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The role of imaging in the management of renal masses

      Highlights

      • Multimodality imaging greatly helps in the management of renal masses.
      • Image-guided ablation represents a validated option for small renal masses.
      • Structured renal tumor template report is essential for precise treatment planning.

      Abstract

      The wide availability of cross-sectional imaging is responsible for the increased detection of small, usually asymptomatic renal masses. More than 50 % of renal cell carcinomas (RCCs) represent incidental findings on noninvasive imaging. Multimodality imaging, including conventional US, contrast-enhanced US (CEUS), CT and multiparametric MRI (mpMRI) is pivotal in diagnosing and characterizing a renal mass, but also provides information regarding its prognosis, therapeutic management, and follow-up. In this review, imaging data for renal masses that urologists need for accurate treatment planning will be discussed. The role of US, CEUS, CT and mpMRI in the detection and characterization of renal masses, RCC staging and follow-up of surgically treated or untreated localized RCC will be presented. The role of percutaneous image-guided ablation in the management of RCC will be also reviewed.

      Abbreviations:

      RCC (renal cell carcinoma), CEUS (contrast-enhanced US), mpMRI (multiparametric MRI), AML (angiomyolipoma), ISUP (International Society of Urological Pathology), TNM (Tumor-Node-Metastasis), CECT (contrast-enhanced CT), NPV (negative predictive value), PPV (positive predictive value), DWI (diffusion-weighted imaging), VHL (von Hippel-Lindau), MDT (Multidisciplinary Team Meeting)

      Keywords

      1. Introduction

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      • Nikolaidis P.
      • Preminger G.M.
      • Purysko A.S.
      • Raman S.S.
      • Taffel M.T.
      • Wang Z.J.
      • Weinfeld R.M.
      • Remer E.M.
      • Lockhart M.E.
      ACR appropriateness criteria renal cell carcinoma staging.
      ,
      • van Oostenbrugge T.J.
      • Fütterer J.J.
      • Mulders P.F.A.
      Diagnostic imaging for solid renal tumors: a pictorial review.
      ]. Multiparametric MRI (mpMRI) represents a useful adjuvant tool in the diagnostic armamentarium of renal masses [
      • Lopes Vendrami C.
      • Villavicencio C.P.
      • DeJulio T.J.
      • Chatterjee A.
      • Casalino D.D.
      • Horowitz J.M.
      • Oberlin D.T.
      • Yang G.
      • Nikolaidis P.
      • Miller F.H.
      Differentiation of solid renal tumors with Multiparametric MR imaging.
      ,
      • Cornelis F.
      • Grenier N.
      Multiparametric magnetic resonance imaging of solid renal tumors: a practical algorithm.
      ].
      In this review, we comment on the role of multimodality imaging, including US, CEUS, CT and mpMRI in the management of renal masses. Specifically, the role of imaging modalities in the characterization of cystic renal masses, differentiation between RCC histologic phenotypes and common benign renal tumors, RCC grading, RCC staging and follow-up of treated or untreated localized RCC is reviewed. The role of minimally invasive, image-guided curative management of RCC is addressed. Urologist’s perspective on requirements regarding the radiology report on renal masses is presented.

      2. What the urologist expects from the radiologist

      Despite excellent reported sensitivity and specificity for cross-sectional imaging in the detection of renal masses, occasionally, small (< 2 cm), usually endophytic renal tumors may be missed [
      • Marconi L.
      • Dabestani S.
      • Lam T.B.
      • Hofmann F.
      • Stewart F.
      • Norrie J.
      • Bex A.
      • Bensalah K.
      • Canfield S.E.
      • Hora M.
      • Kuczyk M.A.
      • Merseburger A.S.
      • Mulders P.F.A.
      • Powles T.
      • Staehler M.
      • Ljungberg B.
      • Volpe A.
      Systematic review and meta-analysis of diagnostic accuracy of percutaneous renal tumour biopsy.
      ]. Potential implications for the treating urologist may exist, if a radiology report misses the diagnosis.
      The probability of a renal mass being malignant is inversely proportional to its size. Since more than 50 % of newly diagnosed renal masses are less than 3 cm, it is obvious that the urologist would want to be certain of mass histology, before deciding treatment. Unfortunately, histologic characterization based on imaging criteria alone is not always possible. Understandably, this is a difficult task, since even renal tumor biopsy can be nondiagnostic in up to 8 % of cases, in centers of excellence [
      • Marconi L.
      • Dabestani S.
      • Lam T.B.
      • Hofmann F.
      • Stewart F.
      • Norrie J.
      • Bex A.
      • Bensalah K.
      • Canfield S.E.
      • Hora M.
      • Kuczyk M.A.
      • Merseburger A.S.
      • Mulders P.F.A.
      • Powles T.
      • Staehler M.
      • Ljungberg B.
      • Volpe A.
      Systematic review and meta-analysis of diagnostic accuracy of percutaneous renal tumour biopsy.
      ]. Fat-poor AMLs, small papillary RCCs and renal oncocytomas pose a diagnostic challenge to both radiologists and pathologists.
      Imaging is cardinal for RCC staging. Table 1 shows the RCC Tumor-Node-Metastasis (TNM) classification system [
      • Ljungberg B.
      • Albiges L.
      • Abu-Ghanem Y.
      • Bensalah K.
      • Dabestani S.
      • Fernández-Pello S.
      • Giles R.H.
      • Hofmann F.
      • Hora M.
      • Kuczyk M.A.
      • Kuusk T.
      • Lam T.B.
      • Marconi L.
      • Merseburger A.S.
      • Powles T.
      • Staehler M.
      • Tahbaz R.
      • Volpe A.
      • Bex A.
      European association of urology guidelines on renal cell carcinoma: the 2019 update.
      ,
      ]. The upper limit of the inferior vena cava neoplastic thrombus guides surgery, since a thrombus reaching the thorax and heart requires cardiothoracic surgeons and special anesthetic requirements. Exact regional lymph node extension mapping will help the surgeon remove palpable lymph nodes. Removal of the ipsilateral adrenal gland is probable if imaging implies invasion by the neighboring tumor. Number, size, and location of distant metastases will predict technical feasibility of metastasectomy and help decide whether to proceed or not with cytoreductive nephrectomy [
      • Ljungberg B.
      • Albiges L.
      • Abu-Ghanem Y.
      • Bensalah K.
      • Dabestani S.
      • Fernández-Pello S.
      • Giles R.H.
      • Hofmann F.
      • Hora M.
      • Kuczyk M.A.
      • Kuusk T.
      • Lam T.B.
      • Marconi L.
      • Merseburger A.S.
      • Powles T.
      • Staehler M.
      • Tahbaz R.
      • Volpe A.
      • Bex A.
      European association of urology guidelines on renal cell carcinoma: the 2019 update.
      ].
      Table 1RCC TNM classification system [
      ].
      T - Primary Tumor
      TX Primary tumor cannot be assessed
      T0 No evidence of primary tumor
      T1 Tumor ≤ 7 cm in greatest diameter, limited to the kidney
       T1a Tumor ≤ 4 cm
       T1b Tumor > 4 cm but ≤ 7 cm
      T2 Tumor > 7 cm in greatest diameter, limited to the kidney
       T2a Tumor > 7 cm but ≤ 10 cm
       T2b Tumor > 10 cm, limited to the kidney
      T3 Tumor extends into major veins or perinephric tissues, but not to the ipsilateral adrenal gland and not beyond Gerota’s fascia
       T3a Tumor grossly extends into the renal vein or its segmental (muscle-containing) branches, or invades perirenal and/or renal sinus fat, but not beyond Gerota’s fascia
       T3b Tumor grossly extends into inferior vena cava below diaphragm
       T3c Tumor grossly extends into inferior vena cava above the diaphragm or invades the wall of the vena cava
      T4 Tumor invades beyond Gerota’s fascia (including contiguous extension into the ipsilateral adrenal gland)
      N - Regional Lymph Nodes
      NX Regional lymph nodes cannot be assessed
      N0 No regional lymph node metastasis
      N1 Metastasis in regional lymph node(s)
      M - Distant Metastasis
      M0 No distant metastasis
      M1 Distant metastasis
      Although a tumor size of 4 cm is the accepted limit for partial nephrectomy, other factors may allow partial resection of a larger tumor or dictate radical removal of a smaller one. Therefore, information regarding the relationship of the tumor to the collecting system, its vicinity to the renal hilum and the endophytic or exophytic nature of the tumor, may define the difficulty of performing partial nephrectomy. Imaging plays an important role in providing the above information, predicting the forthcoming difficulties of such surgery.
      Various nephrometry scores (RENAL, Padua, c-index) have been used to quantify this expected difficulty [
      • Shi N.
      • Zu F.
      • Shan Y.
      • Chen S.
      • Xu B.
      • Du M.
      • Chen M.
      The value of renal score in both determining surgical strategies and predicting complications for renal cell carcinoma: a systematic review and meta-analysis.
      ]. The RENAL nephrometry score, assigns tumor with a score depending on points gathered from the (R)adius of the tumor, the (E)xophytic/endophytic nature, the (N)earness to the collecting system or sinus, the (A)nterior(a)/posterior(p) descriptor, and the (L)ocation relative to the polar line. Various publications have confirmed correlation of RENAL nephrometry score with surgical decision making, surgical complications, postoperative functional outcomes, histologic factors such as stage, grade, and cancer-specific survival rates [
      • Shi N.
      • Zu F.
      • Shan Y.
      • Chen S.
      • Xu B.
      • Du M.
      • Chen M.
      The value of renal score in both determining surgical strategies and predicting complications for renal cell carcinoma: a systematic review and meta-analysis.
      ].
      During partial nephrectomy, renal tumor must be identified and resected. This requires removal of the perinephric fat, which can sometimes be tedious. Imaging may predict this difficulty by measuring perinephric fat thickness, particularly medial and posterior perinephric fat, and reporting perinephric fat stranding [
      • Lee S.M.
      • Robertson I.
      • Stonier T.
      • Simson N.
      • Amer T.
      • Aboumarzouk O.M.
      Contemporary outcomes and prediction of adherent perinephric fat at partial nephrectomy: a systematic review.
      ]. Of equal importance is the position of the kidney in relation to the thoracic cage, especially for open surgery. Information regarding vascular anatomy, and specifically, the origin, number, division, and course of renal arteries and veins is also essential [
      • Alsaikhan N.
      • Alshehri W.
      • Cassidy F.
      • Aganovic L.
      • Vahdat N.
      Renal tumor structured reporting including nephrometry score and beyond: what the urologist and interventional radiologist need to know.
      ].
      Imaging provides a plethora of information to the urologist necessary for treatment planning, therefore, the radiology report is invaluable and should be provided, preferably in a structured format (Table 2) [
      • Alsaikhan N.
      • Alshehri W.
      • Cassidy F.
      • Aganovic L.
      • Vahdat N.
      Renal tumor structured reporting including nephrometry score and beyond: what the urologist and interventional radiologist need to know.
      ].
      Table 2Suggested CT report template for preoperative assessment of solid renal masses, suspected or proven to represent RCC [
      • Alsaikhan N.
      • Alshehri W.
      • Cassidy F.
      • Aganovic L.
      • Vahdat N.
      Renal tumor structured reporting including nephrometry score and beyond: what the urologist and interventional radiologist need to know.
      ].
      Kidney unit with tumor
      Nephrometry score
      • Tumor radius (cm)
      • Exophytic > 50%, Exophytic < 50%, Endophytic
      • Distance to the collecting system [> 7, 4-7, < 4] (mm)
      • Location: Anterior/Posterior (A/P/X)
      • Location regarding to the Polar lines (above/below/cross/ between)
      • Extension into renal vein
      Extrarenal structures adjacent to the lesion (distance to the nearest anatomic structure and renal hilar vasculature)
      Perinephric fat stranding
      Amount of perinephric visceral fat [scant/abundant]
      Extension of tumor into perirenal fat, pararenal fascia, adrenal gland
      Kidney location [standard, high, low, ectopic]
      Kidney size
      Collecting system [standard, duplicated]
      Vessels
      • distance of main renal artery origin to the first branch and to the renal hilum
      • accessory renal arteries
      • length from inferior vena cava to right renal hilum
      • length from aortic edge to the left hilum
      • accessory renal veins
      Parenchymal variant anatomy [standard, dromendary humb, fetal lobulation, column of Bertin, renal cleft, congenital fusion/rotation]
      Benign pathology [cysts, stones/calcifications, scars, AML]
      Contralateral kidney
      Kidney size
      Enhancement [normal, delayed]
      Pathology [cysts, stones/calcifications, scars, AML]
      Other
      Regional lymphadenopathy [location, size, correlation with large vessels]
      Distant metastases

