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History: A 65-year-old male patient with a history of sarcomatoid renal cell carcinoma and prior right nephrectomy developed recurrent disease adjacent to the inferior vena cava. The patient underwent surveillance imaging 7 months after initiation of treatment with maximum-dose pazopanib and less than 1 month after completing a 2-month regimen of palliative stereotactic body radiation therapy to the right nephrectomy bed and site of recurrence. (Stereotactic body radiation therapy was initiated 5 months after pazopanib treatment was initiated.) One month after initiating treatment with pazopanib and 6 months before the surveillance imaging, the patient developed diarrhea and required ongoing treatment with loperamide to control symptoms. He denied any fatigue, mouth sores, or extremity pain, but described some abdominal pain and discomfort associated with the diarrhea. He was not experiencing any fevers, and vital signs were normal. White blood cell count was normal at 5100/μL (5.1 ×10 9 /L) (normal range, 4200-10 200/μL [4.2-10.2 ×10 9 /L]), with all components of the differential count also being normal. A normal serum albumin level of 3.9 g/dL (39 g/L) (normal range, 3.5-5.0 g/dL [35-50 g/L]) and low serum total protein level of 6.1 g/dL (61 g/L) (normal range, 6.3-7.9 g/dL [63-79 g/L]) were noted. A comprehensive metabolic panel was performed, indicating a serum chloride level of 98 mmol/L (normal, 100-108 mmol/L) and alkaline phosphatase level of 121 U/L (2.02 μkat/L) (normal, 45-115 U/L [0.75-1.92 μkat/L]). The patient underwent surveillance imaging with contrast-enhanced CT of the abdomen and pelvis in the venous phase (Figure).

The two primary nephron-sparing interventions for treating renal masses such as renal cell carcinoma are surgical partial nephrectomy (PN) and image-guided percutaneous thermal ablation. Nephron-sparing surgery, such as PN, has been the standard of care for treating many localized renal masses. Although uncommon, complications resulting from PN can range from asymptomatic and mild to symptomatic and life-threatening. These complications include vascular injuries such as hematoma, pseudoaneurysm, arteriovenous fistula, and/or renal ischemia; injury to the collecting system causing urinary leak; infection; and tumor recurrence. The incidence of complications after any nephron-sparing surgery depends on many factors, such as the proximity of the tumor to blood vessels or the collecting system, the skill or experience of the surgeon, and patient-specific factors. More recently, image-guided percutaneous renal ablation has emerged as a safe and effective treatment option for small renal tumors, with comparable oncologic outcomes to those of PN and a low incidence of major complications. Radiologists must be familiar with the imaging findings encountered after these surgical and image-guided procedures, especially those indicative of complications. The authors review cross-sectional imaging characteristics of complications after PN and image-guided thermal ablation of kidney tumors and highlight the respective management strategies, ranging from clinical observation to interventions such as angioembolization or repeat surgery. Work of the U.S. Government published under an exclusive license with the RSNA. Online supplemental material and the slide presentation from the RSNA Annual Meeting are available for this article. Quiz questions for this article are available in the Online Learning Center. See the invited commentary by Chung and Raman in this issue.

Background There is uncertainty in the management of renal masses diagnosed as oncocytomas with image-guided percutaneous biopsy. Purpose To assess the reliability of a diagnosis of oncocytoma based on image-guided percutaneous renal mass biopsy and evaluate patient outcomes following different management strategies. Materials and Methods In this retrospective study, image-guided percutaneous biopsy pathology reports from April 2004 to April 2019 were searched for keywords "oncocytoma" and "oncocytic neoplasm" and compared with surgical pathology or repeat biopsy results. Patients with at least 12 months of clinical follow-up and known cause of death were grouped according to management strategies, and disease-specific survival and metastatic renal cell carcinoma (RCC)-free survival were compared. Mass growth rates were calculated with use of a normal linear mixed model. Results The database yielded 160 biopsy reports of 149 renal masses in 139 patients; 149 masses were categorized as oncocytoma ( n = 107), likely oncocytoma ( n = 12), oncocytic neoplasm ( n = 28), and indeterminate with oncocytoma in differential ( n = 2). Biopsied masses categorized as oncocytoma or likely oncocytoma were oncocytomas in 16 of 17 masses (94%) based on surgical pathology or repeat biopsy; four of eight masses (50%) categorized as oncocytic neoplasms were low-grade RCCs. Outcome analysis included 121 patients (mean age ± SD, 68 years ± 9.1; 82 men); 80 patients initially underwent active surveillance (11 were later treated), 33 underwent ablation, and eight underwent surgery. Disease-specific survival and metastatic-free survival were 100% after each management strategy (median follow-up, 86.6 months; range, 14.2-207.9 months). Mass growth rate (mean, 1.7 mm per year) showed no evidence of a significant difference among biopsy result categories ( P = .37) or initial ( P = .84) or final management strategies ( P = .11). Conclusion Image-guided percutaneous biopsy diagnosis of renal oncocytoma was reliable. Although some masses diagnosed as oncocytic neoplasms were low-grade renal cell carcinomas (RCCs) at final diagnosis, no patients died of RCC, including those managed with active surveillance. © RSNA, 2023 See also the editorial by Lockhart in this issue.

Background Noninvasive in vivo detection of fumarate accumulation may help identify fumarate hydratase deficiency in renal cancer related to hereditary leiomyomatosis and renal cell carcinoma (HLRCC) syndrome. Purpose To investigate the feasibility of MR spectroscopy (MRS) in detecting elevated fumarate levels in HLRCC-associated renal cancers. Materials and Methods This study included an experimental xenograft mouse model and prospective clinical cohort. First, MRS was performed on patient-derived tumor xenograft models and control models to detect fumarate. Then, consecutive participants with clinical suspicion of HLRCC-associated renal tumors were enrolled. For the detection of fumarate, MRS results were classified as detected, borderline, undetected, or technical failure. The sensitivity, specificity, and accuracy of MRS for diagnosing HLRCC-associated renal cancer were assessed. The signal-to-noise ratio (SNR) of the fumarate peak was calculated and evaluated with receiver operating characteristic curve analysis. Results Fumarate peaks were detected at 6.54 parts per million in all three patient-derived xenograft models. A total of 38 participants (21 men; mean age, 47 years [range, 18-71 years]) with 46 lesions were analyzed. All primary HLRCC-associated renal cancers showed a fumarate peak; among the seven metastatic HLRCC-associated lesions, a fumarate peak was detected in three lesions and borderline in two. When only detected peaks were regarded as positive findings, the sensitivity, specificity, and accuracy of MRS at the lesion level were 69% (nine of 13 lesions), 100% (33 of 33 lesions), and 91% (42 of 46 lesions), respectively. When borderline peaks were also included as a positive finding, the sensitivity, specificity, and accuracy reached 85% (11 of 13 lesions), 88% (29 of 33 lesions), and 87% (40 of 46 lesions), respectively. The SNR of fumarate showed an area under the receiver operating characteristic curve of 0.87 for classifying HLRCC-associated tumors. Conclusion MR spectroscopy of fumarate was sensitive and specific for hereditary leiomyomatosis and renal cell carcinoma-associated tumors. © RSNA, 2022 Online supplemental material is available for this article.

Background Solid small renal masses (SRMs) (≤4 cm) represent benign and malignant tumors. Among SRMs, clear cell renal cell carcinoma (ccRCC) is frequently aggressive. When compared with invasive percutaneous biopsies, the objective of the proposed clear cell likelihood score (ccLS) is to classify ccRCC noninvasively by using multiparametric MRI, but it lacks external validation. Purpose To evaluate the performance of and interobserver agreement for ccLS to diagnose ccRCC among solid SRMs. Materials and Methods This retrospective multicenter cross-sectional study included patients with consecutive solid (≥25% approximate volume enhancement) SRMs undergoing multiparametric MRI between December 2012 and December 2019 at five academic medical centers with histologic confirmation of diagnosis. Masses with macroscopic fat were excluded. After a 1.5-hour training session, two abdominal radiologists per center independently rendered a ccLS for 50 masses. The diagnostic performance for ccRCC was calculated using random-effects logistic regression modeling. The distribution of ccRCC by ccLS was tabulated. Interobserver agreement for ccLS was evaluated with the Fleiss κ statistic. Results A total of 241 patients (mean age, 60 years ± 13 [SD]; 174 men) with 250 solid SRMs were evaluated. The mean size was 25 mm ± 8 (range, 10-39 mm). Of the 250 SRMs, 119 (48%) were ccRCC. The sensitivity, specificity, and positive predictive value for the diagnosis of ccRCC when ccLS was 4 or higher were 75% (95% CI: 68, 81), 78% (72, 84), and 76% (69, 81), respectively. The negative predictive value of a ccLS of 2 or lower was 88% (95% CI: 81, 93). The percentages of ccRCC according to the ccLS were 6% (range, 0%-18%), 38% (range, 0%-100%), 32% (range, 60%-83%), 72% (range, 40%-88%), and 81% (range, 73%-100%) for ccLSs of 1-5, respectively. The mean interobserver agreement was moderate (κ = 0.58; 95% CI: 0.42, 0.75). Conclusion The clear cell likelihood score applied to multiparametric MRI had moderate interobserver agreement and differentiated clear cell renal cell carcinoma from other solid renal masses, with a negative predictive value of 88%. © RSNA, 2022 Online supplemental material is available for this article. See also the editorial by Mileto and Potretzke in this issue.

