Characterization of Small Solid Renal Lesions: Can Benign and Malignant Tumors Be Differentiated With CT?

Genitourinary Imaging Original Research Millet et al. CT of Small Solid Renal Lesions Genitourinary Imaging Original Research Ingrid Millet 1 Fernanda Curros Doyon 1 Denis Hoa 1 Rodolphe Thuret 2 Samuel Merigeaud 1 Isabelle Serre 3 Patrice Taourel 1 Millet I, Curros Doyon F, Hoa D, et al. Keywords: biopsy, CT, kidney, malignancy, tumor DOI:10.2214/AJR.10.6276 Received December 9, 2010; accepted after revision March 2, 2011. 1 Department of Radiology, CHU Lapeyronie, 371 Ave du Doyen Gaston Giraud, 34295 Montpellier, France. Address correspondence to P. Taourel (p-taourel@chu-montpellier.fr). 2 Department of Urology, CHU Lapeyronie, Montpellier, France. 3 Department of Pathology, CHU Lapeyronie, Montpellier, France. AJR 2011; 197:887 896 0361 803X/11/1974 887 American Roentgen Ray Society Characterization of Small Solid Renal Lesions: Can Benign and Malignant Tumors Be Differentiated With CT? OBJECTIVE. The purpose of this study was to evaluate the diagnostic performance of CT in determining whether a small solid renal enhancing mass is benign or malignant. MATERIALS AND METHODS. Ninety-nine biopsies of enhancing solid renal masses 4 cm or smaller without fat on CT scans were performed under CT fluoroscopic guidance. The growth pattern, interface with parenchyma, presence of a scar and segmental inversion enhancement, unenhanced CT histogram, and pattern and degree of enhancement on triphasic MDCT images were independently evaluated by two radiologists. Biopsy and pathology reports were used as the reference standard, and imaging follow-up of benign lesions was performed for at least 1 year. Statistical analysis was performed to determine the significance of CT criteria in differentiating malignant from benign lesions. RESULTS. Of the 99 lesions, 74 (75%) were malignant at biopsy, and 25 (25%) were benign. Lesions with gradual enhancement were more likely to be benign. No significant correlation was found between other CT features and a malignant or benign diagnosis. The sensitivity, specificity, and positive and negative predictive values of progressive enhancement for a diagnosis of benignity were 60%, 73%, 43%, and 84%. CONCLUSION. In the evaluation of enhancing small solid renal lesions without fat, no CT criteria were of substantial help in differentiating malignant from benign lesions. T he increasing indications for abdominal CT, MRI, and sonography have led to increased incidental detection of small solid renal masses. With this increase in the number of smaller tumors discovered, there has been a concomitant increase in the rate of benign and malignant lesions encountered. When a solid renal mass is encountered, the first step is to exclude angiomyolipoma by identifying regions of fat within the mass with unenhanced CT [1, 2]. If no fat is detected on CT scans, numerous causes are possible, but the main one is the presence of a malignant lesion, such as renal cell carcinoma (RCC) (clear cell, papillary, and chromophobe subtypes), metastasis, or lymphoma, or of a benign lesion, such as oncocytoma, angiomyolipoma with minimal fat, granuloma, or an inflammatory lesion. Contrary to past trends whereby all enhancing solid renal masses were treated as RCC and proof of malignancy was obtained after nephrectomy [3], biopsy of renal tumors is now largely used in the evaluation of small renal tumors and has been found safe, accurate, and cost-effective [4 8]. Biopsy also is recommended as an aid in differentiating benign from malignant tumors [9]. A major reason for deciding on renal tumor biopsy is that imaging alone is often insufficient for differentiating the benign versus malignant nature of solid renal tumors without fat [4]. However, studies have shown that some imaging features and the degree of enhancement on CT images are helpful in differentiating renal cortical tumor subtypes, despite overlap [10], and that some CT findings can be used to characterize benign tumors. Segmental enhancement inversion in the corticomedullary and excretory phases has been found to be a characteristic enhancement pattern of oncocytoma [11], and homogeneous and prolonged enhancement or a sufficient percentage of voxels and pixels with negative attenuation at histogram analysis has been found useful for characterizing angiomyolipoma without visible fat at CT [12, 13]. Most recently, the presence of an angular interface with the renal parenchyma on coronal and axial slices at MRI a sign that may be investigated on CT has AJR:197, October 2011 887