      3. Ultrasonography/contrast-enhanced ultrasonography

      Ultrasonography represents the first-line imaging modality for the investigation of suspected renal disease [
      • Bertolotto M.
      • Bucci S.
      • Valentino M.
      • Currò F.
      • Sachs C.
      • Cova M.A.
      Contrast-enhanced ultrasound for characterizing renal masses.
      ,
      • Siddaiah M.
      • Krishna S.
      • McInnes M.D.F.
      • Quon J.S.
      • Shabana W.M.
      • Papadatos D.
      • Schieda N.
      Is Ultrasound Useful for Further Evaluation of Homogeneously Hyperattenuating Renal Lesions Detected on CT?.
      ,
      • Burgan C.M.
      • Rupan Sanyal R.
      • Lockhart M.E.
      Ultrasound of renal masses.
      ,
      • Sidhu P.S.
      • Cantisani V.
      • Dietrich C.F.
      • Gilja O.H.
      • Saftoiu A.
      • Bartels E.
      • Bertolotto M.
      • Calliada F.
      • Clevert D.
      • Cosgrove D.
      • Deganello A.
      • D’Onofrio M.
      • Drudi F.M.
      • Freeman S.
      • Harvey C.
      • Jenssen C.
      • Jung E.
      • Klauser A.S.
      • Lassau N.
      • Meloni M.F.
      • Leen E.
      • Nicolau C.
      • Nolsoe C.
      • Piscaglia F.
      • Prada F.
      • Prosch H.
      • Radzina M.
      • Savelli L.
      • Weskott H.
      • Wijkstra H.
      The EFSUMB Guidelines and Recommendations for the Clinical Practice of Contrast-Enhanced Ultrasound (CEUS) in Non-Hepatic Applications: Update 2017 (Long Version).
      ]. US may reliably differentiate between cystic and solid renal lesions and may characterize minimally complex renal cysts [
      • Burgan C.M.
      • Rupan Sanyal R.
      • Lockhart M.E.
      Ultrasound of renal masses.
      ]. US is recommended for the assessment of indeterminate homogeneous, hyperdense renal masses, incidentally found at CT, measuring 20-70HU on unenhanced images or more than 20HU on single-phase contrast-enhanced images [
      • Expert Panel on Urologic Imaging
      • Wang Z.J.
      • Nikolaidis P.
      • Khatri G.
      • Dogra V.S.
      • Ganeshan D.
      • Goldfarb S.
      • Gore J.L.
      • Gupta R.T.
      • Hartman R.P.
      • Heilbrun M.E.
      • Lyshchik A.
      • Purysko A.S.
      • Savage S.J.
      • Smith A.D.
      • Wolfman D.J.
      • Wong-You-Cheong J.J.
      • Lockhart M.E.
      ACR appropriateness criteria® indeterminate renal mass.
      ]. These lesions often represent benign hemorrhagic/proteinaceous cysts and can be safely characterized with US, with a reported sensitivity and specificity of 81.8 % and 92.9 %, respectively [
      • Siddaiah M.
      • Krishna S.
      • McInnes M.D.F.
      • Quon J.S.
      • Shabana W.M.
      • Papadatos D.
      • Schieda N.
      Is Ultrasound Useful for Further Evaluation of Homogeneously Hyperattenuating Renal Lesions Detected on CT?.
      ]. US also remains the primary imaging modality for the detection and preliminary evaluation of solid renal tumors [
      • Burgan C.M.
      • Rupan Sanyal R.
      • Lockhart M.E.
      Ultrasound of renal masses.
      ]. However, the technique cannot always accurately differentiate between benign and malignant solid renal tumors [
      • Bertolotto M.
      • Bucci S.
      • Valentino M.
      • Currò F.
      • Sachs C.
      • Cova M.A.
      Contrast-enhanced ultrasound for characterizing renal masses.
      ,
      • Burgan C.M.
      • Rupan Sanyal R.
      • Lockhart M.E.
      Ultrasound of renal masses.
      ,
      • Sidhu P.S.
      • Cantisani V.
      • Dietrich C.F.
      • Gilja O.H.
      • Saftoiu A.
      • Bartels E.
      • Bertolotto M.
      • Calliada F.
      • Clevert D.
      • Cosgrove D.
      • Deganello A.
      • D’Onofrio M.
      • Drudi F.M.
      • Freeman S.
      • Harvey C.
      • Jenssen C.
      • Jung E.
      • Klauser A.S.
      • Lassau N.
      • Meloni M.F.
      • Leen E.
      • Nicolau C.
      • Nolsoe C.
      • Piscaglia F.
      • Prada F.
      • Prosch H.
      • Radzina M.
      • Savelli L.
      • Weskott H.
      • Wijkstra H.
      The EFSUMB Guidelines and Recommendations for the Clinical Practice of Contrast-Enhanced Ultrasound (CEUS) in Non-Hepatic Applications: Update 2017 (Long Version).
      ].
      CEUS with its lack of nephrotoxicity, absence of ionizing radiation, and the ability to evaluate enhancement patterns, can accurately characterize many renal lesions, without the need of CT or MRI [
      • Bertolotto M.
      • Bucci S.
      • Valentino M.
      • Currò F.
      • Sachs C.
      • Cova M.A.
      Contrast-enhanced ultrasound for characterizing renal masses.
      ,
      • Siddaiah M.
      • Krishna S.
      • McInnes M.D.F.
      • Quon J.S.
      • Shabana W.M.
      • Papadatos D.
      • Schieda N.
      Is Ultrasound Useful for Further Evaluation of Homogeneously Hyperattenuating Renal Lesions Detected on CT?.
      ,
      • Burgan C.M.
      • Rupan Sanyal R.
      • Lockhart M.E.
      Ultrasound of renal masses.
      ,
      • Sidhu P.S.
      • Cantisani V.
      • Dietrich C.F.
      • Gilja O.H.
      • Saftoiu A.
      • Bartels E.
      • Bertolotto M.
      • Calliada F.
      • Clevert D.
      • Cosgrove D.
      • Deganello A.
      • D’Onofrio M.
      • Drudi F.M.
      • Freeman S.
      • Harvey C.
      • Jenssen C.
      • Jung E.
      • Klauser A.S.
      • Lassau N.
      • Meloni M.F.
      • Leen E.
      • Nicolau C.
      • Nolsoe C.
      • Piscaglia F.
      • Prada F.
      • Prosch H.
      • Radzina M.
      • Savelli L.
      • Weskott H.
      • Wijkstra H.
      The EFSUMB Guidelines and Recommendations for the Clinical Practice of Contrast-Enhanced Ultrasound (CEUS) in Non-Hepatic Applications: Update 2017 (Long Version).
      ]. Main renal applications include differentiation between solid renal tumors and pseudotumors, characterization of complex cystic renal masses, characterization of indeterminate renal masses and follow-up of non-surgically treated renal masses [
      • Sidhu P.S.
      • Cantisani V.
      • Dietrich C.F.
      • Gilja O.H.
      • Saftoiu A.
      • Bartels E.
      • Bertolotto M.
      • Calliada F.
      • Clevert D.
      • Cosgrove D.
      • Deganello A.
      • D’Onofrio M.
      • Drudi F.M.
      • Freeman S.
      • Harvey C.
      • Jenssen C.
      • Jung E.
      • Klauser A.S.
      • Lassau N.
      • Meloni M.F.
      • Leen E.
      • Nicolau C.
      • Nolsoe C.
      • Piscaglia F.
      • Prada F.
      • Prosch H.
      • Radzina M.
      • Savelli L.
      • Weskott H.
      • Wijkstra H.
      The EFSUMB Guidelines and Recommendations for the Clinical Practice of Contrast-Enhanced Ultrasound (CEUS) in Non-Hepatic Applications: Update 2017 (Long Version).
      ].
      After ultrasound contrast agent injection, the renal artery and main branches enhance first, followed rapidly by the segmental, interlobar, arcuate and interlobular arteries. Subsequently, complete cortical enhancement is seen (cortical phase, 15−30 s), followed by medullary enhancement (parenchymal phase, where both cortex and medulla enhance homogeneously, 25sec-4 min). As ultrasound contrast agents are not excreted by kidneys, no excretory phase is obtained [
      • Nilsson A.
      Contrast-enhanced ultrasound of the kidneys.
      ,
      • Correas J.M.
      • Claudon M.
      • Tranquart F.
      • Hélénon O.
      The kidney: imaging with microbubble contrast agents.
      ,
      • Harvey C.J.
      • Alsafi A.
      • Kuzmich S.
      • Ngo A.
      • Papadopoulou I.
      • Lakhani A.
      • Berkowitz Y.
      • Moser S.
      • Sidhu P.S.
      • Cosgrove D.O.
      Role of US contrast agents in the assessment of indeterminate solid and cystic lesions in native and transplant kidneys.
      ,
      • Ignee A.
      • Straub B.
      • Schuessler G.
      • Dietrich C.F.
      Contrast enhanced ultrasound of renal masses.
      ,
      • Cokkinos D.D.
      • Antypa E.G.
      • Skilakaki M.
      • Kriketou D.
      • Tavernaraki E.
      • Piperopoulos P.N.
      Contrast Enhanced Ultrasound of the Kidneys: What Is It Capable of?.
      ].
      CEUS is strongly recommended to differentiate between renal tumors and pseudotumors (prominent columns of Bertin, dromedary or splenic humps, persistent fetal lobulations and areas of renal parenchyma adjacent to cortical scarring, which display compensatory hypertrophy), not characterized with conventional US, with an accuracy up to 95 % [
      • Bertolotto M.
      • Bucci S.
      • Valentino M.
      • Currò F.
      • Sachs C.
      • Cova M.A.
      Contrast-enhanced ultrasound for characterizing renal masses.
      ,
      • Sidhu P.S.
      • Cantisani V.
      • Dietrich C.F.
      • Gilja O.H.
      • Saftoiu A.
      • Bartels E.
      • Bertolotto M.
      • Calliada F.
      • Clevert D.
      • Cosgrove D.
      • Deganello A.
      • D’Onofrio M.
      • Drudi F.M.
      • Freeman S.
      • Harvey C.
      • Jenssen C.
      • Jung E.
      • Klauser A.S.
      • Lassau N.
      • Meloni M.F.
      • Leen E.
      • Nicolau C.
      • Nolsoe C.
      • Piscaglia F.
      • Prada F.
      • Prosch H.
      • Radzina M.
      • Savelli L.
      • Weskott H.
      • Wijkstra H.
      The EFSUMB Guidelines and Recommendations for the Clinical Practice of Contrast-Enhanced Ultrasound (CEUS) in Non-Hepatic Applications: Update 2017 (Long Version).
      ]. The criterion to diagnose pseudotumor is the demonstration of the same enhancing pattern as the surrounding parenchyma in all phases (Fig. 1) [
      • Bertolotto M.
      • Bucci S.
      • Valentino M.
      • Currò F.
      • Sachs C.
      • Cova M.A.
      Contrast-enhanced ultrasound for characterizing renal masses.
      ,
      • Sidhu P.S.
      • Cantisani V.
      • Dietrich C.F.
      • Gilja O.H.
      • Saftoiu A.
      • Bartels E.
      • Bertolotto M.
      • Calliada F.
      • Clevert D.
      • Cosgrove D.
      • Deganello A.
      • D’Onofrio M.
      • Drudi F.M.
      • Freeman S.
      • Harvey C.
      • Jenssen C.
      • Jung E.
      • Klauser A.S.
      • Lassau N.
      • Meloni M.F.
      • Leen E.
      • Nicolau C.
      • Nolsoe C.
      • Piscaglia F.
      • Prada F.
      • Prosch H.
      • Radzina M.
      • Savelli L.
