Association of tumor grade, enhancement on multiphasic CT and microvessel density in patients with clear cell renal cell carcinoma

  • Heidi CoyEmail author
  • Jonathan R. Young
  • Allan J. Pantuck
  • Michael L. Douek
  • Anthony Sisk
  • Clara Magyar
  • Matthew S. Brown
  • James Sayre
  • Steven S. Raman
Kidneys, Ureters, Bladder, Retroperitoneum



Clear cell renal cell carcinoma (ccRCC) comprises nearly 90% of all diagnosed RCC subtypes and has the worst prognosis and highest metastatic potential. The strongest prognostic factors for patients with ccRCC include histological subtype and Fuhrman grade, which are incorporated into prognostic models. Since ccRCC is a highly vascularized tumor, there may be differences in enhancement patterns on multidetector CT (MDCT) due to the hemodynamics and microvessel density (MVD) of the lesions. This may provide a noninvasive method to characterize incidentally detected low- and high-grade ccRCCs on MDCT. The purpose of our study was to determine the correlation between MDCT enhancement parameters, ccRCC MVD, and Fuhrman grade to determine its utility and value in assessing tumor vascularity and grade in vivo.


In this retrospective, HIPAA-compliant, institutional review board-approved study with waiver of informed consent, 127 consecutive patients with 89 low-grade (LG), and 43 high-grade (HG) ccRCCs underwent preoperative four-phase MDCT. A 3D volume of interest (VOI) was obtained for every tumor and absolute enhancement and the wash-in/wash-out of enhancement for each phase was assessed. Immunohistochemistry on resected specimens was used to quantify MVD. Linear regression and Pearson correlation were used to investigate the strength of the association between 3D VOI enhancement and MVD. Stepwise logistic regression analysis determined independent predictors of HG ccRCC. Cut-off values and odds Ratio (OR) with 95% CIs were reported. The clinical, radiomic, and pathologic features with the highest performance in the stepwise logistic regression analysis were evaluated using receiver operator characteristics (ROC) and area under the curve (AUC).


Absolute enhancement in the nephrographic phase < 52.1 Hounsfield Units (HU) (HR 0.979, 95% CI 0.964–0.994, p value = 0.006), lesion size > 4.3 cm (HR 1.450, 95% CI 1.211–1.738, p value < 0.001), and an intratumoral MVD < 15% (HR 0.932, 95% CI 0.867–1.002, p value = 0.058) were independent predictors of HG ccRCC with an AUC of 0.818 (95% CI 0.725–0.911). HG ccRCCs had a significant association between 3D VOI enhancement and MVD in each post-contrast phase (r2 = 0.238 to 0.455, p < 0.05).


Absolute enhancement of the entire lesion obtained from a 3D VOI in the nephrographic phase on preoperative MDCT can provide quantitative data that are a significant, independent predictor of a high-grade clear cell RCC and can be used to assess tumor vascularity and grade in vivo.


Clear cell RCC Microvessel density Tumor grade Multiphasic CT Angiogenesis Radiomics 



Funding was provided by Society of Abdominal Radiology Howard S. Stern Research [Grant No. 20163335].

Compliance with ethical standards

Conflict of interest

All authors have no conflict of interest.

Informed consent

All data were acquired with IRB approval, followed HIPAA guidelines, and with a waiver of informed consent.


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© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of Radiological SciencesDavid Geffen School of Medicine at UCLA, Ronald Reagan-UCLA Medical CenterLos AngelesUSA
  2. 2.Department of RadiologyCity of Hope National Medical CenterDuarteUSA
  3. 3.Department of UrologyDavid Geffen School of Medicine at UCLA, Ronald Reagan-UCLA Medical CenterLos AngelesUSA
  4. 4.Department of Pathology and Laboratory MedicineDavid Geffen School of Medicine at UCLALos AngelesUSA
  5. 5.Department of Radiological Sciences, Center for Computer Vision and Imaging BiomarkersDavid Geffen School of Medicine at UCLALos AngelesUSA
  6. 6.Department of BiostatisticsUCLA School of Public HeathLos AngelesUSA
  7. 7.Department of Radiological SciencesDavid Geffen School of Medicine at UCLA, Ronald Reagan-UCLA Medical CenterLos AngelesUSA

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