The widespread use of cross-sectional imaging has led to a continuous increase in the number of incidentally detected indeterminate renal masses. Frequently, these clinical scenarios involve an older patient with comorbidities and a small renal mass (≤4 cm). Despite aggressive treatment in early stages of the disease, a clear positive effect in reducing kidney cancer-specific mortality is lacking, indicating that many renal cancers exhibit an indolent oncologic behavior. Furthermore, in general, one in five small renal masses is histologically benign and may not benefit from aggressive treatment. Although active surveillance is increasingly recognized as a management option for some patients, the absence of reliable clinical and imaging predictive biologic markers of aggressiveness can contribute to patient anxiety and limit its use in clinical practice. A standardized approach to the image interpretation of solid renal masses has not been broadly implemented. The clear cell likelihood score (ccLS) derived from multiparametric MRI is useful in noninvasively identifying the clear cell subtype, the most common and aggressive form of kidney cancer. Herein, a review of the ccLS is presented, including a step-by-step guide for image interpretation and additional guidance for its implementation in clinical practice., (© RSNA, 2021.)

With the expansion in cross-sectional imaging over the past few decades, there has been an increase in the number of incidentally detected renal masses and an increase in the incidence of renal cell carcinomas (RCCs). The complete characterization of an indeterminate renal mass on CT or MR images is challenging, and the authors provide a critical review of the best imaging methods and essential, important, and optional reporting elements used to describe the indeterminate renal mass. While surgical staging remains the standard of care for RCC, the role of renal mass CT or MRI in staging RCC is reviewed, specifically with reference to areas that may be overlooked at imaging such as detection of invasion through the renal capsule or perirenal (Gerota) fascia. Treatment options for localized RCC are expanding, and a multidisciplinary group of experts presents an overview of the role of advanced medical imaging in surgery, percutaneous ablation, transarterial embolization, active surveillance, and stereotactic body radiation therapy. Finally, the arsenal of treatments for advanced renal cancer continues to grow to improve response to therapy while limiting treatment side effects. Imaging findings are important in deciding the best treatment options and to monitor response to therapy. However, evaluating response has increased in complexity. The unique imaging findings associated with antiangiogenic targeted therapy and immunotherapy are discussed. An invited commentary by Remer is available online. Online supplemental material is available for this article. © RSNA, 2021.

Renal cell carcinoma (RCC) is a heterogeneous group of neoplasms derived from the renal tubular epithelial cells. Chromophobe RCC (chRCC) is the third most common subtype of RCC, accounting for 5% of cases. chRCC may be detected as an incidental finding or less commonly may manifest with clinical symptoms. The mainstay of therapy for chRCC is surgical resection. chRCC has a better prognosis compared with the more common clear cell RCC. At gross pathologic analysis, chRCC is a solid well-defined mass with lobulated borders. Histologic findings vary by subtype but include large pale polygonal cells with abundant transparent cytoplasm, crinkled "raisinoid" nuclei with perinuclear halos, and prominent cell membranes. Pathologic analysis reveals only moderate vascularity. The most common imaging pattern is a predominantly solid renal mass with circumscribed margins and enhancement less than that of the renal cortex. The authors discuss chRCC with emphasis on correlative pathologic findings and illustrate the multimodality imaging appearances of chRCC by using cases from the Radiologic Pathology Archives of the American Institute for Radiologic Pathology. © RSNA, 2021.

Background Percutaneous ablation for cT1 renal cell carcinoma (RCC) remains underused, partially because of heterogeneous and limited long-term outcomes data assessing recent cryoablation methods. Purpose To report intermediate- to long-term outcomes of image-guided percutaneous cryoablation of cT1 RCC and to compare outcomes for CT versus MRI guidance. Materials and Methods This HIPAA-compliant retrospective single-institution study assessed patients who underwent percutaneous cryoablation for solitary pathology-proven cT1 RCC between August 2000 and July 2017. Tumors (cT1a, n = 282; cT1b, n = 25; size range, 0.6-6.5 cm; median size, 2.5 cm) underwent cryoablation with CT ( n = 155) or MRI ( n = 152) guidance. Primary end points of overall survival (OS), disease-specific survival (DSS), imaging-confirmed disease-free survival (DFS), and local progression-free survival (LPFS) were calculated by using Kaplan-Meier analysis. Secondary end points of technique efficacy and adverse event rate were also calculated. Primary and secondary end points for CT and MRI guidance were compared by using univariable regression analysis. Results A total of 307 patients (mean age, 68 years ± 11 [standard deviation]; 192 men) were evaluated. Median clinical follow-up lasted 95 months (range, 8-219 months), and median imaging follow-up lasted 41 months (range, 0-189 months). Survival metrics at 3, 5, 10, and 15 years, respectively, included OS of 91% (95% confidence interval [CI]: 88%, 94%), 86% (95% CI: 82%, 90%), 78% (95% CI: 73%, 84%), and 76% (95% CI: 69%, 83%); DSS of 99.6% (95% CI: 99%, 100%), 99% (95% CI: 98%, 100%), 99% (95% CI: 98%, 100%), and 99% (95% CI: 98%, 100%); DFS of 94% (95% CI: 92%, 97%), 91% (95% CI: 88%, 96%), 88% (95% CI: 83%, 93%), and 88% (95% CI: 83%, 93%); and LPFS of 97% (95% CI: 94%, 99%), 95% (95% CI: 93%, 98%), 95% (95% CI: 93%, 98%), and 95% (95% CI: 93%, 98%). Survival did not significantly differ between CT and MRI guidance, with univariable Cox regression analysis hazard ratios of 0.97 (95% CI: 0.57, 1.67; P = .92) for OS, 0.63 (95% CI: 0.26, 1.52; P = .30) for DFS, and 0.83 (95% CI: 0.26, 2.74; P = .77) for LPFS. Primary and secondary technique efficacy were 96% and 99%, respectively. Overall adverse event rate was 14% (43 of 307), including 11 grade 3 events and three grade 4 events according to the Common Terminology Criteria for Adverse Events. Conclusion Percutaneous CT- and MRI-guided cryoablation of cT1 renal cell carcinoma had similar excellent intermediate- and long-term outcomes. © RSNA, 2020 Online supplemental material is available for this article. See also the editorial by Georgiades in this issue.

Background Identification of markers to aid in understanding the growth kinetics of Von Hippel-Lindau (VHL)-associated clear cell renal cell carcinoma (ccRCC) has the potential to allow individualization of patient care, thereby helping prevent unnecessary screening and optimizing intervention. Purpose To determine whether the degree of restricted diffusion at baseline MRI holds predictive potential for the growth rate of VHL-associated ccRCC. Materials and Methods Patients with VHL disease who underwent surgical resection of tumors between November 2014 and October 2017 were analyzed retrospectively in this HIPAA-compliant study. The change in ccRCC volume between two time points and apparent diffusion coefficient (ADC) at baseline was calculated by using segmentations by two readers at nephrographic-phase CT and diffusion-weighted MRI, respectively. Intraclass correlation coefficient was used to assess agreement between readers. Repeated-measures correlation was used to investigate relationships between ADC (histogram parameters) and tumor size at baseline with growth rate and volume doubling time (VDT). Predictive performance of the ADC parameter with highest correlation and tumor size at baseline was reviewed to differentiate tumors based on their VDT (≤1 year or >1 year). Results Forty-six patients (mean age, 46 years ± 7 [standard deviation]; 25 women) with 100 ccRCCs were evaluated. Interreader agreement resulted in mean κ scores of 0.89, 0.82, and 0.93 for mean ADC, baseline tumor volume, and follow-up tumor volume, respectively. ADC percentiles correlated negatively with tumor growth rate but correlated positively with VDT. Lower ADC values demonstrated stronger correlations. The 25th percentile ADC had the strongest correlation with growth rate (ρ = -0.52, P < .001) and VDT (ρ = 0.60, P < .001) and enabled prediction of VDT (≤1 year or >1 year) with an area under the receiver operating characteristic curve of 0.86 (sensitivity, 67%; specificity, 89%) ( P < .001). Conclusion Apparent diffusion coefficient at baseline was negatively correlated with tumor growth rate. Diffusion-weighted MRI may be useful to identify clear cell renal cell carcinomas with higher growth rates. © RSNA, 2020See also the editorial by Goh and Prezzi in this issue.

Thermal ablation of small renal masses is increasingly accepted as an alternative to partial nephrectomy, particularly in patients with multiple comorbidities. Many professional societies support this alternate treatment with updated guidelines. Before performing thermal ablation, it is important to stratify risk and assess technical feasibility by evaluating tumor imaging features such as size, location, and centrality. Routine postablation imaging with CT or MRI is necessary for assessment of residual or recurrent tumor, evidence of complications, or new renal masses outside the ablation zone. The normal spectrum and evolution of findings at CT and MRI include a halo appearance of the ablation zone, ablation zone contraction, and ablation zone calcifications. Tumor recurrence frequently manifests at CT or MRI as new nodular enhancement at the periphery of an expanding ablation zone, although it is normal for the ablation zone to enlarge within the first few months. Recognizing early tumor recurrence is important, as small renal masses are often easily treated with repeat ablations. Potential complications of thermal ablation include vascular injury, urine leak, ureteral stricture, nerve injury, and bowel perforation. The risk of these complications may be related to tumor size and location. © RSNA, 2019.

Locally advanced and metastatic renal cell carcinoma (RCC) present a specific set of challenges to the radiologist. The detection of metastatic disease is confounded by the ability of RCC to metastasize to virtually any part of the human body long after surgical resection of the primary tumor. This includes sites not commonly included in routine surveillance, which come to light after the patient becomes symptomatic. In the assessment of treatment response, the phenomenon of tumor heterogeneity, where clone selection through systemic therapy drives the growth of potentially more aggressive phenotypes, can result in oligoprogression despite overall disease control. Finally, advances in therapy have resulted in the development of immuno-oncologic agents that may result in changes that are not adequately evaluated with conventional size-based response criteria and may even be misinterpreted as progression. This article reviews the common challenges a radiologist may encounter in the evaluation of patients with locally advanced and metastatic RCC. © RSNA, 2019.

