Updates in Surgery

, Volume 64, Issue 4, pp 247–255 | Cite as

Contrast-enhanced ultrasound of hepatocellular carcinoma: correlation between enhancement pattern and cellular differentiation on histopathlogy

  • F. LoriaEmail author
  • G. Loria
  • S. Basile
  • G. Crea
  • D. Randazzo
  • L. Frosina
Original Article


The aim of this study was to evaluate and correlate the enhancement pattern of hepatocellular carcinoma (HCC) on contrast-enhanced ultrasound (CEUS) and tumour cellular differentiation on histopathology. Patients underwent hepatic CEUS, performed with SonoVue and contrast pulse sequencing. The correlation between enhancement time and enhancement level of the lesions in different vascular phases and tumour cellular differentiation was determined. The tumours were graded according to the Edmondson grading system. Then, diagnosis was obtained by histopathological examination following surgery or percutaneous ultrasound-guided biopsy. 189 patients with HCC were examined with CEUS and histopathological examination between 2003 and 2009: 159 had a solitary lesion (85 %), 24 had 2 lesions (12 %) and 6 had multiple lesions (3 %). The final histological grading of the tumours was as follows: 22, 114, 49, 4 grade I–IV, respectively. Significant differences were shown between the time that HCC become hypoenhancing or remained echogenic in late phase and tumour cellular differentiation (p = 0.006, p = 0.036). The timing of HCC becoming hypoenhancing was correlated with tumour cellular differentiation, with better differentiated HCCs washing out more slowly than poorly differentiated ones (p = 0.164, p = 0.113; p = 0.186, p = 0.070). The enhancement pattern of HCC by CEUS correlates with the cellular differentiation. In late phases, hyperechoic lesions are likely to be better differentiated, whereas hypoechoic lesion is more likely to be poorly differentiated.


Hepatic biopsy Hyperechoic hepatic lesion Hypoechoic hepatic lesion Edmondson grading system 


Conflict of interest

The authors declare that they have no conflict of interest.


