in the delayed phase.17 A central scar may not be visualized when the lesion is small. In that case, FNH can be seen as a nonspecific homogeneous enhancing nodule. Central necrosis, hemorrhage, calcification, or intralesional fat on imaging is unusual but rarely seen in FNH.

Figure 6 FNH in a 48-year-old woman. (A) Arterial phase CT scan shows homogeneous hypervascular mass (arrows). (B) On portal phase, the mass shows minimal negative enhancement, “washout” (arrows). Note mild enhancement of central scar (long arrow). (C) T2-weighted MR image shows subtly hyperintense mass (arrows). (D-E) Gd-BOPTAenhanced MR scan. The mass (arrows) shows strong homogeneous enhancement on arterial phase (D) and mild hyperintensity because of retention of contrast on 2-hour delay hepatobiliary (E) phase.

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Figure 7 Hepatic adenoma in a 26-year-old woman. (A-B) Gd-BOPTA-enhanced arterial (A) and 2-hour delay hepatobiliary (B) phase image shows strong enhancement (arrows in A) and hypointensity (arrows in B) of a mass.

Hepatobiliary-specific contrast agents, such as Gd-BOPTA or Gd-EOB-DTPA, have been proved to be useful for differentiating FNH from adenomas.22 FNH (Fig. 6) shows hyper- or isointensity except a central scar in the hepatobiliary specific phase (typically 1-3-hour delay for Gd-BOPTA and 20minute delay for Gd-EOB-DTPA), whereas adenoma usually shows hypointensity (Fig. 7).

Hepatic Adenoma Hepatic adenomas are less common than FNH. Their association of hepatic adenoma with oral contraceptive use and glycogen storage disease is well known.23 The tumor may be asymptomatic, but may present with pain or shock because of bleeding or tumor rupture. Because of its propensity to hemorrhage and the risk of malignant degeneration, surgical resection is recommended,15 although they are occasionally followed up with interval imaging studies. Adenomas have clinical and radiological similarities to FNH. Both are common in childbearing age women and mostly show arterial hypervascularity on imaging.19,20,24 Pathologically, adenomas are usually solitary and well encapsulated, occasionally with fat and calcification. Microscopically, the tumor consists of normal or slightly atypical hepatocytes. Bile ducts and Kupffer cells are few or absent.25 Most adenomas are not specifically diagnosed at sonography and usually require further studies. CT or MR scans often show heterogeneous appearance, with internal necrosis or hemorrhage in large adenomas (Fig. 8), especially in symptomatic cases.25 However, small, incidentally detected adenomas can simulate the appearance of FNH. Adenomas are usually hypervascular in the arterial phase, but the intensity of enhancement is usually less than that of FNH. Washout can occur in adenomas, more commonly than FNH. The presence of fat is suggestive of adenomas if present (Fig. 9). Adenomas typically show hypointensity in the hepatobiliary phase of Gd-BOPTA or Gd-EOB-DTPA-enhanced MR scan because of their lack of bile ductules (Fig. 7).22

On CEUS, most adenomas show strong enhancement in the arterial phase, which can be somewhat heterogeneous in large lesions. Portal venous enhancement is usually sustained but occasionally shows mild washout. Intratumoral hypoechoic areas are occasionally seen and may represent necrosis and/or hemorrhage. Early arterial phase imaging of CEUS often visualizes typical peritumoral arteries with centripetal or diffuse filling of intratumoral enhancement (Fig. 10), which is different from the centrifugal enhancement of FNH (Fig. 5).19

Focal Fat Deposition or Fatty Sparing Focal fat deposition or fatty sparing in the liver can be easily recognized by their morphology and typical location, adjacent to the falciform ligament, portal veins, and gallbladder. Typical morphology includes geographic margin, with no mass effect or undisturbed vessels traversing through the lesion.6 However, they can be nodular and atypical in loca-

Figure 8 Hepatic adenoma with central necrosis in a 32-year-old woman. Arterial phase CT scan shows a hyperattenuating mass (arrows) containing a large irregular nonenhancing area representing necrosis. Smaller adenomas are also seen.

