Abdominal Radiology

, Volume 44, Issue 2, pp 493–508 | Cite as

Pathological variants of hepatocellular carcinoma on MRI: emphasis on histopathologic correlation

  • Hsien Min Low
  • Jin Young Choi
  • Cher Heng TanEmail author
Pictorial essay


Hepatocellular carcinoma (HCC) is a unique tumor because it is one of the few cancers which can be treated based on imaging alone. Magnetic resonance imaging (MRI) carries higher sensitivity and specificity for the diagnosis of HCC than either computed tomography (CT) or ultrasound. MRI is imaging modality of choice for the evaluation of complex liver lesions and HCC because of its inherent ability to depict cellularity, fat, and hepatocyte composition with high soft tissue contrast. The imaging features of progressed HCC are well described. However, many HCC tumors do not demonstrate classical imaging features, posing a diagnostic dilemma to radiologists. Some of these can be attributed to variations in tumor biology and histology, which result in radiological features that differ from the typical progressed HCC. This pictorial review seeks to demonstrate the appearance of different variants of HCC on MRI imaging, in relation to their histopathologic features.


Hepatocellular carcinoma Atypical MRI Histopathology 



The authors would like to thank Dr Cora CHAU, Dr Bernard HO, Dr Yong Howe HO, and Dr Chin Fong WONG from the Department of Pathology, Tan Tock Seng Hospital for their contributions.

Compliance with ethical standards


This study received no funding.

Conflict of interest

All the above-mentioned authors have no conflict of interest to declare.

Ethical approval

This article does not contain any studies with human participants or animals performed by any of the authors.