Background Progression-free survival (PFS) determined by Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) is the reference standard to assess efficacy of treatments in patients with clear cell renal cell carcinoma. Purpose To assess the most common components of radiologic progressive disease as defined by RECIST 1.1 in patients with clear cell renal cell carcinoma and how the progression events impact PFS. Materials and Methods This secondary analysis of the phase III METEOR trial conducted between 2013 and 2014 included patients with metastatic clear cell renal cell carcinoma, with at least one target lesion at baseline and one follow-up time point, who were determined according to RECIST 1.1 to have progressive disease. A chest, abdominal, and pelvic scan were acquired at each time point. Kruskal-Wallis analysis was used to test differences in median PFS among the RECIST 1.1 progression events. The Holm-Bonferroni method was used to compare the median PFS of the progression events for the family-wise error rate of 5% to adjust P values for multiple comparisons. Results Of the 395 patients (296 men, 98 women, and one patient with sex not reported; mean age, 61 years ± 10), 73 (18.5%) had progression due to non-target disease, 105 (26.6%) had new lesions, and 126 (31.9%) had progression of target lesions (defined by an increase in the sum of diameters). Patients with progression of non-target disease and those with new lesions had shorter PFS than patients with progression defined by the target lesions (median PFS, 2.8 months [95% confidence interval {CI}: 1.9 months, 3.7 months] and 3.6 months [95% CI: 3.3 months, 3.7 months] vs 5.4 months [95% CI: 5.0 months, 5.5 months], respectively [ P < .01]). Conclusion The most common causes for radiologic progression of renal cell carcinoma were based on non-target disease and new lesions rather than change in target lesions, despite this being considered uncommon in the Response Evaluation Criteria in Solid Tumors version 1.1 literature. © RSNA, 2019 See also the editorial by Kuhl in this issue.

Renal cell carcinoma (RCC) is a common cancer that is increasing in incidence because of the increased prevalence of risk factors, including tobacco use, hypertension, and obesity, and the improved detection of these tumors due to increased use of imaging. Localized renal cancer now accounts for more than 60%-70% of new RCC cases. Renal masses suggestive of cancer include enhancing solid renal lesions and Bosniak III and IV complex cystic lesions. Most of these tumors are detected incidentally, and many are slow growing with little propensity to metastasize. Radiologists have a vital role in evaluation of these tumors and subsequent patient counseling. Options for managing RCC include radical nephrectomy (RN), partial nephrectomy (PN), thermal ablation, and active surveillance. However, historically, the use of these strategies has varied among practices. Improved understanding of the biologic features of these tumors and data indicating the heterogeneous clinical course of many clinically localized renal tumors led to the development of the American Urological Association (AUA) Localized Renal Cancer Panel Guidelines in 2009, and these guidelines were updated in 2017. The format of the updated guidelines has moved from management recommendations based on index patients to individualized decision making, taking into account patient age and comorbidities, tumor characteristics, and important renal function considerations. A distinct role for RN is defined for cases of tumors with increased oncologic potential in patients with a normal contralateral kidney. Beyond this, nephron-sparing options, particularly PN, should be a priority. The updated guidelines also recommend increased use of renal mass biopsy, thermal ablation, and active surveillance in appropriately selected patients. The 2017 AUA guidelines are reviewed, with emphasis on the implications for practicing radiologists. © RSNA, 2018.

Purpose To evaluate the long-term efficacy of image-guided cryoablation of sporadic clinical T1 (cT1) biopsy-proven renal cell carcinoma (RCC) and the technical success and safety of all cryoablation treatments. Materials and Methods For this retrospective single-institution study, 433 patients (median age, 68 years; range, 19-90 years), of whom 293 were men (median age, 69 years; range, 19-90 years) and 140 were women (median age, 68 years; range, 30-89 years), who had 484 cT1 renal masses (mean size, 33 mm) and who were treated between 2007 and 2016 were identified from a prospectively maintained tumor registry. Treatment efficacy for all treated lesions and complication rates of all procedures were computed. Oncologic outcomes for a subset of 220 patients with sporadic biopsy-proven RCC were analyzed. The Kaplan-Meier method was used to estimate local recurrence-free survival (LRFS), metastasis-free survival (MFS), and overall survival (OS) rates. Results Of the 484 treated cT1 renal masses, 474 were imaged subsequently, with a primary treatment efficacy of 96% (453 of 474), increasing to 98% (465 of 474) after secondary ablation, and a major complication rate (Clavien-Dindo grade ≥ III) of 4.9% (23 of 473 procedures). The estimated LRFS and MFS rates, respectively, for the 220 patients with biopsy-proven RCC were 97.2% (95% confidence interval [CI]: 92.6%, 99.0%) and 97.7% (95% CI: 93.3%, 99.1%) at 3 years and 93.9% (95% CI: 85.8%, 97.4%) and 94.4% (95% CI: 86.7%, 97.7%) at 5 years. The estimated OS of all 433 patients was 91.7% (95% CI: 87.5%, 94.5%) and 78.8% (95% CI: 71.1%, 84.6%) at 3 and 5 years, respectively. Conclusion Five-year oncologic outcomes after image-guided cryoablation for clinical T1 renal cell carcinoma are competitive with those of resection at a lower complication rate. © RSNA, 2018.

Purpose To cross-validate T1-weighted oxygen-enhanced (OE) MRI measurements of tumor hypoxia with intrinsic susceptibility MRI measurements and to demonstrate the feasibility of translation of the technique for patients. Materials and Methods Preclinical studies in nine 786-0-R renal cell carcinoma (RCC) xenografts and prospective clinical studies in eight patients with RCC were performed. Longitudinal relaxation rate changes (∆R1) after 100% oxygen inhalation were quantified, reflecting the paramagnetic effect on tissue protons because of the presence of molecular oxygen. Native transverse relaxation rate (R2*) and oxygen-induced R2* change (∆R2*) were measured, reflecting presence of deoxygenated hemoglobin molecules. Median and voxel-wise values of ∆R1 were compared with values of R2* and ∆R2*. Tumor regions with dynamic contrast agent-enhanced MRI perfusion, refractory to signal change at OE MRI (referred to as perfused Oxy-R), were distinguished from perfused oxygen-enhancing (perfused Oxy-E) and nonperfused regions. R2* and ∆R2* values in each tumor subregion were compared by using one-way analysis of variance. Results Tumor-wise and voxel-wise ∆R1 and ∆R2* comparisons did not show correlative relationships. In xenografts, parcellation analysis revealed that perfused Oxy-R regions had faster native R2* (102.4 sec -1 vs 81.7 sec -1 ) and greater negative ∆R2* (-22.9 sec -1 vs -5.4 sec -1 ), compared with perfused Oxy-E and nonperfused subregions (all P < .001), respectively. Similar findings were present in human tumors (P < .001). Further, perfused Oxy-R helped identify tumor hypoxia, measured at pathologic analysis, in both xenografts (P = .002) and human tumors (P = .003). Conclusion Intrinsic susceptibility biomarkers provide cross validation of the OE MRI biomarker perfused Oxy-R. Consistent relationship to pathologic analyses was found in xenografts and human tumors, demonstrating biomarker translation. Published under a CC BY 4.0 license. Online supplemental material is available for this article.

Purpose To determine if sex differences in abdominal visceral fat composition, measured by using computed tomography (CT), and tumor glucose metabolism, measured by gene expression, can help predict outcomes in patients with clear cell renal cell carcinoma (RCC). Materials and Methods This retrospective cohort study included 222 patients with clear cell RCC from The Cancer Imaging Atlas. By using CT, body fat was segmented into subcutaneous fat and visceral fat areas (VFAs) and normalized to total fat to obtain the relative VFA (rVFA) and relative subcutaneous fat area. Multivariate Cox proportional hazard regression models were performed to identify effects of rVFA on sex-specific survival. Expression profiles for 39 glycolytic genes in tumors from these patients were obtained from The Cancer Genome Atlas to determine sex differences in metabolism and compared with rVFA. Key mutations in clear cell RCC were analyzed for association with rVFA and tumor glycolytic profiles. Results Women with rVFA greater than 30.9% had an increased risk of death (hazard ratio, 3.66 [95% confidence interval: 1.64, 8.19]) for women vs 1.13 ([95% confidence interval: 0.58, 2.18] for men, P = .028). Glycolytic gene expression stratified both men and women, and the combination of low rVFA and low glycolysis identified 19 women with excellent overall survival (P < .001). SETD2 and BAP1 mutations were uniquely enriched in female tumors with high glycolysis (P = .036 and .001, respectively). No significant differences were identified in tumor mutations between patients with high and low rVFA. Conclusion Sex differences in visceral fat and tumor glucose metabolism may provide a new risk-stratification system for patients with clear cell RCC. © RSNA, 2018 Online supplemental material is available for this article.