Imaging of focal liver lesions

Figure 9 Fat-containing hepatic adenoma in a 34-year-old woman. (A) In-phase MR image shows mildly hypointense mass (short arrows) with multifocal hyperintense foci (long arrows). (B) Opposed-phase MR image shows signal drop of multifocal foci (long arrows), representing the presence of fat.

Figure 10 Hepatic adenoma in an 18-year-old woman. (A) Gray scale transverse sonogram shows a heterogeneous hypoechoic mass (arrows). (B-C) Contrast-enhanced sonograms. The mass (arrows) shows diffuse filling of intratumoral enhancement at 5-second delay (B), which progresses into homogeneous enhancement at 16-second delay (C).

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272 tion, which may mimic a neoplasm. The presence of fat can be easily confirmed on chemical shift imaging MRI. On dynamic imaging, these lesions generally show no difference in vascularity from the parenchyma. However, they are related to aberrant nonportal venous supply, it may show earlier enhancement during arterial phase (Fig. 11). Earlier enhancement is caused by its shorter pathway of nonportal venous system, such as gastric, cystic, or pancreaticoduodenal vein as compared with normal portal venous return through superior mesenteric vein. Occasional direct visualization of such an aberrant vein into the lesion would be diagnostic.26 Homogeneous isoenhancement during portal phase with no washout and lack of mass effects are useful differential points from hypervascular tumors.

Malignant Hepatic Neoplasms Hepatocellular Carcinoma HCC is the most common primary malignancy of the liver, most of which occur on a background of cirrhosis. HCC with

expansile growth is nodular, and frequently encapsulated. HCC with infiltrative growth shows an indistinct margin, with frequent tumor thrombosis. A mixed pattern is also common.27,28 In contrast to the common vascular invasion pattern of malignancy, encasement and irregular narrowing of the involved vessel, HCC has a propensity to invade and grow expansively into the portal vein, hepatic vein, and bile duct. HCC may extend into the inferior vena cava and further into the right atrium (Fig. 12). Extrahepatic metastases mostly occur in advanced HCC,29 but are rare in small nodular HCC. Without heterogeneity or hypervascularity, enlarged lymph nodes around hepatic hilum are not necessarily metastatic in case of a small intrahepatic HCC. Intraperitoneal drop metastasis is uncommon, which usually follows rupture of an HCC, percutaneous biopsy, or surgery.30 With the improvement of imaging techniques and availability, more HCCs are detected in their early stages.31 However, it is often challenging to characterize various small focal lesions in a cirrhotic liver. The stepwise development of HCC from a regenerative nodule (RN) through dysplastic nodule (DN) is now well

Figure 11 Focal fat sparing in the liver in a 40-year-old man. (A) Transverse sonogram shows a hypoechoic area (arrows) in the postero-medial aspect of the left lobe in the background of a fatty liver. (B) Color Doppler sonogram shows an undisturbed incoming vessel (long arrow) reflecting the absence of a mass effect, consistent with focal fat sparing. (C) Arterial phase CT scan shows a mild enhancement of the area (arrows) because of its nonportal supply from an aberrant right gastric vein (long arrow).

Imaging of focal liver lesions

Figure 12 HCC with tumor thrombosis into the right atrium in a 55-year-old man. (A) Portal phase CT scan shows expansile, heterogeneous soft tissue consistent with tumor thrombus within the right hepatic vein (arrows). (B) Cranial image to (A) shows a tumor thrombus (arrows) in the right atrium of the heart.

Figure 13 Development of nodule-in-nodule pattern of small HCC in a 50-year-old woman. (A) Oblique sonogram shows a small hemangioma-like hyperechoic nodule (arrow) in a background of cirrhotic liver. (B) Sonogram obtained 6 months later shows an interval growth of the nodule (arrows). (C) Sonogram obtained in another 6 months shows a new hypoechoic focus (arrows) within the hyperechoic nodule showing nodule-in-nodule pattern.

