Current Problems in Diagnostic Radiology ] (]]]]) ]]]–]]]
Current Problems in Diagnostic Radiology journal homepage: www.cpdrjournal.com
Atypical Magnetic Resonance Imaging Findings in Hepatocellular Carcinoma Panayota S. Roumanis, MDa, Puneet Bhargava, MDb,c, Golnaz Kimia Aubin, MDa, Joon-Il Choi, MDa,d, Aram N. Demirjian, MDe, David A. Thayer, MDa, Chandana Lall, MDa,n a
Department of Radiological Sciences, University of California, Irvine, CA Department of Radiology, University of Washington, School of Medicine, Seattle, WA c VA Puget Sound Health Care System, Seattle, WA d Department of Radiology, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea e Department of Hepatobiliary Surgery, University of California, Irvine, CA b
Magnetic resonance imaging (MRI) is currently the modality of choice to evaluate liver lesions in patients with cirrhosis and hepatitis B and C. Hepatocellular carcinoma demonstrates typical imaging findings on contrast-enhanced MRI, which are usually diagnostic. Unfortunately, a subgroup of hepatocellular carcinoma presents with atypical imaging features, and awareness of these atypical presentations is important in ensuring early diagnosis and optimal patient outcomes. Herein, we review some of the more common atypical presentations with a focus on MRI. & 2015 Mosby, Inc. All rights reserved.
Introduction Hepatocellular carcinoma (HCC) is the most common primary hepatic malignancies globally, causing up to 1 million deaths worldwide annually, with a median postdiagnosis survival of 620 months.1-5 Survival is highly dependent on stage, with a 5-year survival rate of 55% for stage I disease in contrast to only 15% for stage III disease.6 Early diagnosis is therefore vital for maximizing patient survival. For patients at high risk of HCC, including those with hepatitis B or C, aflatoxin exposure, hemochromatosis, Wilson disease, or α1 antitrypsin deficiency, the American Association for the Study of Liver Disease recommends hepatic ultrasound surveillance be performed at 6-month intervals, with abnormal nodules larger than 1 cm to be further evaluated with computed tomography (CT) or magnetic resonance imaging (MRI).7 Both CT imaging and MRI can be diagnostic, without the need for biopsy in lesions exhibiting typical radiologic features of HCC.7,8 CT is preferred as an initial study because of the higher cost of MRI. However, MRI has better sensitivity and specificity in cirrhotic patients in whom regenerative nodules can be difficult to distinguish from HCC and is better at differentiating dysplastic nodules from HCC.9,10 MRI also provides better identification of focal fat and is superior for assessing vascular lesions such as hemangiomas. When typical features are present on imaging, HCC can be confidently diagnosed without tissue biopsy. However, HCC often has atypical imaging findings, making it difficult to distinguish from other, potentially benign, conditions. An understanding
n Reprint requests: Chandana Lall, MD, Department of Radiological Sciences, University of California, Irvine, 101 The City Dr South, Suite 1105, Orange, CA 92868 E-mail address: [email protected] (C. Lall).
http://dx.doi.org/10.1067/j.cpradiol.2014.03.002 0363-0188/& 2015 Mosby, Inc. All rights reserved.
of these atypical presentations is important to ensure an early and accurate diagnosis. A high index of suspicion for malignancy should be maintained, as well as a low threshold for biopsy. We review some of the atypical presentations of HCC on MRI with pertinent differential diagnoses. Each diagnosis was validated with a follow-up biopsy.
MRI Protocols Liver imaging has improved significantly with advances in MRI technology. The advent of newer and faster sequences on higher magnetic fields allows for greater temporal and spatial resolution. Dynamic contrast-enhanced imaging of the liver plays a dominant role in lesion characterization. A typical MRI protocol for HCC involves both T1- and T2-weighted imaging with dynamic contrast-enhanced MRI in arterial, venous, and delayed phases. When using hepatobiliary (HPB) agents, far-delayed (from 20 minutes to 1 hour) phase can be obtained for hepatobiliary phase. T1-weighted in-phase and out-of-phase gradient-recall sequences may be obtained using a 2-point Dixon method. Both gadolinium-based chelated agents (GBCAs) and nonGBCAs can be used for HCC diagnosis. GBCA can be divided into extracellular GBCA and hepatobiliary (HB) agents. The non-GBCAs include reticuloendothelial (RE) agents such as superparamagnetic iron oxide and Mangafodipir trisodium (Mn-DPDP). The GBCAs are paramagnetic, whereas the RE agents are superparamagnetic. Based on the biochemical distribution, extracellular GBCAs behave similar to iodinated contrast used in CT by distributing into the extracellular compartment. However, the HB agents are distributed in extracellular space in early phase and also accumulated in the hepatocytes and extracted in bile.11 The RE agents are accumulated in the RE system (ie, Kupffer cells in the liver). HB
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agents (Gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid (Gd-EOB-DTPA) or gadopentetate dimeglumine) can be used to obtain both dynamic imaging and hepatobiliary phase imaging and are now considered as standard contrast agents for liver MRI. With the combination with diffusion-weighted imaging (DWI), a superior diagnostic performance of HB agents for detecting HCC was reported, in comparison with extracellular gadolinium-based contrast agents.12,13
Typical MRI Appearances of HCC HCCs may be classified according to growth patterns and macroscopic aspects with prognostic implications: (1) Expansile, single nodular type, well-defined, encapsulated, and typically with a better prognosis, representing about 50% of HCCs. (2) Infiltrating type, consisting of a lesion with irregular, poorly defined borders, without a definable capsule, and frequently presenting with vascular invasion. This subtype usually has a poorer prognosis. (3) Multifocal with multiple nodules scattered in several hepatic segments. This subtype also has a poor prognosis. Classic HCCs are hypointense on T1-weighted imaging, mildly hyperintense on T2-weighted imaging, and exhibit brisk arterial phase contrast enhancement with rapid washout in the portal venous and delayed phases.14 Intense arterial phase enhancement is therefore characteristic of HCC, decreasing thereafter on subsequent phases. In larger lesions, a mosaic or heterogeneous pattern is seen on MRI because of the presence of fibrosis, hemorrhage, arteriovenous shunting, and intratumoral necrosis. Nodule-in-nodule appearance is another typical imaging feature of HCC. In hepatobiliary phase, most HCCs are hypointense compared with the hepatic parenchyma. However, paradoxical enhancement of HCC is also reported.15
Atypical MRI Appearances of HCC Unusual Enhancement Patterns HCC typically exhibits brisk arterial phase enhancement with rapid washout in the venous phase along with possible persistent rim enhancement in the delayed phase; however, there are variations in enhancement pattern. Enhancement patterns have been shown to be dependent on cellular differentiation.16 A higher proportion of moderate and poorly differentiated, rather than well-differentiated, HCC lesions exhibit the typical pattern of arterial phase enhancement followed by portal venous phase washout.17 Some HCCs however show lack of or poor arterial phase enhancement. Another mechanism that has been proposed is portal vein thrombosis secondary to HCC involvement, resulting in a compensatory increase in hepatic arterial supply to the liver parenchyma. This has been termed the “arterial steal” phenomenon, resulting in decreased blood supply to the tumor and increased enhancement of the hepatic parenchyma. The result is decreased relative enhancement of the HCC lesion. These variations include lack of arterial phase enhancement with persistent enhancement in the venous and delayed phases (Fig 1). Other patterns include quite commonly, nodular enhancement and enhancement of septations, which may be mistaken for abscesses. Continuous rim enhancement can be seen in a subgroup of HCCs and may mimic a metastatic lesion, especially in the setting of previous or concurrent extrahepatic malignancy.
