Skip to main content
SpringerLink
Log in

The “stiff rim” sign of hepatocellular carcinoma on shear wave elastography: correlation with pathological features and potential prognostic value

  • Hepatobiliary
  • Published:
Abdominal Radiology Aims and scope Submit manuscript

Abstract

Purpose

To explore the pathologic basis, the influencing factors and potential prognostic value of the stiff rim sign in two-dimensional shear wave elastography (2D-SWE) of hepatocellular carcinoma (HCC).

Methods

HCC patients who underwent tumor 2D-SWE examination before resection were prospectively enrolled. The stiff rim sign was defined as increased stiffness in the peritumoral region. Interobserver and intraobserver variability of the stiff rim sign was assessed. The correlation between the stiff rim sign and pathological characteristics was analyzed. Multivariate analysis was performed to examine clinical and radiological factors influencing the appearance of stiff rim sign. The Kaplan–Meier method was used to analyze the relationship between recurrence-free survival (RFS) and the stiff rim sign.

Results

The stiff rim sign on 2D-SWE was present in 44.7% of HCC lesions. Interobserver agreement and intraobserver agreement for the stiff rim sign were substantial (κ = 0.772) and almost perfect (κ = 0.895), respectively. Pathologically, the stiff rim sign was associated with capsule status, capsule integrity, capsule thickness, proportion of peritumoral fibrous tissue, and peritumoral fibrous arrangement. Multivariate analysis showed that tumor size was an independent clinical predictor for the appearance of stiff rim sign (OR 1.201, p = 0.008). Kaplan–Meier analysis showed RFS was significantly poorer in the stiff rim sign (+) group than the stiff rim sign (−) group in solitary tumors smaller than 5 cm (p = 0.007) and solitary tumors with intratumoral stiffness less than 33.7 kPa (p = 0.007).

Conclusion

The stiff rim sign on 2D-SWE was mainly correlated with peritumoral fibrous tissue status and was a poor prognostic indicator for HCC.

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

Similar content being viewed by others

Abbreviations

CUS:

Conventional ultrasound

EMT:

Epithelial mesenchymal transition

Emax:

Maximum elastic modulus

Emean:

Mean elastic modulus

HCC:

Hepatocellular carcinoma

RFS:

Recurrence-free survival

ROI:

Round region of interest

US:

Ultrasound

2D-SWE:

Two-dimensional shear wave elastography

References

  1. Forner A, Reig M, Bruix J (2018) Hepatocellular carcinoma. Lancet 391:1301-1314

    Article  PubMed  Google Scholar 

  2. Heimbach JK, Kulik LM, Finn RS et al (2018) AASLD guidelines for the treatment of hepatocellular carcinoma. Hepatology 67:358-380

    Article  PubMed  Google Scholar 

  3. Dietrich CF, Bamber J, Berzigotti A et al (2017) EFSUMB Guidelines and Recommendations on the Clinical Use of Liver Ultrasound Elastography, Update 2017 (Long Version). Ultraschall Med 38:e16-e47

    Article  PubMed  Google Scholar 

  4. Lupsor-Platon M, Serban T, Silion AI, Tirpe A, Florea M (2020) Hepatocellular Carcinoma and Non-Alcoholic Fatty Liver Disease: A Step Forward for Better Evaluation Using Ultrasound Elastography. Cancers (Basel) 12

  5. Gao Y, Zheng J, Liang P et al (2018) Liver Fibrosis with Two-dimensional US Shear-Wave Elastography in Participants with Chronic Hepatitis B: A Prospective Multicenter Study. Radiology 289:407-415

    Article  PubMed  Google Scholar 

  6. Ferraioli G, Filice C, Castera L et al (2015) WFUMB guidelines and recommendations for clinical use of ultrasound elastography: Part 3: liver. Ultrasound Med Biol 41:1161-1179

    Article  PubMed  Google Scholar 

  7. Tian WS, Lin MX, Zhou LY et al (2016) Maximum Value Measured by 2-D Shear Wave Elastography Helps in Differentiating Malignancy from Benign Focal Liver Lesions. Ultrasound Med Biol 42:2156-2166