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274 recognized. The evaluation of blood supply is essential to characterize a hepatocellular nodule, as there are sequential changes in the supplying vessels during hepatocarcinogenesis.28,32 As a DN evolves toward malignancy, abnormal neoplastic arterial supply increases and normal arterial and portal supply decrease. Abnormal arteries because of tumor angiogenesis are markedly increased in advanced HCC and normal portal tracts, including hepatic artery and portal vein, are almost absent. Early HCC or well-differentiated HCC have variable degrees of arterial and portal venous supply and significant overlap with DNs. Early HCC as well as DNs often shows a decrease in both arterial and portal venous supply probably because of decreased normal arterial and portal veins without substantial increase of abnormal arteries.27,32 Sonography is the most commonly used imaging technique for HCC screening.33 HCCs show variable echogenicity. Small tumors without fatty metamorphosis are usually hypoechoic, but the echo pattern tends to become more complex as the size increases. Small tumors with fat or sinusoidal

dilation may appear homogeneously hyperechoic, indistinguishable from hemangioma (Fig. 13).4,34 Both HCC and DN can be seen as a hemangioma-like lesion, but a new hypoechoic focus within an echogenic nodule (nodule-in-nodule) is highly suggestive of a malignant focus (Fig. 13).28,34 Infiltrative HCC appears as an area of heterogeneity and is often difficult to recognize as a tumor. It is important to evaluate portal veins within any suspicious heterogeneous area on ultrasound because portal venous thrombosis is frequently associated with infiltrative HCC (Fig. 14). Tumor thrombosis is mostly contiguous with the parenchymal tumor of a similar echogenicity and vascularity and expands the vessel lumen. The use of CEUS has been increasing in the characterization of HCC and their differentiation from various nodules related to cirrhosis.5,35-39 As a real-time procedure, it is feasible to focus on a small indeterminate nodule from wash-in to wash-out of contrast agents (Fig. 15). Majority of moderately differentiated HCC show classic enhancement features of arterial phase hypervascularity and later washout, whereas

Figure 14 Infiltrative HCC in a 64-year-old man. (A) Oblique sonogram shows diffuse heterogeneous echogenicity of the right hepatic lobe without a focal mass. Noted is an expansile heterogeneous tumor thrombus in the right portal vein (arrows) suggestive of a presence of infiltrative HCC. (B) Arterial phase of contrast-enhanced sonogram reveals a large area containing dysmorphic tumor vessels within the right lobe (arrows) as well as the tumor thrombus (arrowheads). (C) Portal venous phase CT scan shows a huge infiltrative HCC in the right lobe (arrows) invading into the right portal vein (arrowheads).

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Figure 15 Small HCC in a 62-year-old man. On CT scan (not shown), the nodule was seen only on arterial phase as a nonspecific enhancing focus. (A) Oblique sonogram shows a small hypoechoic nodule (arrows). (B-C) Contrastenhanced sonograms. The nodule (arrows) shows hypervascularity at 20-second delay (B) and washout at 245-second delay (C).

well- and poorly differentiated HCC account for the majority of iso- or hypovascular variations of enhancement. Extended observation ⬎3 minutes is important to characterize HCC by demonstrating “eventual” washout, as more than a half of washout occurs later than 90-second delay (Fig. 16). Absence of portal venous washout is rare in advanced HCC.35 However, lack of washout should not be considered diagnostic of a benign lesion in a cirrhotic liver because about a half of well-differentiated tumors fail to show washout. Multiphasic CT scan has been established as the standard imaging technique for characterizing and staging HCC. It is critical to obtain the optimal arterial phase scan to detect and characterize hypervascular HCC with adequate time delay.40 Early HCC often shows hypo- or isovascularity on arterial phase and is difficult to differentiate from benign cirrhotic nodule.32,41 However, after a hypervascular focus develops within a hypoattenuating nodule, it tends to convert rapidly into an entirely hypervascular HCC.42 Hypervascular HCC often does not show washout on portal phase (Fig. 17), and may be isoattenuating or even remain hyperattenuating. However, portal phase scan is also important to evaluate for venous invasion,