Millet et al. been found to be a strong predictor of the benign nature of exophytic renal masses [14]. However, these findings have been made in separate investigations of different original series of patients, and therefore, a multiparametric model cannot be built. In addition, some of these studies [10, 14, 15] did not focus on small solid tumors, which have a higher incidence of being benign and constitute a major problem in clinical practice. The purpose of our study was to retrospectively determine in consecutively registered patients with biopsied solid renal masses 4 cm or smaller whether these tumors might have been differentiated on the basis of their CT morphologic features and enhancement pattern and thus to evaluate the need for biopsy in the care of patients with small solid renal tumors. Materials and Methods Patients Our institutional review board approved this retrospective study and waived the informed consent requirement. We retrospectively reviewed the records of all percutaneous biopsies of renal masses performed under CT guidance at our institution from 2006 to 2009. It was found that 168 biopsies of renal masses were performed during this time; 58 masses were excluded because they were larger than 4 cm in diameter, six masses were excluded because they did not exhibit contrast enhancement, two masses were excluded because retrospective analysis of the CT scans revealed fat within the tumor, two masses were excluded because CT was performed without injection, and one mass was excluded because the core biopsy specimens were insufficient, showing normal renal parenchyma. Our study cohort thus consisted of 99 biopsies of solid enhancing ( 15 HU) masses smaller than 4 cm in diameter performed on 96 patients (52 men, 44 women; age range, 19 86 years; mean, 65 years). Biopsy Procedure After correction of coagulation status when appropriate, biopsies were performed with standard sterile technique and local anesthesia. An 8-MDCT scanner (HighSpeed, GE Healthcare) and CT fluoroscopic guidance were used. Coaxial technique was uniformly implemented with a 17-gauge introducer and an 18-gauge spring-loaded biopsy gun. The introducer remained in position while two to five cores were obtained from each tumor. Biopsy images were obtained immediately after biopsy to rule out complications. Specimens were placed in formalin solution and hand carried to the pathology laboratory. All specimens were prepared with H and E. The decision to perform immunohistochemical staining was made by the pathologist reviewing the sample. Tumor histologic findings were classified according to the World Health Organization 2004 system [16]. CT Examinations All CT examinations were performed with an 8-, 16- or 64-MDCT scanner according to our standard renal mass protocol tailored to each scanner. CT images were obtained during a breath-hold with the following parameters: 120 kvp; 150 300 ma (depending on patient size); pitch, 0.75 1.5; section thickness, 1.25 mm; reconstruction interval, 2.5 mm. All patients underwent triphasic CT, which included unenhanced, corticomedullary, and nephrographic phases. The scan delay time ranged from 30 to 40 seconds for the corticomedullary phase and from 120 to 150 seconds for the nephrographic phase. The unenhanced and corticomedullary phases were performed on the whole kidney, and the entire abdomen was scanned in the nephrographic phase. IV contrast material was administered at a dose of 2 ml/kg of body weight at a rate of 2 3 ml/s, to a maximum of 150 ml, with a power injector. Patients did not receive oral contrast material. All images were sent to our enterprise-wide PACS (Centricity, GE Healthcare) for interpretation on workstations. CT Image Analysis The CT findings were reviewed independently by two radiologists (4 and 7 years of experience in interpreting genitourinary CT images) at the PACS, at which it was possible to measure tumor attenuation in a particular region of interest. Readers were blinded to the pathologic results. For quantitative criteria, discrepancies were resolved by consensus; for qualitative criteria, the results from the two readers were averaged. The radiologist evaluated the tumoral lesion for several qualitative and quantitative criteria. The mass was classified as having a ball versus a bean growth pattern according to the concept detailed by Dyer et al. [17]. Ball-type masses are well limited, grow exophytically, and deform the renal contour. Bean-type masses are infiltrative and use renal parenchyma as scaffolding for growth with the renal shape maintained. Ball-type masses were classified as exophytic when they caused contour deformity in the renal margin and as nonexophytic when they did not cause renal contour deformity. The interface between an exophytic mass and the renal parenchyma was classified as round or angular, according to the MRI sign described by Verma et al. [14]. The morphologic findings (ball versus bean