    Article  PubMed  Google Scholar 

  8. Ronot M, Di Renzo S, Gregoli B et al (2015) Characterization of fortuitously discovered focal liver lesions: additional information provided by shearwave elastography. Eur Radiol 25:346-358

    Article  PubMed  Google Scholar 

  9. Evans A, Whelehan P, Thomson K et al (2010) Quantitative shear wave ultrasound elastography: initial experience in solid breast masses. Breast Cancer Res 12:R104

    Article  PubMed  PubMed Central  Google Scholar 

  10. Tozaki M, Fukuma E (2011) Pattern classification of ShearWave? Elastography images for differential diagnosis between benign and malignant solid breast masses. Acta Radiol 52:1069-1075

    Article  PubMed  Google Scholar 

  11. Zhou J, Zhan W, Chang C et al (2014) Breast lesions: evaluation with shear wave elastography, with special emphasis on the "stiff rim" sign. Radiology 272:63-72

    Article  PubMed  Google Scholar 

  12. Park HS, Shin HJ, Shin KC et al (2018) Comparison of peritumoral stromal tissue stiffness obtained by shear wave elastography between benign and malignant breast lesions. Acta Radiol 59:1168-1175

    Article  PubMed  Google Scholar 

  13. Lee S, Jung Y, Bae Y (2016) Clinical application of a color map pattern on shear-wave elastography for invasive breast cancer. Surg Oncol 25:44-48

    Article  CAS  PubMed  Google Scholar 

  14. Barr RG (2012) Shear wave imaging of the breast: still on the learning curve. J Ultrasound Med 31:347-350

    Article  PubMed  Google Scholar 

  15. Burnside ES, Hall TJ, Sommer AM et al (2007) Differentiating benign from malignant solid breast masses with US strain imaging. Radiology 245:401-410

    Article  PubMed  Google Scholar 

  16. Itoh A, Ueno E, Tohno E et al (2006) Breast disease: clinical application of US elastography for diagnosis. Radiology 239:341-350

    Article  PubMed  Google Scholar 

  17. Cong WM, Bu H, Chen J et al (2016) Practice guidelines for the pathological diagnosis of primary liver cancer: 2015 update. World J Gastroenterol 22:9279-9287

    Article  PubMed  PubMed Central  Google Scholar 

  18. Landis JR, Koch GG (1977) The measurement of observer agreement for categorical data. Biometrics 33:159-174

    Article  CAS  PubMed  Google Scholar 

  19. Zhu Y, Jia XH, Zhou W, Zhan WW, Zhou JQ (2020) Qualitative Evaluation of Virtual Touch Imaging Quantification: A Simple and Useful Method in the Diagnosis of Breast Lesions. Cancer Manag Res 12:2037-2045

    Article  PubMed  PubMed Central  Google Scholar 

  20. Li J, Zormpas-Petridis K, Boult JKR et al (2019) Investigating the Contribution of Collagen to the Tumor Biomechanical Phenotype with Noninvasive Magnetic Resonance Elastography. Cancer Res 79:5874-5883

    Article  CAS  PubMed  Google Scholar 

  21. Bercoff J, Tanter M, Fink M (2004) Supersonic shear imaging: a new technique for soft tissue elasticity mapping. IEEE Trans Ultrason Ferroelectr Freq Control 51:396-409

    Article  PubMed  Google Scholar 

  22. Riegler J, Labyed Y, Rosenzweig S et al (2018) Tumor Elastography and Its Association with Collagen and the Tumor Microenvironment. Clin Cancer Res 24:4455-4467

    Article  CAS  PubMed  Google Scholar 

  23. Torimura T, Ueno T, Inuzuka S, Tanaka M, Abe H, Tanikawa K (1991) Mechanism of fibrous capsule formation surrounding hepatocellular carcinoma. Immunohistochemical study. Arch Pathol Lab Med 115:365-371

    CAS  PubMed  Google Scholar 

  24. Schrader J, Gordon-Walker TT, Aucott RL et al (2011) Matrix stiffness modulates proliferation, chemotherapeutic response, and dormancy in hepatocellular carcinoma cells. Hepatology 53:1192-1205