  1. 1.
    Jemal A, Bray F, Center MM, et al. (2011) Global cancer statistics. CA 61(2):69–90. PubMedCrossRefGoogle Scholar
  2. 2.
    Perz JF, Armstrong GL, Farrington LA, Hutin YJ, Bell BP (2006) The contributions of hepatitis B virus and hepatitis C virus infections to cirrhosis and primary liver cancer worldwide. J Hepatol 45(4):529–538. PubMedCrossRefGoogle Scholar
  3. 3.
    Tan CH, Thng CH, Low AS, et al. (2011) Wash-out of hepatocellular carcinoma: quantitative region of interest analysis on CT. Ann Acad Med Singapore 40(6):269–275PubMedGoogle Scholar
  4. 4.
    Bruix J, Sherman M (2011) Management of hepatocellular carcinoma: an update. Hepatology 53(3):1020–1022. PubMedPubMedCentralCrossRefGoogle Scholar
  5. 5.
    Forner A, Vilana R, Ayuso C, et al. (2008) Diagnosis of hepatic nodules 20 mm or smaller in cirrhosis: Prospective validation of the noninvasive diagnostic criteria for hepatocellular carcinoma. Hepatology 47(1):97–104. PubMedCrossRefGoogle Scholar
  6. 6.
    Marrero JA, Hussain HK, Nghiem HV, et al. (2005) Improving the prediction of hepatocellular carcinoma in cirrhotic patients with an arterially-enhancing liver mass. Liver Transpl 11(3):281–289. PubMedCrossRefGoogle Scholar
  7. 7.
    European Association For The Study Of The L, European Organisation For R, Treatment Of C (2012) EASL-EORTC clinical practice guidelines: management of hepatocellular carcinoma. J Hepatol 56(4):908–943. CrossRefGoogle Scholar
  8. 8.
    American College of Radiology (2014) Liver Imaging and Reporting System version 2014. Accessed 1 May 2017Google Scholar
  9. 9.
    Rosenkrantz AB, Campbell N, Wehrli N, Triolo MJ, Kim S (2015) New OPTN/UNOS classification system for nodules in cirrhotic livers detected with MR imaging: effect on hepatocellular carcinoma detection and transplantation allocation. Radiology 274(2):426–433. PubMedCrossRefGoogle Scholar
  10. 10.
    Kudo M, Matsui O, Izumi N, et al. (2014) JSH Consensus-Based Clinical Practice Guidelines for the Management of Hepatocellular Carcinoma: 2014 Update by the Liver Cancer Study Group of Japan. Liver Cancer 3(3–4):458–468. PubMedPubMedCentralCrossRefGoogle Scholar
  11. 11.
    Lee JM, Park JW, Choi BI (2014) 2014 KLCSG-NCC Korea Practice Guidelines for the management of hepatocellular carcinoma: HCC diagnostic algorithm. Dig Dis 32(6):764–777. PubMedCrossRefGoogle Scholar
  12. 12.
    Yang JD, Roberts LR (2010) Hepatocellular carcinoma: a global view. Nat Rev Gastroenterol Hepatol 7(8):448–458. PubMedPubMedCentralCrossRefGoogle Scholar
  13. 13.
    Lai CL, Ratziu V, Yuen MF, Poynard T (2003) Viral hepatitis B. Lancet 362(9401):2089–2094. PubMedCrossRefGoogle Scholar
  14. 14.
    Omata M, Cheng AL, Kokudo N, et al. (2017) Asia-Pacific clinical practice guidelines on the management of hepatocellular carcinoma: a 2017 update. Hepatol Int 11(4):317–370. PubMedPubMedCentralCrossRefGoogle Scholar
  15. 15.
    Tan CH, Low SC, Thng CH (2011) APASL and AASLD Consensus Guidelines on Imaging Diagnosis of Hepatocellular Carcinoma: a review. Int J Hepatol 2011:519783. PubMedPubMedCentralCrossRefGoogle Scholar
  16. 16.
    Tang A, Bashir MR, Corwin MT, et al. (2018) Evidence supporting LI-RADS major features for CT- and MR imaging-based diagnosis of hepatocellular carcinoma: a systematic review. Radiology 286(1):29–48. PubMedCrossRefGoogle Scholar
  17. 17.
    Cerny M, Bergeron C, Billiard JS, et al. (2018) LI-RADS for MR imaging diagnosis of hepatocellular carcinoma: performance of major and ancillary features. Radiology 288(1):118–128. PubMedCrossRefGoogle Scholar
  18. 18.
    International Consensus Group for Hepatocellular Neoplasia (2009) Pathologic diagnosis of early hepatocellular carcinoma: a report of the international consensus group for hepatocellular neoplasia. Hepatology 49(2):658–664. CrossRefGoogle Scholar
  19. 19.
    Coleman WB (2003) Mechanisms of human hepatocarcinogenesis. Curr Mol Med 3(6):573–588PubMedCrossRefGoogle Scholar
  20. 20.
    Libbrecht L, Craninx M, Nevens F, Desmet V, Roskams T (2001) Predictive value of liver cell dysplasia for development of hepatocellular carcinoma in patients with non-cirrhotic and cirrhotic chronic viral hepatitis. Histopathology 39(1):66–73PubMedCrossRefGoogle Scholar