      • Weskott H.
      • Wijkstra H.
      The EFSUMB Guidelines and Recommendations for the Clinical Practice of Contrast-Enhanced Ultrasound (CEUS) in Non-Hepatic Applications: Update 2017 (Long Version).
      ,
      • Cokkinos D.D.
      • Antypa E.G.
      • Skilakaki M.
      • Kriketou D.
      • Tavernaraki E.
      • Piperopoulos P.N.
      Contrast Enhanced Ultrasound of the Kidneys: What Is It Capable of?.
      ]. On the contrary, enhancement of most solid renal tumors differs from the surrounding renal parenchyma, with a difference in the degree or distribution of enhancement at least in one contrast-enhanced phase [
      • Sidhu P.S.
      • Cantisani V.
      • Dietrich C.F.
      • Gilja O.H.
      • Saftoiu A.
      • Bartels E.
      • Bertolotto M.
      • Calliada F.
      • Clevert D.
      • Cosgrove D.
      • Deganello A.
      • D’Onofrio M.
      • Drudi F.M.
      • Freeman S.
      • Harvey C.
      • Jenssen C.
      • Jung E.
      • Klauser A.S.
      • Lassau N.
      • Meloni M.F.
      • Leen E.
      • Nicolau C.
      • Nolsoe C.
      • Piscaglia F.
      • Prada F.
      • Prosch H.
      • Radzina M.
      • Savelli L.
      • Weskott H.
      • Wijkstra H.
      The EFSUMB Guidelines and Recommendations for the Clinical Practice of Contrast-Enhanced Ultrasound (CEUS) in Non-Hepatic Applications: Update 2017 (Long Version).
      ,
      • Cokkinos D.D.
      • Antypa E.G.
      • Skilakaki M.
      • Kriketou D.
      • Tavernaraki E.
      • Piperopoulos P.N.
      Contrast Enhanced Ultrasound of the Kidneys: What Is It Capable of?.
      ,
      • Mazziotti S.
      • Zimbaro F.
      • Pandolfo A.
      • Racchiusa S.
      • Settineri N.
      • Ascenti G.
      Usefulness of contrast-enhanced ultrasonography in the diagnosis of renal pseudotumors.
      ]. Solid renal tumors do not display specific perfusion patterns, therefore their accurate characterization by CEUS is often not possible [
      • Musaddaq B.
      • Musaddaq T.
      • Gupta A.
      • Ilyas S.
      • von Stempel C.
      Renal cell carcinoma: the evolving role of imaging in the 21st century.
      ,
      • Ignee A.
      • Straub B.
      • Schuessler G.
      • Dietrich C.F.
      Contrast enhanced ultrasound of renal masses.
      ,
      • Cokkinos D.D.
      • Antypa E.G.
      • Skilakaki M.
      • Kriketou D.
      • Tavernaraki E.
      • Piperopoulos P.N.
      Contrast Enhanced Ultrasound of the Kidneys: What Is It Capable of?.
      ,
      • Oh T.H.
      • Lee Y.H.
      • Seo I.Y.
      Diagnostic efficacy of contrast-enhanced ultrasound for small renal masses.
      ,
      • Xu Z.F.
      • Xu H.X.
      • Xie X.Y.
      • Liu G.J.
      • Zheng Y.L.
      • Lu M.D.
      Renal cell carcinoma and renal angiomyolipoma: differential diagnosis with real-time contrast-enhanced ultrasonography.
      ,
      • Xu Z.F.
      • Xu H.X.
      • Xie X.Y.
      • Liu G.J.
      • Zheng Y.L.
      • Liang J.Y.
      • Lu M.D.
      Renal cell carcinoma: real-time contrast-enhanced ultrasound findings.
      ,
      • Atri M.
      • Tabatabaeifar L.
      • Jang H.J.
      • Finelli A.
      • Moshonov H.
      • Jewett M.
      Accuracy of contrast-enhanced US for differentiating benign from malignant solid small renal masses.
      ].
      Fig. 1
      Fig. 1Sagittal (a) grayscale and (b) power Doppler images depict a solid left renal lesion (arrows) in the interpolar region, mainly isoechoic, when compared to normal renal parenchyma. The mass appears to displace the surrounding blood vessels. After ultrasound contrast agent injection (c) the lesion (arrows) shows similar enhancement as the remaining renal parenchyma, a finding suggestive for the presence of renal pseudotumor. (Courtesy: Dr. DD. Kokkinos).
      CEUS can be used to characterize complex cystic renal masses, with accuracy comparable to that of CT and MRI and reported concordance rates between the three imaging techniques approximately of 90 % (Fig. 2) [
      • Bertolotto M.
      • Bucci S.
      • Valentino M.
      • Currò F.
      • Sachs C.
      • Cova M.A.
      Contrast-enhanced ultrasound for characterizing renal masses.
      ,
      • Sidhu P.S.
      • Cantisani V.
      • Dietrich C.F.
      • Gilja O.H.
      • Saftoiu A.
      • Bartels E.
      • Bertolotto M.
      • Calliada F.
      • Clevert D.
      • Cosgrove D.
      • Deganello A.
      • D’Onofrio M.
      • Drudi F.M.
      • Freeman S.
      • Harvey C.
      • Jenssen C.
      • Jung E.
      • Klauser A.S.
      • Lassau N.
      • Meloni M.F.
      • Leen E.
      • Nicolau C.
      • Nolsoe C.
      • Piscaglia F.
      • Prada F.
      • Prosch H.
      • Radzina M.
      • Savelli L.
      • Weskott H.
      • Wijkstra H.
      The EFSUMB Guidelines and Recommendations for the Clinical Practice of Contrast-Enhanced Ultrasound (CEUS) in Non-Hepatic Applications: Update 2017 (Long Version).
      ,
      • Clevert D.A.
      • Minaifar N.
      • Weckbach S.
      • Jung E.M.
      • Stock K.
      • Reiser M.
      • Staehler M.
      Multislice computed tomography versus contrast-enhanced ultrasound in evaluation of complex cystic renal masses using the Bosniak classification system.
      ,
      • Park B.K.
      • Kim B.
      • Kim S.H.
      • Ko K.
      • Lee H.M.
      • Choi H.Y.
      Assessment of cystic renal masses based on Bosniak classification: comparison of CT and contrast-enhanced US.
      ,
      • Ascenti G.
      • Mazziotti S.
      • Zimbaro G.
      • Settineri N.
      • Magno C.
      • Melloni D.
      • Caruso R.
      • Scribano E.
      Complex cystic renal masses: characterization with contrast-enhanced US.
      ,
      • Quaia E.
      • Bertolotto M.
      • Cioffi V.
      • Rossi A.
      • Baratella E.
      • Pizzolato R.
      • Cova M.A.
      Comparison of contrast-enhanced sonography with unenhanced sonography and contrast-enhanced CT in the diagnosis of malignancy in complex cystic renal masses.
      ,
      • Graumann O.
      • Osther S.S.
      • Karstoft J.
      • Horlyck A.
      • Osther P.J.
      Bosniak classification system: a prospective comparison of CT, contrast-enhanced US, and MR for categorizing complex renal cystic masses.
      ]. In addition, CEUS has been reported more sensitive than CT in demonstrating minimal wall and/or septal enhancement and solid, enhancing components in a complex cystic renal mass [
      • Bertolotto M.
      • Bucci S.
      • Valentino M.
      • Currò F.
      • Sachs C.
      • Cova M.A.
      Contrast-enhanced ultrasound for characterizing renal masses.
      ,
      • Sidhu P.S.
      • Cantisani V.
      • Dietrich C.F.
      • Gilja O.H.
      • Saftoiu A.
      • Bartels E.
      • Bertolotto M.
      • Calliada F.
      • Clevert D.
      • Cosgrove D.
      • Deganello A.
      • D’Onofrio M.
      • Drudi F.M.
      • Freeman S.
      • Harvey C.
      • Jenssen C.
      • Jung E.
      • Klauser A.S.
      • Lassau N.
      • Meloni M.F.
      • Leen E.
      • Nicolau C.
      • Nolsoe C.
      • Piscaglia F.
      • Prada F.
      • Prosch H.
      • Radzina M.
      • Savelli L.
      • Weskott H.
      • Wijkstra H.
      The EFSUMB Guidelines and Recommendations for the Clinical Practice of Contrast-Enhanced Ultrasound (CEUS) in Non-Hepatic Applications: Update 2017 (Long Version).
      ,
      • Graumann O.
      • Osther S.S.
      • Karstoft J.
      • Horlyck A.
      • Osther P.J.
      Bosniak classification system: a prospective comparison of CT, contrast-enhanced US, and MR for categorizing complex renal cystic masses.
      ,
      • Chang E.H.
      • Chong W.K.
      • Kasoji S.K.
      • Fielding J.R.
      • Altun E.
      • Mullin L.B.
      • Kim J.I.
      • Fine J.P.
      • Dayton P.A.
      • Rathmell W.K.
      Diagnostic accuracy of contrast-enhanced ultrasound for characterization of kidney lesions in patients with and without chronic kidney disease.
      ]. CEUS is also recommended for the follow-up of non-surgical complex cystic renal lesions [
      • Bertolotto M.
      • Bucci S.
      • Valentino M.
      • Currò F.
      • Sachs C.
      • Cova M.A.
      Contrast-enhanced ultrasound for characterizing renal masses.
      ,
      • Sidhu P.S.
      • Cantisani V.
      • Dietrich C.F.
      • Gilja O.H.
      • Saftoiu A.
      • Bartels E.
      • Bertolotto M.
      • Calliada F.
      • Clevert D.
      • Cosgrove D.
      • Deganello A.
      • D’Onofrio M.
      • Drudi F.M.
      • Freeman S.
      • Harvey C.
      • Jenssen C.
      • Jung E.
      • Klauser A.S.
      • Lassau N.
      • Meloni M.F.
      • Leen E.
      • Nicolau C.
      • Nolsoe C.
      • Piscaglia F.
      • Prada F.
      • Prosch H.
      • Radzina M.
      • Savelli L.
      • Weskott H.
      • Wijkstra H.
      The EFSUMB Guidelines and Recommendations for the Clinical Practice of Contrast-Enhanced Ultrasound (CEUS) in Non-Hepatic Applications: Update 2017 (Long Version).
      ,
      • Gulati M.
      • King K.G.
      • Gill I.S.
      • Pham V.
      • Grant E.
      • Duddalwar V.A.
      Contrast-enhanced ultrasound (CEUS) of cystic and solid renal lesions: a review.
      ].
      Fig. 2
      Fig. 2(a) Grayscale US image demonstrates a right renal cystic lesion with an irregularly thickened internal septum (arrow). (b) Contrast-enhanced US shows this part enhances (arrows); therefore, the lesion is characterized as Bosniak class III. (Courtesy: Dr. DD. Kokkinos).
      CEUS has an important role in the characterization of indeterminate renal lesions, including avascular renal masses, without the typical US findings of a simple cyst, complex renal cysts and masses with equivocal CT enhancement or indeterminate CT findings [
      • Expert Panel on Urologic Imaging
      • Wang Z.J.
      • Nikolaidis P.
      • Khatri G.
      • Dogra V.S.
      • Ganeshan D.
      • Goldfarb S.
      • Gore J.L.
      • Gupta R.T.
      • Hartman R.P.
      • Heilbrun M.E.
      • Lyshchik A.
      • Purysko A.S.
      • Savage S.J.
      • Smith A.D.
      • Wolfman D.J.
      • Wong-You-Cheong J.J.
      • Lockhart M.E.
      ACR appropriateness criteria® indeterminate renal mass.
      ,
      • Bertolotto M.
      • Bucci S.