Purpose To determine the effects of patient age and comorbidity level on life expectancy (LE) benefits associated with imaging follow-up of Bosniak IIF renal cysts and pancreatic side-branch (SB) intraductal papillary mucinous neoplasms (IPMNs). Materials and Methods A decision-analytic Markov model to evaluate LE benefits was developed. Hypothetical cohorts with varied age (60-80 years) and comorbidities (none, mild, moderate, or severe) were evaluated. For each finding, LE projections from two strategies were compared: imaging follow-up and no imaging follow-up. Under follow-up, it was assumed that cancers associated with the incidental finding were successfully treated before they spread. For patients without follow-up, mortality risks from Bosniak IIF cysts (renal cell carcinoma) and SBIPMNs (pancreatic ductal adenocarcinoma) were incorporated. Model assumptions and parameter uncertainty were evaluated in sensitivity analysis. Results In the youngest, healthiest cohorts (age, 60 years; no comorbidities), projected LE benefits from follow-up were as follows: Bosniak IIF cyst, 6.5 months (women) and 5.8 months (men); SBIPMN, 6.4 months (women) and 5.3 months (men). Follow-up of Bosniak IIF cysts in 60-year-old women with severe comorbidities yielded a LE benefit of 3.9 months; in 80-year-old women with no comorbidities, the benefit was 2.8 months, and with severe comorbidities the benefit was 1.5 months. Similar trends were observed in men and for SBIPMN. Results were sensitive to the performance of follow-up for cancer detection; malignancy risks; and stage at presentation of malignant, unfollowed Bosniak IIF cysts. Conclusion With progression of age and comorbidity level, follow-up of low-risk incidental findings yields increasingly limited benefits for patients. © RSNA, 2018 Online supplemental material is available for this article.

Purpose To assess the diagnostic performance and interreader agreement of a standardized diagnostic algorithm in determining the histologic type of small (≤4 cm) renal masses (SRMs) with multiparametric magnetic resonance (MR) imaging. Materials and Methods This single-center retrospective HIPAA-compliant institutional review board-approved study included 103 patients with 109 SRMs resected between December 2011 and July 2015. The requirement for informed consent was waived. Presurgical renal MR images were reviewed by seven radiologists with diverse experience. Eleven MR imaging features were assessed, and a standardized diagnostic algorithm was used to determine the most likely histologic diagnosis, which was compared with histopathology results after surgery. Interreader variability was tested with the Cohen κ statistic. Regression models using MR imaging features were used to predict the histopathologic diagnosis with 5% significance level. Results Clear cell renal cell carcinoma (RCC) and papillary RCC were diagnosed, with sensitivities of 85% (47 of 55) and 80% (20 of 25), respectively, and specificities of 76% (41 of 54) and 94% (79 of 84), respectively. Interreader agreement was moderate to substantial (clear cell RCC, κ = 0.58; papillary RCC, κ = 0.73). Signal intensity (SI) of the lesion on T2-weighted MR images and degree of contrast enhancement (CE) during the corticomedullary phase were independent predictors of clear cell RCC (SI odds ratio [OR]: 3.19; 95% confidence interval [CI]: 1.4, 7.1; P = .003; CE OR, 4.45; 95% CI: 1.8, 10.8; P < .001) and papillary RCC (CE OR, 0.053; 95% CI: 0.02, 0.2; P < .001), and both had substantial interreader agreement (SI, κ = 0.69; CE, κ = 0.71). Poorer performance was observed for chromophobe histology, oncocytomas, and minimal fat angiomyolipomas, (sensitivity range, 14%-67%; specificity range, 97%-99%), with fair to moderate interreader agreement (κ range = 0.23-0.43). Segmental enhancement inversion was an independent predictor of oncocytomas (OR, 16.21; 95% CI: 1.0, 275.4; P = .049), with moderate interreader agreement (κ = 0.49). Conclusion The proposed standardized MR imaging-based diagnostic algorithm had diagnostic accuracy of 81% (88 of 109) and 91% (99 of 109) in the diagnosis of clear cell RCC and papillary RCC, respectively, while achieving moderate to substantial interreader agreement among seven radiologists. © RSNA, 2018 Online supplemental material is available for this article.

Characterization of renal tumors is critical to determine the best therapeutic approach and improve overall patient survival. Because of increased use of high-resolution cross-sectional imaging in clinical practice, renal masses are being discovered with increased frequency. As a result, accurate imaging characterization of these lesions is more important than ever. However, because of the wide array of imaging features encountered as well as overlapping characteristics, identifying reliable imaging criteria for differentiating malignant from benign renal masses remains a challenge. Multiparametric magnetic resonance (MR) imaging based on various anatomic and functional parameters has an important role and adds diagnostic value in detection and characterization of renal masses. MR imaging may allow distinction of benign solid renal masses from several renal cell carcinoma (RCC) subtypes, potentially suggest the histologic grade of a neoplasm, and play an important role in ensuring appropriate patient management to avoid unnecessary surgery or other interventions. It is also a useful noninvasive imaging tool for patients who undergo active surveillance of renal masses and for follow-up after treatment of a renal mass. The purpose of this article is to review the characteristic MR imaging features of RCC and common benign renal masses and propose a diagnostic imaging approach to evaluation of solid renal masses using multiparametric MR imaging. © RSNA, 2017.

For the past decade, advanced renal cell carcinoma (RCC) has been at the forefront of oncologic innovation. Our rapidly evolving understanding of the molecular and genetic basis of RCC has revolutionized the management of advanced RCC; 10 novel molecular targeted agents and immune checkpoint inhibitor have received U.S. Food and Drug Administration approval for treatment of advanced RCC in a little over a decade. Amid this progress, imaging has assumed a central role in metastatic surveillance and follow-up of advanced RCC. State-of-the-art knowledge of the molecular basis of RCC and its treatment and imaging will help ensure that the radiology community remains relevant and central in the care of patients with advanced RCC. This article will review developments in management of advanced RCC from a radiologist's perspective to highlight our clinical role. It will describe how the underlying molecular mechanisms of RCC provide specific targets for novel anticancer agents. The relationship between the mechanisms of action of these novel anticancer agents and the imaging appearance of tumor response will be discussed, along with the available tumor response criteria and their strengths and weaknesses, thus assisting radiologists in response assessment in the setting of clinical trials or routine practice. The class- and drug-specific toxicities and complications associated with the novel anticancer agents will be summarized, since these are frequently missed or misinterpreted and require the radiologist's input in prompt detection and management. The potential role of radiogenomics and texture analysis in the management of advanced RCC will also be discussed. © RSNA, 2017.

Purpose To evaluate the effects of tumor complexity and technique on early and midterm oncologic efficacy and rate of complications for 100 consecutive biopsy-proved stage T1a renal cell carcinomas (RCCs) treated with percutaneous microwave ablation. Materials and Methods This HIPAA-compliant, single-center retrospective study was approved by the institutional review board. The requirement to obtain informed consent was waived. Ninety-six consecutive patients (68 men, 28 women; mean age, 66 years ± 9.4) with 100 stage T1a N0M0 biopsy-proved RCCs (median diameter, 2.6 cm ± 0.8) underwent percutaneous microwave ablation between March 2011 and June 2015. Patient and procedural data were collected, including body mass index, comorbidities, tumor histologic characteristics and grade, RENAL nephrometry score, number of antennas, generator power, and duration of ablation. Technical success, local tumor progression, and presence of complications were assessed at immediate and follow-up imaging. The Kaplan-Meier method was used for survival analyses. Results Technical success was achieved for all 100 tumors (100%), including 47 moderately and five highly complex RCCs. Median clinical and imaging follow-up was 17 months (range, 0-48 months) and 15 months (range, 0-44 months), respectively. No change in estimated glomerular filtration rate was noted after the procedure (P = .49). There were three (3%) procedure-related complications and six (6%) delayed complications, all urinomas. One case of local tumor progression (1%) was identified 25 months after the procedure. Three-year local progression-free survival, cancer-specific survival, and overall survival were 88% (95% confidence interval: 0.52%, 0.97%), 100% (95% confidence interval: 1.0%, 1.0%), and 91% (95% confidence interval: 0.51%, 0.99%), respectively. Conclusion Percutaneous microwave ablation is an effective and safe treatment option for stage T1a RCC, regardless of tumor complexity. Long-term follow-up is needed to establish durable oncologic efficacy and survival relative to competing ablation modalities and surgery. © RSNA, 2017.

Purpose To evaluate the performance of the radius, exophytic or endophytic, nearness to collecting system or sinus, anterior or posterior, and location relative to polar lines (RENAL) nephrometry and preoperative aspects and dimensions used for anatomic classification (PADUA) scoring systems and other tumor biometrics for prediction of local tumor recurrence in patients with renal cell carcinoma after thermal ablation. Materials and Methods This HIPAA-compliant study was performed with a waiver of informed consent after institutional review board approval was obtained. A retrospective evaluation of 207 consecutive patients (131 men, 76 women; mean age, 71.9 years ± 10.9) with 217 biopsy-proven renal cell carcinoma tumors treated with thermal ablation was conducted. Serial postablation computed tomography (CT) or magnetic resonance (MR) imaging was used to evaluate for local tumor recurrence. For each tumor, RENAL nephrometry and PADUA scores were calculated by using imaging-derived tumor morphologic data. Several additional tumor biometrics and combinations thereof were also measured, including maximum tumor diameter. The Harrell C index and hazard regression techniques were used to quantify associations with local tumor recurrence. Results The RENAL (hazard ratio, 1.43; P = .003) and PADUA (hazard ratio, 1.80; P < .0001) scores were found to be significantly associated with recurrence when regression techniques were used but demonstrated only poor to fair discrimination according to Harrell C index results (C, 0.68 and 0.75, respectively). Maximum tumor diameter showed the highest discriminatory strength of any individual variable evaluated (C, 0.81) and was also significantly predictive when regression techniques were used (hazard ratio, 2.98; P < .0001). For every 1-cm increase in diameter, the estimated rate of recurrence risk increased by 198%. Conclusion Maximum tumor diameter demonstrates superior performance relative to existing tumor scoring systems and other evaluated biometrics for prediction of local tumor recurrence after renal cell carcinoma ablation. © RSNA, 2016.

