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Radio-pathologic correlation of biphenotypic primary liver cancer (combined hepatocellular cholangiocarcinoma): changes in the 2019 WHO classification and impact on LI-RADS classification at liver MRI

  • Hepatobiliary-Pancreas
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Abstract

Objectives

To explain the new changes in pathologic diagnoses of biphenotypic primary liver cancer (PLC) according to the updated 2019 World Health Organization (WHO) classification and how it impacts Liver Imaging Reporting and Data System (LI-RADS) classification using gadoxetic acid–enhanced MRI (Gd-EOB-MRI).

Methods

We retrospectively included 209 patients with pathologically proven biphenotypic PLCs according to the 2010 WHO classification who had undergone preoperative Gd-EOB-MRI between January 2009 and December 2018. Imaging analysis including LI-RADS classification and pathologic review including the proportion of tumor components were performed. Frequencies of each diagnosis and subtype according to the 2010 and 2019 WHO classifications were compared, and changes in LI-RADS classification were evaluated. Univariable and multivariable analysis were performed to determine significant tumor component for LI-RADS classification.

Results

Of the 209 biphenotypic PLCs of the 2010 WHO classification, 177 (84.7%) were diagnosed as bipheonotypic PLCs, 25 (12.0%) as hepatocellular carcinomas (HCCs), and 7 (3.3%) as cholangiocarcinomas (CCAs) using the 2019 WHO classification. Of the 177 biphenotypic PLCs, LR-M, LR-4, and LR-5 were assigned in 77 (43.5%), 21 (11.9%), and 63 (35.5%), respectively. There were no significant differences in the proportion of LR-5 and LR-M categories between the WHO 2010 and 2019 classifications (p = 0.941). Proportion of HCC component was the only independent factor for LI-RADS classification (adjusted odds ratio, 1.02; p < 0.001).

Conclusion

According to the 2019 WHO classification, 15% of biphenotypic PLCs from the 2010 WHO classification were re-diagnosed as HCCs or CCAs, and a substantial proportion of biphenotypic PLCs of the 2019 WHO classification could be categorized as LR-4 or LR-5 on Gd-EOB-MRI.

Key Points

• Among 209 diagnosed biphenotypic PLCs according to the 2010 WHO classification, 177 (84.7%) lesions were reclassified as bipheonotypic PLCs, 25 (12.0%) as HCCs, and 7 (3.3%) as CCAs using the 2019 WHO classification.

• Of the 177 biphenotypic PLCs at the 2019 WHO classification, LR-M, LR-4, and LR-5 were assigned in 77 (43.5%), 21 (11.9%), and 63 (35.5%), respectively.

• LI-RADS classification relied on the proportion of HCC component (adjusted odds ratio,1.02; p < 0.001).

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Abbreviations

CCA:

Cholangiocarcinoma

cHCC-CCA:

Combined hepatocellular cholangiocarcinoma

CLC:

Cholangiolocarcinoma

HCC:

Hepatocellular carcinoma

HPC:

Hepatic stem/progenitor cells

IC:

Intermediate cell carcinoma

LI-RADS:

Liver Imaging Reporting and Data System

PLC:

Primary liver cancer

WHO:

World Health Organization

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Acknowledgements

We thank Chris Woo for his assistance in English editing of this manuscript.

Funding

The authors state that this work has not received any funding.

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Author notes

  1. Two first-authors (S.H.C. and S.K.J.) contributed equally to this work; S.H.C and S.K.J performed study data collection from each of two participating institutions and performed data analysis and manuscript writing. Thus, the two authors would like to share co-first authorship.

  2. And two co-corresponding-authors (S.S.L. and J.M.L.) contributed equally to this work; S.S.L. and J.M.L. contributed equally in data conception, manuscript writing, and critical revisions. Thus, the two authors would like to share co-corresponding authorship.

Authors and Affiliations

  1. Department of Radiology and Research Institute of Radiology, University of Ulsan College of Medicine, Asan Medical Center, 88 Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, Korea

    Sang Hyun Choi & Seung Soo Lee

  2. Department of Radiology, Seoul National University Hospital and Seoul National University College of Medicine, 101 Daehangno, Jongno-gu, Seoul, 03080, Korea

    Sun Kyung Jeon, Jeong Min Lee & Hyo-Jin Kang

  3. Department of Radiology, Seoul National University Hospital Gangnam Center, Seoul, Korea

    Bo Yun Hur

  4. Department of Pathology, Seoul National University Hospital and Seoul National University College of Medicine, Seoul, Korea

    Haeryoung Kim

  5. Department of Pathology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea

    Yangsoon Park

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  1. Sang Hyun Choi
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Corresponding authors

Correspondence to Seung Soo Lee or Jeong Min Lee.

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Guarantor

The scientific guarantor of this publication is Jeong Min Lee.

Conflict of Interest

The authors of this manuscript declare no relationships with any companies whose products or services may be related to the subject matter of the article.

Statistics and Biometry

No complex statistical methods were necessary for this paper.

Informed Consent

Written informed consent was waived by the Institutional Review Board.

Ethical Approval

Institutional Review Board approval was obtained.

Study subjects or cohorts overlap

Some study subjects (99 of 209 patients) have been previously reported [1,2,3]. The prior articles evaluated biphenotypic PLCs diagnosed only by the 2010 WHO classification, whereas this study reevaluated the pathologic and radiologic findings of the tumors with emphasis on the changes in pathologic diagnoses and LI-RADS classification results based on the 2010 WHO and 2019 WHO classifications.

References

1Jeon SK, Joo I, Lee DH et al (2019) Combined hepatocellular cholangiocarcinoma: LI-RADS v2017 categorisation for differential diagnosis and prognostication on gadoxetic acid-enhanced MR imaging. Eur Radiol 29:373-382

2Choi SH, Lee SS, Park SH et al (2019) LI-RADS Classification and prognosis of primary liver cancers at gadoxetic acid-enhanced MRI. Radiology 290:388-397

3Park SH, Lee SS, Yu E et al (2017) Combined hepatocellular-cholangiocarcinoma: gadoxetic acid-enhanced MRI findings correlated with pathologic features and prognosis. J Magn Reson Imaging 46:267-280

Methodology

• retrospective

• cross-sectional study

• multicenter study

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Sang Hyun Choi and Sun Kyung Jeon are co-first authors.

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Choi, S.H., Jeon, S.K., Lee, S.S. et al. Radio-pathologic correlation of biphenotypic primary liver cancer (combined hepatocellular cholangiocarcinoma): changes in the 2019 WHO classification and impact on LI-RADS classification at liver MRI. Eur Radiol 31, 9479–9488 (2021). https://doi.org/10.1007/s00330-021-07984-w

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