      • Valentino M.
      • Currò F.
      • Sachs C.
      • Cova M.A.
      Contrast-enhanced ultrasound for characterizing renal masses.
      ,
      • Siddaiah M.
      • Krishna S.
      • McInnes M.D.F.
      • Quon J.S.
      • Shabana W.M.
      • Papadatos D.
      • Schieda N.
      Is Ultrasound Useful for Further Evaluation of Homogeneously Hyperattenuating Renal Lesions Detected on CT?.
      ,
      • Burgan C.M.
      • Rupan Sanyal R.
      • Lockhart M.E.
      Ultrasound of renal masses.
      ,
      • Sidhu P.S.
      • Cantisani V.
      • Dietrich C.F.
      • Gilja O.H.
      • Saftoiu A.
      • Bartels E.
      • Bertolotto M.
      • Calliada F.
      • Clevert D.
      • Cosgrove D.
      • Deganello A.
      • D’Onofrio M.
      • Drudi F.M.
      • Freeman S.
      • Harvey C.
      • Jenssen C.
      • Jung E.
      • Klauser A.S.
      • Lassau N.
      • Meloni M.F.
      • Leen E.
      • Nicolau C.
      • Nolsoe C.
      • Piscaglia F.
      • Prada F.
      • Prosch H.
      • Radzina M.
      • Savelli L.
      • Weskott H.
      • Wijkstra H.
      The EFSUMB Guidelines and Recommendations for the Clinical Practice of Contrast-Enhanced Ultrasound (CEUS) in Non-Hepatic Applications: Update 2017 (Long Version).
      ,
      • Bertolotto M.
      • Cicero C.
      • Perrone R.
      • Degrassi F.
      • Cacciato F.
      • Cova M.A.
      Renal masses with equivocal enhancement at CT: characterization with contrast-enhanced ultrasound.
      ,
      • Barr R.G.
      • Peterson C.
      • Hindi A.
      Evaluation of indeterminate renal masses with contrast-enhanced US: a diagnostic performance study.
      ,
      • Harvey C.J.
      • Alsafi A.
      • Kuzmich S.
      • Ngo A.
      • Papadopoulou I.
      • Lakhani A.
      • Berkowitz Y.
      • Moser S.
      • Sidhu P.S.
      • Cosgrove D.O.
      Role of US contrast agents in the assessment of indeterminate solid and cystic lesions in native and transplant kidneys.
      ]. In a retrospective study, CEUS had a sensitivity of 100 %, specificity of 95 %, positive predictive value (PPV) of 94.7 %, and negative predictive value (NPV) of 100 % in the characterization of indeterminate renal masses [
      • Barr R.G.
      • Peterson C.
      • Hindi A.
      Evaluation of indeterminate renal masses with contrast-enhanced US: a diagnostic performance study.
      ]. CEUS follow-up is also recommended in these cases [
      • Sidhu P.S.
      • Cantisani V.
      • Dietrich C.F.
      • Gilja O.H.
      • Saftoiu A.
      • Bartels E.
      • Bertolotto M.
      • Calliada F.
      • Clevert D.
      • Cosgrove D.
      • Deganello A.
      • D’Onofrio M.
      • Drudi F.M.
      • Freeman S.
      • Harvey C.
      • Jenssen C.
      • Jung E.
      • Klauser A.S.
      • Lassau N.
      • Meloni M.F.
      • Leen E.
      • Nicolau C.
      • Nolsoe C.
      • Piscaglia F.
      • Prada F.
      • Prosch H.
      • Radzina M.
      • Savelli L.
      • Weskott H.
      • Wijkstra H.
      The EFSUMB Guidelines and Recommendations for the Clinical Practice of Contrast-Enhanced Ultrasound (CEUS) in Non-Hepatic Applications: Update 2017 (Long Version).
      ].
      CEUS may highlight renal vein invasion by RCC at the initial evaluation, as arterial thrombus vascularization differentiates bland thrombus from a neoplastic one, with a reported sensitivity, specificity, PPV, NPV and accuracy of 83 %, 96 %, 71 %, 98 % and 94 %, respectively [
      • Vikram R.
      • Beland M.D.
      • Blaufox M.D.
      • Moreno C.C.
      • Gore J.L.
      • Harvin H.J.
      • Heilbrun M.E.
      • Liauw S.L.
      • Nguyen P.L.
      • Nikolaidis P.
      • Preminger G.M.
      • Purysko A.S.
      • Raman S.S.
      • Taffel M.T.
      • Wang Z.J.
      • Weinfeld R.M.
      • Remer E.M.
      • Lockhart M.E.
      ACR appropriateness criteria renal cell carcinoma staging.
      ,
      • Siddaiah M.
      • Krishna S.
      • McInnes M.D.F.
      • Quon J.S.
      • Shabana W.M.
      • Papadatos D.
      • Schieda N.
      Is Ultrasound Useful for Further Evaluation of Homogeneously Hyperattenuating Renal Lesions Detected on CT?.
      ,
      • Sidhu P.S.
      • Cantisani V.
      • Dietrich C.F.
      • Gilja O.H.
      • Saftoiu A.
      • Bartels E.
      • Bertolotto M.
      • Calliada F.
      • Clevert D.
      • Cosgrove D.
      • Deganello A.
      • D’Onofrio M.
      • Drudi F.M.
      • Freeman S.
      • Harvey C.
      • Jenssen C.
      • Jung E.
      • Klauser A.S.
      • Lassau N.
      • Meloni M.F.
      • Leen E.
      • Nicolau C.
      • Nolsoe C.
      • Piscaglia F.
      • Prada F.
      • Prosch H.
      • Radzina M.
      • Savelli L.
      • Weskott H.
      • Wijkstra H.
      The EFSUMB Guidelines and Recommendations for the Clinical Practice of Contrast-Enhanced Ultrasound (CEUS) in Non-Hepatic Applications: Update 2017 (Long Version).
      ,
      • Li Q.
      • Wang Z.
      • Ma X.
      • Tang J.
      • Luo Y.
      Diagnostic accuracy of contrast-enhanced ultrasound for detecting bland thrombus from inferior vena cava tumor thrombus in patients with renal cell carcinoma.
      ]. Finally, CEUS is helpful in the follow-up of post-ablated RCC, allowing the detection of intralesional enhancement, indicative of residual or recurrent tumor, with a sensitivity, specificity, PPV, NPV, and overall accuracy of 96.6 %, 100 %, 100 %, 95.8 %, and 98.1 %, respectively [
      • Expert Panel on Urological Imaging
      • Purysko A.S.
      • Nikolaidis P.
      • Dogra V.S.
      • Ganeshan D.
      • Gore J.L.
      • Gupta R.T.
      • Heilbrun M.E.
      • Khatri G.
      • Kishan A.U.
      • Lyshchik A.
      • Savage S.J.
      • Smith A.D.
      • Wang Z.J.
      • Wolfman D.J.
      • Wong-You-Cheong J.J.
      • Yoo D.C.
      • Lockhart M.E.
      ACR appropriateness criteria post-treatment follow-up and active surveillance of clinically localized renal cell Cancer.
      ,
      • Sidhu P.S.
      • Cantisani V.
      • Dietrich C.F.
      • Gilja O.H.
      • Saftoiu A.
      • Bartels E.
      • Bertolotto M.
      • Calliada F.
      • Clevert D.
      • Cosgrove D.
      • Deganello A.
      • D’Onofrio M.
      • Drudi F.M.
      • Freeman S.
      • Harvey C.
      • Jenssen C.
      • Jung E.
      • Klauser A.S.
      • Lassau N.
      • Meloni M.F.
      • Leen E.
      • Nicolau C.
      • Nolsoe C.
      • Piscaglia F.
      • Prada F.
      • Prosch H.
      • Radzina M.
      • Savelli L.
      • Weskott H.
      • Wijkstra H.
      The EFSUMB Guidelines and Recommendations for the Clinical Practice of Contrast-Enhanced Ultrasound (CEUS) in Non-Hepatic Applications: Update 2017 (Long Version).
      ,
      • Meloni M.F.
      • Bertolotto M.
      • Alberzoni C.
      • Lazzaroni S.
      • Filice C.
      • Livraghi T.
      • Ferraioli G.
      Follow-up after percutaneous radiofrequency ablation of renal cell carcinoma: contrast-enhanced sonography versus contrast-enhanced CT or MRI.
      ]. Table 3 shows main clinical indications for renal US and CEUS.
      Table 3Clinical indications for renal US and contrast-enhanced US [
      • Cokkinos D.D.
      • Antypa E.G.
      • Skilakaki M.
      • Kriketou D.
      • Tavernaraki E.
      • Piperopoulos P.N.
      Contrast Enhanced Ultrasound of the Kidneys: What Is It Capable of?.
      ].
      Clinical indicationsColor Doppler US findingsContrast-enhanced US findings
      Differential diagnosis between solid renal tumors and pseudotumorsmay be nonspecificrenal tumor vascularity differs from that of normal parenchyma, at least in one post-contrast phase/ pseudotumors enhance parallel to renal parenchyma in all phases
      Characterization of solid renal tumorsoften nonspecific Color Doppler has limitations in assessing neoplastic invasion of the renal vein in RCCoften nonspecific neoplastic renal vein thrombus enhances/bland thrombus shows lack of enhancement
      Differentiation between cystic and solid renal masseslimitations in assessing possible perfusion in echogenic cystssolid hypovascular renal tumors enhance, even slightly/debris do not enhance superior to CT/MRI in diagnosing cystic RCC
      Characterization of complex cystic renal masseslimitations in assessing possible perfusion in septa and/or cyst nodulesdepicts wall/septal and/or nodules enhancement similar or higher accuracy compared to CT for renal cystic lesions classification, according to Bosniak criteria
      RCC post-ablationno roleconfirms treatment results similar accuracy to that of CT/MRI post-ablation contrast-enhancing areas are considered residual or recurrent tumor
      Nevertheless, the widespread use of CEUS in everyday practice is still questionable. Continuing training, experience, revising of Bosniak classification, additional research for including CEUS in clinical urological guidelines and new technologies, such as, fusion imaging may improve the diagnostic accuracy of the technique, guarantee its safety, and confirm its role in the management of renal masses [
      • Tenant S.C.
      • Gutteridge C.M.
      The clinical use of contrast-enhanced ultrasound in the kidney.
      ,
      • Schnitzer M.L.
      • Sabel L.
      • Schwarze V.
      • Marschner C.
      • Froelich M.F.
      • Nuhn P.
      • Falck Y.
      • Nuhn M.M.
      • Afat S.
      • Staehler M.
      • Rückel J.
      • Clevert D.-A.
      • Rübenthaler J.
      • Geyer T.
      Structured reporting in the characterization of renal cysts by contrast-enhanced ultrasound (CEUS) using the bosniak classification system-improvement of report quality and interdisciplinary communication.
      ,
      • Schwarze V.
      • Rübenthaler J.
      • Marschner C.
      • Fabritius M.P.
      • Rueckel J.
      • Fink N.
      • Puhr-Westerheide D.
      • Gresser E.
      • Froelich M.F.
      • Schnitzer M.L.
      • Große Hokamp N.
      • Afat S.
      • Staehler M.
      • Geyer T.
      • Clevert D.-A.
      Advanced fusion imaging and contrast-enhanced imaging (CT/MRI–CEUS) in oncology.
      ,
      • Frinking P.
      • Segers T.
      • Luan Y.
      • Tranquart F.C.
      Three decades of ultrasound contrast agents: a review of the past, present and future improvements.
      ].