A fibrotic capsule is commonly seen in HCC, which may show persistent enhancement in the delayed phase. A subgroup of HCCs demonstrates a central enhancing scar, usually because of the presence of central necrosis and subsequent fibrosis. These lesions may mimic focal nodular hyperplasia (FNH) if a proper history is not sought, leading to misdiagnosis. Another atypical finding is persistent enhancement of the HCC in the venous and delayed phases (Fig 2). This is usually seen in small HCCs, because of uncertain reasons. Larger HCC lesions are more likely to exhibit more typical enhancement kinetics. In contrast, small (subcentimeter) HCC lesions are seen to follow this pattern in only 24% of cases.18-20 Rather than showing brisk arterial phase enhancement, small HCC lesions may frequently show isoattenuation during the arterial and portal venous phases making the diagnosis of these lesions difficult.16 A group of HCCs demonstrates a dominant hypervascular pattern with massive intratumoral vessels including large draining veins mimicking vascular tumors such as hepatic angiosarcoma.21 The diagnosis can be made on the basis of serum alpha-fetoprotein (AFP) levels and history of chronic liver disease, as a biopsy may not be feasible because of extreme tumor hypervascularity (Fig 3). HCC may also exhibit nodular peripheral enhancement, which can be mistaken for hemangioma. This nodular enhancement in HCC has been proposed to be because of variations in tumor differentiation.14 A stepwise progression model for the development of HCC has been proposed, beginning with a regenerative nodule and progressing through dysplastic nodules of increasing grade, to dysplastic nodules with foci of HCC, and finally to small and large HCC.14 In this model, the nodular enhancement pattern sometimes seen in HCC is actually because of the foci of HCC on a dysplastic background, resulting in a nodular appearance. This may be mistaken for a hemangioma, which also frequently presents with a nodular peripheral enhancing pattern. Fibrolamellar carcinomas is particular may show peripheral irregular pattern of enhancement with gradual centripetal fill-in on delayed images, which can lead to a misdiagnosis of hemangioma, especially in the setting of normal liver function and AFP. DWI has been proposed as an aide for small lesions showing abnormal enhancement kinetics and may help identify HCC in cases where enhancement kinetics are equivocal.22 These sequences are highly susceptible to motion artifact, which has limited their use for HCC imaging. Respiratory and, possibly, cardiac gating should be considered to minimize artifact. In rare cases, HCC can mimic an abscess on imaging. The presence of a rim-enhancing lesion with or without internal septations can raise suspicion for an abscess. Biopsy is usually necessary in such cases for a diagnosis.23 Imaging findings should be correlated with the patient’s clinical status to help differentiate HCC from abscess. HCC With Atypical Signal From Intralesional Fat HCCs, in particular the clear cell type, may contain intracytoplasmic fat in 17%-20% of cases, and in approximately 2% of cases, this fat is radiographically apparent.18,24 The microscopic intravoxel fat can be seen as decreased signal in opposed-phased MRI (Fig 4). HCCs containing microscopic fat may be mistaken for hepatic adenoma, angiomyolipoma, or a fat-containing metastasis. Alternatively, in HCCs areas of macroscopic fat are apparent as a decrease in signal intensity in opposed-phase MR or fatsuppressed images or fat attenuation on CT imaging. These fatty areas may be mistaken for a hepatic lipoma, focal steatosis, fatcontaining adenoma, angiomyolipoma, or even hepatic liposarcoma.19,25 HCC with fatty metamorphoses tend to appear hyperintense on T1, with a concomitant loss of signal on out-of-phase, T1-weighted images. Presence of contrast washout during the
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Fig 1. Lack of arterial enhancement and persistent enhancement on delayed phase in HCC after extracellular gadolinium-based contrast agent injection. (A) Noncontrast T1weighted MR image shows no definite focal lesion in liver. (B) Arterial phase MR image shows a small hypointense nodular lesion (arrow) noted in segment 4. (C) Portal venous MR phase shows mild enhancement (arrow) compared with liver parenchyma. (D) Delayed enhancement is noted on equilibrium phase.
Fig 2. A persistent enhancement of HCC from arterial to delayed phase after injection of extracellular gadolinium-based contrast agents. (A) Arterial phase, (B) portal venous phase, and (C) delayed phase MR images after injection of extracellular gadolinium-based contrast agent show persistent enhancement of small nodular HCC (arrow).
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Fig 3. A dominant hypervascular mass with massive intratumoral vessels in HCC. (A) Coronal T2-weighted MR image shows multiple, heterogeneously high signal masses in the right lobe of the liver. Central hyperintensity is noted because of hypervascularity. (B) Axial T2-weighted MR image shows multiple, heterogeneously high signal masses in the right lobe of the liver. Central hyperintensity from hypervascularity is again noted. (C) Arterial phase MR image shows peripheral enhancement of the tumor and slight enhancement of central area of the tumor. (D) Delayed phase MR image shows multiple intratumoral vessels with prominent veins (arrowheads) are noted.
Fig 4. Fat-containing HCC. (A) In-phase T1-weighted gradient echo image shows a hyperintense mass (arrow) in segment 4 of the liver. (B) Out-of-phase T1-weighted image shows signal dropout within the mass (arrow), confirming the presence of microscopic intracellular fat. Eccentric area of enhancement with washout is not shown. This lesion was confirmed as fat-containing HCC on histopathology.