pattern, exophytic pattern in ball lesion, rounded versus angular interface with the renal parenchyma) were evaluated on axial and coronal reconstructions in the nephrographic phase. The homogeneity of tumor enhancement was qualitatively determined by visual enhancement: homogeneous enhancement was considered present when the tumor area had uniform enhancement in both the corticomedullary and the nephrographic phases. Otherwise, enhancement was regarded as heterogeneous. The presence of a hypodense central scar was systematically investigated. Segmental inversion enhancement, described as a useful finding for characterizing small oncocytomas [11], was also assessed. A mass was considered to exhibit segmental inversion enhancement when the enhancement could be subdivided into relatively highly enhancing and less-enhancing segments in the corticomedullary phase. The relative enhancement of the two segments was reversed in the nephrographic or delayed phase. Tumor attenuation and the degree of enhancement were quantitatively assessed. For homogeneous lesions, a round or elliptic region of interest was placed in the center of the lesion. For heterogeneous lesions, the region of interest was placed in the area that had the greatest degree of enhancement in the corticomedullary or nephrographic phase. The regions of interest measured 0.2 1 cm 2 and were consistent in size and location on images obtained during all three scanning passes. The amount of tumor enhancement in the corticomedullary and nephrographic phases was measured by calculation of the difference between tumor attenuation and the values noted on the unenhanced scans. The time-course enhancement pattern was classified as follows according to criteria used in previous studies [11, 12]. An early washout pattern was considered present when a tumor had peak enhancement in the corticomedullary phase and washout of at least 20 HU in the nephrographic phase. A gradual enhancement pattern was considered present when the tumor attenuation in the nephrographic phase was at least 20 HU greater than that in the corticomedullary phase (Fig. 1). A prolonged enhancement pattern was considered present when the difference in tumor attenuation between the corticomedullary and nephrographic phases ranged from 20 to 20 HU. Analysis of unenhanced CT histograms was performed by analysis of the distribution of attenuation according to pixel units and calculation of the percentage of pixels with attenuation less than 10 HU. As the diagnostic criterion, we used 6% or more of pixels with attenuation less than 10 HU. This value has been found to be the best trade-off, having 100% specificity and 20% sensitivity in differentiating angiomyolipoma without fat from renal carcinoma [13]. For CT histograms, a region of interest at the middle of the tumor on 2.5-mm axial reconstructed slices was drawn to include the entire tumor area. 888 AJR:197, October 2011

CT of Small Solid Renal Lesions Reference Standard The reference standard was established by histopathologic analysis of resected masses for patients who had undergone total or partial nephrectomy and on the basis of biopsy results for the other patients. A special attempt was made to perform at least 1 year of cross-sectional imaging follow-up for patients with benign masses who did not undergo surgery. A lesion was considered benign when the biopsy result was benign and the size of the lesion had decreased or remained stable over at least 1 year of follow-up. Statistical Analysis Statistical software (SAS version 9.2, SAS Institute) was used to perform the statistical analyses. For statistical analysis, lesions were differentiated according to the pathologic data. Malignant lesions included carcinomas and noncarcinomas, and benign lesions included oncocytomas, angiomyolipomas, rare benign tumors, and nonneoplastic lesions. Differences between benign and malignant lesions were tested with the chi-square test or Fisher exact test for CT morphologic features and enhancement pattern and the Wilcoxon rank sum test for tumor size and attenuation. A value of p < 0.05 denoted statistical significance. Multivariate logistic regression analysis was used to assess the value of the CT findings for malignancy. Findings with p < 0.20 in the univariate analysis were entered into multivariate models to determine which combination of findings would be most predictive of malignancy. The diagnostic value of each qualitative and quantitative variable in predicting whether a mass was benign was evaluated by calculation of sensitivity, specificity, positive predictive value, and negative predictive value. Reader agreement on qualitative findings (ball versus bean pattern, exophytic pattern, rounded or angular interface, enhancement homogeneity, presence