      4. Computed tomography

      Contrast-enhanced CT (CECT) represents the gold standard imaging technique for the detection and characterization of renal masses [
      • Jayson M.
      • Sanders H.
      Increased incidence of serendipitously discovered renal cell carcinoma.
      ,
      • Ljungberg B.
      • Albiges L.
      • Abu-Ghanem Y.
      • Bensalah K.
      • Dabestani S.
      • Fernández-Pello S.
      • Giles R.H.
      • Hofmann F.
      • Hora M.
      • Kuczyk M.A.
      • Kuusk T.
      • Lam T.B.
      • Marconi L.
      • Merseburger A.S.
      • Powles T.
      • Staehler M.
      • Tahbaz R.
      • Volpe A.
      • Bex A.
      European association of urology guidelines on renal cell carcinoma: the 2019 update.
      ,
      • Campbell S.
      • Uzzo R.G.
      • Allaf M.E.
      • Remer E.M.
      Renal Mass and Localized Renal Cancer: AUA Guideline.
      ,
      • Ward R.D.
      • Tanaka H.
      • Campbell S.C.
      • Remer E.M.
      2017 AUA renal mass and localized renal Cancer guidelines: imaging implications.
      ,
      • Herts B.R.
      • Silverman S.G.
      • Hindman N.M.
      • Uzzo R.G.
      • Hartman R.P.
      • Israel G.M.
      • Baumgarten D.A.
      • Berland L.L.
      • Pandharipande P.V.
      Management of the Incidental Renal Mass on CT: A White Paper of the ACR Incidental Findings Committee.
      ,
      • Expert Panel on Urologic Imaging
      • Wang Z.J.
      • Nikolaidis P.
      • Khatri G.
      • Dogra V.S.
      • Ganeshan D.
      • Goldfarb S.
      • Gore J.L.
      • Gupta R.T.
      • Hartman R.P.
      • Heilbrun M.E.
      • Lyshchik A.
      • Purysko A.S.
      • Savage S.J.
      • Smith A.D.
      • Wolfman D.J.
      • Wong-You-Cheong J.J.
      • Lockhart M.E.
      ACR appropriateness criteria® indeterminate renal mass.
      ,
      • Kay F.U.
      • Pedrosa I.
      Imaging of solid renal masses.
      ,
      • Musaddaq B.
      • Musaddaq T.
      • Gupta A.
      • Ilyas S.
      • von Stempel C.
      Renal cell carcinoma: the evolving role of imaging in the 21st century.
      ,
      • Kaur R.
      • Juneja M.
      • Mandal A.K.
      An overview of non-invasive imaging modalities for diagnosis of solid and cystic renal lesions.
      ,
      • Pavlica P.
      • Derchi L.
      • Martorana G.
      • Brunocilla E.
      • Bertaccini A.
      • Manferrari F.
      • Franceschelli A.
      • Barozzi L.
      Renal cell carcinoma imaging.
      ,
      • van Oostenbrugge T.J.
      • Fütterer J.J.
      • Mulders P.F.A.
      Diagnostic imaging for solid renal tumors: a pictorial review.
      ,
      • Sasaguri K.
      • Takahashi N.
      CT and MR imaging for solid renal mass characterization.
      ,
      • Wang Z.J.
      • Westphalen A.C.
      • Zagoria R.J.
      CT and MRI of small renal masses.
      ,
      • Krishna S.
      • Murray C.A.
      • McInnes M.D.
      • Chatelain R.
      • Siddaiah M.
      • Al-Dandan O.
      • Narayanasamy S.
      • Schieda N.
      CT imaging of solid renal masses: pitfalls and solutions.
      ]. Renal CT protocol consists of an unenhanced phase, combined with one or more contrast-enhanced phases, namely the corticomedullary phase (40−70 sec), the nephrographic phase (100−120 sec) and the delayed-excretory phase (7−10 min) [
      • Wang Z.J.
      • Davenport M.S.
      • Silverman S.G.
      • Chandarana H.
      • Doshi A.
      • Israel G.M.
      • Leyendecker J.R.
      • Pedrosa I.
      • Raman S.
      • Remer E.M.
      • Shinagare A.B.
      • Smith A.D.
      • Vikram R.
      CT Renal Mass Protocol v1.0: Society of Abdominal Radiology Disease Focused Panel on Renal Cell Carcinoma.
      ]. The nephrographic phase is optimal for RCC detection, as tumor contrast washout becomes visible, against the homogeneously enhancing renal parenchyma [
      • van Oostenbrugge T.J.
      • Fütterer J.J.
      • Mulders P.F.A.
      Diagnostic imaging for solid renal tumors: a pictorial review.
      ,
      • Birnbaum B.A.
      • Jacobs J.E.
      • Ramchandani P.
      Multiphasic renal CT: comparison of renal mass enhancement during the corticomedullary and nephrographic phases.
      ,
      • Egbert N.D.
      • Caoili E.M.
      • Cohan R.H.
      • Davenport M.S.
      • Francis I.R.
      • Kunju L.P.
      • Ellis J.H.
      Differentiation of papillary renal cell carcinoma subtypes on CT and MRI.
      ]. The corticomedullary phase may help in sub-typing RCC, as clear cell RCC enhances avidly in this phase [
      • Wang Z.J.
      • Davenport M.S.
      • Silverman S.G.
      • Chandarana H.
      • Doshi A.
      • Israel G.M.
      • Leyendecker J.R.
      • Pedrosa I.
      • Raman S.
      • Remer E.M.
      • Shinagare A.B.
      • Smith A.D.
      • Vikram R.
      CT Renal Mass Protocol v1.0: Society of Abdominal Radiology Disease Focused Panel on Renal Cell Carcinoma.
      ].
      CECT is the modality of choice for the evaluation of cystic renal masses [
      • Silverman S.G.
      • Pedrosa I.
      • Ellis J.H.
      • Hindman N.M.
      • Schieda N.
      • Smith A.D.
      • Remer E.M.
      • Shinagare A.B.
      • Curci N.E.
      • Raman S.S.
      • Wells S.A.
      • Kaffenberger S.D.
      • Wang Z.J.
      • Chandarana H.
      • Davenport M.S.
      Bosniak classification of cystic renal masses, version 2019: an update proposal and needs assessment.
      ,
      • Krishna S.
      • Schieda N.
      • Pedrosa I.
      • Hindman N.
      • Baroni R.H.
      • Silverman S.G.
      • Davenport M.S.
      Update on MRI of cystic renal masses including bosniak version 2019.
      ,
      • Ward R.D.
      • Remer E.M.
      Cystic renal masses: an imaging update.
      ,
      • Narayanasamy S.
      • Krishna S.
      • Prasad Shanbhogue A.K.
      • Flood T.A.
      • Sadoughi N.
      • Sathiadoss P.
      • Schieda N.
      Contemporary update on imaging of cystic renal masses with histopathological correlation and emphasis on patient management.
      ,
      • Schieda N.
      • Davenport M.S.
      • Krishna S.
      • Edney E.A.
      • Pedrosa I.
      • Hindman N.
      • Baroni R.H.
      • Curci N.E.
      • Shinagare A.
      • Silverman S.G.
      Bosniak classification of cystic renal masses, version 2019: a pictorial guide to clinical use.
      ,
      • Edney E.
      • Davenport M.S.
      • Curci N.
      • Schieda N.
      • Krishna S.
      • Hindman N.
      • Silverman S.G.
      • Pedrosa I.
      Bosniak classification of cystic renal masses, version 2019: interpretation pitfalls and recommendations to avoid misclassification.
      ]. Table 4 shows CT characteristics of renal cystic masses based on the recent Bosniak classification [
      • Silverman S.G.
      • Pedrosa I.
      • Ellis J.H.
      • Hindman N.M.
      • Schieda N.
      • Smith A.D.
      • Remer E.M.
      • Shinagare A.B.
      • Curci N.E.
      • Raman S.S.
      • Wells S.A.
      • Kaffenberger S.D.
      • Wang Z.J.
      • Chandarana H.
      • Davenport M.S.
      Bosniak classification of cystic renal masses, version 2019: an update proposal and needs assessment.
      ,
      • Krishna S.
      • Schieda N.
      • Pedrosa I.
      • Hindman N.
      • Baroni R.H.
      • Silverman S.G.
      • Davenport M.S.
      Update on MRI of cystic renal masses including bosniak version 2019.
      ]. A homogeneous renal mass measuring between -10HU and +20HU on unenhanced CT corresponds to a simple benign cyst, without the need for additional imaging. A homogeneous hyperdense lesion measuring more than 70HU on non-contrast CT, indicates a benign hemorrhagic or proteinaceous cyst [
      • Expert Panel on Urologic Imaging
      • Wang Z.J.
      • Nikolaidis P.
      • Khatri G.
      • Dogra V.S.
      • Ganeshan D.
      • Goldfarb S.
      • Gore J.L.
      • Gupta R.T.
      • Hartman R.P.
      • Heilbrun M.E.
      • Lyshchik A.
      • Purysko A.S.
      • Savage S.J.
      • Smith A.D.
      • Wolfman D.J.
      • Wong-You-Cheong J.J.
      • Lockhart M.E.
      ACR appropriateness criteria® indeterminate renal mass.
      ]. Lesions either homogeneous or inhomogeneous within the 20-70HU range, are considered indeterminate and require further evaluation [
      • Expert Panel on Urologic Imaging
      • Wang Z.J.
      • Nikolaidis P.
      • Khatri G.
      • Dogra V.S.
      • Ganeshan D.
      • Goldfarb S.
      • Gore J.L.
      • Gupta R.T.
      • Hartman R.P.
      • Heilbrun M.E.
      • Lyshchik A.
      • Purysko A.S.
      • Savage S.J.
      • Smith A.D.
      • Wolfman D.J.
      • Wong-You-Cheong J.J.
      • Lockhart M.E.
      ACR appropriateness criteria® indeterminate renal mass.
      ]. The most commonly used method to characterize indeterminate renal masses, including both cystic and solid renal lesions is CECT [
      • Herts B.R.
      • Silverman S.G.
      • Hindman N.M.
      • Uzzo R.G.
      • Hartman R.P.
      • Israel G.M.
      • Baumgarten D.A.
      • Berland L.L.
      • Pandharipande P.V.
      Management of the Incidental Renal Mass on CT: A White Paper of the ACR Incidental Findings Committee.
      ,
      • Expert Panel on Urologic Imaging
      • Wang Z.J.
      • Nikolaidis P.
      • Khatri G.
      • Dogra V.S.
      • Ganeshan D.
      • Goldfarb S.
      • Gore J.L.
      • Gupta R.T.
      • Hartman R.P.
      • Heilbrun M.E.
      • Lyshchik A.
      • Purysko A.S.
      • Savage S.J.
      • Smith A.D.
      • Wolfman D.J.
      • Wong-You-Cheong J.J.
      • Lockhart M.E.
      ACR appropriateness criteria® indeterminate renal mass.
      ]. Enhancing solid renal tumours or enhancing components in cystic renal masses (Fig. 3) are strongly suggestive of malignancy [
      • Krishna S.
      • Murray C.A.
      • McInnes M.D.
      • Chatelain R.
      • Siddaiah M.
      • Al-Dandan O.
      • Narayanasamy S.
      • Schieda N.
      CT imaging of solid renal masses: pitfalls and solutions.
      ]. Differences of at least 10HU between unenhanced and CECT have been proposed to differentiate renal cysts from solid masses [
      • Expert Panel on Urologic Imaging
      • Wang Z.J.
      • Nikolaidis P.
      • Khatri G.
      • Dogra V.S.
      • Ganeshan D.
      • Goldfarb S.
      • Gore J.L.
      • Gupta R.T.
      • Hartman R.P.
      • Heilbrun M.E.
      • Lyshchik A.
      • Purysko A.S.
      • Savage S.J.
      • Smith A.D.
      • Wolfman D.J.
      • Wong-You-Cheong J.J.
      • Lockhart M.E.