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the T2 hyperintensity and delayed enhancement of FNH, the scar of fibrolamellar HCC is hypointense on T2-weighted imaging with minimal delayed enhancement (Fig 6). Hypovascular tumors include well-differentiated HCC, fatty metamorphosis, tumor necrosis, and abundant interstitial fibrosis. Collision Lesions: For Example, Mixed HCC and CC
Fig 5. Ruptured HCC with intra-abdominal bleeding. Segment 6 exophytic HCC mass (straight arrow) with heterogeneously high signal intensity on T2-weighted image. Perihepatic fluid shows intermediate to high signal intensity from hemorrhage (curved arrow), compared with fluid in the gall bladder (*).
venous phase can distinguish HCC with fatty metamorphoses from angiomyolipoma and other fat-containing lesions. Capsular enhancement, peaking in the delayed phase, may also help distinguish HCC.25 Cystic Degeneration HCC with cystic degeneration is rare with very few reported cases in literature.20 It is usually the result of internal necrosis in large lesions that have outgrown their blood supply or after locoregional and systemic treatment. Presence of signs or complications of underlying cirrhosis on CT and MRI in addition to intrinsic tumor characteristics such as a capsule, increased vascularity of solid parts, and biliary and vascular invasion can lead to the diagnosis.26 On precontrast MRI, low signal on T1-weighted images and bright signal on T2-weighted images demonstrates cystic components. In addition, T1 high signal can be noted when hemorrhage is present. Presence of contrast washout in the portal venous or delayed phase further aids in diagnosis. HCC Rupture With Intra-Abdominal Bleeding Rupture of HCC is seen in 3%-15% of patients with HCC. Usually, CT scan is the cornerstone for urgent diagnosis but MRI can be obtained in this situation rarely. The presence of hemoperitoneum, perihepatic hematoma, extravasation of contrast material, discontinuity of liver surface, and enucleation sign (hypointense mass surrounded by enhancing rim with focal discontinuity on arterial phase) suggests rupture of a mass. Findings of a large HCC, contour protrusion, and portal vein thrombosis are considered risk factors for subsequent rupture (Fig 5).27 Fibrolamellar HCC The fibrolamellar variant of HCC is not associated with hepatitis or cirrhosis and may look similar to FNH, hemangioma with scarring, metastasis, cholangiocarcinoma (CC), or hepatic adenoma.28-30 Fibrolamellar HCC is most often seen in young adults and presents as an abdominal mass or abdominal pain. Fibrolamellar HCC may have a central radiating scar, seen in 20%71% of cases, similar to the central scar of FNH.31 Both hepatic adenoma and FNH tend to show a homogeneous arterial phase enhancement pattern, unlike fibrolamellar HCC, which is heterogeneous. Adenomas may have areas of hemorrhage and focal fat, both of which are uncommon in fibrolamellar HCC. In contrast to
One of the more commonly described collision lesions is the biphenotypic tumor consisting of coexistence of HCC with CC. Combined HCC-CC is an uncommon form of primary liver collision tumor displaying hepatocellular and biliary epithelial differentiation. This type of lesion constitutes less than 1% of all HCCs and roughly 7% of all primary liver tumors.32 Electron microscopic studies confirmed the presence of dual differentiation with venous and invasion into adjacent liver parenchyma and microsatellite formation, similar to that seen with a typical HCC. Imaging is unusual in that the HCC component may show brisk arterial enhancement and subsequent washout on the portal venous and delayed phases whereas the CC component shows poor enhancement on the arterial phase, enhancing mildly during the portal venous phase with persistent enhancement on the delayed phase because of predominance of fibrous component (Fig 7). On T1- and T2-weighted MR images, these tumors are hypointense and heterogeneously hyperintense, respectively. Preoperative diagnosis of biphenotypic tumors with HCC and CC purely on the basis of imaging may not be easy, although assessment of HCC or CC tumor markers, AFP and carbohydrate antigen-19-9 as well as risk factors can increase overall accuracy. In the absence of typical imaging features, biopsy is indicated for confirmation.33 Simultaneous occurrence of HCC and lymphoma has also been reported in literature. HCC component on imaging generally shows early arterial enhancement on CT and MRI with characteristic washout in the portal venous phase. In addition, changes consistent with lymphoma (ie, splenomegaly, lymphadenopathy, or hypodense or isodense masses) are seen on imaging, depending on the type and location of lymphoma.34 Infiltrating HCC Infiltrative HCC is a rare aggressive form that is characterized by poorly defined margins and atypical enhancement patterns (Fig 8). Involvement of the portal and hepatic veins with associated thrombosis occurs in 29%-65% and 12%-54% of cases, respectively.35 Bile duct invasion is also possible, although less common, and may lead to obstructive jaundice. These lesions can be difficult to visualize on both T1- and T2-weighted MRI and may only demonstrate mild heterogeneous enhancement on the arterial and venous phases. These are best seen on low–b value DWI. The presence of a thrombosed portal vein may therefore be a clue to an underlying infiltrative HCC in a cirrhotic patient and his finding should be viewed with a high index of suspicion (Fig 9). HCC-related malignant thrombosis needs to be distinguished from benign thrombus to which patients with cirrhosis with portal hypertension without HCC are predisposed. Thrombi caused by HCC tend to be contiguous with HCC lesions and cause dilation of the portal vein, features seen less commonly in bland thrombi. Malignant thrombi also tend to be T2 hyperintense and show a similar enhancement pattern as HCC, indicative of intrathrombus neovascularity, in contrast to bland thrombi, which show no enhancement and low T2 signal intensity. Transient hepatic intensity difference, may also be seen around HCC as an area of hypervascularity in the arterial phase, which is usually wedge shaped and conforms to a segment or lobe supplied by a particular portal venous branch. This is thought to represent vascular invasion of the portal vein and indicates malignancy.36 Invasion
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Fig 6. Fibrolamellar HCC. (A) T2-weighted MR image shows a high–signal intensity mass (arrowheads) in segment 6 of the liver with a hypointense central scar (arrow). (B) Arterial phase MR image shows peripheral enhancement in the mass (arrowheads). Central scar (arrow) is avascular and hypointense. (C) Portal venous phase MR image shows mild filling in the central scar tissue (arrow) while persistent enhancement is seen in the remainder of the tumor. (D) Equilibrium phase MR image shows continued filling-in of the central scar tissue (arrow) and persistent enhancement in the remainder of the tumor. (E) Delayed phase MR image shows persistent enhancement within the tumor (arrowheads) but central scar is not clearly visible because of delayed enhancement.
of the hepatic vein may propagate into the inferior vena cava as far as the right atrium. An important point to also understand is that a large proportion of HCCs with portal vein thrombosis lack characteristic arterial hypervascularity, which may be secondary to compensatory increased arterial supply to the background liver.