History A 47-year-old man presented with palpitations and decreased exercise tolerance. A peripheral blood smear revealed anemia, thrombocytopenia, and blast cells, and a diagnosis of acute myeloid leukemia was made. Immunohistochemistry revealed positivity for cluster of differentiation (or CD) markers, which have been reported to be associated with an increased risk of extramedullary leukemic involvement. Thus, contrast material-enhanced computed tomography (CT) of the thorax, abdomen, and pelvis was requested to enable exclusion of any extramedullary extension of leukemia. Unenhanced and contrast-enhanced nephrographic phase CT was performed. Follow-up CT 3 months later showed minimal interval change in the lesion (images not shown).

Purpose To quantify initial changes in the vascular tumor burden (VTB), a measure of the area of vascularized tumor on computed tomographic (CT) images, and predict tumor response to antiangiogenic therapy in patients with metastatic renal cell carcinoma (RCC). Materials and Methods For this institutional review board-approved HIPAA-compliant secondary analysis of a prospective phase III trial, adult patients with digital CT images and metastatic clear-cell RCC treated with sunitinib were included (n = 275). Target lesions were selected by using Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 guidelines, and the CT images obtained after one cycle of sunitinib therapy were evaluated in comparison with baseline images. Tumor-response software was created to quantify tumor metrics (length, area, VTB, and mean attenuation) and automate response assessment. Progression-free survival (PFS) in responders and nonresponders according to VTB criteria was compared by using the Cox proportional hazard ratio (HR). The intraclass correlation coefficient (ICC) was used to assess interobserver agreement among three readers evaluating 28 randomly selected patients. Results VTB criteria nonresponders (n = 120) according to the initial posttherapy CT study were 5.7 times more likely to experience progression of disease (HR = 5.70; 95% confidence interval [CI]: 4.07, 7.97; P < .001) than responders (n = 155). There was not a statistically significant difference in PFS between RECIST nonresponders (n = 255) and responders (n = 20; HR = 1.54; 95% CI: 0.85, 2.77; P = .148). In a patient-level analysis, interobserver agreement was very good for assessing percentage change in length, area, and VTB (ICC = 0.82 [95% CI: 0.67, 0.91], 0.89 [95% CI: 0.79, 0.94], and 0.88 [95% CI: 0.79, 0.94], respectively) but was very poor for assessing percentage change in mean attenuation (ICC = 0.17 [95% CI: -0.05, 0.45]). Conclusion A quantitative CT imaging biomarker designed to measure initial changes in the VTB separated patients into responders and nonresponders, each with significantly different PFS, and showed very good interobserver agreement in patients with metastatic RCC treated with sunitinib. © RSNA, 2016 Online supplemental material is available for this article.

Purpose To retrospectively determine if homogeneous high T1 signal intensity (SI) masses with smooth borders on unenhanced magnetic resonance (MR) images can be characterized as benign. Materials and Methods Institutional review board approval was obtained for this HIPAA-compliant retrospective study, with waiver of informed consent. MR images in 84 patients with hemorrhagic or proteinaceous cysts and 50 patients with renal cell carcinoma (RCC) were evaluated. Sixty-three cysts and 49 RCCs underwent unenhanced computed tomography (CT). SI ratio and CT attenuation were determined. Two radiologists evaluated lesions as follows: score 1, homogeneous with smooth borders; score 2, mildly heterogeneous with mildly lobulated borders; score 3, moderately heterogeneous and irregular borders; and score 4, markedly heterogeneous with markedly irregular borders. Statistical analysis was performed by using multivariable logistic regression, Welch t test, Z test, Fisher-exact test, Shapiro-Wilk test, and receiver operating characteristic curve analysis. A diagnostic criterion was formulated by using classification and regression tree analysis. Results SI ratio and attenuation of hemorrhagic or proteinaceous cysts were significantly higher than those of RCCs (SI ratio: cyst 2.4 ± 0.8, RCC 1.5 ± 0.3; attenuation: cyst 51.9 ± 21.5, RCC: 34.8 ± 10.0). Reader 1 scored morphology of 68 (81%) hemorrhagic or proteinaceous cysts as score 1 on MR images and as score 45 (71%) on CT scans. Reader 2 scored morphology of 59 (70%) hemorrhagic or proteinaceous cysts as score 1 on MR images and as score 43 (68%) on CT scans. Two-step classification tree suggested that homogeneous high T1 SI lesions with smooth borders and SI ratio of greater than 1.6 predict the lesion as benign cysts. Similar algorithm for CT suggested threshold of 51 HU. Increasing threshold to 2.5 for SI ratio and 66 for Hounsfield units resulted in 99.9% confidence for characterizing benign cysts. Conclusion The retrospective assessment shows that morphologic assessment and SI quantification on unenhanced T1-weighted MR images can be used to differentiate benign hemorrhagic or proteinaceous cysts from RCC, although prospective assessment will be needed to confirm these results. (©) RSNA, 2016.

Purpose: To investigate whether dual-energy multidetector row computed tomographic (CT) imaging with iodine quantification is able to distinguish between clear cell and papillary renal cell carcinoma ( RCC renal cell carcinoma ) subtypes., Materials and Methods: In this retrospective, HIPAA-compliant, institutional review board-approved study, 88 patients (57 men, 31 women) with diagnosis of either clear cell or papillary RCC renal cell carcinoma at pathologic analysis, who underwent contrast material-enhanced dual-energy nephrographic phase study between December 2007 and June 2013, were included. Five readers, blinded to pathologic diagnosis, independently evaluated all cases by determining the lesion iodine concentration on color-coded iodine maps. The receiving operating characteristic curve analysis was adopted to estimate the optimal threshold for discriminating between clear cell and papillary RCC renal cell carcinoma , and results were validated by using a leave-one-out cross-validation. Interobserver agreement was assessed by using an intraclass correlation coefficient. The correlation between tumor iodine concentration and tumor grade was investigated., Results: A tumor iodine concentration of 0.9 mg/mL represented the optimal threshold to discriminate between clear cell and papillary RCC renal cell carcinoma , and it yielded the following: sensitivity, 98.2% (987 of 1005 [95% confidence interval: 97.7%, 98.7%]); specificity, 86.3% (272 of 315 [95% confidence interval: 85.0%, 87.7%]); positive predictive value, 95.8% (987 of 1030 [95% confidence interval: 95.0%, 96.6%]); negative predictive value, 93.7% (272 of 290 [95% confidence interval: 92.8%, 94.7%]); overall accuracy of 95.3% (1259 of 1320 [95% confidence interval: 94.6%, 96.2%]), with an area under the curve of 0.923 (95% confidence interval: 0.913, 0.933). An excellent agreement was found among the five readers in measured tumor iodine concentration (intraclass correlation coefficient, 0.9990 [95% confidence interval: 0. 9987, 0.9993). A significant correlation was found between tumor iodine concentration and tumor grade for both clear cell (τ = 0.85; P < .001) and papillary RCC renal cell carcinoma (τ = 0.53; P < .001)., Conclusion: Dual-energy multidetector CT with iodine quantification can be used to distinguish between clear cell and papillary RCC renal cell carcinoma , and it provides insights regarding the tumor grade., (© RSNA, 2014.)

Purpose: To compare revised Choi criteria that incorporate concurrent size and attenuation changes at early follow-up imaging with Response Evaluation Criteria in Solid Tumors ( RECIST Response Evaluation Criteria in Solid Tumors ) 1.1 and original Choi criteria in stratification of clinical outcomes in patients with metastatic renal cell carcinoma ( mRCC metastatic renal cell carcinoma ) treated with sunitinib., Materials and Methods: Institutional review board approved this retrospective study and waived informed consent. Baseline and first follow-up computed tomographic scans in 69 patients (50 men, 19 women; mean age, 60.3 years; range, 19-83 years) with mRCC metastatic renal cell carcinoma treated with sunitinib from October 1, 2008, to March 1, 2013, were evaluated for tumor response by using RECIST Response Evaluation Criteria in Solid Tumors 1.1, original Choi criteria, and revised Choi criteria. Correlations with overall survival ( OS overall survival ) and progression-free survival ( PFS progression-free survival ) were compared and stratified according to each radiologic criteria with Kaplan-Meier and multivariate Cox regression analysis., Results: Median follow-up time was 29.7 months (95% confidence interval [ CI confidence interval ]: 18.9, 45.9). Response according to revised Choi criteria was independently correlated with OS overall survival (hazard ratio, 0.47 [95% CI confidence interval : 0.23, 0.99]; P = .046) and PFS progression-free survival (hazard ratio, 0.53 [95% CI confidence interval : 0.29, 0.99]; P = .047). Response according to RECIST Response Evaluation Criteria in Solid Tumors was not significantly correlated with OS overall survival (hazard ratio, 0.65 [95% CI confidence interval : 0.27, 1.58]; P = .344) or PFS progression-free survival (hazard ratio, 0.89 [95% CI confidence interval : 0.42, 1.91]; P = .768). Response according to original Choi criteria was not significantly correlated with OS overall survival (hazard ratio, 0.60 [95% CI confidence interval : 0.32, 1.11]; P = .106) or PFS progression-free survival (hazard ratio, 0.59 [95% CI confidence interval : 0.34, 1.02]; P = .060). Median OS overall survival and PFS progression-free survival in responders according to revised Choi criteria was 39.4 months (95% CI confidence interval : 9.1, upper limit not estimated) and 13.7 months (95% CI confidence interval : 6.4, 24.6), respectively, compared with 12.8 months (95% CI confidence interval : 8.7, 18.0) and 5.3 months (95% CI confidence interval : 3.9, 8.4), respectively, in nonresponders., Conclusion: Contemporaneous reduction in tumor size and attenuation were correlated with favorable clinical outcomes. Response according to revised Choi criteria showed better correlation with clinical outcomes compared with that according to RECIST Response Evaluation Criteria in Solid Tumors or original Choi criteria in patients with mRCC metastatic renal cell carcinoma treated with sunitinib.