      ACR appropriateness criteria® indeterminate renal mass.
      ]. However, more conservative values, such as 15-20HU are often used to account for partial volume-averaging artifacts [
      • Birnbaum B.A.
      • Hindman N.
      • Lee J.
      • Babb J.S.
      Renal cyst pseudoenhancement: influence of multidetector CT reconstruction algorithm and scanner type in phantom model.
      ].
      Table 4Bosniak Classification of Cystic Renal Masses, Version 2019 [
      • Silverman S.G.
      • Pedrosa I.
      • Ellis J.H.
      • Hindman N.M.
      • Schieda N.
      • Smith A.D.
      • Remer E.M.
      • Shinagare A.B.
      • Curci N.E.
      • Raman S.S.
      • Wells S.A.
      • Kaffenberger S.D.
      • Wang Z.J.
      • Chandarana H.
      • Davenport M.S.
      Bosniak classification of cystic renal masses, version 2019: an update proposal and needs assessment.
      ,
      • Krishna S.
      • Schieda N.
      • Pedrosa I.
      • Hindman N.
      • Baroni R.H.
      • Silverman S.G.
      • Davenport M.S.
      Update on MRI of cystic renal masses including bosniak version 2019.
      ].
      CategoryCT findingsMRI findings
      Iwell-defined cystic mass, homogeneous, watery density (-10 to +20 HU), smooth, thin wall (≤ 2 mm) that may enhance, absence of septa and/or calcificationswell-defined cystic mass, homogeneous, hyperintense T2 signal, similar to cerebrospinal fluid, smooth, thin wall (≤ 2 mm) that may enhance, absence of septa and/or calcifications
      IIwell-defined mass, smooth, thin wall (≤ 2 mm)well-defined mass, smooth, thin wall (≤ 2 mm)
      • cystic mass, few (1-3) thin (≤ 2 mm) septa; wall and septa may enhance; calcifications of any type
      • homogeneous hyperdense (≥ 70HU) mass at unenhanced CT
      • homogeneous nonenhancing mass > 20HU at renal mass protocol CT; may have calcifications
      • homogeneous mass -10 to +20HU at unenhanced CT
      • homogeneous mass 21-30HU at portal phase CT
      • homogeneous hypodense mass, too small to characterize
      • cystic mass, few (1-3) thin (≤ 2 mm) contrast-enhancing septa or any nonenhancing septa; may contain calcifications of any type
      • homogeneous, markedly hyperintense T2 signal, similar to cerebrospinal fluid
      • homogeneous, markedly hyperintense fat-suppressed T1 signal, equal or 2.5 times higher than that of normal renal parenchyma
      IIFcystic mass, smooth, minimally thickened (3 mm) enhancing wall and/or septa, or many (≥ 4) smooth, thin enhancing septa
      • cystic mass, smooth, minimally thickened (3 mm) enhancing wall and/or septa, or many (≥ 4) smooth, thin enhancing septa
      • cystic mass, heterogeneously hyperintense fat-suppressed T1 signal
      IIIcystic mass, thickened (≥ 4 mm) enhancing wall and/or septa, or enhancing nodule(s): convex protrusion(s) arising from the wall and/or septa, irregularly thickened (≤ 3 mm), with obtuse marginscystic mass, thickened (≥ 4 mm) enhancing wall and/or septa, or enhancing nodule(s): convex protrusion(s) arising from the wall and/or septa, irregularly thickened (≤ 3 mm), with obtuse margins
      IVcystic mass, one or more enhancing nodule(s): convex protrusion(s), arising from the wall and/or septa, ≥ 4 mm, with obtuse margins, or of any size, with acute marginscystic mass, one or more enhancing nodule(s): convex protrusion(s), arising from the wall and/or septa, ≥ 4 mm, with obtuse margins, or of any size, with acute margins
      Fig. 3
      Fig. 3Clear cell RCC of the left kidney. (a) Coronal and (b) sagittal contrast-enhanced CT images during the corticomedullary phase depict a <50 % exophytic left renal cystic lesion (arrow), with a 5 mm contrast-enhancing nodule (long arrow, b, Bosniak class IV). Left simple benign renal cyst (asterisk). (c) Coronal three-dimensional maximum intensity projection reconstructed image shows distance of the left renal artery origin to the first branch (arrow).
      Because CT is considered the gold standard for the detection of renal masses, the accuracy of the technique in the detection of renal tumors is difficult to define, based on literature data [
      • van Oostenbrugge T.J.
      • Fütterer J.J.
      • Mulders P.F.A.
      Diagnostic imaging for solid renal tumors: a pictorial review.
      ,
      • Kim J.H.
      • Sun H.Y.
      • Hwang J.
      • Hong S.S.
      • Cho Y.J.
      • Doo S.W.
      • Yang W.J.
      • Song Y.S.
      Diagnostic accuracy of contrast-enhanced computed tomography and contrast-enhanced magnetic resonance imaging of small renal masses in real practice: sensitivity and specificity according to subjective radiologic interpretation.
      ,
      • Kwon T.
      • Jeong I.G.
      • Yoo S.
      • Lee S.J.
      • Hong S.
      • You D.
      • Hong J.H.
      • Ahn H.
      • Kim C.
      Role of MRI in indeterminate renal mass: diagnostic accuracy and impact on clinical decision making.
      ]. In a retrospective study of small (≤ 4 cm) indeterminate renal masses, CECT accuracy in predicting RCC diagnosis was 79.4 % [
      • Kim J.H.
      • Sun H.Y.
      • Hwang J.
      • Hong S.S.
      • Cho Y.J.
      • Doo S.W.
      • Yang W.J.
      • Song Y.S.
      Diagnostic accuracy of contrast-enhanced computed tomography and contrast-enhanced magnetic resonance imaging of small renal masses in real practice: sensitivity and specificity according to subjective radiologic interpretation.
      ]. Moreover, CT evaluation of small (≤ 1.5 cm) renal masses may be problematic, due to lesion pseudoenhancement and partial volume-averaging artifacts, which limit the assessment of contrast enhancement [
      • Patel J.
      • Davenport M.S.
      • Khalatbari S.
      • Cohan R.H.
      • Ellis J.H.
      • Platt J.F.
      In vivo predictors of renal cyst pseudoenhancement at 120 kVp.
      ,
      • Patel N.S.
      • Poder L.
      • Wang Z.J.
      • Yeh B.M.
      • Qayyum A.
      • Jin H.
      • Coakley F.V.
      The characterization of small hypoattenuating renal masses on contrast-enhanced CT.
      ,
      • Israel G.M.
      • Bosniak M.A.
      Pitfalls in renal mass evaluation and how to avoid them.
      ].
      CT findings related to lesion homogeneity and enhancement patterns are reported to correlate with RCC histologic subtypes [
      • van Oostenbrugge T.J.
      • Fütterer J.J.
      • Mulders P.F.A.
      Diagnostic imaging for solid renal tumors: a pictorial review.
      ,
      • Sheir K.Z.
      • El-Azab M.
      • Mosbah A.
      • El-Baz M.
      • Shaaban A.A.
      Differentiation of renal cell carcinoma subtypes by multislice computerized tomography.
      ,
      • Young J.R.
      • Margolis D.
      • Sauk S.
      • Pantuck A.J.
      • Sayre J.
      • Raman S.S.
      Clear cell renal cell carcinoma: discrimination from other renal cell carcinoma subtypes and oncocytoma at multiphasic multidetector CT.
      ,
      • Kim J.K.
      • Park S.Y.
      • Shon J.H.
      • Cho K.S.
      Angiomyolipoma with minimal fat: differentiation from renal cell carcinoma at biphasic helical CT.
      ]. Typical clear cell RCC enhances strongly in the corticomedullary phase (114 ± 44 HU), with a rapid washout in the nephrographic phase (66 ± 24 HU) [
      • van Oostenbrugge T.J.
      • Fütterer J.J.
      • Mulders P.F.A.
      Diagnostic imaging for solid renal tumors: a pictorial review.
      ,
      • Sheir K.Z.
      • El-Azab M.
      • Mosbah A.
      • El-Baz M.
      • Shaaban A.A.
      Differentiation of renal cell carcinoma subtypes by multislice computerized tomography.
      ]. Large clear cell RCCs are often heterogeneous, due to the presence of necrosis and/or cystic degeneration [
      • Sheir K.Z.
      • El-Azab M.
      • Mosbah A.
      • El-Baz M.
      • Shaaban A.A.
      Differentiation of renal cell carcinoma subtypes by multislice computerized tomography.
      ]. Papillary RCC is usually small, homogenous and hypovascular, with weak enhancement in the corticomedullary phase, up to 20 HU [
      • van Oostenbrugge T.J.
      • Fütterer J.J.
      • Mulders P.F.A.
      Diagnostic imaging for solid renal tumors: a pictorial review.
      ,
      • Egbert N.D.
      • Caoili E.M.
      • Cohan R.H.
      • Davenport M.S.
      • Francis I.R.
      • Kunju L.P.
      • Ellis J.H.
      Differentiation of papillary renal cell carcinoma subtypes on CT and MRI.
      ]. Absence of enhancement is seen in up to 25 % of papillary RCCs, and further evaluation with CEUS or mpMRI is advised to verify the presence of an enhancing solid tumor [
      • van Oostenbrugge T.J.
      • Fütterer J.J.
      • Mulders P.F.A.
      Diagnostic imaging for solid renal tumors: a pictorial review.
      ].
      Chromophobe RCC and renal oncocytoma share similar histologic and imaging features [
      • Lopes Vendrami C.
      • Villavicencio C.P.
      • DeJulio T.J.
      • Chatterjee A.
      • Casalino D.D.
      • Horowitz J.M.
      • Oberlin D.T.
      • Yang G.
      • Nikolaidis P.
      • Miller F.H.
      Differentiation of solid renal tumors with Multiparametric MR imaging.
      ,
      • Cornelis F.
      • Grenier N.
      Multiparametric magnetic resonance imaging of solid renal tumors: a practical algorithm.
      ,
      • Rosenkrantz A.B.
      • Hindman N.
      • Fitzgerald E.F.
      • Niver B.E.
      • Melamed J.
      • Babb J.S.
      MRI features of renal oncocytoma and chromophobe renal cell carcinoma.
      ,
      • Choudhary S.
      • Rajesh A.
      • Mayer N.J.
      • Mulcahy K.A.
      • Haroon A.
      Renal oncocytoma: CT features cannot reliably distinguish oncocytoma from other renal neoplasms.
      ,
      • Gakis G.
      • Kramer U.
      • Schilling D.
      • Kruck S.
      • Stenzl A.
      • Schlemmer H.P.
      Small renal oncocytomas: differentiation with multiphase CT.
      ]. Therefore, differential diagnosis is often difficult and histologic exploration may be needed (Fig. 4) [
      • Kay F.U.
      • Pedrosa I.
      Imaging of solid renal masses.
      ,
      • Lopes Vendrami C.
      • Villavicencio C.P.
      • DeJulio T.J.
      • Chatterjee A.
      • Casalino D.D.
      • Horowitz J.M.
      • Oberlin D.T.
      • Yang G.
      • Nikolaidis P.
      • Miller F.H.
      Differentiation of solid renal tumors with Multiparametric MR imaging.
      ,
      • Cornelis F.
      • Grenier N.
      Multiparametric magnetic resonance imaging of solid renal tumors: a practical algorithm.