Bile duct invasion resulting in thrombus, termed bile duct tumor thrombus, is much rarer than either portal venous or hepatic venous infiltration, occurring in only up to 9% of HCCs. Biliary dilatation is seen proximal to the area of invasion and thrombus. These thrombi and areas of invasion tend to show
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Fig 7. Mixed HCC and cholangiocarcinoma. (A) Arterial phase MR image shows a hypointense mass (arrowheads) located in segments 5-6 of the liver with a small area of enhancement (arrow). (B) Portal venous and (C) delayed phase MR images show prominent enhancement in the cholangiocarcinoma component (arrows). The remainder of the tumor itself shows no enhancement and remains hypointense (arrowheads). Imaging features of this tumor are those of cholangiocarcinoma. However, pathologic examination after surgical resection revealed mixed HCC-cholangiocarcinoma. Collision tumors of HCC and other tumors are difficult to diagnose on imaging appearance.
Fig 8. Infiltrative HCC with indistinct margin. (A) T1-weighted MR image shows an ill-defined, hypointense mass (arrowheads) in segments 4, 5, and 8 of the liver. (B) T2weighted MR image shows a mildly hyperintense poorly marginated mass (arrowheads). (C) Arterial phase MR image shows mild patchy enhancement of the tumor (arrowheads). However, because of dilatation of bile ducts (arrows), the extent of the tumor and area involved by cholangiohepatitis is not clearly differentiated. (D) Delayed phase MR image shows ill-defined tumor margins. Dilated biliary ducts are again appreciated (arrows).
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Fig 9. Infiltrative HCC with portal vein invasion. (A) T2-weighted MR image shows a high-signal tumor thrombus (arrowheads) in the left portal vein. (B) Delayed phase MR image shows a striated appearance typical for an enhancing tumor thrombus (arrowheads) in the dilated portal vein. There are low-signal parenchymal tumor components (arrows) in the left lateral section of the liver. (C) Another delayed phase MR image shows peripheral tumor thrombi in left portal vein (arrowheads). (D) Diffusion-weighted image shows area of diffusion restriction within the tumor thrombus (arrowheads).
arterial enhancement with portal venous phase washout. Bile duct tumor thrombus may coexist with portal venous thrombus, with distinction between them made on the basis of patency of the portal vein, location of thrombus, and presence and degree of biliary ductal dilatation.36 Infiltrative HCC may not exhibit the brisk arterial phase enhancement typically seen in HCC and tends to be most prominent on diffusion- or T2-weighted imaging.
Conclusions HCC is one of the most common causes of cancer-related deaths worldwide. Imaging with CT or MRI can be diagnostic when typical imaging findings are present. However, HCC commonly presents in an atypical fashion and may easily be mistaken for another process. Ensuring accurate diagnosis, early treatment, and optimal patient outcomes require recognition of these atypical presentations. A high index of suspicion for malignancy should be maintained with a low threshold for further study, biopsy, or shortterm follow-up imaging. References 1. Okuda K. Epidemiology of Primary Liver Cancer. Primary Liver Cancer in Japan. Tokyo, Japan: Springer Japan; 1992, 3–15. 2. Parkin DM, Bray F, Ferlay J, et al. Global cancer statistics, 2002. CA Cancer J Clin 2005;55:74–108. 3. Bruix J, Llovet JM. Prognostic prediction and treatment strategy in hepatocellular carcinoma. Hepatology 2002;35:519–24. 4. Curado MP, Edwards B, Shin HR, et al. Cancer Incidence in Fiver Continents. Lyon, France: International Agency for Research on Cancer; 2007.
5. McGlynn KA, London WT. The global epidemiology of hepatocellular carcinoma: Present and future. Clin Liver Dis 2011;15:223–43 [vii-x]. 6. Vauthey JN, Lauwers GY, Esnaola NF, et al. Simplified staging for hepatocellular carcinoma. J Clin Oncol 2002;20:1527–36. 7. Bruix J, Sherman M. Management of hepatocellular carcinoma: An update. Hepatology 2011;53:1020–2. 8. Szklaruk J, Silverman PM, Charnsangavej C. Imaging in the diagnosis, staging, treatment, and surveillance of hepatocellular carcinoma. Am J Roentgenol 2003;180:441–54. 9. Colli A, Fraquelli M, Casazza G, et al. Accuracy of ultrasonography, spiral CT, magnetic resonance, and alpha-fetoprotein in diagnosing hepatocellular carcinoma: A systematic review. Am J Gastroenterol 2006;101: 513–23. 10. Yu NC, Chaudhari V, Raman SS, et al. CT and MRI improve detection of hepatocellular carcinoma, compared with ultrasound alone, in patients with cirrhosis. Clin Gastroenterol Hepatol 2011;9:161–7. 11. Golfieri R, Renzulli M, Lucidi V, et al. Contribution of the hepatobiliary phase of Gd-EOB-DTPA-enhanced MRI to dynamic MRI in the detection of hypovascular small (o/ ¼ 2 cm) HCC in cirrhosis. Eur Radiol 2011;21:1233–42. 12. Ahn SS, Kim MJ, Lim JS, et al. Added value of gadoxetic acid-enhanced hepatobiliary phase MR imaging in the diagnosis of hepatocellular carcinoma. Radiology 2010;255:459–66. 13. Kim JE, Kim SH, Lee SJ, et al. Hypervascular hepatocellular carcinoma 1 cm or smaller in patients with chronic liver disease: Characterization with gadoxetic acid-enhanced MRI that includes diffusion-weighted imaging. Am J Roentgenol 2011;196:W758–65. 14. Hussain SM, Zondervan PE, IJ JN, et al. Benign versus malignant hepatic nodules: MR imaging findings with pathologic correlation. Radiographics 2002;22:1023–36 [discussion 37-9]. 15. Kim SH, Jeong WK, Kim Y, et al. Hepatocellular carcinoma composed of two different histologic types: Imaging features on gadoxetic acid-enhanced liver MRI. Clin Mol Hepatol 2013;19:92–6. 16. Yoon SH, Lee JM, So YH, et al. Multiphasic MDCT enhancement pattern of hepatocellular carcinoma smaller than 3 cm in diameter: Tumor size and cellular differentiation. Am J Roentgenol 2009;193:W482–9. 17. Asayama Y, Yoshimitsu K, Nishihara Y, et al. Arterial blood supply of hepatocellular carcinoma and histologic grading: Radiologic-pathologic correlation. Am J Roentgenol 2008;190:W28–34.