Purpose: To investigate associations between computed tomographic (CT) features of clear cell renal cell carcinoma (RCC) and mutations in VHL, PBRM1, SETD2, KDM5C, or BAP1 genes., Materials and Methods: The institutional review board approved this retrospective, hypothesis-generating study of 233 patients with clear cell RCC and waived the informed consent requirement. The study was HIPAA compliant. Three radiologists independently reviewed pretreatment CT images of all clear cell RCCs without knowledge of their genomic profile. One radiologist measured largest diameter and enhancement parameters of each clear cell RCC. Associations between CT features and mutations in VHL, PBRM1, SETD2, KDM5C, and BAP1 genes were tested by using the Fisher exact test. Associations between mutations and size and enhancement were assessed by using the independent t test. Interreader agreement was calculated by using the Fleiss κ., Results: Mutation frequencies among clear cell RCCs were as follows: VHL, 53.2% (124 of 233); PBRM1, 28.8% (67 of 233); SETD2, 7.3% (17 of 233); KDM5C, 6.9% (16 of 233); and BAP1, 6.0% (14 of 233). Mutations of VHL were significantly associated with well-defined tumor margins (P = .013), nodular tumor enhancement (P = .021), and gross appearance of intratumoral vascularity (P = .018). Mutations of KDM5C and BAP1 were significantly associated with evidence of renal vein invasion (P = .022 and .046, respectively). The genotype of solid clear cell RCC differed significantly from the genotype of multicystic clear cell RCC. While mutations of SETD2, KDM5C, and BAP1 were absent in multicystic clear cell RCC, mutations of VHL (P = .016) and PBRM1 (P = .017) were significantly more common among solid clear cell RCC. Interreader agreement for CT feature assessments ranged from substantial to excellent (κ = 0.791-0.912)., Conclusion: This preliminary radiogenomics analysis of clear cell RCC revealed associations between CT features and underlying mutations that warrant further investigation and validation., (©RSNA, 2013)

Recent advances in treatment of metastatic renal cell carcinoma (RCC), such as new molecular therapies that use novel antiangiogenic agents, have led to revision of the most frequently used guideline to evaluate tumor response to therapy: Response Evaluation Criteria in Solid Tumors (RECIST 1.1). Assessment of the response of metastatic RCC to therapy has traditionally been based on changes in target lesion size. However, the mechanism of action of newer antiangiogenic therapies is more cytostatic than cytotoxic, which leads to disease stabilization rather than to tumor regression. This change in tumor response makes RECIST 1.1--a system whose criteria are based exclusively on tumor size--inadequate to discriminate patients with early tumor progression from those with more progression-free disease and prolonged survival. New criteria such as changes in attenuation, morphology, and structure, as seen at contrast-enhanced multidetector computed tomography (CT), are being incorporated into new classifications used to assess response of metastatic RCC to antiangiogenic therapies. The new classifications provide better assessments of tumor response to the new therapies, but they have some limitations. The authors provide a practical review of these systems--the Choi, modified Choi, and Morphology, Attenuation, Size, and Structure (MASS) criteria--by explaining their differences and limitations that may influence the feasibility and reproducibility of these classifications. The authors review the use of multidetector CT in the detection of metastatic RCC and the different appearances and locations of these lesions. They also provide an overview of the new antiangiogenic therapies and their mechanisms of action and a brief introduction to functional imaging techniques. Functional imaging techniques, especially dynamic contrast-enhanced CT, seem promising for assessing response of metastatic RCC to treatment. Nonetheless, further studies are needed before functional imaging can be used in routine clinical practice.

Purpose: To determine whether enhancement at multiphasic multidetector computed tomography (CT) can help differentiate clear cell renal cell carcinoma (RCC) from oncocytoma, papillary RCC, and chromophobe RCC., Materials and Methods: With institutional review board approval for this HIPAA-compliant retrospective study, the pathology database was queried to derive a cohort of 298 cases of RCC and oncocytoma with preoperative multiphasic multidetector CT with as many as four phases (unenhanced, corticomedullary, nephrographic, and excretory). A total of 170 clear cell RCCs, 57 papillary RCCs, 49 oncocytomas, and 22 chromophobe RCCs were evaluated for multiphasic enhancement and compared by using t tests. Cutoff analysis was performed to determine optimal threshold levels to discriminate among the four groups., Results: Mean enhancement of clear cell RCCs and oncocytomas peaked in the corticomedullary phase; mean enhancement of papillary and chromophobe RCCs peaked in the nephrographic phase. Enhancement of clear cell RCCs was greater than that of oncocytomas in the corticomedullary (125 HU vs 106 HU, P = .045) and excretory (80 HU vs 67 HU, P = .034) phases. Enhancement of clear cell RCCs was greater than that of papillary RCCs in the corticomedullary (125 HU vs 54 HU, P < .001), nephrographic (103 HU vs 64 HU, P < .001), and excretory (80 HU vs 54 HU, P < .001) phases. Enhancement of clear cell RCCs was greater than that of chromophobe RCCs in the corticomedullary (125 HU vs 74 HU, P < .001) and excretory (80 HU vs 60 HU, P = .008) phases. Thresholding of enhancement helped to discriminate clear cell RCC from oncocytoma, papillary RCC, and chromophobe RCC with accuracies of 77% (83 of 108 cases), 85% (101 of 119 cases), and 84% (81 of 97 cases)., Conclusion: Enhancement at multiphasic multidetector CT, if prospectively validated, may assist in the discrimination of clear cell RCC from oncocytoma, papillary RCC, and chromophobe RCC., (© RSNA, 2013.)

Purpose: To retrospectively review intermediate-term (median, 20.1 months) clinical outcomes after microwave ablation (MWA) of renal cell carcinoma (RCC)., Materials and Methods: This retrospective study was approved by the institutional review board. The results from 46 patients with 49 RCC nodules (diameter, 0.6-7.7 cm; mean, 3.0 cm ± 1.5 [standard deviation]) treated with ultrasonography (US)-guided percutaneous MWA with cooled-shaft needle antenna from April 2006 to December 2010 were reviewed. One antenna was used for tumors smaller than 2 cm; two, for tumors 2 cm or larger. The patients were followed up with contrast material-enhanced US and computed tomography or magnetic resonance imaging at 1, 3, and 6 months and every 6 months thereafter. The effect of changes in key parameters (including overall survival, disease-free survival, and local tumor progression rate) was statistically analyzed by using the log-rank test., Results: Technical effectiveness (complete ablation at follow-up enhanced imaging 1 month after MWA) was achieved in 48 of 49 (98.0%) tumors, and the metastasis-free rate was 100% (46 of 46). The 1-, 2-, and 3-year local tumor progression rates were 4.6%, 7.7%, and 7.7%, respectively. The cancer-specific survival rate was 100% (46 of 46), and 1-, 2-, and 3-year overall survival rates were 100%, 100%, and 97.8%, respectively. The 1-, 2-, and 3-year disease-free survival rates were 95.4%, 92.3%, and 92.3%, respectively. No major complications occurred. Multivariate analysis showed that tumor number (P = .046), tumor growth patterns (P = .003), and ablation time (P = .04) were independent unfavorable prognostic factors., Conclusion: In the intermediate term, US-guided percutaneous MWA appears to be a safe and effective technique for the management of RCC, especially small RCC, in selected patients.

Purpose: To evaluate clinical outcomes, pathologic subtypes, metastatic disease rate, and clinical features associated with malignancy in Bosniak category IIF and III cystic renal lesions., Materials and Methods: This retrospective study was institutional review board approved and HIPAA compliant. Informed consent was waived. Radiology and hospital information systems were searched for Bosniak IIF and Bosniak III lesions in computed tomographic (CT) reports from January 1, 1994 to August 31, 2009. Patients 18 years and older with unenhanced and contrast material-enhanced CT results and with lesions either surgically resected or with 1 year or more of surveillance were included. Data recorded were history of renal cell carcinoma, number of renal lesions, presence of a coexistent solid renal mass, surgical pathologic findings, and presence of metastatic disease from a renal malignancy. Sixty-two patients with 69 Bosniak IIF lesions and 131 patients with 144 Bosniak III lesions were identified. Proportions from independent groups were compared by using the Fisher exact test; continuous variables were compared by using a two-tailed two-sample t test or a Wilcoxon two-sample test., Results: The malignancy rate of resected Bosniak IIF lesions was 25% (four of 16) and that for Bosniak III lesions was 54% (58 of 107) (P = .03). Thirteen percent (nine of 69) of Bosniak IIF lesions progressed at follow-up, and 50% (four of eight) of these resected cysts were malignant. History of primary renal malignancy, coexisting Bosniak category IV lesion and/or solid renal mass, and multiplicity of Bosniak III lesions were each associated with an increased malignancy rate in Bosniak III lesions. No patients developed locally advanced or metastatic disease from a Bosniak IIF or III lesion., Conclusion: Although the malignancy rate in surgically excised Bosniak IIF and Bosniak III cystic renal lesions was 25% and 54%, respectively, in our study, the malignancy rate was higher in patients with a history of primary renal malignancy or coexisting Bosniak IV lesion and/or solid renal neoplasm., (© RSNA, 2011.)

