Skip to main content

Advertisement

SpringerLink
Log in

Hepatocellular carcinoma: metastatic pathways and extra-hepatic findings

  • Special Section: HCC Treatment
  • Published:
Abdominal Radiology Aims and scope Submit manuscript

Abstract

Although a small portion of patients with hepatocellular carcinoma (HCC) have radiologically evident extrahepatic disease at the initial presentation, a larger number of them develop metastatic disease later during the course of treatment or after definitive treatment. Furthermore, early metastatic disease could be overlooked by imaging due to small size and non-specificity of findings. Extrahepatic spread of HCC occurs via different pathways and is directly fueled by tumor biology and its molecular characteristics. Early and accurate detection of extrahepatic disease in patients with HCC has significant impact on management and selection of treatment options. Additionally, precise staging of disease will allow for better prediction of survival and outcome. Different pathways of regional and systemic spread of HCC with their proposed mechanisms and relevant underlying molecular derangement will be discussed in this article. Potential roles in management of patients with HCC will be discussed and reviewed in this article.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8
Fig. 9

Similar content being viewed by others

References

  1. Natsuizaka, M., et al., Clinical features of hepatocellular carcinoma with extrahepatic metastases. J Gastroenterol Hepatol, 2005. 20(11): p. 1781-7.

    Article  PubMed  Google Scholar 

  2. Katyal, S., et al., Extrahepatic metastases of hepatocellular carcinoma. Radiology, 2000. 216(3): p. 698-703.

    Article  CAS  PubMed  Google Scholar 

  3. Schutte, K., et al., Impact of Extrahepatic Metastases on Overall Survival in Patients with Advanced Liver Dominant Hepatocellular Carcinoma: A Subanalysis of the SORAMIC Trial. Liver Cancer, 2020. 9(6): p. 771-786.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  4. Yokoo, T., et al., Extrahepatic metastasis risk of hepatocellular carcinoma based on alpha-fetoprotein and tumor staging parameters at cross-sectional imaging. Cancer Manag Res, 2017. 9: p. 503-511.

    Article  PubMed  PubMed Central  Google Scholar 

  5. Han, T.S., et al., The Epigenetic Regulation of HCC Metastasis. Int J Mol Sci, 2018. 19(12).

  6. Wong, S.Y. and R.O. Hynes, Lymphatic or hematogenous dissemination: how does a metastatic tumor cell decide? Cell Cycle, 2006. 5(8): p. 812-7.

    Article  CAS  PubMed  Google Scholar 

  7. Zhao, H., et al., Prognostic value and preoperative predictors of microvascular invasion in solitary hepatocellular carcinoma </= 5 cm without macrovascular invasion. Oncotarget, 2017. 8(37): p. 61203-61214.

    Article  PubMed  PubMed Central  Google Scholar 

  8. Costentin, C.E., et al., Hepatocellular Carcinoma with Macrovascular Invasion: Defining the Optimal Treatment Strategy. Liver Cancer, 2017. 6(4): p. 360-374.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Mahringer-Kunz, A., et al., Extent of portal vein tumour thrombosis in patients with hepatocellular carcinoma: The more, the worse? Liver Int, 2019. 39(2): p. 324-331.

    Article  PubMed  Google Scholar 

  10. Guglielmi, A., et al., Hepatocellular carcinoma: surgical perspectives beyond the barcelona clinic liver cancer recommendations. World J Gastroenterol, 2014. 20(24): p. 7525-33.

    Article  PubMed  PubMed Central  Google Scholar 

  11. Chu, H.H., et al., A prediction model for overall survival after transarterial chemoembolization for hepatocellular carcinoma invading the hepatic vein or inferior vena cava. Eur Radiol, 2021. 31(6): p. 4232-4242.

    Article  PubMed  Google Scholar 

  12. Ikai, I., et al., Results of hepatic resection for hepatocellular carcinoma invading major portal and/or hepatic veins. Surg Oncol Clin N Am, 2003. 12(1): p. 65-75, ix.

  13. Shi, J., et al., A new classification for hepatocellular carcinoma with portal vein tumor thrombus. J Hepatobiliary Pancreat Sci, 2011. 18(1): p. 74-80.