    Article  CAS  PubMed  Google Scholar 

  25. Affo S, Yu LX, Schwabe RF (2017) The Role of Cancer-Associated Fibroblasts and Fibrosis in Liver Cancer. Annu Rev Pathol 12:153-186

    Article  CAS  PubMed  Google Scholar 

  26. Song M, He J, Pan QZ et al (2021) Cancer-associated fibroblast-mediated cellular crosstalk supports hepatocellular carcinoma progression. Hepatology

  27. Kubo N, Araki K, Kuwano H, Shirabe K (2016) Cancer-associated fibroblasts in hepatocellular carcinoma. World J Gastroenterol 22:6841-6850

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Cheng JT, Deng YN, Yi HM et al (2016) Hepatic carcinoma-associated fibroblasts induce IDO-producing regulatory dendritic cells through IL-6-mediated STAT3 activation. Oncogenesis 5:e198

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Liu G, Sun J, Yang ZF et al (2021) Cancer-associated fibroblast-derived CXCL11 modulates hepatocellular carcinoma cell migration and tumor metastasis through the circUBAP2/miR-4756/IFIT1/3 axis. Cell Death Dis 12:260

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Ju MJ, Qiu SJ, Fan J et al (2009) Peritumoral activated hepatic stellate cells predict poor clinical outcome in hepatocellular carcinoma after curative resection. Am J Clin Pathol 131:498-510

    Article  CAS  PubMed  Google Scholar 

  31. Iguchi T, Aishima S, Sanefuji K et al (2009) Both fibrous capsule formation and extracapsular penetration are powerful predictors of poor survival in human hepatocellular carcinoma: a histological assessment of 365 patients in Japan. Ann Surg Oncol 16:2539-2546

    Article  PubMed  Google Scholar 

Download references

Funding

This study has received funding by National Natural Science Foundation of China (Nos. 92059201 and 81901768).

Author information

Authors and Affiliations

  1. Department of Ultrasound, The First Affiliated Hospital of Sun Yat-Sen University, No. 58 Zhongshan Second Road, Guangzhou, 510080, China

    Xian Zhong, Haiyi Long, Ruiying Zheng, Liya Su, Yu Duan, Xiaoyan Xie & Manxia Lin

  2. Department of Pathology, The First Affiliated Hospital of Sun Yat-Sen University, 58 Zhongshan Second Road, Guangzhou, 510080, China

    Lili Chen

Authors
  1. Xian Zhong
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Lili Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Haiyi Long
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Ruiying Zheng
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Liya Su
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Yu Duan
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Xiaoyan Xie
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Manxia Lin
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

XZ: Conceptualization, Data curation, Investigation, Methodology, Software, Validation, Writing—original draft, Writing—review & editing. LC: Data curation, Writing—original draft, Writing—review & editing. HL: Data curation, Writing—original draft, Writing—review & editing. RZ: Data curation, Writing—original draft. Writing—review & editing. LS: Data curation. YD: Data curation. XX: Conceptualization, Investigation, Project administration, Resources, Supervision, Writing—review & editing. ML: Conceptualization, Data curation, Funding acquisition, Project administration, Supervision, Writing—review & editing.

Corresponding author

Correspondence to Manxia Lin.

Ethics declarations

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.

Ethical approval

This prospective study was approved by the ethics committee of First Affiliated hospital of Sun Yat-Sen University.

Informed consent

Written informed consents were obtained from all patients before their enrollment.

Additional information

Publisher's Note

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

Supplementary Information

Below is the link to the electronic supplementary material.

Supplementary file1 (DOCX 20 kb)

Rights and permissions

Springer Nature or its licensor holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Zhong, X., Chen, L., Long, H. et al. The “stiff rim” sign of hepatocellular carcinoma on shear wave elastography: correlation with pathological features and potential prognostic value. Abdom Radiol 47, 4115–4125 (2022). https://doi.org/10.1007/s00261-022-03628-9

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00261-022-03628-9

Keywords

Search

Navigation