P.S. Roumanis et al. / Current Problems in Diagnostic Radiology ] (]]]]) ]]]–]]] 18. Chung YE, Park MS, Park YN, et al. Hepatocellular carcinoma variants: Radiologic-pathologic correlation. Am J Roentgenol 2009;193:W7–13. 19. Prasad SR, Wang H, Rosas H, et al. Fat-containing lesions of the liver: Radiologic-pathologic correlation. Radiographics 2005;25:321–31. 20. Nagano K, Fukuda Y, Nakano I, et al. An autopsy case of multilocular cystic hepatocellular carcinoma without liver cirrhosis. Hepatogastroenterology 2000;47:1419–21. 21. Bhargava P, Iyer RS, Moshiri M, et al. Radiologic-pathologic correlation of uncommon mesenchymal liver tumors. Curr Probl Diagn Radiol 2013;42: 183–90. 22. Kim DJ, Yu JS, Kim JH, et al. Small hypervascular hepatocellular carcinomas: Value of diffusion-weighted imaging compared with “washout” appearance on dynamic MRI. Br J Radiol 2012;85:e879–86. 23. Chung YF, Thng CH, Lui HF, et al. Clinical mimicry of hepatocellular carcinoma: Imaging-pathological correlation. Singapore Med J 2005;46:31–6 [quiz 7]. 24. Basaran C, Karcaaltincaba M, Akata D, et al. Fat-containing lesions of the liver: Cross-sectional imaging findings with emphasis on MRI. Am J Roentgenol 2005;184:1103–10. 25. Balci NC, Befeler AS, Bieneman BK, et al. Fat containing HCC: Findings on CT and MRI including serial contrast-enhanced imaging. Acad Radiol 2009;16:963–8. 26. Mortele KJ, Ros PR. Cystic focal liver lesions in the adult: Differential CT and MR imaging features. Radiographics 2001;21:895–910. 27. Kim HC, Yang DM, Jin W, et al. The various manifestations of ruptured hepatocellular carcinoma: CT imaging findings. Abdom Imaging 2008;33: 633–42.
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28. El-Serag HB, Davila JA. Is fibrolamellar carcinoma different from hepatocellular carcinoma? A US population-based study. Hepatology 2004;39:798–803. 29. Ichikawa T, Federle MP, Grazioli L, et al. Fibrolamellar hepatocellular carcinoma: imaging and pathologic findings in 31 recent cases. Radiology 1999;213: 352–61. 30. McLarney JK, Rucker PT, Bender GN, et al. Fibrolamellar carcinoma of the liver: Radiologic-pathologic correlation. Radiographics 1999;19:453–71. 31. Smith MT, Blatt ER, Jedlicka P, et al. Best cases from the AFIP: Fibrolamellar hepatocellular carcinoma. Radiographics 2008;28:609–13. 32. Pua U, Low SC, Tan YM, et al. Combined hepatocellular and cholangiocarcinoma with sarcomatoid transformation: Radiologic-pathologic correlation of a case. Hepatol Int 2009;3:587–92. 33. Fowler KJ, Sheybani A, Parker RA 3rd, et al. Combined hepatocellular and cholangiocarcinoma (biphenotypic) tumors: Imaging features and diagnostic accuracy of contrast-enhanced CT and MRI. Am J Roentgenol 2013;201:332–9. 34. Heidecke S, Stippel DL, Hoelscher AH, et al. Simultaneous occurrence of a hepatocellular carcinoma and a hepatic non-Hodgkin's lymphoma infiltration. World J Hepatol 2010;2:246–50. 35. Sneag DB, Krajewski K, Giardino A, et al. Extrahepatic spread of hepatocellular carcinoma: Spectrum of imaging findings. Am J Roentgenol 2011;197: W658–W664. 36. Liu QY, Zhang WD, Chen JY, et al. Hepatocellular carcinoma with bile duct tumor thrombus: Dynamic computed tomography findings and histopathologic correlation. J Comput Assist Tomogr 2011;35:187–94.
Current Problems in Diagnostic Radiology journal homepage: www.cpdrjournal.com
Atypical Magnetic Resonance Imaging Findings in Hepatocellular Carcinoma Panayota S. Roumanis, MDa, Puneet Bhargava, MDb,c, Golnaz Kimia Aubin, MDa, Joon-Il Choi, MDa,d, Aram N. Demirjian, MDe, David A. Thayer, MDa, Chandana Lall, MDa,n a
Department of Radiological Sciences, University of California, Irvine, CA Department of Radiology, University of Washington, School of Medicine, Seattle, WA c VA Puget Sound Health Care System, Seattle, WA d Department of Radiology, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea e Department of Hepatobiliary Surgery, University of California, Irvine, CA b
Magnetic resonance imaging (MRI) is currently the modality of choice to evaluate liver lesions in patients with cirrhosis and hepatitis B and C. Hepatocellular carcinoma demonstrates typical imaging findings on contrast-enhanced MRI, which are usually diagnostic. Unfortunately, a subgroup of hepatocellular carcinoma presents with atypical imaging features, and awareness of these atypical presentations is important in ensuring early diagnosis and optimal patient outcomes. Herein, we review some of the more common atypical presentations with a focus on MRI. & 2015 Mosby, Inc. All rights reserved.
Introduction Hepatocellular carcinoma (HCC) is the most common primary hepatic malignancies globally, causing up to 1 million deaths worldwide annually, with a median postdiagnosis survival of 620 months.1-5 Survival is highly dependent on stage, with a 5-year survival rate of 55% for stage I disease in contrast to only 15% for stage III disease.6 Early diagnosis is therefore vital for maximizing patient survival. For patients at high risk of HCC, including those with hepatitis B or C, aflatoxin exposure, hemochromatosis, Wilson disease, or α1 antitrypsin deficiency, the American Association for the Study of Liver Disease recommends hepatic ultrasound surveillance be performed at 6-month intervals, with abnormal nodules larger than 1 cm to be further evaluated with computed tomography (CT) or magnetic resonance imaging (MRI).7 Both CT imaging and MRI can be diagnostic, without the need for biopsy in lesions exhibiting typical radiologic features of HCC.7,8 CT is preferred as an initial study because of the higher cost of MRI. However, MRI has better sensitivity and specificity in cirrhotic patients in whom regenerative nodules can be difficult to distinguish from HCC and is better at differentiating dysplastic nodules from HCC.9,10 MRI also provides better identification of focal fat and is superior for assessing vascular lesions such as hemangiomas. When typical features are present on imaging, HCC can be confidently diagnosed without tissue biopsy. However, HCC often has atypical imaging findings, making it difficult to distinguish from other, potentially benign, conditions. An understanding
n Reprint requests: Chandana Lall, MD, Department of Radiological Sciences, University of California, Irvine, 101 The City Dr South, Suite 1105, Orange, CA 92868 E-mail address: [email protected] (C. Lall).
http://dx.doi.org/10.1067/j.cpradiol.2014.03.002 0363-0188/& 2015 Mosby, Inc. All rights reserved.
of these atypical presentations is important to ensure an early and accurate diagnosis. A high index of suspicion for malignancy should be maintained, as well as a low threshold for biopsy. We review some of the atypical presentations of HCC on MRI with pertinent differential diagnoses. Each diagnosis was validated with a follow-up biopsy.