Purpose: To determine whether imaging characteristics at multiphasic multidetector computed tomography (CT) correlate with common karyotypic abnormalities in patients with clear cell renal cell carcinomas (ccRCCs)., Materials and Methods: Institutional review board approval was obtained, and informed consent was waived for this HIPAA-compliant retrospective study. From January 2000 through September 2007, the prenephrectomy multiphasic (corticomedullary, nephrographic, and excretory phases), multidetector helical CT images of 58 histologically proved and karyotyped ccRCCs were reviewed by two readers with experience in abdominal imaging. Imaging features assessed included degree of attenuation, contour, and presence of calcifications and neovascularity. These features were independently correlated with specific karyotypic abnormalities on the resected specimens. Degree of attenuation data were analyzed with logistic regression for significance (P < .05), and morphologic characteristics were analyzed with odds ratios for assessing their diagnostic power., Results: On unenhanced scans, 7% (two of 28) of ccRCCs with the loss of chromosome 3p were calcified, whereas 37% (11 of 30) of lesions without this anomaly were calcified (odds ratio, 0.13). During the corticomedullary phase, ccRCCs with the loss of chromosome Y enhanced more than those without this anomaly (130.0 vs 102.5 HU, P = .04), and ccRCCs with trisomy 7 enhanced less than those without this anomaly (105.8 vs 139.3 HU, P = .04). During the excretory phase, ccRCCs with trisomy 5 enhanced more than those without this anomaly (115.5 vs 83.4 HU, P = .03)., Conclusion: The genetic makeup of ccRCCs affects their imaging features at multidetector CT examinations. Multidetector CT imaging characteristics may help suggest differences at the cytogenetic level among ccRCCs., (© RSNA, 2011.)

Purpose: To assess changes in tumor computed tomographic (CT) texture after two cycles of treatment with tyrosine kinase inhibitors (TKIs) and to determine if tumor texture correlates with measured time to progression in patients with metastatic renal cell cancer who received TKIs., Materials and Methods: A waiver of institutional review board approval was obtained for this retrospective analysis. Contrast material-enhanced CT texture parameters were assessed in 39 patients with metastatic renal cell cancer who received a TKI. A total of 87 metastases were analyzed at baseline and after two treatment cycles. Changes in tumor entropy and uniformity were derived with a software algorithm that selectively filters and extracts texture at different scales (fine to coarse detail: 1.0-2.5) and were recorded. Response assessment was also obtained by using response evaluation criteria in solid tumors (RECIST), as well as Choi and modified Choi criteria. The correlation of texture parameters and standard criteria with measured time to progression was assessed by using Kaplan-Meier analysis and a Cox regression model. Statistical significance was set at 5%., Results: Tumor entropy decreased by 3%-45% and uniformity increased by 5%-21% for the different scale values after administration of a TKI. With a threshold change of -2% or less for uniformity at a coarse scale value of 2.5, Kaplan-Meier curves of the proportion of patients without disease progression were significantly different and better than those for standard response assessment (P = .008 vs P = .267, P = .053, and P = .042 for RECIST, Choi, and modified Choi criteria, respectively). Cox regression analysis showed that texture uniformity was an independent predictor of time to progression (odds ratio, 4.02; 95% confidence interval: 1.52, 10.65; P = .005)., Conclusion: CT texture analysis reflecting tumor heterogeneity is an independent factor associated with time to progression and has potential as a predictive imaging biomarker of response of metastatic renal cancer to targeted therapy., (© RSNA, 2011.)

Purpose: To develop and implement an evidence-based protocol for characterizing vascular response of renal cell carcinoma (RCC) to targeted therapy by using dynamic contrast material-enhanced (DCE) ultrasonography (US)., Materials and Methods: The study was approved by the institutional research ethics board; written informed consent was obtained from all patients. Seventeen patients (four women; median age, 58 years; range, 42-72 years; 13 men, median age, 62 years; range, 45-81 years) with metastatic RCC were examined by using DCE US before and after 2 weeks of treatment with sunitinib (May 2007 to October 2009). Two contrast agent techniques--bolus injection and disruption-replenishment infusion of microbubbles--were compared. Changes in tumor blood velocity and fractional blood volume were measured with both methods, together with reproducibility and effect of compensation for respiratory motion. Tumor changes were assessed with computed tomography, by using the best response with the Response Evaluation Criteria in Solid Tumors (RECIST) and progression-free survival (PFS). Follow-up RECIST measurements were performed at 6-week intervals until progressive disease was detected., Results: In response to treatment, median tumor fractional blood volume measured with the disruption-replenishment infusion method decreased by 73.2% (interquartile range, 46%-87%) (P < .002), with repeated-measure reproducibility of 9%-15%. Significant decreases were also seen with the bolus method, but with poor correlation of changes in bolus peak (r = 0.46, P = .066) and area under the curve (r = 0.47, P = .058), compared with infusion measurements. Changes in DCE US parameters over 2 weeks did not correlate with PFS and could not be used to predict long-term assessment of best response by using RECIST. Follow-up times ranged 28-501 days; the median was 164 days., Conclusion: DCE US provides reproducible and sensitive assessment of vascular changes in response to antiangiogenic therapy. The disruption-replenishment infusion protocol is a flexible method suitable for many tumor types, but further studies are needed to assess whether this protocol may be predictive of patient outcome., (© RSNA, 2011.)

Purpose: To retrospectively determine the optimal Hounsfield unit threshold and region of interest (ROI) size required to accurately diagnose renal angiomyolipoma (AML) and differentiate it from renal cell carcinoma (RCC)., Materials and Methods: This retrospective study was institutional review board approved and HIPAA compliant, and the requirement for written informed patient consent was waived. The radiologic reports on 4502 dual-phase abdominal computed tomography (CT) examinations (nonenhanced and nephrographic phases, 5-mm collimation, 120-140 kVp, variable milliampere-second settings) performed in 2872 patients from June 2002 through October 2007 were reviewed. Solid-component masses reported as suspicious for RCC or AML were correlated with histologic and/or follow-up imaging findings. ROIs of three different sizes-tiny (8-13 mm(2)), small (19-24 mm(2)), and medium (30-35 mm(2))-were drawn in the lowest-attenuation focus on images obtained during both phases. The test characteristics (sensitivity, specificity, positive predictive value, negative predictive value, false-positive rate, false-negative rate) of multiple attenuation thresholds at each combination of ROI size and contrast enhancement phase were calculated, and receiver operating characteristic (ROC) curves were derived. Areas under the ROC curve were calculated., Results: There were 217 RCCs and 65 AMLs. With an attenuation threshold of -10 HU or lower at nonenhanced CT, RCC would be misdiagnosed as AML in 11 (5.1%) cases, one (0.5%) case, and one (0.5%) case with use of the tiny, small, and medium ROIs, respectively. With use of the tiny, small, and medium ROIs, misdiagnosis rates would be 2.3%, 0.5%, and 0.5%, respectively, at a threshold of -15 HU or lower and 1.8%, 0%, and 0%, respectively, at a threshold of -20 HU or lower. Areas under the ROC curve for the nonenhanced phase images (range, 0.874-0.889) were superior to those for the nephrographic phase images (range, 0.790-0.826)., Conclusion: Nonenhanced CT images were superior to nephrographic phase CT images for the diagnosis of AML. An attenuation threshold of -10 HU or lower with an ROI of at least 19-24 mm(2) is optimal for the diagnosis of AML. This threshold is not accurate with use of smaller (8-13-mm(2)) ROIs.

Purpose: To determine whether tumor perfusion parameters assessed by using dynamic contrast material-enhanced computed tomography (CT) could help predict and detect response in patients receiving antiangiogenic therapy for metastatic renal cell carcinoma., Materials and Methods: Institutional ethics committee approval and informed consent were obtained. In two phase-III trials involving 51 patients with metastatic renal cell carcinoma (38 men, 13 women; age range, 30-80 years) receiving antiangiogenic drugs (sorafenib [n = 10], sunitinib [n = 22]), a placebo (n = 12), or interferon alfa (n = 7), serial dynamic contrast-enhanced CT was performed, during 90 seconds before and after injection of 80 mL of iobitridol. Perfusion parameters of a target metastatic tumor (tumor blood flow [TBF], tumor blood volume [TBV], mean transit time, and vascular permeability-surface area product) were calculated. Values before and after treatment were compared by using a Wilcoxon signed rank test, and relative changes in groups were compared by using the Wilcoxon rank sum test. Results were compared with Response Evaluation Criteria in Solid Tumors response and with progression-free and overall survival by using Kaplan-Meier curves., Results: Among patients receiving antiangiogenic drugs, baseline perfusion parameters were higher in responders than in stable patients (TBF = 245.3 vs 119.5 mL/min/100 mL, P = .04; TBV = 15.5 vs 8.2 mL/100 mL, P = .02) but were not significantly predictive of survival. After the first cycle of treatment, there was a significant decrease in TBF (162.5 vs 76.7 mL/min/100 mL, P = .0002) and TBV (9.1 vs 3.9 mL/100 mL, P < .0001) in patients receiving antiangiogenic treatment., Conclusion: Renal carcinoma perfusion parameters determined with dynamic contrast-enhanced CT can help predict biologic response to antiangiogenic drugs before beginning therapy and help detect an effect after a single cycle of treatment.