    Article  PubMed  Google Scholar 

  14. Kudo, M., et al., Report of the 19th follow-up survey of primary liver cancer in Japan. Hepatol Res, 2016. 46(5): p. 372-90.

    Article  PubMed  Google Scholar 

  15. Cheng, S., et al., Chinese Expert Consensus on Multidisciplinary Diagnosis and Treatment of Hepatocellular Carcinoma with Portal Vein Tumor Thrombus (2018 Edition). Liver Cancer, 2020. 9(1): p. 28-40.

  16. Cerrito, L., et al., Treatment of hepatocellular carcinoma in patients with portal vein tumor thrombosis: Beyond the known frontiers. World J Gastroenterol, 2019. 25(31): p. 4360-4382.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Wang, J.C., et al., Comprehensive treatments for hepatocellular carcinoma with portal vein tumor thrombosis. J Cell Physiol, 2019. 234(2): p. 1062-1070.

    Article  CAS  PubMed  Google Scholar 

  18. Sneag, D.B., et al., Extrahepatic spread of hepatocellular carcinoma: spectrum of imaging findings. AJR Am J Roentgenol, 2011. 197(4): p. W658-64.

    Article  PubMed  Google Scholar 

  19. Hu, M.L., et al., Gastric metastasis of hepatocellular carcinoma via a possible existing retrograde hematogenous pathway. J Gastroenterol Hepatol, 2010. 25(2): p. 408-12.

    Article  CAS  PubMed  Google Scholar 

  20. Tamaki, K., et al., A patient with spinal metastasis from hepatocellular carcinoma discovered from neurological findings. World J Gastroenterol, 2007. 13(19): p. 2758-60.

    Article  PubMed  PubMed Central  Google Scholar 

  21. Schieda, N. and E.S. Siegelman, Update on CT and MRI of Adrenal Nodules. AJR Am J Roentgenol, 2017. 208(6): p. 1206-1217.

    Article  PubMed  Google Scholar 

  22. Tu, W., et al., Utility of T2-weighted MRI to Differentiate Adrenal Metastases from Lipid-Poor Adrenal Adenomas. Radiol Imaging Cancer, 2020. 2(6): p. e200011.

    Article  PubMed  PubMed Central  Google Scholar 

  23. Xia, F., et al., Positive lymph node metastasis has a marked impact on the long-term survival of patients with hepatocellular carcinoma with extrahepatic metastasis. PLoS One, 2014. 9(4): p. e95889.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  24. Uka, K., et al., Clinical features and prognosis of patients with extrahepatic metastases from hepatocellular carcinoma. World J Gastroenterol, 2007. 13(3): p. 414-20.

    Article  PubMed  PubMed Central  Google Scholar 

  25. Becker, A.K., et al., Extrahepatic metastases of hepatocellular carcinoma: A spectrum of imaging findings. Can Assoc Radiol J, 2014. 65(1): p. 60-6.

    Article  PubMed  Google Scholar 

  26. Wu, W., et al., Pattern of distant extrahepatic metastases in primary liver cancer: a SEER based study. J Cancer, 2017. 8(12): p. 2312-2318.

    Article  PubMed  PubMed Central  Google Scholar 

  27. Sun, H.C., et al., Incidence and prognostic values of lymph node metastasis in operable hepatocellular carcinoma and evaluation of routine complete lymphadenectomy. J Surg Oncol, 2007. 96(1): p. 37-45.

    Article  PubMed  Google Scholar 

  28. Yang, X., et al., The Prognostic Comparison Between Hepatocellular Carcinoma with Portal Vein Tumor Thrombus and Bile Duct Cancer Thrombus After Liver Resection. Cancer Manag Res, 2020. 12: p. 12077-12086.

    Article  PubMed  PubMed Central  Google Scholar 

  29. Sasahira, N., et al., Extrahepatic biliary obstruction after percutaneous tumour ablation for hepatocellular carcinoma: aetiology and successful treatment with endoscopic papillary balloon dilatation. Gut, 2005. 54(5): p. 698-702.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Qin, L.X. and Z.Y. Tang, Hepatocellular carcinoma with obstructive jaundice: diagnosis, treatment and prognosis. World J Gastroenterol, 2003. 9(3): p. 385-91.