of a scar, inversion) was assessed with weighted kappa statistics. The degree of observer agreement, indicated by kappa values, was interpreted as follows: 0 0.20, slight agreement; 0.21 0.40, fair agreement; 0.41 0.60, moderate agreement; 0.61 A 0.80, substantial agreement; and 0.81 1.00, almost perfect agreement [18]. The intraclass correlation coefficient of the two readers was used for quantitative criteria (size of the tumor, measurement of enhancement, CT histogram analysis). Results Lesions Malignancy, including RCC and other malignant conditions, was found in 74 (75%) of the diagnostic biopsy specimens (Table 1). The diagnosis was benign in 25 (25%) of the specimens: 12 oncocytomas, seven other benign tumors, and six nontumoral lesions (Table 1). The average maximal mass diameter measured on axial CT slices was 2.3 cm (range, 0.9 4 cm) and did not significantly differ between benign and malignant lesions (2.1 ± 0.7 cm versus 2.4 ± 0.9 cm, p = 0.24). Thirty-eight of the 61 RCCs diagnosed at biopsy were managed surgically, 16 were treated by percutaneous ablation, four were not treated because of the poor medical conditions B C Fig. 1 45-year-old woman with metanephric adenoma exhibiting gradual enhancement. A, Transverse unenhanced CT scan shows mass (1) has attenuation of 43 HU. B, Transverse corticomedullary phase CT scan shows mass (1) has attenuation of 54 HU. C, Transverse nephrographic phase CT scan shows mass (1) has attenuation of 88 HU. AJR:197, October 2011 889

Millet et al. TABLE 1: Distribution of Lesions Finding No. of Lesions Renal cell carcinoma (n = 61) Clear cell 43 Chromophobe 11 Papillary 5 Unclassified 2 Other malignant (n = 13) Lymphoma 7 Metastases 4 Transitional cell carcinoma 2 Oncocytoma (n = 12) 12 Other benign (n = 7) Angiomyolipoma 5 Metanephric adenoma 1 Juxtaglomerular tumor 1 Nontumoral lesion (n = 6) Inflammatory 3 Ischemic 2 Granuloma (Wegener disease) 1 of three patients and because of Von Hippel Lindau disease in one patient, and three patients were lost to follow-up. The other malignant lesions were mainly lymphomas and metastatic lesions. In the lesion subtype assessment, the surgical findings confirmed the biopsy results in 37 of the 38 surgically treated RCC cases. One lesion was reclassified from unclassified RCC to clear cell RCC. The benign biopsy findings included 19 benign neoplasms and six nonneoplastic results. Among the nonneoplastic results, one case involved granulomas associated with Wegener disease; three cases were inflammatory lesions, including two cases of focal pyelonephritis and one case of inflammatory fibrosis; and two cases were ischemic lesions. In cases of ischemic or inflammatory lesions, the biopsy results were consistent with the clinical and CT findings, and lesions were followed up. CT follow-up showed a decrease in the size of the lesion in three cases (Fig. 2) and stability after follow-up of at least 1 year in two cases. In the 19 cases of tumors with benign biopsy findings, partial nephrectomy confirmed the diagnosis of one juxtaglomerular tumor and one metanephric adenoma, and the others were followed up. Crosssectional images obtained over at least 1 year of follow-up (range, 13 35 months; mean, 21 months) were available for all the nonsurgically treated benign tumors, and no change in tumor size was found. One patient died after 14 months of follow-up for reasons unrelated to the kidney condition. CT Features The CT features according to the histologic findings on the lesions are summarized in Table 2 for malignant lesions and Table 3 for benign lesions. Comparison of malignant and benign lesions is detailed in Table 4. There was no significant association between CT growth pattern (ball versus bean) and the benign or malignant nature of the lesion (Figs. 3 and 4). The presence of a scar was not significantly associated with benign or malignant findings because scarring was encountered in only one oncocytoma and three malignant lesions (Fig. 5). A renal mass was classified as exophytic in 53 of the malignant cases and 19 of the benign cases. In these cases, the interface between the mass and the renal parenchyma could be evaluated. An angular interface was encountered in two benign lesions (two angiomyolipomas) and four malignant lesions (Fig. 6) without a significant difference between benign and malignant lesions with respect to the distribution of angular, intermediate, and round interfaces. In seven lesions, 6% or more of pixels had an attenuation less than 10 HU: five carcinomas, one angiomyolipoma, and one nonneoplastic lesion. Segmental enhancement inversion was not detected in malignant or benign lesions. There was a significant association between enhancement pattern and benign or malignant nature of the lesion (p = 0.03) with a higher rate of gradual enhancement in benign lesions. However, there was no difference between malignant and benign lesions with respect to quantitative enhancement values (Fig. 7). The results of stepwise multivariate analysis indicated that combining enhancement pattern and homogeneity, which were the two findings differentiating benign from malignant lesions at p < 0.20, did not provide diagnostic superiority. CT Accuracy The sensitivity, specificity, accuracy, and predictive values of CT findings in determining whether a lesion is benign are summarized in Table 5. The pre-ct probability that Fig. 2 73-year-old man with ischemic lesion in bean pattern. A, Initial CT scan shows bean pattern. B, Control CT scan 1 year after A shows size of lesion has decreased. A B 890 AJR:197, October 2011

CT of Small Solid Renal Lesions a renal lesion was benign was 25% (25/99) in this patient cohort. Consequently, the pretest positive predictive value was 25%, and the pretest negative predictive value was 75%. Because all CT findings evaluated for the ability to diagnose benignity had a positive predictive value close to 25% and a negative predictive value close to 75%, we assumed that the presence of a single feature did not substantially help in predicting whether a lesion was benign. Reader Agreement Reader agreement was excellent for all the criteria evaluated except angular interface assessment, for which the agreement was good. Discussion The renal tumor landscape has recently changed. Most renal tumors are small and found incidentally at imaging of patients who have no symptoms [19 21]. Several publications have reported a high rate of benign small tumors. Frank et al. [22] retrospectively examined 2935 solid renal tumors of all sizes that had been treated over a 25-year period and reported that 22.4% and 19.9% of renal lesions smaller than 2 cm and 4 cm were benign. Remzi et al. [21], however, found that renal tumors smaller than 2 cm, 2 3 cm, and 3 4 cm were benign in 24.6%, 20.4%, and 16% of cases. It is now recognized that as many as 20% of all enhancing small renal tumors are benign and that tumor size alone is not adequate information for a treatment decision. The results of our study fall in this range; 25% of lesions were diagnosed as benign, making our results about predictive value meaningful. As have other investigators [21, 22], we observed no size difference between benign and malignant lesions. Because radical nephrectomy and even nephron-sparing surgery are not advisable in the management of benign tumors, it is essential to differentiate benign from malignant lesions [23]. Image characterization and biopsy and tumor sampling are two approaches to the treatment of patients with small solid renal masses. TABLE 2: CT Features According to Histologic Findings: Malignant Lesions Feature All Malignant Lesions (n = 74) Renal Cell Carcinoma (n = 61) Other Neoplasms (n = 13) Morphologic finding Ball/bean (no.) 68/6 (92/8) 60/1 (98/2) 8/5 (62/38) Central scar (no.) 3 (4) 2 (3) 1 (8) Size (cm) 2.25 (0.9 4.0) 2.25 (0.9 4.0) 2.25 (1.2 4.0) Interface (no.) Angular 4 (8) 4 (8) 0 (0) Intermediate 14 (26) 13 (27) 1 (20) Round 35 (66) 31 (65) 4 (80) Visual enhancement (no.) Inversion 0 (0) 0 (0) 0 (0) Homogeneity 27 (36) 18 (29) 9 (69) Attenuation 10% of pixels less than 10 HU (no.) 4 (5) 4 (7) 0 (0) 6% of pixels less than 10 HU (no.) 5 (7) 5 (8) 0 (0) Unenhanced (HU) 39 (13 57) 39 (13 57) 38 (34 48) Quantitative enhancement (HU) Corticomedullary 61 (8 209) 70 (8 209) 26 (9 97) Tubular 65 (11 184) 78 (11 184) 49 (28 56) Enhancement pattern (no.) Washout 15 (20) 14 (23) 1 (7) Plateau 39 (53) 31 (51) 8 (62) Progressive 20 (27) 16 (26) 4 (31) Note Single values in parentheses are percentages; values with dash are ranges. We used biopsy results as the reference standard and had a follow-up time of at least 1 year for lesions classified as benign on the basis of biopsy findings. This aspect of the study constitutes a potential drawback. It cannot be theoretically ruled out that some lesions diagnosed at biopsy as benign were not carcinoma. Although some malignant lesions would be expected not to grow during longer follow-up periods, this is seldom the case. In a study of the distribution of growth rates of renal tumors [24], in the 10% of stable cases of renal cancer, the follow-up period was less than 1 year in 80% of cases. We therefore presume that a lesion diagnosed as benign with precise diagnosis of the type of lesion and imaging follow-up of at least 1 year is benign. In the same way, malignant lesions not treated surgically because they have been treated by percutaneous ablation can theoretically be false-positive biopsy findings. This scenario is unlikely, however, in consideration of data in the