REVIEW ARTICLE
Multimodality imaging of hepatocellular carcinoma and intrahepatic cholangiocarcinoma
Haneyeh Shahbazian MD,
Mohammad Mirza-Aghazadeh-Attari MD,
Ali Borhani MD,
Alireza Mohseni MD,
Seyedeh Panid Madani MD,
Golnoosh Ansari MD,
Timothy M. Pawlik MD, MPH, PhD, FACS, FRACS,
Ihab R. Kamel MD, PhD, FSABI,
Haneyeh Shahbazian MD
Russell H. Morgan Department of Radiology and Radiological Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
Search for more papers by this authorMohammad Mirza-Aghazadeh-Attari MD
Russell H. Morgan Department of Radiology and Radiological Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
Search for more papers by this authorAli Borhani MD
Russell H. Morgan Department of Radiology and Radiological Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
Search for more papers by this authorAlireza Mohseni MD
Russell H. Morgan Department of Radiology and Radiological Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
Search for more papers by this authorSeyedeh Panid Madani MD
Russell H. Morgan Department of Radiology and Radiological Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
Search for more papers by this authorGolnoosh Ansari MD
Russell H. Morgan Department of Radiology and Radiological Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
Search for more papers by this authorTimothy M. Pawlik MD, MPH, PhD, FACS, FRACS
Department of Surgery, The Ohio State University Wexner Medical Center, and James Cancer Center, Columbus, Ohio, USA
Search for more papers by this authorCorresponding Author
Ihab R. Kamel MD, PhD, FSABI
Russell H. Morgan Department of Radiology and Radiological Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
Correspondence Ihab R. Kamel, MD, PhD, FSABI, Russell H. Morgan Department of Radiology and Radiological Sciences, Johns Hopkins University School of Medicine, 600 N Wolfe St, Room 143, Baltimore, MD 21287, USA.
Email: [email protected]
Search for more papers by this authorHaneyeh Shahbazian MD,
Mohammad Mirza-Aghazadeh-Attari MD,
Ali Borhani MD,
Alireza Mohseni MD,
Seyedeh Panid Madani MD,
Golnoosh Ansari MD,
Timothy M. Pawlik MD, MPH, PhD, FACS, FRACS,
Ihab R. Kamel MD, PhD, FSABI,
Haneyeh Shahbazian MD
Russell H. Morgan Department of Radiology and Radiological Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
Search for more papers by this authorMohammad Mirza-Aghazadeh-Attari MD
Russell H. Morgan Department of Radiology and Radiological Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
Search for more papers by this authorAli Borhani MD
Russell H. Morgan Department of Radiology and Radiological Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
Search for more papers by this authorAlireza Mohseni MD
Russell H. Morgan Department of Radiology and Radiological Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
Search for more papers by this authorSeyedeh Panid Madani MD
Russell H. Morgan Department of Radiology and Radiological Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
Search for more papers by this authorGolnoosh Ansari MD
Russell H. Morgan Department of Radiology and Radiological Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
Search for more papers by this authorTimothy M. Pawlik MD, MPH, PhD, FACS, FRACS
Department of Surgery, The Ohio State University Wexner Medical Center, and James Cancer Center, Columbus, Ohio, USA
Search for more papers by this authorCorresponding Author
Ihab R. Kamel MD, PhD, FSABI
Russell H. Morgan Department of Radiology and Radiological Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
Correspondence Ihab R. Kamel, MD, PhD, FSABI, Russell H. Morgan Department of Radiology and Radiological Sciences, Johns Hopkins University School of Medicine, 600 N Wolfe St, Room 143, Baltimore, MD 21287, USA.
Email: [email protected]
Search for more papers by this authorFirst published: 13 July 2023
Abstract
Hepatocellular carcinoma and intrahepatic cholangiocarcinoma are the two most common primary malignant tumors of the liver. The similarities and variations in imaging characteristics that may aid in distinguishing between these two primary tumors will be discussed and outlined in this review. Knowledge of imaging techniques that are currently available would assist in the differentiation between these primary malignancies.