    Article  PubMed  PubMed Central  Google Scholar 

  31. Park, H.C., et al., Acute obstructive cholangitis complicated by tumor migration after transarterial chemoembolization: a case report and literature review. Korean J Gastroenterol, 2014. 63(3): p. 171-5.

    Article  PubMed  Google Scholar 

  32. Zimmermann, A., Invasion Patterns and Metastatic Patterns of Hepatocellular Carcinoma, in Tumors and Tumor-Like Lesions of the Hepatobiliary Tract: General and Surgical Pathology. 2017, Springer International Publishing: Cham. p. 91-119.

    Chapter  Google Scholar 

  33. Hong, S.S., et al., Extrahepatic spread of hepatocellular carcinoma: a pictorial review. Eur Radiol, 2003. 13(4): p. 874-82.

    Article  PubMed  Google Scholar 

  34. Szpakowski, J.L., T.E. Drasin, and L.L. Lyon, Rate of seeding with biopsies and ablations of hepatocellular carcinoma: A retrospective cohort study. Hepatol Commun, 2017. 1(9): p. 841-851.

    Article  PubMed  PubMed Central  Google Scholar 

  35. Yu, J., et al., Needle track seeding after percutaneous microwave ablation of malignant liver tumors under ultrasound guidance: analysis of 14-year experience with 1462 patients at a single center. Eur J Radiol, 2012. 81(10): p. 2495-9.

    Article  PubMed  Google Scholar 

  36. Francica, G., Needle track seeding after radiofrequency ablation for hepatocellular carcinoma: prevalence, impact, and management challenge. J Hepatocell Carcinoma, 2017. 4: p. 23-27.

    Article  PubMed  PubMed Central  Google Scholar 

  37. Schaffler-Schaden, D., et al., Risk of needle tract seeding after coaxial ultrasound-guided percutaneous biopsy for primary and metastatic tumors of the liver: report of a single institution. Abdom Radiol (NY), 2020. 45(10): p. 3301-3306.

    Article  Google Scholar 

  38. Patidar, Y., et al., Radiofrequency ablation of surface v/s intraparenchymal hepatocellular carcinoma in cirrhotic patients. Indian J Radiol Imaging, 2017. 27(4): p. 496-502.

    Article  PubMed  PubMed Central  Google Scholar 

  39. Sartori, S., et al., Subcapsular liver tumors treated with percutaneous radiofrequency ablation: a prospective comparison with nonsubcapsular liver tumors for safety and effectiveness. Radiology, 2008. 248(2): p. 670-9.

    Article  PubMed  Google Scholar 

  40. Kim, Y.J., et al., Radiofrequency ablation of hepatocellular carcinoma: can subcapsular tumors be safely ablated? AJR Am J Roentgenol, 2008. 190(4): p. 1029-34.

    Article  PubMed  Google Scholar 

  41. Patel, P.A., et al., No-touch wedge ablation technique of microwave ablation for the treatment of subcapsular tumors in the liver. J Vasc Interv Radiol, 2013. 24(8): p. 1257-62.

    Article  PubMed  Google Scholar 

  42. Meier, J.M., et al., Intraperitoneal metastases after transarterial embolization of hepatocellular carcinoma: An observational study. Abdom Radiol (NY), 2017. 42(6): p. 1794-1798.

    Article  Google Scholar 

  43. Lee, C.H., et al., MRI findings of recurrent hepatocellular carcinoma after liver transplantation: preliminary results. J Magn Reson Imaging, 2011. 33(6): p. 1399-405.

    Article  PubMed  Google Scholar 

  44. National Comprehensive Cancer Network. Available from: http://www.nccn.org/professionals/physiscian_gls/pdf/hepatobiliary.pdf. Accessed May, 19th 2021.

  45. John, B.V., et al., Addition of [(18) F]Fluorodeoxyglucose Positron Emission Tomography With Computed Tomography to Cross-Sectional Imaging Improves Staging and Alters Management in Hepatocellular Carcinoma. Liver Transpl, 2020. 26(6): p. 774-784.

    Article  PubMed  PubMed Central  Google Scholar 

  46. Bak-Fredslund, K.P., et al., [(18) F]-Fluoro-2-deoxy-D-galactose positron emission tomography/computed tomography as complementary imaging tool in patients with hepatocellular carcinoma. Liver Int, 2020. 40(2): p. 447-455.