literature and the fact that the carcinoma subtype was confirmed at surgery in all but one case. Our biopsy results were excellent (only one inconclusive biopsy, the mass being excluded because core biopsy showed normal renal parenchyma), particularly for small lesions. It has been found [25] that the sensitivity of biopsy for 1- to 3-cm lesions (84%) is lower than that of 4- to 6-cm lesions (97%). In the only study to our knowledge in which small tumor biopsies were specifically assessed [7], there were three failed and five inconclusive biopsies among the 88 biopsies performed. Three main factors may account for the high frequency of biopsy in our study. The first was that CT fluoroscopic guidance, performed for all patients, has been found likely to improve the accuracy of biopsy of small tumors [7, 26]. Second, use of the coaxial technique enabled us to obtain two to five core biopsy specimens. Third, most biopsies were performed by the same radiologist and assessed by the same pathologist, but this last point is a limitation because it makes our data less widely applicable. In our department, biopsy of renal tumors is performed under CT guidance. The classic disadvantages of CT compared with ultrasound guidance are higher cost, exposure to ionizing radiation, and lack of realtime monitoring during needle insertion [27]. However, real-time monitoring is now feasible with CT and fluoroscopic guidance. The three main advantages of CT guidance of biopsy of small renal masses are that most renal tumors can be identified, gas and other structures do AJR:197, October 2011 891

Millet et al. not obscure visibility, and there is better needle visualization [9, 27]. However, we recognize that the ideal approach may combine ultrasound and CT guidance in accordance with TABLE 3: CT Features According to Histologic Findings: Benign Lesions Feature All Benign Conditions (n = 25) Oncocytoma (n = 12) Other Benign Nonneoplastic Lesions (n = 7) Conditions (n = 6) Morphologic finding Ball/bean (no.) 22/3 (88/12) 12/0 (100/0) 7/0 (100/0) 3/3 (50/50) Central scar (no.) 1 (4) 1 (8) 0 (0) 0 (0) Size (cm) 1.95 (1.1 3.9) 2.3 (1.5 3.9) 1.9 (1.1 2.6) 1.83 (1.2 2.7) Interface (no.) Angular 2 (11) 0 (0) 2 (33) 0 (0) Intermediate 8 (42) 5 (45) 2 (33) 1 (50) Round 9 (47) 6 (55) 2 (33) 1 (50) Visual enhancement (no.) Inversion 0 (0) 0 (0) 0 (0) 0 (0) Homogeneity 13 (52) 5 (42) 6 (86) 2 (33) Attenuation 10% of pixels less than 10 HU (no.) 0 (0) 0 (0) 0 (0) 0 (0) 6% of pixels less than 10 HU (no.) 2 (8) 0 (0) 1 (14) 1 (17) Unenhanced (HU) 39 (15 53) 40 (31 43) 44 (15 53) 35 (22 40) Quantitative enhancement (HU) Corticomedullary 68 (3 177) 83 (40 177) 64 (3 86) 28 (8 144) Tubular 82 (25 209) 103 (40 144) 82 (45 94) 66 (25 162) Enhancement pattern (no.) Washout 3 (10) 2 (17) 0 (0) 1 (17) Plateau 7 (30) 4 (33) 1 (14) 2 (33) Progressive 15 (60) 6 (50) 6 (86) 3 (50) Note Single values in parentheses are percentages; values with dash are ranges. ultrasound visualization of the renal tumor and the morphotype of the patient. Unlike other investigators [11, 12], we decided not to evaluate the accuracy of CT criteria for differentiating specific tumor types, that is, RCC versus oncocytoma and angiomyolipoma, but to assess the use of CT in differentiating malignant from benign lesions, which is critical information needed for patient care. The distribution of the lesions analyzed in our study matched that in other published studies, RCCs being 82% of malignant tumors and oncocytomas being 48% of benign lesions. We found no CT criteria that would be useful in differentiating malignant from benign lesions. A retrospective study including 543 surgically treated solid renal tumors [28] also showed that in clinical practice CT was not accurate in differentiating RCC from benign lesions. Nevertheless, it also showed that 17% of all benign lesions were correctly identified as benign at preoperative CT. However, most of these lesions (77%) were fat-containing angiomyolipomas, which are not biopsied in our practice. A strategy for the evaluation of renal masses has been based on ball-type and bean-type growth patterns [17]. However, because these two categories include both benign and malignant lesions, it was assumed that the ball versus bean growth pattern growth did not allow differentiation of benign from malignant renal neoplasms. By contrast, the shape of the interface with the renal parenchyma has been found useful for such differentiation, the presence of an angular interface being a strong predictor of a benign finding with a sensitivity of 78% and a specificity of 100% [14]. We did not have the same results. In our study, an angular interface was encountered in only two benign lesions but in four malignant lesions. This dis- A Fig. 3 Ball pattern in two masses that deform renal contour and have sharp distinct interface between mass and surrounding renal parenchyma. A and B, 60-year-old man with renal cell carcinoma. CT scans show early washout pattern with washout of at least 20 HU between corticomedullary (A) and nephrographic (B) phases. (Fig. 3 continues on next page) B 892 AJR:197, October 2011