      ]. Peripheral location, presence of a central stellate scar or spoke-wheel enhancement and segmental enhancement inversion are common findings for both entities [
      • Kay F.U.
      • Pedrosa I.
      Imaging of solid renal masses.
      ,
      • Lopes Vendrami C.
      • Villavicencio C.P.
      • DeJulio T.J.
      • Chatterjee A.
      • Casalino D.D.
      • Horowitz J.M.
      • Oberlin D.T.
      • Yang G.
      • Nikolaidis P.
      • Miller F.H.
      Differentiation of solid renal tumors with Multiparametric MR imaging.
      ,
      • Cornelis F.
      • Grenier N.
      Multiparametric magnetic resonance imaging of solid renal tumors: a practical algorithm.
      ,
      • Rosenkrantz A.B.
      • Hindman N.
      • Fitzgerald E.F.
      • Niver B.E.
      • Melamed J.
      • Babb J.S.
      MRI features of renal oncocytoma and chromophobe renal cell carcinoma.
      ,
      • Choudhary S.
      • Rajesh A.
      • Mayer N.J.
      • Mulcahy K.A.
      • Haroon A.
      Renal oncocytoma: CT features cannot reliably distinguish oncocytoma from other renal neoplasms.
      ,
      • Gakis G.
      • Kramer U.
      • Schilling D.
      • Kruck S.
      • Stenzl A.
      • Schlemmer H.P.
      Small renal oncocytomas: differentiation with multiphase CT.
      ,
      • Giambelluca D.
      • Pellegrino S.
      • Midiri M.
      • Salvaggio G.
      The "central stellate scar" sign in renal oncocytoma.
      ,
      • Kim J.I.
      • Cho J.Y.
      • Moon K.C.
      • Lee H.J.
      • Kim S.H.
      Segmental enhancement inversion at biphasic multidetector CT: characteristic finding of small renal oncocytoma.
      ,
      • Schieda N.
      • Al-Subhi M.
      • Flood T.A.
      • El-Khodary M.
      • McInnes M.D.F.
      Diagnostic accuracy of segmental enhancement inversion for the diagnosis of renal oncocytoma using biphasic computed tomography (CT) and multiphase contrast-enhanced magnetic resonance imaging (MRI).
      ,
      • Moldovanu C.G.
      • Petresc B.
      • Lebovici A.
      • Tamas-Szora A.
      • Suciu M.
      • Crisan N.
      • Medan P.
      • Buruian M.M.
      Differentiation of clear cell renal cell carcinoma from other renal cell carcinoma subtypes and benign oncocytoma using quantitative MDCT enhancement parameters.
      ]. Most fat-poor AMLs are hyperdense on unenhanced CT, homogeneously enhancing after contrast administration [
      • van Oostenbrugge T.J.
      • Fütterer J.J.
      • Mulders P.F.A.
      Diagnostic imaging for solid renal tumors: a pictorial review.
      ,
      • Sasaguri K.
      • Takahashi N.
      CT and MR imaging for solid renal mass characterization.
      ]. However, differentiation between fat-poor AML and RCC by CT alone is often difficult and further evaluation with mpMRI, biopsy, or even surgical resection may be required [
      • van Oostenbrugge T.J.
      • Fütterer J.J.
      • Mulders P.F.A.
      Diagnostic imaging for solid renal tumors: a pictorial review.
      ,
      • Sasaguri K.
      • Takahashi N.
      CT and MR imaging for solid renal mass characterization.
      ,
      • Park B.K.
      Renal Angiomyolipoma: Radiologic Classification and Imaging Features According to the Amount of Fat.
      ,
      • Takahashi N.
      • Leng S.
      • Kitajima K.
      • Gomez-Cardona D.
      • Thapa P.
      • Carter R.E.
      • Leibovich B.C.
      • Sasiwimonphan K.
      • Sasaguri K.
      • Kawashima A.
      Small (< 4 cm) renal masses: differentiation of angiomyolipoma without visible fat from renal cell carcinoma using unenhanced and contrast-enhanced CT.
      ,
      • Silverman S.G.
      • Israel G.M.
      • Trinh Q.D.
      Incompletely characterized incidental renal masses: emerging data support conservative management.
      ].
      Fig. 4
      Fig. 4Clear cell RCC in a woman with a history of breast cancer. (a) Axial unenhanced CT shows a left renal mass (arrow). The lesion has a CT density mainly similar to that of normal renal parenchyma and small calcifications. (b) In the corticomedullary phase, the lesion (arrow) shows strong, heterogeneous enhancement, with a washout effect in the nephrographic phase (c). (d) Renal tumor biopsy revealed a clear cell RCC.
      Recently, contrast-enhanced dual energy CT has been reported to improve the diagnostic performance of CT in the characterization of renal masses, with sensitivity and specificity greater than 95 % in the evaluation of renal tumors [
      • Salameh J.
      • McInnes M.D.F.
      • McGrath T.A.
      • Salameh G.
      • Schieda N.
      Diagnostic accuracy of dual-energy CT for evaluation of renal masses: systematic review and meta-analysis.
      ,
      • Marin D.
      • Davis D.
      • Choudhury K.R.
      • Patel B.
      • Gupta R.T.
      • Mileto A.
      • Nelson R.C.
      Characterization of small focal renal lesions: diagnostic accuracy with single-phase contrast-enhanced dual-energy CT with material attenuation analysis compared with conventional attenuation measurements.
      ]. New techniques, including CT perfusion, CT texture analysis and CT-based radiomics may provide important additional information in renal mass characterization [
      • Mazzei F.G.
      • Mazzei M.A.
      • Squitieri N.C.
      • Pozzessere C.
      • Righi L.
      • Cirigliano A.
      • Guerrini S.
      • D’Elia D.
      • Ambrosio M.R.
      • Barone A.
      • del Vecchio M.T.
      • Volterrani L.
      CT perfusion in the characterization of renal lesions: an added value to multiphasic CT.
      ,
      • Feng Z.
      • Shen Q.
      • Li Y.
      • Hu Z.
      CT texture analysis: a potential tool for predicting the Fuhrman grade of clear-cell renal carcinoma.
      ,
      • Deng Y.
      • Soule E.
      • Samuel A.
      • Shah S.
      • Cui E.
      • Asare-Sawiri M.
      • Sundaram C.
      • Lall C.
      • Sandrasegaran K.
      CT texture analysis in the differentiation of major renal cell carcinoma subtypes and correlation with Fuhrman grade.
      ,
      • Shu J.
      • Tang Y.
      • Cui J.
      • Yang R.
      • Meng X.
      • Cai Z.
      • Zhang J.
      • Xu W.
      • Wen D.
      • Yin H.
      Clear cell renal cell carcinoma: CT-based radiomics features for the prediction of Fuhrman grade.
      ,
      • Bhandari A.
      • Ibrahim M.
      • Sharma C.
      • Liong R.
      • Gustafson S.
      • Prior M.
      CT-based radiomics for differentiating renal tumours: a systematic review.
      ,
      • Lubner M.G.
      Radiomics and artificial intelligence for renal mass characterization.
      ]
      Up to now, multimodality imaging cannot always accurately characterize renal masses discovered incidentally, especially, small renal masses (≤ 4 cm) [
      • Finelli A.
      • Ismaila N.
      • Bro B.
      • Russo P.
      Management of small renal masses: american society of clinical oncology clinical practice guideline.
      ]. Percutaneous renal tumor biopsy has been shown to help avoid surgery in up to 33 % of cases initially considered to be malignant, based on imaging [
      • Vasudevan A.
      • Davies R.J.
      • Shannon B.A.
      • Cohen R.J.
      Incidental renal tumours: the frequency of benign lesions and the role of preoperative core biopsy.
      ]. Indications for renal tumor biopsy in localized RCC include small renal masses, when the results may alter management (Fig. 5) and masses with findings suggestive of lymphoma, metastasis, infectious or inflammatory lesions [
      • Sanchez A.
      • Feldman A.S.
      • Ari Hakimi A.
      Current management of small renal masses, including patient selection, renal tumor biopsy, active surveillance, and thermal ablation.
      ]. Renal tumor biopsy is also recommended before thermal ablation, as a separate procedure or just prior to treatments [
      • Sanchez A.
      • Feldman A.S.
      • Ari Hakimi A.
      Current management of small renal masses, including patient selection, renal tumor biopsy, active surveillance, and thermal ablation.
      ]. Biopsies can be performed under US or CT-guidance.
      Fig. 5
      Fig. 5Renal incidentaloma detected on US. (a) Unenhanced CT depicts an isoattenuating renal mass (arrow) in the middle of the right kidney. (b) An inhomogeneous enhancement pattern (arrow) is seen in the corticomedullary phase. The lesion (arrow) has a subtle washout effect (c) in the nephrogenic phase, becoming more intense (d) in the excretory phase. Renal tumor biopsy showed renal oncocytoma.
      CECT is widely accepted as the diagnostic modality of choice for RCC staging, with sensitivity and specificity up to 90 % [
      • Ljungberg B.
      • Albiges L.
      • Abu-Ghanem Y.
      • Bensalah K.
      • Dabestani S.
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      • Hofmann F.
      • Hora M.
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      • Kuusk T.
      • Lam T.B.
      • Marconi L.
      • Merseburger A.S.
      • Powles T.
      • Staehler M.
      • Tahbaz R.
      • Volpe A.
      • Bex A.
      European association of urology guidelines on renal cell carcinoma: the 2019 update.
      ,
      • Campbell S.
      • Uzzo R.G.
      • Allaf M.E.
      • Remer E.M.
      Renal Mass and Localized Renal Cancer: AUA Guideline.
      ,
      • Ward R.D.
      • Tanaka H.
      • Campbell S.C.
      • Remer E.M.
      2017 AUA renal mass and localized renal Cancer guidelines: imaging implications.
      ,
      • Vikram R.
      • Beland M.D.
      • Blaufox M.D.
      • Moreno C.C.
      • Gore J.L.
      • Harvin H.J.
      • Heilbrun M.E.
      • Liauw S.L.
      • Nguyen P.L.
      • Nikolaidis P.
      • Preminger G.M.
      • Purysko A.S.
      • Raman S.S.
      • Taffel M.T.
      • Wang Z.J.
      • Weinfeld R.M.
      • Remer E.M.
      • Lockhart M.E.
      ACR appropriateness criteria renal cell carcinoma staging.
      ,
      • Nakashima K.
      • Kitagawa Y.
      • Izumi K.
      • Mizokami A.
      • Gabata T.
      • Namiki M.
      Diagnostic accuracy of pre-operative imaging findings in presumed clinical T1a renal cell carcinomas.
      ,
      • Bradley A.J.
      • MacDonald L.
      • Whiteside S.
      • Johnson R.J.
      • Ramani V.A.C.
      Accuracy of preoperative CT T staging of renal cell carcinoma: which features predict advanced stage?.
      ]. RCC size and degree of local invasion determine the T stage (Table 1). Although, some studies have reported that CT often overestimates tumor size, compared to surgical specimen, discrepancies are minimal and clinically insignificant in most cases [