  21. 21.
    Park YN (2011) Update on precursor and early lesions of hepatocellular carcinomas. Arch Pathol Lab Med 135(6):704–715. PubMedCrossRefGoogle Scholar
  22. 22.
    Choi JY, Lee JM, Sirlin CB (2014) CT and MR imaging diagnosis and staging of hepatocellular carcinoma: part I. Development, growth, and spread: key pathologic and imaging aspects. Radiology 272(3):635–654. PubMedPubMedCentralCrossRefGoogle Scholar
  23. 23.
    Monzawa S, Omata K, Shimazu N, et al. (1999) Well-differentiated hepatocellular carcinoma: findings of US, CT, and MR imaging. Abdom Imaging 24(4):392–397PubMedCrossRefGoogle Scholar
  24. 24.
    Li CS, Chen RC, Tu HY, et al. (2006) Imaging well-differentiated hepatocellular carcinoma with dynamic triple-phase helical computed tomography. Br J Radiol 79(944):659–665. PubMedCrossRefGoogle Scholar
  25. 25.
    Van Beers BE, Pastor CM, Hussain HK (2012) Primovist, Eovist: what to expect? J Hepatol 57(2):421–429. PubMedCrossRefGoogle Scholar
  26. 26.
    Kitao A, Zen Y, Matsui O, et al. (2010) Hepatocellular carcinoma: signal intensity at gadoxetic acid-enhanced MR Imaging–correlation with molecular transporters and histopathologic features. Radiology 256(3):817–826. PubMedCrossRefGoogle Scholar
  27. 27.
    Kitao A, Matsui O, Yoneda N, et al. (2011) The uptake transporter OATP8 expression decreases during multistep hepatocarcinogenesis: correlation with gadoxetic acid enhanced MR imaging. Eur Radiol 21(10):2056–2066. PubMedCrossRefGoogle Scholar
  28. 28.
    Kogita S, Imai Y, Okada M, et al. (2010) Gd-EOB-DTPA-enhanced magnetic resonance images of hepatocellular carcinoma: correlation with histological grading and portal blood flow. Eur Radiol 20(10):2405–2413. PubMedCrossRefGoogle Scholar
  29. 29.
    Narita M, Hatano E, Arizono S, et al. (2009) Expression of OATP1B3 determines uptake of Gd-EOB-DTPA in hepatocellular carcinoma. J Gastroenterol 44(7):793–798. PubMedCrossRefGoogle Scholar
  30. 30.
    Kim JW, Lee CH, Kim SB, et al. (2016) Washout appearance in Gd-EOB-DTPA-enhanced MR imaging: A differentiating feature between hepatocellular carcinoma with paradoxical uptake on the hepatobiliary phase and focal nodular hyperplasia-like nodules. J Magn Reson Imaging . CrossRefPubMedPubMedCentralGoogle Scholar
  31. 31.
    Niendorf E, Spilseth B, Wang X, Taylor A (2015) Contrast enhanced MRI in the diagnosis of HCC. Diagnostics (Basel) 5(3):383–398. CrossRefGoogle Scholar
  32. 32.
    Tsuboyama T, Onishi H, Kim T, et al. (2010) Hepatocellular carcinoma: hepatocyte-selective enhancement at gadoxetic acid-enhanced MR imaging–correlation with expression of sinusoidal and canalicular transporters and bile accumulation. Radiology 255(3):824–833. PubMedCrossRefGoogle Scholar
  33. 33.
    Kitao A, Matsui O, Yoneda N, et al. (2012) Hypervascular hepatocellular carcinoma: correlation between biologic features and signal intensity on gadoxetic acid-enhanced MR images. Radiology 265(3):780–789. PubMedPubMedCentralCrossRefGoogle Scholar
  34. 34.
    Kim JY, Kim MJ, Kim KA, Jeong HT, Park YN (2012) Hyperintense HCC on hepatobiliary phase images of gadoxetic acid-enhanced MRI: correlation with clinical and pathological features. Eur J Radiol 81(12):3877–3882. PubMedCrossRefGoogle Scholar
  35. 35.
    Yamashita T, Kitao A, Matsui O, et al. (2014) Gd-EOB-DTPA-enhanced magnetic resonance imaging and alpha-fetoprotein predict prognosis of early-stage hepatocellular carcinoma. Hepatology 60(5):1674–1685. PubMedPubMedCentralCrossRefGoogle Scholar
  36. 36.
    Ueno A, Masugi Y, Yamazaki K, et al. (2014) OATP1B3 expression is strongly associated with Wnt/beta-catenin signalling and represents the transporter of gadoxetic acid in hepatocellular carcinoma. J Hepatol 61(5):1080–1087. PubMedCrossRefGoogle Scholar
  37. 37.
    Kitao A, Matsui O, Yoneda N, et al. (2015) Hepatocellular carcinoma with beta-catenin mutation: imaging and pathologic characteristics. Radiology 275(3):708–717. PubMedCrossRefGoogle Scholar
  38. 38.