  1. 1.
    Albrecht T, Blomley M, Bolondi L et al (2004) (EFSUMB Study Group). Guidlines for the use of contrast agents in ultrasound. Ultraschall Med 25:249–256PubMedCrossRefGoogle Scholar
  2. 2.
    Amano S, Ebara M, Yajima T, Fukuda H, Yoshikawa M, Sugiura N et al (2003) Assessment of cancer cell differentiation in small hepatocellular carcinoma by computed tomography and magnetic resonance imaging. J Gastroenterol Hepatol 18:273–279PubMedCrossRefGoogle Scholar
  3. 3.
    Bolondi L, Gaiani S, Celli N et al (2005) Characterizazion of small nodules in cirrhosis by assessment of vascularity the problem of hypovascular hepatocellular carcinoma. Hepatology 42:27–34PubMedCrossRefGoogle Scholar
  4. 4.
    Brannigan M, Burns PN, Wilson SR (2004) Blood flow patterns in focal liver lesions at microbubble-enanched US. Radiographics 24:921–935PubMedCrossRefGoogle Scholar
  5. 5.
    Bruix J, Sherman M (2005) Management of hepatocellular carcinoma Hepatology 42:1208–1236Google Scholar
  6. 6.
    Chen RC, Wang CK, Wang CS, Chen WT, Shih LS, Chiang LC et al (2002) Depiction of vasculature in small hepatocellular carcinoma, and dysplastic nodules evaluated with carbon dioxide ultrasonography and angiography. Acta Radiol 43:66–70PubMedCrossRefGoogle Scholar
  7. 7.
    Chhieng DC (2004) Fine needle aspiration biopsy of liver—an update. World J Surg Oncol 2:5–15PubMedCrossRefGoogle Scholar
  8. 8.
    Choi BI, Takayasu K, Han MC (1993) Small hepatocellular carcinomas and associated nodular lesions of the liver: pathology, pathogenesis, and imaging findings. AJR Am J Roentgenol 160:1177–1187PubMedGoogle Scholar
  9. 9.
    Edmondson HA, Steiner PE (1954) Primary carcinoma of the liver: a study of 100 cases among 48,900 necropsies. Cancer 7:462–503PubMedCrossRefGoogle Scholar
  10. 10.
    Gaiani S, Casali A, Serra C, Piscaglia F, Gramantieri L, Volpe L et al (2000) Assessment of vascular patterns of small liver mass lesions: value and limitation of the different Doppler ultrasound modalities. Am J Gastroenterol 95:3537–3546PubMedCrossRefGoogle Scholar
  11. 11.
    Hayashi M, Matsui O, Ueda K, Kawamori Y, Gabata T, Kadoya M (2002) Progression to hypervascular hepatocellular carcinoma: correlation with intranodular blood supplì evacuate with CT during intraarterial injection of contrast material. Radiology 225:143–149PubMedCrossRefGoogle Scholar
  12. 12.
    Honda H, Tajima T, Kajiyama K, Kuroiwa T, Yoshimitsu K, Irie H et al (1999) Vascular changes in hepatocellular carcinoma: correlation of radiologic and pathologic findings. AJR Am J Roentgenol 173:1213–1217PubMedGoogle Scholar
  13. 13.
    Honda H, Tajima T, Taguchi K, Kuroiwa T, Yoshimitsu K, Irie H et al (2000) Recent developments in imaging diagnostics for HCC: CT arteriography and CT arteriopotography evaluation of vascular changes in premalignant and malignant hepatic nodules. J Hepatobiliary Pancreat Surg 7:245–251PubMedCrossRefGoogle Scholar
  14. 14.
    Hussain SM, Zondervan PE, IJzermans JN, Schalm SW, de Man RA, Krestin GP (2002) Bening versus malignant hepatic nodules: MR imaging findings with pathologic correlation. RadioGraphics 22:1023–1039Google Scholar
  15. 15.
    Kudo M, Tomita S, Tochio H, Mimura J, Okabe Y, Kashida H et al (1992) Sonography with intaarterial infusion of carbon dioxide microbubbles (sonographic angiography): value in differential diagnosis of hepatic tumors. AJR Am J Roentgenol 158:65–74PubMedGoogle Scholar
  16. 16.
    Kumada T, Nakano S, Toyoda H, Hayashi K, Kiriyama S, Sone Y et al (2004) Assessment of tumor hemodynamics in small hepatocellular carcinoma: comparison of Doppler ultrasonography, angiography- assisted computed tomography, and pathological findings. Liver Int 24:425–431PubMedCrossRefGoogle Scholar
  17. 17.
    Lencioni R, Pinto F, Armillotta N, Bartolozzi C (1996) Assessment of tumor vascularity in hepatocellular carcinoma: comparision of power Doppler US and color Doppler US. Radiology 201:353–358PubMedGoogle Scholar
  18. 18.
    Matsui O, Kadoya M, Kameyama T, Yoshikawa J, Takashima T, Nakanuma Y et al (1991) Bening and malignant nodules in cirrhotic livers: distinction based on blood supply. Radiology 178:493–497PubMedGoogle Scholar
  19. 19.
    Ng IO (1998) Prognostic significance of pathological and biological factors in hepatocellular carcinoma. J Gastroenterol Hepatol 13:666–670PubMedCrossRefGoogle Scholar
  20. 20.