CT of Small Solid Renal Lesions C D Fig. 3 (continued) Ball pattern in two masses that deform renal contour and have sharp distinct interface between mass and surrounding renal parenchyma. C and D, 72-year-old man with oncocytoma. CT scans show early washout pattern with washout of at least 20 HU between corticomedullary (C) and nephrographic (D) phases. crepancy can be partially explained by differences in the tumors included. Most of the benign lesions included in the study by Verna et al. [14] were cysts, whereas we included only solid enhancing tumors. Our results nevertheless indicate that the presence of an angular interface does not exclude a malignant tumor. Typical central stellate fibrotic scars are found in as many as one third of oncocytomas [16, 29]. However, such scars are mainly encountered in large tumors. Furthermore, central scars can be detected in RCC. The lack of reliability of central scars as a factor for differentiating benign from malignant lesions that we observed was expected. In contrast, the lack of reliability of the segmental enhancement inversion findings was a disappointing result. Segmental enhancement inversion has been described as a diagnostic sign of oncocytoma [11]. We did not observe this finding in malignant or benign lesions. In contrast to the results of Kim et al. [13], we did not find CT histogram analysis useful in differentiating angiomyolipomas with minimal fat from RCC. By using the same diagnostic cutoff, that is, 6% of pixels with attenuation less than 10 HU, we found the same sensitivity of 20% (one of five angiomyolipomas) but not the same 100% specificity because five of the RCCs in our study matched this criterion. Our sensitivity results are weakened by the small number of angiomyolipomas assessed, but we noted that CT histogram analysis cannot exclude RCC. We found a significant difference between malignant and benign tumors in terms of enhancement parameters with a higher rate of progressive enhancement in benign tumors. However, this finding had a positive predictive value of 43% and a negative predictive value of 84%, relatively close to the pre-ct TABLE 4: Comparison of Malignant and Benign Lesions predictive values (25% and 75%), so this finding would not be helpful in clinical practice. Numerous studies [10, 17, 30 35] have shown that degree of enhancement is the most valuable Feature Malignant (n = 74) Benign (n = 25) p Morphologic finding Ball/bean (no.) 68/6 (92/8) 22/3 (88/12) 0.69 Central scar (no.) 3 (4) 1 (4) 1.0 Size (cm) 2.25 (0.9 4.0) 1.95 (1.1 3.9) 0.23 Interface (no.) 0.33 Angular 4 (8) 2 (11) Intermediate 14 (26) 8 (42) Round 35 (66) 9 (47) Visual enhancement (no.) Inversion 0 (0) 0 (0) NS Homogeneity 27 (36) 13 (52) 0.14 Attenuation 10% of pixels less than 10 HU (no.) 4 (5) 0 (0) 0.57 6% of pixels less than 10 HU (no.) 5 (7) 2 (8) 1.0 Unenhanced (HU) 39 (13 57) 39 (15 53) 0.80 Quantitative enhancement (HU) Corticomedullary 61 (8 209) 68 (3 177) 0.78 Tubular 65 (11 184) 82 (25 209) 0.21 Enhancement pattern (no.) Washout 15 (20) 3 (10) 0.03 Plateau 39 (53) 7 (30) Progressive 20 (27) 15 (60) Note Single values in parentheses are percentages; values with dash are ranges. NS = not significant. AJR:197, October 2011 893

Millet et al. Fig. 4 Bean pattern. A, 50-year-old man with lymphoma. CT scan shows ill-defined borders and no deformity of renal contours. B, 64-year-old woman with Wegener disease. CT scan shows ill-defined borders and no deformity of renal contours. Fig. 5 Corticomedullary phase CT scans showing radial scar. A, 40-year-old man with oncocytoma. B, 60-year-old woman with renal cell carcinoma. TABLE 5: Diagnostic Value of CT Findings in Determining Benign Nature of a Renal Mass Finding Morphologic feature Interobserver Agreement Sensitivity (%) Specificity (%) A A Positive Predictive Value (%) Negative Predictive Value (%) Accuracy (%) Bean 1.0 (1.0 1.0) 12 (4 30) 92 (83 96) 33 (12 65) 76 (66 83) 72 (62 80) Central scar 0.88 (0.66 1.0) 4 (0.7 20) 96 (89 99) 25 (5 70) 75 (65 82) 72 (63 80) Angular interface 0.34 (0.19 0.50) 11 (3 31) 93 (82 97) 33 (10 70) 74 (63 83) 71 (60 80) 10% of pixels less than 10 HU 0.63 (0.48 0.74) 0 (0 13) 95 (85 98) 0 (0 49) 74 (63 82) 70 (58 77) 6% of pixels less than 10 HU 0.63 (0.48 0.74) 8 (1 27) 93 (84 97) 29 (8 64) 75 (65 83) 72 (61 80) Enhancement Homogeneity 0.96 (0.90 1.0) 52 (32 72) 64 (52 73) 33 (20 48) 80 (69 89) 61 (51 70) Progressive enhancement pattern 0.82 (0.73 0.91) 60 (39 78) 73 (61 82) 43 (27 60) 84 (73 92) 70 (60 79) Note Values in parentheses are ranges. B B 894 AJR:197, October 2011

