key to understanding the pattern of contrast enhancement of HCC. Most well-differentiated

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1 Pictorial Essay H emodynamics of contrast material is a key to the diagnosis of focal liver lesions. Lesions with arterial dominant vascularity will show brisk enhancement during the arterial dominant phase (20-30 sec after contrast injection), whereas lesions with portal vein blood supply can appear as hyperenhancing lesions in the portal veindominant phase (60-70 sec after contrast injection). Additionally, some lesions with dense fibrous stroma will show persistent enhancement in the equilibrium phase (2-5 mm after contrast injection). The purpose of this essay is to illustrate the spectrum of helical CT features of hyperenhancing liver lesions according to the phases of hepatic enhancement. Hyperenhancing Liver Lesions in the Arterial Phase Hepotocellular Carcinoma (HCC) HCC is the most frequent primary liver malignancy. The histologic features are the Fig. 1.-Hepatocellular carcinoma (HCC) in 66-year-old cirrhotic patient A, Arterial phase helical CT scan shows hyperenhancing mass (arrow) in right lobe of liver. B, Photomicrograph of corresponding histologic specimen shows HCC arranged in large plates and large, thick-walled arterial vessels (arrows). (HandE,x50) Received January 11, 1999; accepted after revision March 8, Hyperenhancing Focal Liver Lesions: Differential Diagnosis with Helical CT Carlos VaIls1, Eduard AndIa1, Anna Sanchez1, Anna Gum#{224}1, Teresa key to understanding the pattern of contrast enhancement of HCC. Most well-differentiated HCCs are hypervascular lesions with a predominant arterial blood supply [ 1]. These tumors show brisk transient hyperenhancement during the arterial phase and are readily detected with biphasic helical CT against the background of minimally enhancing normal liver parenchyma (Fig. 1). Hemangioma Hemangioma is the most common benign liver neoplasm, with an overall incidence as high as 7%. Hemangiomas are always benign and are usually asymptomatic. Roughly 30% of hemangiomas may appear as homogeneously hyperenhancing lesions in the arterial phase [2] and may mimic HCC, particularly in a patient with chronic liver disease (Fig. 2). However, hemangiomas are exceedingly rare in patients with cirrhosis and therefore will rarely present a diagnostic Serrano2 challenge. Moreover, most small hemangiomas tend to be progressively hyperdense in the portal vein and equilibrium phases, allowing distinction from HCCs, which are usually hypovascular in the portal vein or equilibrium phase. Focal Nodular Hyperplasia Focal nodular hyperplasia is a vascular malformation associated with focal nodules of hepatocellular hyperplasia [3]. Typically, the growth of focal nodular hyperplasia is proportional to its vascular supply; these tumors almost never present with hemorrhage or necrosis (Fig. 3). These lesions have fibrous septa that divide the lesion into small nodules of hyperplastic cells. Relatively large arterial vessels are found along those septa extending from the central portion of the lesion to the periphery (Fig. 4). The increased arterial blood supply accounts for the brisk homogeneous hyperenhancing pattern of focal nodular hyperplasia during the arterial phase. Presented atthe annual meeting ofthe Radiological Society of North America, Chicago, November Institut de Diagnostic per Ia lmatge, Hospital Duran i Reynals, Ciutat Sanit#{224}ria i Universit#{224}riade Bellvitge, Autovia de Castelldefels km 2.7, L Hospitalet de Uobregat, Barcelona, Spain. Address correspondence to C. Valls. 2Department of Pathology, Hospital Princeps d Espanya, Ciutat Sanit#{224}ria i Universit#{224}riade Bellvitge, LHospitalet de Llobregat, Barcelona, Spain. AJR 1999;173: X/99/ American Roentgen Ray Society AJR:173, September