CONFLICT OF INTEREST STATEMENT
The authors declare no conflicts of interest.
Open Research
DATA AVAILABILITY STATEMENT
Data sharing is not applicable to this article as no new data were created or analyzed in this study.
REFERENCES
- 1Yang JD, Hainaut P, Gores GJ, Amadou A, Plymoth A, Roberts LR. A global view of hepatocellular carcinoma: trends, risk, prevention and management. Nat Rev Gastroenterol Hepatol. 2019; 16(10): 589-604.
- 2Chen YJ, Shen CJ, Yu SH, Lin CL, Shih HM. Increased risk of hepatocellular carcinoma in patients with traumatic liver injury: real-world data from a nationwide population-based study. Medicine. 2022; 101(6):e28837.
- 3Veracruz N, Gish RG, Cheung R, Chitnis AS, Wong RJ. Global incidence and mortality of hepatitis B and hepatitis C acute infections, cirrhosis and hepatocellular carcinoma from 2010 to 2019. J Viral Hepatitis. 2022; 29(5): 352-365.
- 4Blach S, Zeuzem S, Manns M, et al. Global prevalence and genotype distribution of hepatitis C virus infection in 2015: a modelling study. Lancet Gastroenterol Hepatol. 2017; 2(3): 161-176.
- 5Razavi-Shearer D, Gamkrelidze I, Nguyen MH, et al. Global prevalence, treatment, and prevention of hepatitis B virus infection in 2016: a modelling study. Lancet Gastroenterol Hepatol. 2018; 3(6): 383-403.
- 6Terzi E, Ayuso C, Piscaglia F, Bruix J Liver imaging reporting and data system: Review of pros and cons. Paper presented at: Seminars in Liver Disease2022.
- 7Elvevi A, Laffusa A, Scaravaglio M, et al. Clinical treatment of cholangiocarcinoma: an updated comprehensive review. Annals of Hepatology. 2022; 27(5):100737.
- 8Kendall T, Verheij J, Gaudio E, et al. Anatomical, histomorphological and molecular classification of cholangiocarcinoma. Liver Int. 2019; 39: 7-18.
- 9Veldhuijzen van Zanten SEM, Pieterman KJ, Wijnhoven BPL, et al. FAPI PET versus FDG PET, CT or MRI for staging pancreatic-, gastric-and cholangiocarcinoma: systematic review and head-to-head comparisons of diagnostic performances. Diagnostics. 2022; 12(8): 1958.
- 10Liu J, Ren WX, Shu J. Multimodal molecular imaging evaluation for early diagnosis and prognosis of cholangiocarcinoma. Insights Imaging. 2022; 13(1): 10.
- 11Valle JW, Borbath I, Khan SA, Huguet F, Gruenberger T, Arnold D. Biliary cancer: ESMO clinical practice guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2016; 27: v28-v37.
- 12Yao J, Liang X, Liu Y, Li S, Zheng M. Trends in incidence and prognostic factors of two subtypes of primary liver cancers: a surveillance, epidemiology, and end results-based population study. Cancer Control. 2022; 29:107327482110515.
- 13Bertuccio P, Malvezzi M, Carioli G, et al. Global trends in mortality from intrahepatic and extrahepatic cholangiocarcinoma. J Hepatol. 2019; 71(1): 104-114.
- 14Khan SA, Tavolari S, Brandi G. Cholangiocarcinoma: epidemiology and risk factors. Liver Int. 2019; 39: 19-31.
- 15Ayuso C, Rimola J, García-Criado Á. Imaging of HCC. Abdom Imaging. 2012; 37(2): 215-230.
- 16Sugimoto K, Kakegawa T, Takahashi H, et al. Usefulness of modified CEUS LI-RADS for the diagnosis of hepatocellular carcinoma using sonazoid. Diagnostics. 2020; 10(10): 828.
- 17Schwarze V, Marschner C, Völckers W, et al. Diagnostic value of contrast-enhanced ultrasound versus computed tomography for hepatocellular carcinoma: a retrospective, single-center evaluation of 234 patients. J Int Med Res. 2020; 48(6):030006052093015.