CT of Small Solid Renal Lesions Fig. 6 48-year-old woman with renal cell carcinoma. CT scan shows angular interface with renal parenchyma (arrows). parameter for differentiation of RCC subtypes, because clear cell RCC is enhancing to a greater degree than other RCC subtypes, especially papillary RCC. It has been found [10] that by inclusion of benign and malignant lesions, clear cell RCC and oncocytoma are avidly enhancing in the parenchymal phase, whereas chromophobe carcinoma and lipid-poor angiomyolipoma are moderately enhancing and papillary tumors are the least enhancing. Consequently, it is not surprising that quantitative enhancement parameters were not strong predictors for differentiating benign and malignant lesions. The same results were obtained in a study of 466 solitary solid renal masses measuring 0.7 19.5 cm without a statistical difference between benign and malignant masses with respect to attenuation and quantitative amount of enhancement [15]. Fig. 7 Graph shows quantitative enhancement in cortical and tubular nephrogram phases for benign and malignant lesions (median, quartiles, and minimum and maximum enhancement values). Enhancement (HU) 250 200 150 100 50 0 Benign Malignant Benign Malignant Cortical Nephrogram Phase Tubular Nephrogram Phase Our study had several limitations. The retrospective design might have introduced patient selection bias with respect to biopsy, which would have been performed for patients with atypical patterns at CT. However, a computer search of the pathology reports at our institution revealed that only eight solid renal masses (six RCC, two oncocytoma) smaller than 4 cm had been treated surgically without preoperative biopsy during the study period. Although to our knowledge our study included the largest series of tumors smaller than 4 cm only, some categories of benign lesions were poorly represented. As in other retrospective studies in which renal mass core biopsies were evaluated, the absence of surgical confirmation of the benign nature of most of the benign lesions and the short follow-up time of at least 1 year for lesions classified at biopsy as benign constitute a limitation. However, stability of renal cancer after a follow-up period of 1 year or more is rare [24], and removal of small masses with a tissue diagnosis of benign, precise diagnosis of the type of lesion, and stability of the mass would be unethical. Conclusion In solid enhancing renal lesions without fat, no morphologic or CT enhancement criteria are helpful for differentiating small malignant from benign lesions. Because of the relatively high rate of benign findings, biopsy is thus recommended in the management of all small enhancing solid renal tumors that do not exhibit fat at imaging. References 1. Bosniak MA, Megibow AJ, Hulnick DH, Horii S, Raghavendra BN. CT diagnosis of renal angiomyolipoma: the importance of detecting small amounts of fat. AJR 1988; 151:497 501 2. Silverman SG, Israel GM, Herts BR, Richie JP. Management of the incidental renal mass. Radiology 2008; 249:16 31 3. Bosniak MA. Problems in the radiologic diagnosis of renal parenchymal tumors. Urol Clin North Am 1993; 20:217 230 4. Beland MD, Mayo-Smith WW, Dupuy DE, Cronan JJ, DeLellis RA. Diagnostic yield of 58 consecutive imaging-guided biopsies of solid renal masses: should we biopsy all that are indeterminate? AJR 2007; 188:792 797 5. Maturen KE, Nghiem HV, Caoili EM, Higgins EG, Wolf JS Jr, Wood DP Jr. Renal mass core biopsy: accuracy and impact on clinical management. AJR 2007; 188:563 570 6. Schmidbauer J, Remzi M, Memarsadeghi M, et al. Diagnostic accuracy of computed tomographyguided percutaneous biopsy of renal masses. Eur Urol 2008; 53:1003 1011 7. Neuzillet Y, Lechevallier E, Andre M, Daniel L, Coulange C. Accuracy and clinical role of fine needle percutaneous biopsy with computerized tomography guidance of small (less than 4.0 cm) renal masses. J Urol 2004; 171:1802 1805 8. Pandharipande PV, Gervais DA, Hartman RI, et al. Renal mass biopsy to guide treatment decisions for small incidental renal tumors: a cost-effectiveness analysis. Radiology 2010; 256:836 846 9. Remzi M, Marberger M. Renal tumor biopsies for evaluation of small renal tumors: why, in whom, and how? Eur Urol 2009; 55:359 367 10. Zhang J, Lefkowitz RA, Ishill NM, et al. Solid renal cortical tumors: differentiation with CT. Radiology 2007; 244:494 504 11. Kim JI, Cho JY, Moon KC, Lee HJ, Kim SH. Segmental enhancement inversion at biphasic multidetector CT: characteristic finding of small renal AJR:197, October 2011 895

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