European Radiology

, Volume 25, Issue 9, pp 2789–2796 | Cite as

Subcentimeter hypervascular nodule with typical imaging findings of hepatocellular carcinoma in patients with history of hepatocellular carcinoma: natural course on serial gadoxetic acid-enhanced MRI and diffusion-weighted imaging

  • Kyoung Doo Song
  • Seong Hyun KimEmail author
  • Hyo Keun Lim
  • Sin-Ho Jung
  • Insuk Sohn
  • Hyung Sik Kim



To evaluate the natural course of subcentimeter hypervascular nodules at high risk for developing into hepatocellular carcinomas (SHNHR) using serial magnetic resonance imaging (MRI) in patients with a history of hepatocellular carcinoma (HCC).


An SHNHR was defined as a subcentimeter hypervascular nodule having typical imaging findings of HCC on gadoxetic acid-enhanced MRI and diffusion-weighted imaging. We included 39 patients with 46 SHNHRs (mean size ± standard deviation, 6.1 ± 1.6 mm; range, 3.2 – 9.0 mm). Overt HCC was defined as pathology proven HCC or a nodule larger than 1 cm with typical imaging findings of HCC. The cumulative rate and the independent predictive factors for progression to overt HCC were evaluated.


The median follow-up period was 139 days (range, 64 – 392 days). The cumulative progression rate to overt HCC at 3, 6, 9, and 12 months was 13.9 %, 61.7 %, 83.2 %, and 89.9 %. The initial size of SHNHR was a significant predictor of progression to overt HCC, with an optimal cut-off value of 5.5 mm.


The progression rate of SHNHR to overt HCC within 12 months was high (89.9 %) in patients with history of HCC. The initial size of SHNHR was an important predictor for progression to overt HCC.

Key Points

Most SHNHRs (89.9 %) progressed to overt HCCs within 12 months.

Initial size was an important predictor for progression to overt HCCs.

The optimal cut-off value for initial nodule size was 5.5 mm.


Subcentimeter Hypervascular nodule Hepatocellular carcinoma Natural course Progression rate 



Magnetic resonance imaging


Hepatocellular carcinoma, DWI, Diffusion-weighted imaging


T2-weighted image


Signal intensity


Subcentimeter hypervascular nodule at high risk for developing into hepatocellular carcinoma


American Association for the Study of Liver Disease


Radiofrequency ablation


Transcatheter arterial chemoembolization




Tumour volume doubling time


Barcelona Clinic Liver Cancer



The scientific guarantor of this publication is Young Soo Do, the head of radiology department. 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. The authors state that this work has not received any funding. Two of the authors have significant statistical expertise. Sin-Ho Jung and Insuk Sohn.

Institutional review board approval was obtained. Written informed consent was waived by the Institutional review board. No study subjects or cohorts have been previously reported. Methodology: retrospective, observational, performed at one institution.