- 18Lim JH, Choi D, Park CK, Lee WJ, Lim HK. Encapsulated hepatocellular carcinoma: CT-pathologic correlations. Eur Radiol. 2006; 16(10): 2326-2333.
- 19Ishigami K, Yoshimitsu K, Nishihara Y, et al. Hepatocellular carcinoma with a pseudocapsule on gadolinium-enhanced MR images: correlation with histopathologic findings. Radiology. 2009; 250(2): 435-443.
- 20Ponnoprat D, Inkeaw P, Chaijaruwanich J, et al. Classification of hepatocellular carcinoma and intrahepatic cholangiocarcinoma based on multi-phase CT scans. Med Biol Eng Comput. 2020; 58(10): 2497-2515.
- 21Navin PJ, Venkatesh SK. Hepatocellular carcinoma: state of the art imaging and recent advances. J Clin Transl Hepatol. 2019; 7(1): 1-14.
- 22Tang A, Singal AG, Mitchell DG, et al. Introduction to the liver imaging reporting and data system for hepatocellular carcinoma. Clin Gastroenterol Hepatol. 2019; 17(7): 1228-1238.
- 23Chernyak V, Fowler KJ, Kamaya A, et al. Liver imaging reporting and data system (LI-RADS) version 2018: imaging of hepatocellular carcinoma in at-risk patients. Radiology. 2018; 289(3): 816-830.
- 24Tang A, Bashir MR, Corwin MT, et al. Evidence supporting LI-RADS major features for CT-and MR imaging–based diagnosis of hepatocellular carcinoma: a systematic review. Radiology. 2018; 286(1): 29-48.
- 25Park YN, Yang CP, Fernandez GJ, Cubukcu O, Thung SN, Theise ND. Neoangiogenesis and sinusoidal “capillarization” in dysplastic nodules of the liver. Am J Surg Pathol. 1998; 22(6): 656-662.
- 26Matsui O. Imaging of multistep human hepatocarcinogenesis by CT during intra-arterial contrast injection. Intervirology. 2004; 47(3-5): 271-276.
- 27Sano K, Ichikawa T, Motosugi U, et al. Imaging study of early hepatocellular carcinoma: usefulness of gadoxetic acid-enhanced MR imaging. Radiology. 2011; 261(3): 834-844.
- 28Rimola J, Forner A, Tremosini S, et al. Non-invasive diagnosis of hepatocellular carcinoma ≤2 cm in cirrhosis. Diagnostic accuracy assessing fat, capsule and signal intensity at dynamic MRI. J Hepatol. 2012; 56(6): 1317-1323.
- 29Jang HJ, Kim TK, Khalili K, et al. Characterization of 1-to 2-cm liver nodules detected on hcc surveillance ultrasound according to the criteria of the American Association for the study of liver disease: is quadriphasic CT necessary? Am J Roentgenol. 2013; 201(2): 314-321.
- 30Valls C, Cos M, Figueras J, et al. Pretransplantation diagnosis and staging of hepatocellular carcinoma in patients with cirrhosis: value of dual-phase helical CT. Am J Roentgenol. 2004; 182(4): 1011-1017.
- 31Kim TK, Noh SY, Wilson SR, et al. Contrast-enhanced ultrasound (CEUS) liver imaging reporting and data system (LI-RADS) 2017 - a review of important differences compared to the CT/MRI system. Clin Mol Hepatol. 2017; 23(4): 280-289.
- 32Forner A, Vilana R, Ayuso C, et al. Diagnosis of hepatic nodules 20 mm or smaller in cirrhosis: prospective validation of the noninvasive diagnostic criteria for hepatocellular carcinoma. Hepatology. 2008; 47(1): 97-104.
- 33van den Bos IC, Hussain SM, Dwarkasing RS, et al. MR imaging of hepatocellular carcinoma: relationship between lesion size and imaging findings, including signal intensity and dynamic enhancement patterns. J Magn Reson Imaging. 2007; 26(6): 1548-1555.
