The independent indicators for differentiating renal cell carcinoma from renal angiomyolipoma by contrast-enhanced ultrasound

This was a single-institution retrospective study. This study was approved by the Review Board of Huadong Hospital, and written informed consent was obtained from all patients. Between August 2012 and January 2019, 165 patients with 172 renal masses were recruited for the study, included 145 patients (117 males and 33 females, age range 25–86 years, mean age 61.2 ± 12.4 years) with 150 RCCs and 20 patients (5 males and 17 females, age range 22–75 years, mean age 55.7 ± 16.0 years) with 22 AMLs. Inclusion criteria were as follows: 1) patients underwent CUS and CEUS before radical or partial nephrectomy; 2) renal tumor pathologically confirmed as RCC or AML; 3) sufficient normal renal tissue around mass; and 4) patient had not undergone any invasive treatments before CUS and CEUS. Exclusion criteria were 1) pure cystic mass; 2) the video clips of CEUS were incomplete; and 3) a history of cardiac failure or respiratory disorders.

Both CUS and CEUS were performed by a single radiologist (C.L.) with 17 years of experience in abdominal US and 13 years in CEUS at our institution. The examinations were performed using an ultrasound scanner (4C1 probe, 3–5 MHz, mechanical index < 0.10, Aplio500, Toshiba Medical Systems, Otawara, Japan). Initial CUS was conducted to obtain the position, shape, echogenicity, size, margins, homogeneity, and orientation of the tumor. Then color Doppler flow imaging (CDFI) was used to assess the blood flow of the tumor. Subsequently, optimal section containing both renal lesion and normal adjacent parenchyma was selected, and the ultrasound scanner was switched to CEUS mode. The US contrast agent of SonoVue (Bracco, Milan, Italy), a sulfur hexafluoride (SF6) microbubble stabilized by phospholipids, was used in this study. The freeze-dried powder of SonoVue was shaken with 5.0 ml of normal saline into suspension. According to the weight, height, and age of the patients, a dose of 1.6–2.4 ml of this suspension was individually administered into the antecubital vein in a bolus fashion, followed by a flush of 5.0 ml saline. At the time of contrast agent injection, the keys of the timer and video recorder were pressed simultaneously. Maintain slow shallow breath was required for all patients, and each dynamic contrast image was observed at least 3 min. If a tumor was incompletely assessed, a second injection was repeated 15 min after the first injection. The single images and video clips of CUS and CEUS were stored in the local hard disk for subsequent analysis.

The images and video clips saved on the local hard disk were independently reviewed in random by two radiologists (D.X.H. and Z.J.), both blinded to the pathological results. Both radiologists had more than 10 years of experience in urinary US and 8 years in reading CEUS images. The CUS characteristics included the mass position, shape, echogenicity, size, margins, homogeneity, orientation, and color flow signals. Referring to the normal renal cortex adjacent to renal mass, the enhancement characteristics of renal mass were analyzed. The CEUS features included the enhancement intensity at peak time, the homogeneity of enhancement, the perilesional rim-like enhancement and the “wash in” and “wash out” mode. The enhancement intensity at peak time was described into hyper-, iso-, and hypo-enhancement. The homogeneity at peak enhancement was classified into homogeneous and heterogeneous. The homogeneous was defined as a renal mass with uniform enhancement, and the heterogeneous was defined as a renal mass with inconsistent enhancement. The perilesional rim-like enhancement, more distinct in the late phase of enhancement, was classified as present or absent. Both the “wash in” and “wash out” of renal masses contrast enhancement were classified as fast, synchronous, or slow. The value of these features was calculated and analyzed to differentiate the diagnosis between RCC and AML. If conclusions of the two radiologists were different, they consulted with a third reviewer to reach a final conclusion by discussions.

Continuous variables were expressed as mean ± standard deviation (SD), and discrete variables as numbers and percentages. The Shapiro-Wilk W test was used to determine whether data was normally distributed, and the F test determine whether the variables had homogeneity of variance. Differences between RCC and AML were analyzed using Independent-Sample t test and Mann-Whitney U test for continuous variables, and Pearson’s chi-square test and Fisher’s exact tests for discrete variables. The variables that showed strong performance in basic statistics were subjected to the multivariate logistic regression analysis for predicting RCC. We calculated odds ratio (OR), 95% confidence intervals (CIs), and P value. Those variables with significant and independent influence were isolated and used to fit the receiver operating characteristic (ROC) curve determining the area under the ROC curve (AUC). We determined the optimal cut-off values for the represented indices that showed the highest AUC. The corresponding sensitivity, specificity, and AUC were calculated with 95% CIs. Statistical analysis was performed by using IBM SPSS Statistics version 22.0 for Windows (IBM Corp., Armonk, NY, USA) and MedCalc Statistics version 15.2. A P value < 0.05 was considered statistically significant.

A pathologic diagnosis was obtained for all masses via a laparoscopic or open radical or partial nephrectomy. One single mass was detected in 142 patients with RCCs and 16 patients with AMLs, and two masses were detected in the remaining 7 patients. Of the patients with two nodules, 2 had AML in each kidney, 2 had RCC in each kidney, 1had RCC in the left kidney, 1had RCC and AML in the left kidney, and 1had AML in the left kidney and RCC in the right kidney. Thus, a total of 165 patients with172 renal masses were recruited, 150 (87.2%) were RCCs and 22 (12.8%) were AMLs. The RCCs were clear cell carcinoma (129, 86.0%), papillary carcinoma (11, 7.3%), chromophobe carcinoma (10, 6.7%), respectively. Though age distribution, tumor location, and surgical method were not significantly different between RCCs and AMLs, more percentage of patients with RCC were male than that with AML (P = 0.000) (Table 1).

The diameter of RCCs (mean, 40.4 ± 22.1 mm; range, 7-130 mm) and AMLs (mean, 34.7 ± 22.2 cm; range, 9-80 mm) made no significant difference (P = 0.258) (Table 2). There were also no significant differences in terms of shape, margin, orientation, and homogeneity between RCCs and AMLs. Significant differences existed in echogenicity and CDFI pattern.

CEUS characteristics of renal masses are listed in Table 3. All the indices (peak intensity, homogeneity, wash in, wash out, and perilesional rim-like enhancement) are significantly different between RCCs and AMLs (P < 0.05 for all).

Multivariate analysis was used to identify the potential indicators of RCCs. The results showed that perilesional rim-like enhancement and fast wash out were independent indicators correlated with RCCs (Table 4). Figure 1 shows the ROC curves of perilesional rim-like enhancement and fast wash out correlated with RCCs. The AUC of perilesional rim-like enhancement was 0.838 (95% CI:0.774–0.890) with 76.7% sensitivity and 90.9% specificity, while the AUC of fast wash out was 0.833 (95% CI: 0.768–0.885) with 74.7% sensitivity and 81.8% specificity (Table 5).