  1. 1.
    Kim SH, Kim SH, Lee J et al (2009) Gadoxetic acid-enhanced MRI versus triple-phase MDCT for the preoperative detection of hepatocellular carcinoma. AJR Am J Roentgenol 192:1675–1681PubMedCrossRefGoogle Scholar
  2. 2.
    Kim JE, Kim SH, Lee SJ, Rhim H (2011) Hypervascular hepatocellular carcinoma 1 cm or smaller in patients with chronic liver disease: characterization with gadoxetic acid-enhanced MRI that includes diffusion-weighted imaging. AJR Am J Roentgenol 196:W758–W765PubMedCrossRefGoogle Scholar
  3. 3.
    Park MJ, Kim YK, Lee MW et al (2012) Small hepatocellular carcinomas: improved sensitivity by combining gadoxetic acid-enhanced and diffusion-weighted MR imaging patterns. Radiology 264:761–770PubMedCrossRefGoogle Scholar
  4. 4.
    Willatt JM, Hussain HK, Adusumilli S, Marrero JA (2008) MR Imaging of hepatocellular carcinoma in the cirrhotic liver: challenges and controversies. Radiology 247:311–330PubMedCrossRefGoogle Scholar
  5. 5.
    Nasu K, Kuroki Y, Tsukamoto T, Nakajima H, Mori K, Minami M (2009) Diffusion-weighted imaging of surgically resected hepatocellular carcinoma: imaging characteristics and relationship among signal intensity, apparent diffusion coefficient, and histopathologic grade. AJR Am J Roentgenol 193:438–444PubMedCrossRefGoogle Scholar
  6. 6.
    Bruix J, Sherman M (2011) Management of hepatocellular carcinoma: an update. Hepatology 53:1020–1022PubMedCentralPubMedCrossRefGoogle Scholar
  7. 7.
    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 47:97–104PubMedCrossRefGoogle Scholar
  8. 8.
    Schwartz M (1961) A biomathematical approach to clinical tumor growth. Cancer 14:1272–1294PubMedCrossRefGoogle Scholar
  9. 9.
    Landis JR, Koch GG (1977) The measurement of observer agreement for categorical data. Biometrics 33:159–174PubMedCrossRefGoogle Scholar
  10. 10.
    Lee EW, Wei LJ, Amato DA (1992) Cox-type regression analysis for large number of small groups of correlated failure time observations. In: Klein JP, Goel PK (eds) Survival analysis: state of the art. Kluwer Academic Publishers, Dordrecht, pp 237–247CrossRefGoogle Scholar
  11. 11.
    Heagerty PJ, Lumley T, Pepe MS (2000) Time-dependent ROC curves for censored survival data and a diagnostic marker. Biometrics 56:337–344PubMedCrossRefGoogle Scholar
  12. 12.
    Hwang SH, Yu JS, Kim KW, Kim JH, Chung JJ (2008) Small hypervascular enhancing lesions on arterial phase images of multiphase dynamic computed tomography in cirrhotic liver: fate and implications. J Comput Assist Tomogr 32:39–45PubMedCrossRefGoogle Scholar
  13. 13.
    Byrnes V, Shi H, Kiryu S, Rofsky NM, Afdhal NH (2007) The clinical outcome of small (<20 mm) arterially enhancing nodules on MRI in the cirrhotic liver. Am J Gastroenterol 102:1654–1659PubMedCrossRefGoogle Scholar
  14. 14.
    Park MJ, Kim YS, Lee WJ, Lim HK, Rhim H, Lee J (2010) Outcomes of follow-up CT for small (5-10-mm) arterially enhancing nodules in the liver and risk factors for developing hepatocellular carcinoma in a surveillance population. Eur Radiol 20:2397–2404PubMedCrossRefGoogle Scholar
  15. 15.
    Guo L, Liang C, Yu T et al (2012) 3 T MRI of hepatocellular carcinomas in patients with cirrhosis: does T2-weighted imaging provide added value? Clin Radiol 67:319–328PubMedCrossRefGoogle Scholar
  16. 16.
    Wu LM, Xu JR, Lu Q, Hua J, Chen J, Hu J (2013) A pooled analysis of diffusion-weighted imaging in the diagnosis of hepatocellular carcinoma in chronic liver diseases. J Gastroenterol Hepatol 28:227–234PubMedCrossRefGoogle Scholar
  17. 17.
    Haimerl M, Wachtler M, Platzek I et al (2013) Added value of Gd-EOB-DTPA-enhanced Hepatobiliary phase MR imaging in evaluation of focal solid hepatic lesions. BMC Med Imaging 13:41PubMedCentralPubMedCrossRefGoogle Scholar
  18. 18.
    Barbara L, Benzi G, Gaiani S et al (1992) Natural history of small untreated hepatocellular carcinoma in cirrhosis: a multivariate analysis of prognostic factors of tumor growth rate and patient survival. Hepatology 16:132–137PubMedCrossRefGoogle Scholar
  19. 19.
    Kubota K, Ina H, Okada Y, Irie T (2003) Growth rate of primary single hepatocellular carcinoma: determining optimal screening interval with contrast enhanced computed tomography. Dig Dis Sci 48:581–586PubMedCrossRefGoogle Scholar
  20. 20.
    Okazaki N, Yoshino M, Yoshida T et al (1989) Evaluation of the prognosis for small hepatocellular carcinoma based on tumor volume doubling time. A preliminary report. Cancer 63:2207–2210PubMedCrossRefGoogle Scholar
  21. 21.
    Park Y, Choi D, Lim HK et al (2008) Growth rate of new hepatocellular carcinoma after percutaneous radiofrequency ablation: evaluation with multiphase CT. AJR Am J Roentgenol 191:215–220PubMedCrossRefGoogle Scholar
  22. 22.
    Taouli B, Goh JS, Lu Y et al (2005) Growth rate of hepatocellular carcinoma: evaluation with serial computed tomography or magnetic resonance imaging. J Comput Assist Tomogr 29:425–429PubMedCrossRefGoogle Scholar
  23. 23.
    Sheu JC, Sung JL, Chen DS et al (1985) Growth rate of asymptomatic hepatocellular carcinoma and its clinical implications. Gastroenterology 89:259–266PubMedGoogle Scholar
  24. 24.
    Takayasu K, Arii S, Sakamoto M et al (2013) Clinical implication of hypovascular hepatocellular carcinoma studied in 4,474 patients with solitary tumour equal or less than 3 cm. Liver Int 33:762–770PubMedCrossRefGoogle Scholar

Copyright information

© European Society of Radiology 2015

Authors and Affiliations

  • Kyoung Doo Song
    • 1
  • Seong Hyun Kim
    • 1
    Email author
  • Hyo Keun Lim
    • 1
  • Sin-Ho Jung
    • 2
    • 3
  • Insuk Sohn
    • 2
  • Hyung Sik Kim
    • 4
  1. 1.Department of Radiology and Center for Imaging Science, Samsung Medical CenterSungkyunkwan University School of MedicineSeoulRepublic of Korea
  2. 2.Center for Biostatistics and Clinical Epidemiology, Samsung Medical CenterSungkyunkwan University School of MedicineSeoulRepublic of Korea
  3. 3.Samsung Advanced Institute for Health Sciences and TechnologySungkyunkwan University School of MedicineSeoulRepublic of Korea
  4. 4.Department of Radiology, Gil Medical CenterGachon Medical SchoolIncheonRepublic of Korea

Personalised recommendations