- 34Marrero JA, Hussain HK, Nghiem HV, Umar R, Fontana RJ, Lok AS. Improving the prediction of hepatocellular carcinoma in cirrhotic patients with an arterially-enhancing liver mass. Liver Transpl. 2005; 11(3): 281-289.
- 35Sofue K, Sirlin CB, Allen BC, Nelson RC, Berg CL, Bashir MR. How reader perception of capsule affects interpretation of washout in hypervascular liver nodules in patients at risk for hepatocellular carcinoma. J Magn Reson Imaging. 2016; 43(6): 1337-1345.
- 36Luca A, Caruso S, Milazzo M, et al. Multidetector-row computed tomography (MDCT) for the diagnosis of hepatocellular carcinoma in cirrhotic candidates for liver transplantation: prevalence of radiological vascular patterns and histological correlation with liver explants. Eur Radiol. 2010; 20(4): 898-907.
- 37Joo I, Lee JM, Lee DH, Jeon JH, Han JK, Choi BI. Noninvasive diagnosis of hepatocellular carcinoma on gadoxetic acid-enhanced MRI: can hypointensity on the hepatobiliary phase be used as an alternative to washout? Eur Radiol. 2015; 25(10): 2859-2868.
- 38Haradome H, Grazioli L, Tinti R, et al. Additional value of gadoxetic acid-DTPA-enhanced hepatobiliary phase MR imaging in the diagnosis of early-stage hepatocellular carcinoma: comparison with dynamic triple-phase multidetector CT imaging. J Magn Reson Imaging. 2011; 34(1): 69-78.
- 39Nakayama H. High molecular weight caldesmon positive stromal cells in the capsule of hepatocellular carcinomas. J Clin Pathol. 2004; 57(7): 776-777.
- 40Bruix J, Sherman M. Management of hepatocellular carcinoma: an update. Hepatology. 2011; 53(3): 1020-1022.
- 41Procurement O, Network T Policy 9: allocation of livers and liver-intestines. 2015.
- 42Chung YE, Park M-S, Park YN, et al. Hepatocellular carcinoma variants: radiologic-pathologic correlation. Am J Roentgenol. 2009; 193(1): W7-W13.
- 43An C, Rakhmonova G, Choi J-Y, Kim M-J. Liver imaging reporting and data system (LI-RADS) version 2014: understanding and application of the diagnostic algorithm. Clin Mol Hepatol. 2016; 22(2): 296-307.
- 44Wald C, Russo MW, Heimbach JK, Hussain HK, Pomfret EA, Bruix J. New OPTN/UNOS policy for liver transplant allocation: standardization of liver imaging, diagnosis, classification, and reporting of hepatocellular carcinoma. In Radiology. 2013; 266: 376-382.
- 45Tezuka M, Hayashi K, Kubota K, et al. Growth rate of locally recurrent hepatocellular carcinoma after transcatheter arterial chemoembolization: comparing the growth rate of locally recurrent tumor with that of primary hepatocellular carcinoma. Dig Dis Sci. 2007; 52(3): 783-788.
- 46Kudo M, Tochio H. Intranodular blood supply correlates well with biological malignancy grade determined by tumor growth rate in pathologically proven hepatocellular carcinoma. Oncology. 2008; 75(suppl 1): 55-64.
- 47Yu J-S, Cho E-S, Kim K-H, Chung W-S, Park M-S, Kim KW. Newly developed hepatocellular carcinoma (HCC) in chronic liver disease: MR imaging findings before the diagnosis of HCC. J Comput Assist Tomogr. 2006; 30(5): 765-771.
- 48Hyodo T, Murakami T, Imai Y, et al. Hypovascular nodules in patients with chronic liver disease: risk factors for development of hypervascular hepatocellular carcinoma. Radiology. 2013; 266(2): 480-490.