distant metastases, and extrahepatic abnormalities. Careful exclusion of tumor thrombosis in the portal venous branches close to a HCC is critical to determine treatment modality, especially for potential candidates of transplantation. Delayed phase scan obtained in at least 3 minutes is helpful to characterize HCC by demonstrating washout (Fig. 17).43 On MR, the signal intensity of HCC on T1-weighted images can be varied with histologic differentiation and biochemical composition. Advanced HCC usually shows T1 hypointensity and T2 hyperintensity, in general like other malignancies. Borderline lesions, such as DN and well-differentiated HCC, tend to show hyperintensity on T1-weighted imaging that is partly because of their fat content, but mostly because of unknown mechanism.44 Although iso- or hypointensity of a nodule on T2-weighted imaging cannot exclude the presence of HCC,44 mild T2 hyperintensity of a nodule in a cirrhotic liver is highly suggestive of malignancy (Fig. 18). Dynamic gadolinium-enhanced T1-weighted imaging shows similar enhancement patterns to those on CT, and is reported to be the most important sequence to characterize HCC in a cirrhotic liver.45

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Figure 16 Typical HCC with late washout in a 45-year-old woman. (A) Contrast-enhanced sonogram at 9-second delay shows dysmorphic intratumoral arteries within a mass (arrows). (B) At 16-second delay, the mass (arrows) shows strong diffuse enhancement. (C) The mass (arrows) shows washout at 189-second delay.

Nonspecific Arterial Enhancing Foci in Cirrhosis Nonspecific arterial enhancing foci are very frequently seen in cirrhosis and may mimic HCC. A study with triphasic CT46 reported that, of 32 small (1-2 cm) nodular arterially enhancing lesions with no washout in a high-risk group of HCC, only 28% (9/32) were HCC. An MR study regarding enhancing lesions (ⱕ2 cm) of a cirrhotic liver seen only in the arterial phase reported that 93% of them were not HCC on whole explanted livers. Although HCC may not show washout because of such a high incidence of hypervascular pseudolesions on CT and MRI, arterial hypervascularity alone without washout is regarded as insufficient to make a diagnosis of small HCC.33 By contrast, the specificity of arterial hypervascularity alone for HCC is higher on CEUS: these foci are not seen on gray-scale ultrasound scan and CEUS examination is generally carried out for a targeted lesion identified on baseline scan.37 These hypervascular pseudolesions are mostly caused by benign perfusion abnormalities, such as nontumorous arterioportal (AP) shunting. The typical findings (Fig. 19) include homogeneous, wedge-shaped, and subcap-

sular-enhancing lesions on arterial phase scan.47,48 AP shunting can be occasionally nodular but never shows washout, unlike hypervascular tumors.

Peripheral Cholangiocarcinoma Peripheral cholangiocarcinoma (CCA) is a malignant tumor arising from small intrahepatic bile duct branches and accounts for 10% of primary liver malignancies. Histology reveals a glandular adenocarcinoma with extensive intralesional fibrosis. The morphology of peripheral CCA on imaging as well as on histology is similar to that of metastatic adenocarcinoma, but CCA is more likely to be solitary, large, with occasional association with peripheral ductal dilatation.49,50 The peripheral portion has viable cancer cells that show incomplete rim enhancement on arterial phase and peripheral washout, and the central portion contains more fibrous tissue and shows mild centripetal progression of enhancement over time, on dynamic CT (Fig. 20) or MR scans.50 On CEUS, CCA invariably shows rapid and complete washout within 60 seconds.51 The discordance is most likely because of interstitial retention of CT or MR contrast agents within exuberant fibrous

Imaging of focal liver lesions

Figure 17 Small HCC on mutiphasic CT in a 56-year-old man. (A) Arterial phase scan shows a small hypervascular nodule (arrows). (B) On portal phase scan, the nodule is isoattenuating and not visualized. (C) Three-minute delay phase scan clearly shows washout of the nodule (arrows), providing a confident diagnosis of HCC.