2 Valls et al. Fig. 2.-Hemangioma in 57-year-old cirrhotic patient A, Arterial phase helical CT scan reveals small homogeneous, hypervascular nodule located in segment IV. Lesion remained homogeneously hyperdense during portal vein phase (not shown). B, Equilibrium phase helical CT scan at same level as A shows marked hyperenhancement oflesion (arrow), which is isodense with venous structures. This pattern of enhancement in arterial, portal vein, and equilibrium phases is diagnostic of hemangioma. r, -, I,.- -. I -,. tt. t. y... 1 Fig. 3-Focal nodular hyperplasia in 27.year-old woman. Arterial phase helical CT scan shows large, densely enhancing lesion in right lobe ofliver. Note that in spite of its large size, lesion is extremely homogeneous. Fig.4.-Focal nodularhyperplasia in45-year-oldwoman. A, Arterial phase helical CT scan shows hypervascular nodule with smooth lobulated margins (arrow) in segment VII. B, Portal vein-phase helical CT scan at same level as A shows that lesion is homogeneously enhancing. Note that in this patient lesion appears slightly hyperdense because of background offatty liver parenchyma. C, Gross histologic specimen shows well-demarcated lesion with confluent nodules separated by fibrous cords. D, Photomicrograph of corresponding microscopic study shows multinodular proliferation of benign hepatocytes (stars) and fibrous septa with enlarged arterioles (arrows). (H and E, x50) p? *..,. 7t 4 ; I : 4 t. I. :,,, #{149} :. :#{149}.. :. 606 AJR:173, September 1999

3 Helical CT of Liver Lesions Fig. 5.-Liver cell adenoma in 25- year-old woman. A, Arterial phase CT scan shows heterogeneous hypervascular lesion involving segments V and VI. B, Photomicrograph of corresponding microscopic specimen shows proliferation of disorganized hepatocyte cords separated by normal sinusoids. (H and E, x50) Fig. 6.-Liver cell adenoma in 24-year-old man. A, Arterial phase helical CT scan shows hyperenhanc. ing lesion with central area of necrosis (arrow). B, Corresponding gross specimen shows well-demarcated lesion with central area of hemorrhagic necrosis (arrow). HepatocellularAdenoma Hepatic adenomas are benign tumors composed entirely ofcells that closely resemble normal hepatocytes and the appropriate supporting connective tissue framework. However, these cells are disorganized hepatocyte cords that do not contain a normal lobular architecture. The most common setting for their appearance is in women who use oral contraceptives. In the arterial phase, hepatic adenomas usually present transient marked hypervascularity. Generally, the contrast enhancement of these tumors is far more heterogeneous than the enhancement of focal nodular hyperplasia (Fig. 5). In some cases, central areas of necrosis or hemorrhage are also visible (Fig. 6). Hypervascular Metastases Hepatic metastases receive a substantial proportion of their blood supply from the hepatic artery in contradistinction to normal liver parenchyma, which has a portal veindominant vascular supply. Most hepatic metastases are hypovascular lesions that are optimally imaged during the portal vein phase. However, a small proportion of liver metastases from tumors such as carcinoid and pancreatic islet cell tumor are hypervascular relative to normal liver parenchyma [41. These tumors are best imaged during the arterial phase as hyperenhancing lesions against the background of a relatively hypodense normal liver parenchyma (Fig. 7). Hyperenhancing Liver Lesions in the PortalVein Phase Hemangioma Microscopically, cavernous hemangiomas consist of normal sinusoids with blood-filled spaces lined by endothelial cells. On contrast-enhanced CT, hemangiomas typically present peripheral globular, noncontinuous enhancement that is isodense with the aorta in the portal vein phase (Fig. 8). HCC Most HCCs show bnsk enhancement during the arterial phase and rapidly become iso- or hypoattenuating during the portal vein phase. However, in a small number ofcases these tumors may AJR:173, September