- 49Furlan A, Marin D, Agnello F, et al. Hepatocellular carcinoma presenting at contrast-enhanced multi–detector-row computed tomography or gadolinium-enhanced magnetic resonance imaging as a small (≤2 cm), indeterminate nodule: growth rate and optimal interval time for imaging follow-up. J Comput Assist Tomogr. 2012; 36(1): 20-25.
- 50Jang KM, Kim SH, Kim YK, Choi D. Imaging features of subcentimeter hypointense nodules on gadoxetic acid-enhanced hepatobiliary phase MR imaging that progress to hypervascular hepatocellular carcinoma in patients with chronic liver disease. Acta Radiol. 2015; 56(5): 526-535.
- 51Park Y, Choi D, Lim HK, et al. Growth rate of new hepatocellular carcinoma after percutaneous radiofrequency ablation: evaluation with multiphase CT. Am J Roentgenol. 2008; 191(1): 215-220.
- 52De Rose AM, Cucchetti A, Clemente G, et al. Prognostic significance of tumor doubling time in mass-forming type cholangiocarcinoma. J Gastrointest Surg. 2013; 17(4): 739-747.
- 53Galle PR, Forner A, Llovet JM, et al., Liver EAFTSOT EASL clinical practice guidelines: management of hepatocellular carcinoma. J Hepatol. 2018; 69(1): 182-236.
- 54Vogel A, Cervantes A, Chau I, et al. Hepatocellular carcinoma: ESMO clinical practice guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2018; 29: iv238-iv255.
- 55Benson AB, D'Angelica MI, Abbott DE, et al. Guidelines insights: hepatobiliary cancers, version 2. 2019. J Natl Compr Canc Netw. 2019; 17(4): 302-310.
- 56Marrero JA, Kulik LM, Sirlin CB, et al. Diagnosis, staging, and management of hepatocellular carcinoma: 2018 practice guidance by the American Association for the study of liver diseases. Hepatology. 2018; 68(2): 723-750.
- 57Corvera CU, Blumgart LH, Akhurst T, et al. 18F-fluorodeoxyglucose positron emission tomography influences management decisions in patients with biliary cancer. J Am Coll Surg. 2008; 206(1): 57-65.
- 58Kluge R. Positron emission tomography with [18 F] fluoro-2-deoxy-D-glucose for diagnosis and staging of bile duct cancer. Hepatology. 2001; 33(5): 1029-1035.
- 59Breitenstein S, Apestegui C, Clavien PA. Positron emission tomography (PET) for cholangiocarcinoma. HPB. 2008; 10(2): 120-121.
- 60Iavarone M, Piscaglia F, Vavassori S, et al. Contrast enhanced CT-scan to diagnose intrahepatic cholangiocarcinoma in patients with cirrhosis. J Hepatol. 2013; 58(6): 1188-1193.
- 61Rimola J, Forner A, Reig M, et al. Cholangiocarcinoma in cirrhosis: absence of contrast washout in delayed phases by magnetic resonance imaging avoids misdiagnosis of hepatocellular carcinoma. Hepatology. 2009; 50(3): 791-798.
- 62Gardeur D, Lautrou J, Millard JC, Berger N, Metzger J. Pharmacokinetics of contrast media: experimental results in dog and man with CT implications. J Comput Assist Tomogr. 1980; 4(2): 178-185.
- 63Horvat N, Nikolovski I, Long N, et al. Imaging features of hepatocellular carcinoma compared to intrahepatic cholangiocarcinoma and combined tumor on MRI using liver imaging and data system (LI-RADS) version 2014. Abdominal Radiology. 2018; 43(1): 169-178.
- 64Nicholson C, Phillips JM. Ion diffusion modified by tortuosity and volume fraction in the extracellular microenvironment of the rat cerebellum. J Physiol. 1981; 321(1): 225-257.
- 65Szafer A, Zhong J, Anderson AW, Gore JC. Diffusion-weighted imaging in tissues: theoretical models. NBM. 1995; 8(7): 289-296.