    An C, Rhee H, Han K, et al. (2017) Added value of smooth hypointense rim in the hepatobiliary phase of gadoxetic acid-enhanced MRI in identifying tumour capsule and diagnosing hepatocellular carcinoma. Eur Radiol 27(6):2610–2618. PubMedCrossRefGoogle Scholar
  39. 39.
    Ojima H, Masugi Y, Tsujikawa H, et al. (2016) Early hepatocellular carcinoma with high-grade atypia in small vaguely nodular lesions. Cancer Sci 107(4):543–550. PubMedPubMedCentralCrossRefGoogle Scholar
  40. 40.
    Motosugi U, Bannas P, Sano K, Reeder SB (2015) Hepatobiliary MR contrast agents in hypovascular hepatocellular carcinoma. J Magn Reson Imaging 41(2):251–265. PubMedCrossRefGoogle Scholar
  41. 41.
    Sano K, Ichikawa T, Motosugi U, et al. (2011) Imaging study of early hepatocellular carcinoma: usefulness of gadoxetic acid-enhanced MR imaging. Radiology 261(3):834–844. PubMedCrossRefGoogle Scholar
  42. 42.
    Schlageter M, Terracciano LM, D’Angelo S, Sorrentino P (2014) Histopathology of hepatocellular carcinoma. World J Gastroenterol 20(43):15955–15964. PubMedPubMedCentralCrossRefGoogle Scholar
  43. 43.
    Reynolds AR, Furlan A, Fetzer DT, et al. (2015) Infiltrative hepatocellular carcinoma: what radiologists need to know. Radiographics 35(2):371–386. PubMedCrossRefGoogle Scholar
  44. 44.
    Rosenkrantz AB, Lee L, Matza BW, Kim S (2012) Infiltrative hepatocellular carcinoma: comparison of MRI sequences for lesion conspicuity. Clin Radiol 67(12):e105–111. PubMedCrossRefGoogle Scholar
  45. 45.
    Kanematsu M, Semelka RC, Leonardou P, Mastropasqua M, Lee JK (2003) Hepatocellular carcinoma of diffuse type: MR imaging findings and clinical manifestations. J Magn Reson Imaging 18(2):189–195. PubMedCrossRefGoogle Scholar
  46. 46.
    Park YS, Lee CH, Kim BH, et al. (2013) Using Gd-EOB-DTPA-enhanced 3-T MRI for the differentiation of infiltrative hepatocellular carcinoma and focal confluent fibrosis in liver cirrhosis. Magn Reson Imaging 31(7):1137–1142. PubMedCrossRefGoogle Scholar
  47. 47.
    Kneuertz PJ, Demirjian A, Firoozmand A, et al. (2012) Diffuse infiltrative hepatocellular carcinoma: assessment of presentation, treatment, and outcomes. Ann Surg Oncol 19(9):2897–2907. PubMedPubMedCentralCrossRefGoogle Scholar
  48. 48.
    Kurogi M, Nakashima O, Miyaaki H, Fujimoto M, Kojiro M (2006) Clinicopathological study of scirrhous hepatocellular carcinoma. J Gastroenterol Hepatol 21(9):1470–1477. PubMedCrossRefGoogle Scholar
  49. 49.
    Lee JH, Choi MS, Gwak GY, et al. (2012) Clinicopathologic characteristics and long-term prognosis of scirrhous hepatocellular carcinoma. Dig Dis Sci 57(6):1698–1707. PubMedCrossRefGoogle Scholar
  50. 50.
    Choi SY, Kim YK, Min JH, et al. (2018) Added value of ancillary imaging features for differentiating scirrhous hepatocellular carcinoma from intrahepatic cholangiocarcinoma on gadoxetic acid-enhanced MR imaging. Eur Radiol . PubMedCentralCrossRefPubMedGoogle Scholar
  51. 51.
    Park MJ, Kim YK, Park HJ, Hwang J, Lee WJ (2013) Scirrhous hepatocellular carcinoma on gadoxetic acid-enhanced magnetic resonance imaging and diffusion-weighted imaging: emphasis on the differentiation of intrahepatic cholangiocarcinoma. J Comput Assist Tomogr 37(6):872–881. PubMedCrossRefGoogle Scholar
  52. 52.
    Chong YS, Kim YK, Lee MW, et al. (2012) Differentiating mass-forming intrahepatic cholangiocarcinoma from atypical hepatocellular carcinoma using gadoxetic acid-enhanced MRI. Clin Radiol 67(8):766–773. PubMedCrossRefGoogle Scholar
  53. 53.
    Agni RM (2016) Diagnostic histopathology of hepatocellular carcinoma: a case-based review. Semin Diagn Pathol . PubMedCrossRefGoogle Scholar
  54. 54.
    Arai T, Akita S, Sakon M, et al. (2014) Hepatocellular carcinoma associated with sarcoidosis. Int J Surg Case Rep 5(8):562–565. PubMedPubMedCentralCrossRefGoogle Scholar
  55. 55.
    Chalasani P, Vohra M, Sheagren JN (2005) An association of sarcoidosis with hepatocellular carcinoma. Ann Oncol 16(10):1714–1715. PubMedCrossRefGoogle Scholar
  56. 56.
    Wong VS, Adab N, Youngs GR, Sturgess R (1999) Hepatic sarcoidosis complicated by hepatocellular carcinoma. Eur J Gastroenterol Hepatol 11(3):353–355PubMedCrossRefGoogle Scholar