    Nicolau C, Catala V, Vilana R, Gilabert R, Bianchi L, Sole M et al (2004) Evaluation of hepatocellular using SonoVue, a second generation ultrasound contrast agent: correlation with cellular differentiation. Eur Radiol 14:1092–1099PubMedCrossRefGoogle Scholar
  21. 21.
    Quaia E, Calliada F, Bertolotto M, Rossi S, Garioni L, Rosa L et al (2004) Characterization of focal liver lesions with contrast-specific US modes and a sulfur hexafluoride-filled microbubble contrast agent: diagnostic performance and confidence. Radiology 232:420–430PubMedCrossRefGoogle Scholar
  22. 22.
    Rahbin N, Siosteen AK, Elvin A, Blomqvist L, Hagen K, Hultcrantz R, Aleman S (2008) Detection and characterization of local liver lesion with contrast-enhanced ultrasonography in patients with hepatitis c-induced liver cirrhosis. Acta Radiol 49(3):251–257PubMedCrossRefGoogle Scholar
  23. 23.
    Reinhold C, Hammers L, Taylor CR, Quedens-Case CL, Holland CK, Taylor KJ (1995) Characterization of focal hepatic lesions with duplex sonography: findings in 198 patients. AJR Am J Roentegenol 164:1131–1135Google Scholar
  24. 24.
    Ruby SG (2000) Protocol for the examination of specimens from patients with hepatocellular carcinoma and cholangiocarcinoma, including intrahepatic bile ducts. Arch Pathol Lab Med 124(1):41–45Google Scholar
  25. 25.
    Sakabe K, Yamamoto T, Kubo S, HIrohashi K, Hamuro M, Nakamura K et al (2004) Correlation between dynamic computed tomographic and histopathological findings in the diagnosis of small hepatocellular carcinoma. Dig Surg 21:413–420Google Scholar
  26. 26.
    Solbiati L, Tonolini M, Cova L, Goldberg SN (2001) The role of contrast-enanched ultrasound in the detection of focal liver lesions. Eur Radiol 11 Suppl 3:E15–E26Google Scholar
  27. 27.
    Tajima T, Honda H, Taguchi K, Asayama Y, Kuroiwa T, Yoshimitsu K et al (2002) Sequential hemodynamic change in hepatocellular carcinoma dysplastic nodules: CT angiography and pathologic correlation. AJR Am J Roentgenol 178:885–897PubMedGoogle Scholar
  28. 28.
    Takayasu K, Muramatsu Y, Furukawa H, Wakao F, Moiyama N, Takayama T et al (1995) Early hepatocellular carcinoma: appearance at CT during arterial portography and CT arteriography with pathologic correlation. Radiology 194:101–105PubMedGoogle Scholar
  29. 29.
    Tarhan NC, Hatipoglu T, Ercan E, Bener M, Keles G, Basaran C, Bilezikci B (2011) Correlation of dynamic multidetector CT findings with pathological grades of hepatocellular carcinoma. Diagn Interv Radiol. doi: 10.4261/1305-3825.DIR.2682-09
  30. 30.
    Tchelepi H, Ralls PW (2004) Ultrasound of focal liver masses. Ultrasound Q 20:155–169PubMedCrossRefGoogle Scholar
  31. 31.
    Ueda K, Terada T, Nakanuma Y, Matsui O (1992) Vascular supply in adenomatous hyperplasia of the liver and hepatocellular carcinoma: a morphometric study. Hum Pathol 23:619–626PubMedCrossRefGoogle Scholar
  32. 32.
    Von Herbay A, Vogt C, Westendorff J, Haussinger D, Gregor M (2009) Correlation between SonoVue enhancement in CEUS, HCC differentiation an diameter: analysis of 130 patients with hepatocellular carcinoma (HCC). Ultraschall Med 30(6):544–550CrossRefGoogle Scholar
  33. 33.
    Wang Z, Tang J, An L (2007) Contrast-enhanced ultrasonography for assessment of tumor vascularity in hepatocellular carcinoma. J Ultrasound Med 26:757–762PubMedGoogle Scholar
  34. 34.
    Xiao J-D, Zhu W-H, Shen S-R (2010) Evaluation of hepatocellular carcinoma using contrast-enhanced ultrasonography: correlation with microvessel morphology. Hepatobiliary Pancreatic Dis Int 9(6):605–610Google Scholar
  35. 35.
    Xu H-X, Xie X-Y, Lu M-D et al (2008) Contrast-enhanced sonography in the diagnosis of small hepatocellular carcinoma <2 cm. J Clin Ultrasound 2008 36(5):257–266Google Scholar
  36. 36.
    Yamashita Y, Fan ZM, Yamamoto H, Matsukawa T, Yoshimatsu S, Miyazaki T et al (1994) Spin-echo and dynamic gadolinium-enhanced FLASH MR imaging of hepatocellular carcinoma: correlation with histopathologic findings. J Magn Reson Imaging 4:83–90PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2012

Authors and Affiliations

  • F. Loria
    • 1
    Email author
  • G. Loria
    • 1
  • S. Basile
    • 1
  • G. Crea
    • 1
  • D. Randazzo
    • 2
  • L. Frosina
    • 2
  1. 1.Department of RadiologyPO Palmi ASP 5PalmiItaly
  2. 2.School of Medicine, University of MessinaMessinaItaly

Personalised recommendations