    Article  CAS  PubMed  Google Scholar 

  47. Seo, H.J., et al., (1)(8)F-FDG PET/CT in hepatocellular carcinoma: detection of bone metastasis and prediction of prognosis. Nucl Med Commun, 2015. 36(3): p. 226-33.

    Article  CAS  PubMed  Google Scholar 

  48. Marrero, J.A., 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): p. 723-750.

    Article  PubMed  Google Scholar 

  49. Mehta, N., et al., Validation of a Risk Estimation of Tumor Recurrence After Transplant (RETREAT) Score for Hepatocellular Carcinoma Recurrence After Liver Transplant. JAMA Oncol, 2017. 3(4): p. 493-500.

    Article  PubMed  PubMed Central  Google Scholar 

  50. An, C., et al., Single Hepatocellular Carcinoma: Preoperative MR Imaging to Predict Early Recurrence after Curative Resection. Radiology, 2015. 276(2): p. 433-43.

    Article  PubMed  Google Scholar 

  51. Zhang, J., et al., Texture Analysis Based on Preoperative Magnetic Resonance Imaging (MRI) and Conventional MRI Features for Predicting the Early Recurrence of Single Hepatocellular Carcinoma after Hepatectomy. Acad Radiol, 2019. 26(9): p. 1164-1173.

    Article  PubMed  Google Scholar 

  52. Guo, D., et al., Radiomics analysis enables recurrence prediction for hepatocellular carcinoma after liver transplantation. Eur J Radiol, 2019. 117: p. 33-40.

    Article  PubMed  Google Scholar 

  53. Lei, Z., et al., Nomogram for Preoperative Estimation of Microvascular Invasion Risk in Hepatitis B Virus-Related Hepatocellular Carcinoma Within the Milan Criteria. JAMA Surg, 2016. 151(4): p. 356-63.

    Article  PubMed  Google Scholar 

  54. Kim, K.A., et al., Prediction of microvascular invasion of hepatocellular carcinoma: usefulness of peritumoral hypointensity seen on gadoxetate disodium-enhanced hepatobiliary phase images. J Magn Reson Imaging, 2012. 35(3): p. 629-34.

    Article  PubMed  Google Scholar 

  55. Chen, F., et al., The Significance of Circulating Tumor Cells in Patients with Hepatocellular Carcinoma: Real-Time Monitoring and Moving Targets for Cancer Therapy. Cancers (Basel), 2020. 12(7).

  56. Cohen, S.J., et al., Prognostic significance of circulating tumor cells in patients with metastatic colorectal cancer. Ann Oncol, 2009. 20(7): p. 1223-9.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Radiology (Current Appointment), Yale School of Medicine, New Haven, CT, USA

    Sandeep Arora

  2. Department of Radiology (Previous Appointment), Vanderbilt University Medical Center, Nashville, TN, USA

    Sandeep Arora

  3. Department of Radiology, University of Chicago Pitzkar School of Medicine, Chicago, IL, USA

    Carla Harmath

  4. Department of Radiology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA

    Roberta Catania

  5. George Washington University School of Medicine and Health Sciences, Washington, DC, USA

    Ari Mandler

  6. University of California San Diego, San Diego, CA, USA

    Kathryn J. Fowler

  7. Department of Radiology, Northwestern University Feinberg School of Medicine, 676 N Saint Claire Street, Chicago, IL, 60611, USA

    Amir A. Borhani

  8. Department of Radiology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA

    Amir A. Borhani

Authors
  1. Sandeep Arora
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Carla Harmath
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Roberta Catania
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Ari Mandler
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Kathryn J. Fowler
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Amir A. Borhani
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Amir A. Borhani.

Ethics declarations

Conflict of interest

The authors have nothing relevant to disclose.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Arora, S., Harmath, C., Catania, R. et al. Hepatocellular carcinoma: metastatic pathways and extra-hepatic findings. Abdom Radiol 46, 3698–3707 (2021). https://doi.org/10.1007/s00261-021-03151-3

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00261-021-03151-3

Keywords

Search

Navigation