  57. 57.
    Ogata S, Horio T, Sugiura Y, et al. (2010) Sarcoidosis-associated hepatocellular carcinoma. Acta Med Okayama 64(6):407–410. PubMedCrossRefGoogle Scholar
  58. 58.
    Askling J, Grunewald J, Eklund A, Hillerdal G, Ekbom A (1999) Increased risk for cancer following sarcoidosis. Am J Respir Crit Care Med 160(5 Pt 1):1668–1672. PubMedCrossRefGoogle Scholar
  59. 59.
    Romer FK, Hommelgaard P, Schou G (1998) Sarcoidosis and cancer revisited: a long-term follow-up study of 555 Danish sarcoidosis patients. Eur Respir J 12(4):906–912PubMedCrossRefGoogle Scholar
  60. 60.
    Potretzke TA, Tan BR, Doyle MB, et al. (2016) Imaging features of biphenotypic primary liver carcinoma (hepatocholangiocarcinoma) and the potential to mimic hepatocellular carcinoma: LI-RADS Analysis of CT and MRI features in 61 cases. AJR Am J Roentgenol 207(1):25–31. PubMedCrossRefGoogle Scholar
  61. 61.
    Shetty AS, Fowler KJ, Brunt EM, et al. (2014) Combined hepatocellular-cholangiocarcinoma: what the radiologist needs to know about biphenotypic liver carcinoma. Abdom Imaging 39(2):310–322. PubMedCrossRefGoogle Scholar
  62. 62.
    Sammon J, Fischer S, Menezes R, et al. (2018) MRI features of combined hepatocellular- cholangiocarcinoma versus mass forming intrahepatic cholangiocarcinoma. Cancer Imaging 18(1):8. PubMedPubMedCentralCrossRefGoogle Scholar
  63. 63.
    de Campos RO, Semelka RC, Azevedo RM, et al. (2012) Combined hepatocellular carcinoma-cholangiocarcinoma: report of MR appearance in eleven patients. J Magn Reson Imaging 36(5):1139–1147. PubMedCrossRefGoogle Scholar
  64. 64.
    Horvat N, Nikolovski I, Long N, et al. (2018) Imaging features of hepatocellular carcinoma compared to intrahepatic cholangiocarcinoma and combined tumor on MRI using liver imaging and data system (LI-RADS) version 2014. Abdom Radiol (NY) 43(1):169–178. CrossRefGoogle Scholar
  65. 65.
    Choi JY, Lee JM, Sirlin CB (2014) CT and MR imaging diagnosis and staging of hepatocellular carcinoma: part II. Extracellular agents, hepatobiliary agents, and ancillary imaging features. Radiology 273(1):30–50. PubMedPubMedCentralCrossRefGoogle Scholar
  66. 66.
    Salomao M, Remotti H, Vaughan R, et al. (2012) The steatohepatitic variant of hepatocellular carcinoma and its association with underlying steatohepatitis. Hum Pathol 43(5):737–746. PubMedCrossRefGoogle Scholar
  67. 67.
    Sanyal A, Poklepovic A, Moyneur E, Barghout V (2010) Population-based risk factors and resource utilization for HCC: US perspective. Curr Med Res Opin 26(9):2183–2191. PubMedCrossRefGoogle Scholar
  68. 68.
    Streba LA, Vere CC, Rogoveanu I, Streba CT (2015) Nonalcoholic fatty liver disease, metabolic risk factors, and hepatocellular carcinoma: an open question. World J Gastroenterol 21(14):4103–4110. PubMedPubMedCentralCrossRefGoogle Scholar
  69. 69.
    Koo HR, Park MS, Kim MJ, et al. (2008) Radiological and clinical features of sarcomatoid hepatocellular carcinoma in 11 cases. J Comput Assist Tomogr 32(5):745–749. PubMedCrossRefGoogle Scholar
  70. 70.
    Maeda T, Adachi E, Kajiyama K, et al. (1996) Spindle cell hepatocellular carcinoma. A clinicopathologic and immunohistochemical analysis of 15 cases. Cancer 77(1):51–57. 10.1002/(SICI)1097-0142(19960101)77:1<51::AID-CNCR10>3.0.CO;2-7PubMedCrossRefGoogle Scholar
  71. 71.
    Honda H, Hayashi T, Yoshida K, et al. (1996) Hepatocellular carcinoma with sarcomatous change: characteristic findings of two-phased incremental CT. Abdom Imaging 21(1):37–40PubMedCrossRefGoogle Scholar
  72. 72.
    Hung Y, Hsieh TY, Gao HW, Chang WC, Chang WK (2014) Unusual computed tomography features of ruptured sarcomatous hepatocellular carcinoma. J Chin Med Assoc 77(5):265–268. PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Hsien Min Low
    • 1
  • Jin Young Choi
    • 2
  • Cher Heng Tan
    • 1
    • 3
    Email author
  1. 1.Department of Diagnostic RadiologyTan Tock Seng HospitalSingaporeSingapore
  2. 2.Department of RadiologyYonsei University College of MedicineSeoulSouth Korea
  3. 3.Lee Kong Chian School of MedicineSingaporeSingapore

Personalised recommendations