MRI Protocols Liver imaging has improved significantly with advances in MRI technology. The advent of newer and faster sequences on higher magnetic fields allows for greater temporal and spatial resolution. Dynamic contrast-enhanced imaging of the liver plays a dominant role in lesion characterization. A typical MRI protocol for HCC involves both T1- and T2-weighted imaging with dynamic contrast-enhanced MRI in arterial, venous, and delayed phases. When using hepatobiliary (HPB) agents, far-delayed (from 20 minutes to 1 hour) phase can be obtained for hepatobiliary phase. T1-weighted in-phase and out-of-phase gradient-recall sequences may be obtained using a 2-point Dixon method. Both gadolinium-based chelated agents (GBCAs) and nonGBCAs can be used for HCC diagnosis. GBCA can be divided into extracellular GBCA and hepatobiliary (HB) agents. The non-GBCAs include reticuloendothelial (RE) agents such as superparamagnetic iron oxide and Mangafodipir trisodium (Mn-DPDP). The GBCAs are paramagnetic, whereas the RE agents are superparamagnetic. Based on the biochemical distribution, extracellular GBCAs behave similar to iodinated contrast used in CT by distributing into the extracellular compartment. However, the HB agents are distributed in extracellular space in early phase and also accumulated in the hepatocytes and extracted in bile.11 The RE agents are accumulated in the RE system (ie, Kupffer cells in the liver). HB
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agents (Gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid (Gd-EOB-DTPA) or gadopentetate dimeglumine) can be used to obtain both dynamic imaging and hepatobiliary phase imaging and are now considered as standard contrast agents for liver MRI. With the combination with diffusion-weighted imaging (DWI), a superior diagnostic performance of HB agents for detecting HCC was reported, in comparison with extracellular gadolinium-based contrast agents.12,13
Typical MRI Appearances of HCC HCCs may be classified according to growth patterns and macroscopic aspects with prognostic implications: (1) Expansile, single nodular type, well-defined, encapsulated, and typically with a better prognosis, representing about 50% of HCCs. (2) Infiltrating type, consisting of a lesion with irregular, poorly defined borders, without a definable capsule, and frequently presenting with vascular invasion. This subtype usually has a poorer prognosis. (3) Multifocal with multiple nodules scattered in several hepatic segments. This subtype also has a poor prognosis. Classic HCCs are hypointense on T1-weighted imaging, mildly hyperintense on T2-weighted imaging, and exhibit brisk arterial phase contrast enhancement with rapid washout in the portal venous and delayed phases.14 Intense arterial phase enhancement is therefore characteristic of HCC, decreasing thereafter on subsequent phases. In larger lesions, a mosaic or heterogeneous pattern is seen on MRI because of the presence of fibrosis, hemorrhage, arteriovenous shunting, and intratumoral necrosis. Nodule-in-nodule appearance is another typical imaging feature of HCC. In hepatobiliary phase, most HCCs are hypointense compared with the hepatic parenchyma. However, paradoxical enhancement of HCC is also reported.15
Atypical MRI Appearances of HCC Unusual Enhancement Patterns HCC typically exhibits brisk arterial phase enhancement with rapid washout in the venous phase along with possible persistent rim enhancement in the delayed phase; however, there are variations in enhancement pattern. Enhancement patterns have been shown to be dependent on cellular differentiation.16 A higher proportion of moderate and poorly differentiated, rather than well-differentiated, HCC lesions exhibit the typical pattern of arterial phase enhancement followed by portal venous phase washout.17 Some HCCs however show lack of or poor arterial phase enhancement. Another mechanism that has been proposed is portal vein thrombosis secondary to HCC involvement, resulting in a compensatory increase in hepatic arterial supply to the liver parenchyma. This has been termed the “arterial steal” phenomenon, resulting in decreased blood supply to the tumor and increased enhancement of the hepatic parenchyma. The result is decreased relative enhancement of the HCC lesion. These variations include lack of arterial phase enhancement with persistent enhancement in the venous and delayed phases (Fig 1). Other patterns include quite commonly, nodular enhancement and enhancement of septations, which may be mistaken for abscesses. Continuous rim enhancement can be seen in a subgroup of HCCs and may mimic a metastatic lesion, especially in the setting of previous or concurrent extrahepatic malignancy.
A fibrotic capsule is commonly seen in HCC, which may show persistent enhancement in the delayed phase. A subgroup of HCCs demonstrates a central enhancing scar, usually because of the presence of central necrosis and subsequent fibrosis. These lesions may mimic focal nodular hyperplasia (FNH) if a proper history is not sought, leading to misdiagnosis. Another atypical finding is persistent enhancement of the HCC in the venous and delayed phases (Fig 2). This is usually seen in small HCCs, because of uncertain reasons. Larger HCC lesions are more likely to exhibit more typical enhancement kinetics. In contrast, small (subcentimeter) HCC lesions are seen to follow this pattern in only 24% of cases.18-20 Rather than showing brisk arterial phase enhancement, small HCC lesions may frequently show isoattenuation during the arterial and portal venous phases making the diagnosis of these lesions difficult.16 A group of HCCs demonstrates a dominant hypervascular pattern with massive intratumoral vessels including large draining veins mimicking vascular tumors such as hepatic angiosarcoma.21 The diagnosis can be made on the basis of serum alpha-fetoprotein (AFP) levels and history of chronic liver disease, as a biopsy may not be feasible because of extreme tumor hypervascularity (Fig 3). HCC may also exhibit nodular peripheral enhancement, which can be mistaken for hemangioma. This nodular enhancement in HCC has been proposed to be because of variations in tumor differentiation.14 A stepwise progression model for the development of HCC has been proposed, beginning with a regenerative nodule and progressing through dysplastic nodules of increasing grade, to dysplastic nodules with foci of HCC, and finally to small and large HCC.14 In this model, the nodular enhancement pattern sometimes seen in HCC is actually because of the foci of HCC on a dysplastic background, resulting in a nodular appearance. This may be mistaken for a hemangioma, which also frequently presents with a nodular peripheral enhancing pattern. Fibrolamellar carcinomas is particular may show peripheral irregular pattern of enhancement with gradual centripetal fill-in on delayed images, which can lead to a misdiagnosis of hemangioma, especially in the setting of normal liver function and AFP. DWI has been proposed as an aide for small lesions showing abnormal enhancement kinetics and may help identify HCC in cases where enhancement kinetics are equivocal.22 These sequences are highly susceptible to motion artifact, which has limited their use for HCC imaging. Respiratory and, possibly, cardiac gating should be considered to minimize artifact. In rare cases, HCC can mimic an abscess on imaging. The presence of a rim-enhancing lesion with or without internal septations can raise suspicion for an abscess. Biopsy is usually necessary in such cases for a diagnosis.23 Imaging findings should be correlated with the patient’s clinical status to help differentiate HCC from abscess. HCC With Atypical Signal From Intralesional Fat HCCs, in particular the clear cell type, may contain intracytoplasmic fat in 17%-20% of cases, and in approximately 2% of cases, this fat is radiographically apparent.18,24 The microscopic intravoxel fat can be seen as decreased signal in opposed-phased MRI (Fig 4). HCCs containing microscopic fat may be mistaken for hepatic adenoma, angiomyolipoma, or a fat-containing metastasis. Alternatively, in HCCs areas of macroscopic fat are apparent as a decrease in signal intensity in opposed-phase MR or fatsuppressed images or fat attenuation on CT imaging. These fatty areas may be mistaken for a hepatic lipoma, focal steatosis, fatcontaining adenoma, angiomyolipoma, or even hepatic liposarcoma.19,25 HCC with fatty metamorphoses tend to appear hyperintense on T1, with a concomitant loss of signal on out-of-phase, T1-weighted images. Presence of contrast washout during the
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Fig 1. Lack of arterial enhancement and persistent enhancement on delayed phase in HCC after extracellular gadolinium-based contrast agent injection. (A) Noncontrast T1weighted MR image shows no definite focal lesion in liver. (B) Arterial phase MR image shows a small hypointense nodular lesion (arrow) noted in segment 4. (C) Portal venous MR phase shows mild enhancement (arrow) compared with liver parenchyma. (D) Delayed enhancement is noted on equilibrium phase.