- 66Detsky JS, Keith J, Conklin J, et al. Differentiating radiation necrosis from tumor progression in brain metastases treated with stereotactic radiotherapy: utility of intravoxel incoherent motion perfusion MRI and correlation with histopathology. JNO. 2017; 134(2): 433-441.
- 67Feng S-T, Wu L, Cai H, et al. Cholangiocarcinoma: spectrum of appearances on Gd-EOB-DTPA-enhanced MR imaging and the effect of biliary function on signal intensity. BMC Cancer. 2015; 15(1): 38.
- 68Zhang H, Zhu J, Ke F, et al. Radiological imaging for assessing the respectability of hilar cholangiocarcinoma: a systematic review and meta-analysis. BioMed Res Int. 2015; 2015: 1-11.
- 69Lee JJ, Schindera ST, Jang H-J, Fung S, Kim TK. Cholangiocarcinoma and its mimickers in primary sclerosing cholangitis. Abdominal Radiology. 2017; 42(12): 2898-2908.
- 70Blachar A, Federle MP, Brancatelli G. Hepatic capsular retraction: spectrum of benign and malignant etiologies. Abdom Imaging. 2002; 27(6): 690-699.
- 71Lacomis JM, Baron RL, Oliver 3rd, JH, Nalesnik MA, Federle MP. Cholangiocarcinoma: delayed CT contrast enhancement patterns. Radiology. 1997; 203(1): 98-104.
- 72Soyer P, Bluemke DA, Vissuzaine C, Beers BV, Barge J, Levesque M. CT of hepatic tumors: prevalence and specificity of retraction of the adjacent liver capsule. Am J Roentgenol. 1994; 162(5): 1119-1122.
- 73VanSonnenberg E, Wroblicka JT, D'Agostino HB, et al. Symptomatic hepatic cysts: percutaneous drainage and sclerosis. Radiology. 1994; 190(2): 387-392.
- 74Lee JW, Han JK, Kim TK, et al. CT features of intraductal intrahepatic cholangiocarcinoma. Am J Roentgenol. 2000; 175(3): 721-725.
- 75Chiow SM, Khoo HW, Low JK, Tan CH, Low HM. Imaging mimickers of cholangiocarcinoma: a pictorial review. Abdominal Radiology. 2022; 47: 981-997.
- 76Zou X, Luo Y, Morelli JN, Hu X, Shen Y, Hu D. Differentiation of hepatocellular carcinoma from intrahepatic cholangiocarcinoma and combined hepatocellular-cholangiocarcinoma in high-risk patients matched to MR field strength: diagnostic performance of LI-RADS version 2018. Abdominal Radiology. 2021; 46(7): 3168-3178.
- 77Bello HR, Mahdi ZK, Lui SK, Nandwana SB, Harri PA, Davarpanah AH. Hepatocellular carcinoma with atypical imaging features: review of the morphologic hepatocellular carcinoma subtypes with radiology-pathology correlation. J Magn Reson Imaging. 2022; 55(3): 681-697.
- 78Kim JH, Joo I, Lee JM, et al. Atypical appearance of hepatocellular carcinoma and its mimickers: how to solve challenging cases using gadoxetic acid-enhanced liver magnetic resonance imaging. Korean J Radiol. 2019; 20(7): 1019-1041.
- 79Zhou Q, Cai H, Xu M-H, et al. Do the existing staging systems for primary liver cancer apply to combined hepatocellular carcinoma-intrahepatic cholangiocarcinoma? Hepatobiliary Pancreat Dis Int. 2021; 20(1): 13-20.
- 80Yang J, Huang J-Y, Chen X, et al. Combined hepatocellular-cholangiocarcinoma: can we use contrast-enhanced ultrasound liver imaging reporting and data system (LI-RADS) to predict the patient's survival? Eur Radiol. 2021; 31(8): 6397-6405.
- 81Zhou C, Wang Y, Ma L, Qian X, Yang C, Zeng M. Combined hepatocellular carcinoma-cholangiocarcinoma: MRI features correlated with tumor biomarkers and prognosis. Eur Radiol. 2022; 32(1): 78-88.