4 Fig. 1.-Hypervascular metastasis in 63-year-old man. A, Arterial phase CT scan shows large hypervascular metastasis of carcinoid tumor in segment VII (arrow). B, Photomicrograph of microscopic study shows monotonous proliferation of small cells with nesting pattern and large arterial vessels (arrows) interspersed. (H and E, x50) Fig. 8.-Liver hemangioma in 50-year-old woman. A, Portal vein-phase helical CT scan shows large cavernous hemangioma in segment VII, with globular hyperenhancing areas in periphery of lesion (arrowheads). B, Equilibrium phase CT scan at same level as A shows progressive peripheral pooling of contrast material. C, Photomicrograph of corresponding microscopic study shows blood-filled dilated cavernous spaces (arrows)., I,, #{149} t4:fr,_ fl,..!.4,.,? -,ae ,.. - :;,; persist as hyperattenuating lesions during the portal vein phase, and occasionally those lesions are better seen than in the arterial phase (Fig. 9). Focal Nodular Hyperplasia During the portal vein phase, focal nodular hyperplasia typically enhances to the same degree as normal liver parenchyma. During this phase focal nodular hyperplasia may become iso- or hyperattenuating relative to normal liver parenchyma and thus could easily be missed if only portal vein-phase imaging is performed (Fig. 4B). Fig. 9.-Hepatocellular carcinoma (HCC) in 76-year-old man. Portal vein-phase helical CT scan shows hypervascular HCC with mosaic pattern (arrow). Solitary Fibrous Tumor Solitary fibrous tumor is an unusual neoplasm of mesenchymal origin and spindle 608 AJR:173, September 1999

5 Helical CT of Liver Lesions cell morphology that typically involves the pleura [5]. Recently, some cases involving the liver have been described [5]. On portal vein-phase CT, this highly vascular tumor shows heterogeneous and amorphous contrast enhancement (Fig. 10). Angiomyolipoma Angiomyolipoma is a rare benign lipomatous tumor of the liver consisting of fat cells intermixed with smooth muscle elements and blood vessels. The CT appearance of this tumor during the portal vein phase is described as a hypodense mass with globular or lineal areas with stronger enhancement (Fig. 1 1). Occasionally moderate amounts of fat can be detected with either CT or MR imaging [6]. Hot Spot Lesion In cases of obstruction of the superior vena cava, venous collateral branches to the inferior vena cava via the hepatic veins may develop in the hepatic parenchyma. This collateral flow may be detected on portal vein-phase CT as geographic areas of liver parenchyma with intense opacification. This so-called liver hot spot may mimic hypervascular lesions such as hemangiomas (Fig. 12). Hyperenhancing Liver Lesions in the Equilibrium Phase Hemangioma After IV contrast administration, hemangiomas typically show progressive fill-in and 1 \...,....,...,,..,.. -,.,.. d ,,.4..._ ,,,... - #{149} : -.,.. p. -.. #{149} ;..... )...,..... Fig. 10.-Solitary fibrous liver tumor in 47-year-old man. A, Portal vein-phase helical CT scan shows heterogeneous areas of enhancement in this solitary fibrous liver tumor in segment VII. B, Equilibrium phase CT scan at same location as A shows marked hyperenhancement of lesion. C, Gross specimen shows well-defined solid mass in subcapsular location. C Fig. 11.-Angiomyolipoma in 52-year-old woman. Fig year-old woman with Hodgkin s lymphoma and A, Portal vein-phase CT scan shows hypodense lesion with globular hyperenhancing areas in tumor pe- superior vena cava thrombosis. Portal vein-phase CT scan riphery (arrow), mimicking cavernous hemangioma. shows geographic hyperenhancing hot spot lesion at B, Opposed-phase MR image shows marked loss of signal in tumor, confirming its fatty content dome of liver (arrow). AJR:173, September