Fig 2. A persistent enhancement of HCC from arterial to delayed phase after injection of extracellular gadolinium-based contrast agents. (A) Arterial phase, (B) portal venous phase, and (C) delayed phase MR images after injection of extracellular gadolinium-based contrast agent show persistent enhancement of small nodular HCC (arrow).
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Fig 3. A dominant hypervascular mass with massive intratumoral vessels in HCC. (A) Coronal T2-weighted MR image shows multiple, heterogeneously high signal masses in the right lobe of the liver. Central hyperintensity is noted because of hypervascularity. (B) Axial T2-weighted MR image shows multiple, heterogeneously high signal masses in the right lobe of the liver. Central hyperintensity from hypervascularity is again noted. (C) Arterial phase MR image shows peripheral enhancement of the tumor and slight enhancement of central area of the tumor. (D) Delayed phase MR image shows multiple intratumoral vessels with prominent veins (arrowheads) are noted.
Fig 4. Fat-containing HCC. (A) In-phase T1-weighted gradient echo image shows a hyperintense mass (arrow) in segment 4 of the liver. (B) Out-of-phase T1-weighted image shows signal dropout within the mass (arrow), confirming the presence of microscopic intracellular fat. Eccentric area of enhancement with washout is not shown. This lesion was confirmed as fat-containing HCC on histopathology.
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the T2 hyperintensity and delayed enhancement of FNH, the scar of fibrolamellar HCC is hypointense on T2-weighted imaging with minimal delayed enhancement (Fig 6). Hypovascular tumors include well-differentiated HCC, fatty metamorphosis, tumor necrosis, and abundant interstitial fibrosis. Collision Lesions: For Example, Mixed HCC and CC
Fig 5. Ruptured HCC with intra-abdominal bleeding. Segment 6 exophytic HCC mass (straight arrow) with heterogeneously high signal intensity on T2-weighted image. Perihepatic fluid shows intermediate to high signal intensity from hemorrhage (curved arrow), compared with fluid in the gall bladder (*).
venous phase can distinguish HCC with fatty metamorphoses from angiomyolipoma and other fat-containing lesions. Capsular enhancement, peaking in the delayed phase, may also help distinguish HCC.25 Cystic Degeneration HCC with cystic degeneration is rare with very few reported cases in literature.20 It is usually the result of internal necrosis in large lesions that have outgrown their blood supply or after locoregional and systemic treatment. Presence of signs or complications of underlying cirrhosis on CT and MRI in addition to intrinsic tumor characteristics such as a capsule, increased vascularity of solid parts, and biliary and vascular invasion can lead to the diagnosis.26 On precontrast MRI, low signal on T1-weighted images and bright signal on T2-weighted images demonstrates cystic components. In addition, T1 high signal can be noted when hemorrhage is present. Presence of contrast washout in the portal venous or delayed phase further aids in diagnosis. HCC Rupture With Intra-Abdominal Bleeding Rupture of HCC is seen in 3%-15% of patients with HCC. Usually, CT scan is the cornerstone for urgent diagnosis but MRI can be obtained in this situation rarely. The presence of hemoperitoneum, perihepatic hematoma, extravasation of contrast material, discontinuity of liver surface, and enucleation sign (hypointense mass surrounded by enhancing rim with focal discontinuity on arterial phase) suggests rupture of a mass. Findings of a large HCC, contour protrusion, and portal vein thrombosis are considered risk factors for subsequent rupture (Fig 5).27 Fibrolamellar HCC The fibrolamellar variant of HCC is not associated with hepatitis or cirrhosis and may look similar to FNH, hemangioma with scarring, metastasis, cholangiocarcinoma (CC), or hepatic adenoma.28-30 Fibrolamellar HCC is most often seen in young adults and presents as an abdominal mass or abdominal pain. Fibrolamellar HCC may have a central radiating scar, seen in 20%71% of cases, similar to the central scar of FNH.31 Both hepatic adenoma and FNH tend to show a homogeneous arterial phase enhancement pattern, unlike fibrolamellar HCC, which is heterogeneous. Adenomas may have areas of hemorrhage and focal fat, both of which are uncommon in fibrolamellar HCC. In contrast to
One of the more commonly described collision lesions is the biphenotypic tumor consisting of coexistence of HCC with CC. Combined HCC-CC is an uncommon form of primary liver collision tumor displaying hepatocellular and biliary epithelial differentiation. This type of lesion constitutes less than 1% of all HCCs and roughly 7% of all primary liver tumors.32 Electron microscopic studies confirmed the presence of dual differentiation with venous and invasion into adjacent liver parenchyma and microsatellite formation, similar to that seen with a typical HCC. Imaging is unusual in that the HCC component may show brisk arterial enhancement and subsequent washout on the portal venous and delayed phases whereas the CC component shows poor enhancement on the arterial phase, enhancing mildly during the portal venous phase with persistent enhancement on the delayed phase because of predominance of fibrous component (Fig 7). On T1- and T2-weighted MR images, these tumors are hypointense and heterogeneously hyperintense, respectively. Preoperative diagnosis of biphenotypic tumors with HCC and CC purely on the basis of imaging may not be easy, although assessment of HCC or CC tumor markers, AFP and carbohydrate antigen-19-9 as well as risk factors can increase overall accuracy. In the absence of typical imaging features, biopsy is indicated for confirmation.33 Simultaneous occurrence of HCC and lymphoma has also been reported in literature. HCC component on imaging generally shows early arterial enhancement on CT and MRI with characteristic washout in the portal venous phase. In addition, changes consistent with lymphoma (ie, splenomegaly, lymphadenopathy, or hypodense or isodense masses) are seen on imaging, depending on the type and location of lymphoma.34 Infiltrating HCC Infiltrative HCC is a rare aggressive form that is characterized by poorly defined margins and atypical enhancement patterns (Fig 8). Involvement of the portal and hepatic veins with