Purpose: To retrospectively determine the usefulness of segmental enhancement inversion during the corticomedullary phase (CMP) and early excretory phase (EEP) of biphasic multidetector computed tomography (CT) in differentiating small renal oncocytoma from renal cell carcinoma (RCC)., Materials and Methods: This retrospective study was institutional review board approved; informed consent was waived. Between January 2004 and December 2006, 98 patients with pathologically confirmed renal masses smaller than 4 cm (10 renal oncocytomas and 88 RCCs) were included in this study. Segmental enhancement inversion was defined as follows: In a mass with two segments showing different degrees of enhancement during CMP, the relatively highly enhanced segment became less enhanced during EEP, whereas the less-enhanced segment during CMP became highly enhanced during EEP. Two experienced radiologists retrospectively assessed the presence of segmental inversion in all masses and measured attenuation with consensus. The Fisher exact test was used to determine the significance of segmental enhancement inversion in differentiating small renal oncocytoma from RCC., Results: Eight of 10 renal oncocytomas and only one of 88 RCCs showed segmental inversion during CMP and EEP, which significantly differentiated small renal oncocytomas and RCCs (P < .0001). For differentiating oncocytoma from RCC, segmental inversion was found to have a sensitivity of 80% (eight of 10), a specificity of 99% (87 of 88), a positive predictive value of 89% (eight of nine), and a negative predictive value of 98% (87 of 89). The mean values of the attenuation differences shown by two segments during CMP and EEP were 62.75 HU +/- 36.96 (standard deviation) and -36.88 HU +/- 20.02, respectively., Conclusion: Segmental enhancement inversion during CMP and EEP was found to be a characteristic enhancement pattern of small renal oncocytoma at biphasic multidetector CT and it may help in differentiating small oncocytoma from RCC., Supplemental Material: http://radiology.rsnajnls.org/cgi/content/full/2522081180/DC1.

Papillary renal cell carcinoma (pRCC) is the second most common type of renal cell carcinoma (RCC). pRCC has unique imaging and clinical features that may allow differentiation from clear cell RCC (cRCC). There have been significant advances in our knowledge of the natural history and treatment of pRCC, with data suggesting that it may be best to manage pRCC differently from the other subtypes of RCC. At contrast material-enhanced computed tomography, pRCC enhances less than does cRCC in all phases of contrast-enhanced imaging. The difference in the degree of enhancement between pRCC and cRCC is due to differences in their intratumoral vascularity. In general, if a heterogeneous mass enhances to a degree similar to that manifested by the renal cortex, it is likely to be a cRCC. A mass that enhances to a lesser degree is likely to be a non-clear cell RCC. It is common for metastatic lesions from pRCC to show enhancement characteristics similar to those of the primary tumor and be hypovascular.

Purpose: To retrospectively determine the distribution of growth rates across different sizes and subtypes of renal cortical tumors by assessing tumor volume and maximum tumor diameter at serial volumetric computed tomographic (CT) examinations., Materials and Methods: The institutional review board approved this retrospective, HIPAA-compliant study. Fifty-three of 2304 patients (34 men, 19 women; mean age, 67 years +/- 10 [standard deviation; range, 39-88 years) who underwent nephrectomy from 1989 to 2006 did not receive preoperative chemotherapy or radiation therapy and underwent at least two preoperative contrast material-enhanced CT examinations (at least 3 months apart) with identical section thickness that was no more than one-fifth of longitudinal tumor diameter. Tumor volume and maximum diameter were measured on CT scans. Reciprocal of doubling time (DT) (RDT) was calculated. Analysis of variance and Student t tests were performed., Results: Thirty-two clear cell carcinomas, 10 papillary carcinomas, six chromophobe carcinomas, four oncocytomas, and one angiomyolipoma were analyzed. Median tumor size was 2.9 cm (range, 1-12 cm). Seven tumors did not increase in volume. DT ranged from -78476.54 to 18057.43 days (mean, -1230.73 days; median, 590.51 days). [corrected] Growth rate determined by using maximum diameter ranged from -10.8 to 33.2 mm/y (mean, 5.1 mm/y; median, 3.5 mm/y). Faster-growing tumors were more likely to be clear cell carcinomas, those of higher grade had higher growth rates. No significant correlation was found between RDT and tumor initial volume, subtype, or grade. Small renal tumors (

Purpose: To retrospectively determine if pixel histogram analysis of unenhanced computed tomographic (CT) images can be used to distinguish angiomyolipomas (AMLs) with minimal fat from clear cell renal cell carcinomas (CCRCCs)., Materials and Methods: The human studies committee approved this HIPAA-complaint study, with waiver of informed consent. Patients with pathologically proved AMLs lacking visible macroscopic fat at CT and patients with pathologically proved CCRCCs were included. Lesions were measured, and a histogram (number of pixels with each attenuation) was calculated electronically within a central region of interest. The percentage of pixels below the attenuation thresholds -20 HU and 10 HU was calculated in both cohorts. The unpaired Student t test was used to compare the average percentage of subthreshold pixels at each threshold. P < .05 indicated a significant difference. The number of lesions with more than the selected percentage of subthreshold pixels was calculated in both groups, and the chi(2) test was used to test the significance of differences between cohorts. The area under the receiver operating characteristic (ROC) curve was used to determine if any percentage of subthreshold pixels could be used to differentiate between the two cohorts., Results: There were 22 patients with pathologically proved AMLs lacking visible macroscopic fat on CT images. Tuberous sclerosis affected three of these patients. Mean maximal transverse lesion diameter was 20 mm (range, 11-38 mm). There were 28 patients in the CCRCC comparison group. Mean maximal transverse lesion diameter was 26 mm (range, 15-36 mm). Neither the Student t test (P > .2 for all thresholds <0 HU) nor the chi(2) test (P > .15 for all thresholds <0 HU) revealed a significant difference between cohorts. A lesion with more low-attenuation pixels was significantly more likely to be characterized as CCRCC than as AML with ROC curve analysis., Conclusion: Once AMLs with visible fat on CT images are excluded, pixel histogram analysis cannot be used to distinguish between AMLs and CCRCCs., ((c) RSNA, 2008.)

Purpose: To retrospectively evaluate the diagnostic performance of computed tomographic (CT) histogram analysis for differentiating angiomyolipoma (AML) without visible fat from renal cell carcinoma (RCC) at CT, by using pathologic analysis and clinical diagnosis as the reference standard., Materials and Methods: This retrospective study was approved by the institutional review board; informed consent was waived. The authors reviewed the medical records of 144 patients with pathologic confirmation of RCC or AML (105 men, 39 women; mean age, 52 years). Analysis of unenhanced CT histograms was performed on 34 AMLs without visible fat at CT and 110 size-matched RCCs. The percentages of voxels and pixels were compared in the two groups according to the CT number categories. The diagnostic performance of CT histogram analysis in differentiating AML from RCC was determined by using receiver operating characteristic (ROC) analysis., Results: The percentages of voxels and pixels with a CT number less than -30 HU (2.7% and 3.4% vs 0.1% and 0.0%), less than -20 HU (4.3% and 5.1% vs 0.2% and 0.1%), less than -10 HU (7.0% and 8.1% vs 0.6% and 0.4%), and less than 0 HU (12.0% and 13.9% vs 2.0% and 2.0%) were significantly greater in the AML group than in the RCC group (P < .01), respectively. The area under the ROC curve was as high as 0.706 when a pixel percentage with a CT number less than -10 HU was used as a differentiating parameter. Corresponding to the specificity of 100% for differentiating AML from RCC, the sensitivity was as high as 20% when a pixel percentage of 6% with a CT number less than -10 HU was used as a criterion., Conclusion: CT histogram analysis may be useful for differentiating AML without visible fat from RCC at CT., ((c) RSNA, 2007.)

Purpose: To retrospectively determine if renal cell carcinoma can be differentiated from high-attenuation renal cysts at unenhanced computed tomography (CT) based on Hounsfield unit measurements and heterogeneity., Materials and Methods: The Human Investigation Committee at our institution approved this study with waiver of informed consent. This study was compliant with the HIPAA. Fifty-four pathologically proved renal cell carcinomas in 54 patients (36 men and 18 women; average age, 53 years; range, 23-90 years) and 56 high-attenuation renal cysts in 51 patients (30 men and 21 women; average age, 63 years; range, 28-86 years) were retrospectively evaluated at unenhanced CT. Two independent readers reviewed randomized unenhanced CT images and obtained Hounsfield unit readings of each mass. A subjective determination of lesion heterogeneity was also performed by using a four-point scale (1: homogeneous, 2: mildly heterogeneous, 3: moderately heterogeneous, 4: markedly heterogeneous). Statistical analysis was performed by using Bland-Altman regression tree, classification and regression tree, and Shapiro-Wilk normality test., Results: The average attenuation of cysts for reader 1 was 53.4 HU (range, 23-113 HU) and for reader 2 was 53.8 HU (range, 21-108 HU). The average attenuation of neoplasms for reader 1 was 34.7 HU (range, 21-60 HU) and for reader 2 was 38.4 HU (range, 22-60 HU). For cyst heterogeneity, a score of 1 was given in 55 of 56 (98%) cysts for reader 1 and in 53 of 56 (95%) cysts for reader 2. For neoplasm heterogeneity, a score of 1 was given in 35 of 54 (65%) neoplasms for reader 1 and in 36 of 54 (67%) for reader 2. Given the distribution of cyst and tumor attenuation values and lesion heterogeneity, a homogeneous mass measuring 70 HU or greater at unenhanced CT has a greater than 99.9% chance of representing a high-attenuation renal cyst., Conclusion: The findings from this study may help differentiate high-attenuation renal cysts from renal cell carcinomas at unenhanced CT and may suggest the next appropriate imaging study for definitive characterization.