6 Valls et al. become hyperdense relative to liver parenchyma in the portal vein phase. On delayed imaging, the lesions tend to be progressively hyperdense (Fig. 8B). This pattern of contrast enhancement is related to slowly circulating blood in the dilated cavernous spaces in the periphery of the lesion that progressively diffuses to the rest of the tumor. Cholangiocarcinoma Intrahepatic (or peripheral) cholangiocarcinoma is a primary adenocarcinoma of the liver that arises from the small and distal intrahepatic bile ducts. Although intrahepatic cholangiocarcinoma accounts for only 10% of all primary hepatic malignancies, it is the second most common primary malignant hepatic neoplasm after HCC. The usual CT appearance is that of a hypoattenuating mass during the portal vein phase, with irregular margins that shows mild peripheral enhancement and pooling ofcontrast material on delayed images [7]. The characteristic hyperenhancement pattern during the equilibrium phase is related to the large tumoral fibrous stroma. Slow diffusion of contrast medium to the interstitial space results in prolonged enhancement of the tumor on delayed imaging (Fig. 13). Solitary Fibrous Tumor ofthe Liver Solitary fibrous tumor of the liver consists of variable spindle cell proliferation and large areas of stromal tissue with dense collagenous fibers [5]. On CT this tumor presents as a large lesion with marked contrast hyperenhancement in the equilibrium phase (Fig. lob). This pattern of contrast uptake on delayed-phase imaging is related to the slow diffusion of iodine from the vascular space to the fibrous interstitial space of the tumor. Inflammatory Pseudotumor Inflammatory pseudotumor is a rare liver tumor consisting of a proliferation of inflammatory cells, spindle cells, and fibroblastic tissue [8]. On CT, inflammatory pseudotumor presents as a large lesion with heterogeneous and variable contrast enhancement in the portal vein phase. During the equilibrium phase, there is slow diffusion of iodine to the fibrous interstitial space, resulting in delayed hyperenhancement [8] (Fig. 14). Fig Cholangiocarcinoma in 79-year-old woman. A, Delayed-phase CT scan shows spiculated nodule with marked hyperenhancement and focal biliary dilatation (arrow). B, Photomicrograph of corresponding microscopic study confirms tubular adenocarcinoma set in abundantfibrous stroma with dense collagen fibers (arrows). (H and E, xloo) Fig. 14.-Inflammatory pseudotumor of liver in 30- year-old man. A, Delayed-phase helical CT scan shows hyperenhancing, wedge-shaped lesion (arrow). B, Gross resected specimen shows solid lesion in subcapsular location. 610 AJR:173, September 1999

7 Helical CT of Liver Lesions Fig. 15.-Treated liver metastases in 51-year-old man with liver metastases from carcinoid ileum tumor. Helical CT scan during equilibrium phase shows hyperenhancing lesion (arrow) in segment VIII. Treated Liver Metastasis Liver metastases treated with systemic chemotherapy may undergo tumor necrosis and fibrotic changes. Occasionally, fibrotic changes can predominate, leading to intense desmoplastic changes in and around the tumor. On contrast-enhanced CT, these lesions appears as densely hyperenhancing lesions during the equilibrium phase (Fig. 15). References 1. Stevens WR, Johnson CD, Stephens DH, Batts KR CT findings in hepatocellular carcinoma: correlation of tumor characteristics with causative factors, tumor size and histologic grade. Radiolog 1994:191: Hanafusa K, Ohashi I, Himeno Y, Suzuki S. Shibuya H. Hepatic hemangiomas: findings with two phase CT. Radiolog 1995:196: Buetow PC, Pantongrag-Brown L, Buck JL, Ros PR, Goodman ZD. Focal nodular hyperplasia: pathologic radiologic correlation. RadioGraphies 1996:16: Paulson EK, McDermott VG, Keogan MT. Dc- Long DM, Frederick MG, Nelson RC. Carcinoid metastases to the liver: role of triple-phase helical CT. Radiology 1998:206: 143-I Levine IS, Rose DSC. Solitary fibrous tumor of the liver. Hi.stopathologv 1997:30: Low VHS, Breidahl WH, Robbins PD. Hepatic angiomyolipoma. Abdom hnaging 1994:19: Kim 1K, Choi BI, Han JK. Jang Hi, Cho 5G. Han MC. Peripheral cholangiocarcinoma of the liver: two-phase spiral CT findings. Radiology l997;204: Nam K-i, Heoung KK. Lim JH. Inflammatory pseudotumor of the liver: CT and sonographic findings. AiR 1996:167: AJR:173, September