associated thrombosis occurs in 29%-65% and 12%-54% of cases, respectively.35 Bile duct invasion is also possible, although less common, and may lead to obstructive jaundice. These lesions can be difficult to visualize on both T1- and T2-weighted MRI and may only demonstrate mild heterogeneous enhancement on the arterial and venous phases. These are best seen on low–b value DWI. The presence of a thrombosed portal vein may therefore be a clue to an underlying infiltrative HCC in a cirrhotic patient and his finding should be viewed with a high index of suspicion (Fig 9). HCC-related malignant thrombosis needs to be distinguished from benign thrombus to which patients with cirrhosis with portal hypertension without HCC are predisposed. Thrombi caused by HCC tend to be contiguous with HCC lesions and cause dilation of the portal vein, features seen less commonly in bland thrombi. Malignant thrombi also tend to be T2 hyperintense and show a similar enhancement pattern as HCC, indicative of intrathrombus neovascularity, in contrast to bland thrombi, which show no enhancement and low T2 signal intensity. Transient hepatic intensity difference, may also be seen around HCC as an area of hypervascularity in the arterial phase, which is usually wedge shaped and conforms to a segment or lobe supplied by a particular portal venous branch. This is thought to represent vascular invasion of the portal vein and indicates malignancy.36 Invasion
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Fig 6. Fibrolamellar HCC. (A) T2-weighted MR image shows a high–signal intensity mass (arrowheads) in segment 6 of the liver with a hypointense central scar (arrow). (B) Arterial phase MR image shows peripheral enhancement in the mass (arrowheads). Central scar (arrow) is avascular and hypointense. (C) Portal venous phase MR image shows mild filling in the central scar tissue (arrow) while persistent enhancement is seen in the remainder of the tumor. (D) Equilibrium phase MR image shows continued filling-in of the central scar tissue (arrow) and persistent enhancement in the remainder of the tumor. (E) Delayed phase MR image shows persistent enhancement within the tumor (arrowheads) but central scar is not clearly visible because of delayed enhancement.
of the hepatic vein may propagate into the inferior vena cava as far as the right atrium. An important point to also understand is that a large proportion of HCCs with portal vein thrombosis lack characteristic arterial hypervascularity, which may be secondary to compensatory increased arterial supply to the background liver.
Bile duct invasion resulting in thrombus, termed bile duct tumor thrombus, is much rarer than either portal venous or hepatic venous infiltration, occurring in only up to 9% of HCCs. Biliary dilatation is seen proximal to the area of invasion and thrombus. These thrombi and areas of invasion tend to show
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Fig 7. Mixed HCC and cholangiocarcinoma. (A) Arterial phase MR image shows a hypointense mass (arrowheads) located in segments 5-6 of the liver with a small area of enhancement (arrow). (B) Portal venous and (C) delayed phase MR images show prominent enhancement in the cholangiocarcinoma component (arrows). The remainder of the tumor itself shows no enhancement and remains hypointense (arrowheads). Imaging features of this tumor are those of cholangiocarcinoma. However, pathologic examination after surgical resection revealed mixed HCC-cholangiocarcinoma. Collision tumors of HCC and other tumors are difficult to diagnose on imaging appearance.
Fig 8. Infiltrative HCC with indistinct margin. (A) T1-weighted MR image shows an ill-defined, hypointense mass (arrowheads) in segments 4, 5, and 8 of the liver. (B) T2weighted MR image shows a mildly hyperintense poorly marginated mass (arrowheads). (C) Arterial phase MR image shows mild patchy enhancement of the tumor (arrowheads). However, because of dilatation of bile ducts (arrows), the extent of the tumor and area involved by cholangiohepatitis is not clearly differentiated. (D) Delayed phase MR image shows ill-defined tumor margins. Dilated biliary ducts are again appreciated (arrows).
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Fig 9. Infiltrative HCC with portal vein invasion. (A) T2-weighted MR image shows a high-signal tumor thrombus (arrowheads) in the left portal vein. (B) Delayed phase MR image shows a striated appearance typical for an enhancing tumor thrombus (arrowheads) in the dilated portal vein. There are low-signal parenchymal tumor components (arrows) in the left lateral section of the liver. (C) Another delayed phase MR image shows peripheral tumor thrombi in left portal vein (arrowheads). (D) Diffusion-weighted image shows area of diffusion restriction within the tumor thrombus (arrowheads).
arterial enhancement with portal venous phase washout. Bile duct tumor thrombus may coexist with portal venous thrombus, with distinction between them made on the basis of patency of the portal vein, location of thrombus, and presence and degree of biliary ductal dilatation.36 Infiltrative HCC may not exhibit the brisk arterial phase enhancement typically seen in HCC and tends to be most prominent on diffusion- or T2-weighted imaging.
Conclusions HCC is one of the most common causes of cancer-related deaths worldwide. Imaging with CT or MRI can be diagnostic when typical imaging findings are present. However, HCC commonly presents in an atypical fashion and may easily be mistaken for another process. Ensuring accurate diagnosis, early treatment, and optimal patient outcomes require recognition of these atypical presentations. A high index of suspicion for malignancy should be maintained with a low threshold for further study, biopsy, or shortterm follow-up imaging. References 1. Okuda K. Epidemiology of Primary Liver Cancer. Primary Liver Cancer in Japan. Tokyo, Japan: Springer Japan; 1992, 3–15. 2. Parkin DM, Bray F, Ferlay J, et al. Global cancer statistics, 2002. CA Cancer J Clin 2005;55:74–108. 3. Bruix J, Llovet JM. Prognostic prediction and treatment strategy in hepatocellular carcinoma. Hepatology 2002;35:519–24. 4. Curado MP, Edwards B, Shin HR, et al. Cancer Incidence in Fiver Continents. Lyon, France: International Agency for Research on Cancer; 2007.
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