Figure 18 Small HCC in a 35-year-old man. (A) Gadolinium-enhanced arterial phase MR image shows a few small enhancing foci (arrow). (B) On T2-weighted MR image, one of the foci on A shows a mild hyperintensity (arrow), which was proved to be an HCC.

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Figure 19 Typical nontumorous arterioportal shunting in a 46-yearold man. Arterial phase CT scan shows subcapsular areas (arrows) of wedge-shaped enhancement. These areas were not seen on portalor delayed phase (not shown).

component, whereas purely intravascular contrast of CEUS shows complete washout.52 Other common findings of CCA (Figs. 20 and 21) include frequent capsular retraction because of desmoplastic reaction, marked hypoattenuation from mucin component, satellite nodules, extracapsular extension, lymphadenopathy, and vascular encasement within the mass. Most common etiologies of CCA are liver fluke infestation (clonorchiasis), recurrent pyogenic cholangitis, and chronic hepatitis B or C in Eastern population, whereas in Western population those are primary sclerosing cholangitis and chronic hepatitis C. In an endemic population, diffuse, mild peripheral IHD dilatation with normal CBD caliber is diagnostic of clonorchiasis, and an associated mass should raise a suspicion of CCA (Fig. 21).50 When CCA is associated with recurrent pyogenic cholangitis, it usually occurs in the atro-

Figure 21 Peripheral CCA associated with clonorchiasis in a 60year-old man. Portal phase CT scan shows a heterogeneous hypoattenuating mass with extracapsular extension (arrowheads) and a small satellite nodule (arrow). Note diffuse minimal dilatation of peripheral ducts without obstruction, characteristic of clonorchiasis.

phied, more diseased segment. On surveillance of primary sclerosing cholangitis, a new or focally progressed dominant stricture should raise a suspicion of CCA.53

Metastatic Disease There are suggestive findings of metastasis on sonography, although the features are not confirmatory; multiple solid lesions in a noncirrhotic liver and the presence of a hypoechoic halo that mostly reflects compressed liver parenchyma by the rapidly expanding tumor. Metastases are generally hypoechoic with occasional target appearance. Variable appearances can be seen; however, echogenic metastasis may mimic a hemangioma.54 Calcified metastasis is most frequently associated with mucinous adenocarcinoma of the

Figure 20 Typical peripheral CCA in a 55-year-old man. (A) Arterial phase CT scan shows a large mass (arrows) with irregular peripheral enhancement. (B) Three-minute delay phase scan shows heterogeneous progression of enhancement within the mass (arrows) because of exuberant fibrosis in the central portion. Note associated mild dilatation of the adjacent bile duct (arrowheads) as well as the encasement of right portal vein (long arrows).

Imaging of focal liver lesions colon. Cystic metastases are from cystic primary or because of secondary cystic and/or necrotic change typically from neuroendocrine tumor or sarcoma.55 Diffuse infiltrative form of metastasis without discrete mass frequently from breast cancer or melanoma is most difficult to recognize.56 Extensive metastases after chemotherapy can result in retracted tumors and regeneration referred to as pseudocirrhosis, also frequently associated with breast cancer.57 Both infiltrative metastasis and pseudocirrhosis may complicate with portal hypertension and are easily mistaken as cirrhosis related to chronic liver disease (Fig. 22). CT is most commonly used for staging malignancy. Because the majority of metastases are hypovascular, single portal-phase CT is routinely obtained and arterial phase is usually reserved for hypervascular variants or for the evaluation of vascular detail by obtaining CT angiography. Metastases are mostly hypoattenuating on portal- or delayed phase but a subset may show delayed enhancement because of intratumoral fibrosis. MRI offers diagnostic information, including vascularity, hemorrhage, fibrosis, necrosis, fat, and water mole-

279 cule diffusion in metastases. Many studies suggest that various liver-specific contrast agents, such as superparamagnetic iron oxide, liposoluble gadolinium chelate, and manganese, may improve the detection and characterization of liver metastases.58 Tiny hypoattenuating lesions are frequently seen on CT, and are often problematic in oncological patients. Because these are mostly too small to characterize, the knowledge of prevalence and significance is important for interpretation. In a single-slice CT study, 26% of preoperative staging CT of gastric or colorectal cancer patients showed hypoattenuating lesions ⱕ15 mm and 11% of them were metastases. However, metastases only manifested as ⱕ15 mm lesions were only 2.2% and none of metastases was seen as ⱕ5 mm lesions only.59 In a study using multislice CT, a thinner collimation ⬍5 mm improved the detection of small lesions overall, but no difference was observed regarding the detection of small metastasis.60 The incidence of small hypoattenuating lesions is increasing with advances of CT techniques, but is mainly attributable to the improved visibility of benign lesions. Tiny

Figure 22 Pseudocirrhosis from metastatic breast cancer on chemotherapy in a 66-year-old woman. (A) Sagittal sonogram shows markedly nodular liver with ascites mimicking cirrhosis. (B) Sonogram of another level shows surface retraction (arrows) at the site of calcified lesion representing a treated metastasis. (C) Portal phase CT scan shows multiple hypoattenuating masses. Note the nodular surface because of multiple retractions (arrows) at the subjacent small metastases.

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Figure 23 Small single metastasis from colon cancer in a 52-year-old woman. Previous CT and MR scans showed an indeterminate hypoattenuating and/or hypointense nodule only seen on portal phase of each scan (not shown). (A, B) Contrast-enhanced sonograms at 17- (A) and 40-second delay (B) demonstrate clear enhancement of a nodule (arrow in A) and rapid complete washout (arrow in B), characteristic of metastasis.

Figure 24 Hepatic epithelioid hemangioendothelioma in a 51-year-old man. (A) T2-weighted MR image shows multiple hyperintense masses (arrow) with target appearance. (B, C) Gd-enhanced arterial- (B) and 5-minute delay (C) phase MR images show delayed thick peripheral enhancement (arrows in C) of the masses.

Imaging of focal liver lesions metastases are still not well detected on CT, even at a very thin collimation. In CEUS, almost all metastases, including the ones known to be hypovascular, show hypervascularity for a very short time and show complete washout by 45 seconds.61,62 The capability of CEUS to depict such a rapid dynamic change is largely attributed to the real-time scanning and high temporal resolution. Because of very consistent enhancement features of metastases – transient hypervascularity and rapid complete washout – CEUS is helpful in distinguishing metastasis from benign lesions, especially in the characterization of small indeterminate lesion on CT or MR in oncological patient (Fig. 23).51

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Hepatic Epithelioid Hemangioendothelioma Epithelioid hemangioendothelioma is a rare, low-grade malignant tumor, originating from vascular endothelial cells and spindle cells. They are often multiple in a predominantly peripheral distribution with coalescence over time. Peripheral lesions often produce capsular retraction, secondary to fibrosis incited by the tumor. Foci of calcification may be present.63 On contrast-enhanced CT or MR (Fig. 24), such peripheral masses with capsular retraction show persistent or gradual thick peripheral enhancement (target pattern) correlating with the hyperemic rim at pathologic evaluation.64

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Conclusion Careful analysis with the knowledge of characteristic appearances on various cross-sectional imaging in the proper clinical context, liver imaging can provide an accurate diagnosis of various hepatic focal lesions noninvasively.

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