      • Chen W.
      • Wang L.
      • Yang Q.
      • Liu B.
      • Sun Y.
      Comparison of radiographic and pathologic sizes of renal tumors.
      ,
      • Lee S.E.
      • Lee W.K.
      • Kim D.S.
      • Doo S.H.
      • Park H.Z.
      • Yoon C.Y.
      • Hwang S.I.
      • Lee H.J.
      • Choe G.
      • Hong S.K.
      Comparison of radiographic and pathologic sizes of renal tumors.
      ]. Perinephric or renal sinus fat invasion is not always easily detected on CT [
      • Catalano C.
      • Fraioli F.
      • Laghi A.
      • Napoli A.
      • Pediconi F.
      • Danti M.
      • Nardis P.
      • Passariello R.
      High-resolution multidetector CT in the preoperative evaluation of patients with renal cell carcinoma.
      ]. Thin sections and multiplanar reformations have improved the detection of perinephric fat infiltration, although false-positives, due to inflammation, oedema, vascular engorgement, or fibrosis may be encountered [
      • Catalano C.
      • Fraioli F.
      • Laghi A.
      • Napoli A.
      • Pediconi F.
      • Danti M.
      • Nardis P.
      • Passariello R.
      High-resolution multidetector CT in the preoperative evaluation of patients with renal cell carcinoma.
      ,
      • Sokhi H.K.
      • Mok W.Y.
      • Patel U.
      Stage T3a renal cell carcinoma: staging accuracy of CT for sinus fat, perinephric fat or renal vein invasion.
      ,
      • Hallscheidt P.J.
      • Bock M.
      • Riedasch G.
      • Zuna I.
      • Schoenberg S.O.
      • Autschbach F.
      • Soder M.
      • Noeldge G.
      Diagnostic accuracy of staging renal cell carcinomas using multidetector-row computed tomography and magnetic resonance imaging: a prospective study with histopathologic correlation.
      ]. CT is highly accurate in the diagnosis of RCC spread into the renal vein, with a NPV of 97 % and PPV of 92 % [
      • Vikram R.
      • Beland M.D.
      • Blaufox M.D.
      • Moreno C.C.
      • Gore J.L.
      • Harvin H.J.
      • Heilbrun M.E.
      • Liauw S.L.
      • Nguyen P.L.
      • Nikolaidis P.
      • Preminger G.M.
      • Purysko A.S.
      • Raman S.S.
      • Taffel M.T.
      • Wang Z.J.
      • Weinfeld R.M.
      • Remer E.M.
      • Lockhart M.E.
      ACR appropriateness criteria renal cell carcinoma staging.
      ,
      • Hallscheidt P.J.
      • Fink C.
      • Haferkamp A.
      • Bock M.
      • Luburic A.
      • Zuna I.
      • Noeldge G.
      • Kauffmann G.
      Preoperative staging of renal cell carcinoma with inferior vena cava thrombus using multi- detector CT and MRI: prospective study with histopathological correlation.
      ]. CT is also effective in assessing the superior extent of inferior vena cava thrombus [
      • Lawrentschuk N.
      • Gani J.
      • Riordan R.
      • Esler S.
      • Bolton D.M.
      Multidetector computed tomography vs magnetic resonance imaging for defining the upper limit of tumour thrombus in renal cell carcinoma: a study and review.
      ].
      CT offers a high NPV in excluding adjacent organ involvement beyond the Gerota΄s fascia or involvement of the ipsilateral adrenal gland [
      • Vikram R.
      • Beland M.D.
      • Blaufox M.D.
      • Moreno C.C.
      • Gore J.L.
      • Harvin H.J.
      • Heilbrun M.E.
      • Liauw S.L.
      • Nguyen P.L.
      • Nikolaidis P.
      • Preminger G.M.
      • Purysko A.S.
      • Raman S.S.
      • Taffel M.T.
      • Wang Z.J.
      • Weinfeld R.M.
      • Remer E.M.
      • Lockhart M.E.
      ACR appropriateness criteria renal cell carcinoma staging.
      ,
      • Sawai Y.
      • Kinouchi T.
      • Mano M.
      • Meguro N.
      • Maeda O.
      • Kuroda M.
      • Usami M.
      Ipsilateral adrenal involvement from renal cell carcinoma: retrospective study of the predictive value of computed tomography.
      ,
      • Nason G.J.
      • Aslam A.
      • Giri S.K.
      Predictive ability of preoperative CT scan in determining whether the adrenal gland is spared at radical nephrectomy.
      ]. In a retrospective observational study, CT had a sensitivity of 100 %, specificity of 95.2 % and NPV of 100 % in diagnosing adrenal gland invasion [
      • Nason G.J.
      • Aslam A.
      • Giri S.K.
      Predictive ability of preoperative CT scan in determining whether the adrenal gland is spared at radical nephrectomy.
      ]. However, CT cannot always discriminate abutment from direct invasion [
      • Vikram R.
      • Beland M.D.
      • Blaufox M.D.
      • Moreno C.C.
      • Gore J.L.
      • Harvin H.J.
      • Heilbrun M.E.
      • Liauw S.L.
      • Nguyen P.L.
      • Nikolaidis P.
      • Preminger G.M.
      • Purysko A.S.
      • Raman S.S.
      • Taffel M.T.
      • Wang Z.J.
      • Weinfeld R.M.
      • Remer E.M.
      • Lockhart M.E.
      ACR appropriateness criteria renal cell carcinoma staging.
      ].
      CT tends to overdiagnose lymph node spread, which is defined as a lymph node with a short axis diameter greater than 1 cm and disruption of normal lymph node architecture. However, based on size criterion, CT has 10 % of false-negatives, while approximately 50 % of enlarged lymph nodes are proved benign [
      • Vikram R.
      • Beland M.D.
      • Blaufox M.D.
      • Moreno C.C.
      • Gore J.L.
      • Harvin H.J.
      • Heilbrun M.E.
      • Liauw S.L.
      • Nguyen P.L.
      • Nikolaidis P.
      • Preminger G.M.
      • Purysko A.S.
      • Raman S.S.
      • Taffel M.T.
      • Wang Z.J.
      • Weinfeld R.M.
      • Remer E.M.
      • Lockhart M.E.
      ACR appropriateness criteria renal cell carcinoma staging.
      ,
      • Sheth S.
      • Scatarige J.C.
      • Horton K.M.
      • Corl F.M.
      • Fishman E.K.
      Current concepts in the diagnosis and management of renal cell carcinoma: role of multidetector ct and three-dimensional CT.
      ]. Distant metastases from RCC are often found in the lungs, bones, liver, and brain and less commonly in the thyroid, pancreas, muscle, skin, and soft tissue [
      • Vikram R.
      • Beland M.D.
      • Blaufox M.D.
      • Moreno C.C.
      • Gore J.L.
      • Harvin H.J.
      • Heilbrun M.E.
      • Liauw S.L.
      • Nguyen P.L.
      • Nikolaidis P.
      • Preminger G.M.
      • Purysko A.S.
      • Raman S.S.
      • Taffel M.T.
      • Wang Z.J.
      • Weinfeld R.M.
      • Remer E.M.
      • Lockhart M.E.
      ACR appropriateness criteria renal cell carcinoma staging.
      ,
      • Griffin N.
      • Gore M.E.
      • Sohaib S.A.
      Imaging in metastatic renal cell carcinoma.
      ]. Chest CT is useful to detect lung metastases and metastatic mediastinal lymph nodes and is mainly recommended in large-sized RCCs [
      • Vikram R.
      • Beland M.D.
      • Blaufox M.D.
      • Moreno C.C.
      • Gore J.L.
      • Harvin H.J.
      • Heilbrun M.E.
      • Liauw S.L.
      • Nguyen P.L.
      • Nikolaidis P.
      • Preminger G.M.
      • Purysko A.S.
      • Raman S.S.
      • Taffel M.T.
      • Wang Z.J.
      • Weinfeld R.M.
      • Remer E.M.
      • Lockhart M.E.
      ACR appropriateness criteria renal cell carcinoma staging.
      ]. Visceral metastases tend to be hypervascular and corticomedullary phase may help detect arterial enhancement [
      • Vikram R.
      • Beland M.D.
      • Blaufox M.D.
      • Moreno C.C.
      • Gore J.L.
      • Harvin H.J.
      • Heilbrun M.E.
      • Liauw S.L.
      • Nguyen P.L.
      • Nikolaidis P.
      • Preminger G.M.
      • Purysko A.S.
      • Raman S.S.
      • Taffel M.T.
      • Wang Z.J.
      • Weinfeld R.M.
      • Remer E.M.
      • Lockhart M.E.
      ACR appropriateness criteria renal cell carcinoma staging.
      ,
      • Griffin N.
      • Gore M.E.
      • Sohaib S.A.
      Imaging in metastatic renal cell carcinoma.
      ].
      Multiplanar reformations and three-dimensional reconstructions greatly help in preoperative planning, providing important anatomic information, such as kidney position relative to the surrounding bones, tumor location and depth of extension into the kidney, relationship of the tumor to the renal collecting system, and accurate delineation of the arterial and venous anatomy [
      • Coll D.M.
      • Herts B.R.
      • Davros W.J.
      • Uzzo R.G.
      • Novick A.C.
      Preoperative use of 3D volume rendering to demonstrate renal tumors and renal anatomy.
      ,
      • Rocco F.
      • Cozzi L.A.
      • Cozzi G.
      Study of the renal segmental arterial anatomy with contrast-enhanced multi-detector computed tomography.
      ] Preoperative CT also provides information on the morphology and function of the contralateral kidney. Synchronous primary tumors should be searched for, as RCC can be multifocal [
      • Vikram R.
      • Beland M.D.
      • Blaufox M.D.
      • Moreno C.C.
      • Gore J.L.
      • Harvin H.J.
      • Heilbrun M.E.
      • Liauw S.L.
      • Nguyen P.L.
      • Nikolaidis P.
      • Preminger G.M.
      • Purysko A.S.
      • Raman S.S.
      • Taffel M.T.
      • Wang Z.J.
      • Weinfeld R.M.
      • Remer E.M.
      • Lockhart M.E.
      ACR appropriateness criteria renal cell carcinoma staging.
      ].
      CT is indicated for RCC follow-up after surgery or post-ablation, in moderate to high-risk patients [
      • Expert Panel on Urological Imaging
      • Purysko A.S.
      • Nikolaidis P.
      • Dogra V.S.
      • Ganeshan D.
      • Gore J.L.
      • Gupta R.T.
      • Heilbrun M.E.
      • Khatri G.
      • Kishan A.U.
      • Lyshchik A.
      • Savage S.J.
      • Smith A.D.
      • Wang Z.J.
      • Wolfman D.J.
      • Wong-You-Cheong J.J.
      • Yoo D.C.
      • Lockhart M.E.
      ACR appropriateness criteria post-treatment follow-up and active surveillance of clinically localized renal cell Cancer.
      ]. A baseline chest and abdominal CT within three to six months after surgery is recommended, followed by imaging every six months for at least three years and annually thereafter, for two years [
      • Donat S.
      • Diaz M.
      • Bishoff J.
      • Coleman J.A.
      • Dahm P.
      • Derweesh I.H.
      • Duke Herrell 3rd, S.
      • Hilton S.
      • Jonasch E.
      • Lin D.W.
      • Reuter V.E.
      • Chang S.S.
      Follow-up for clinically localized renal neoplasms AUA guideline.
      ].

      5. Multiparametric MRI

      Multiparametric MRI represents a valuable complementary imaging technique for the assessment of renal masses, providing both morphologic and functional information [
      • Herts B.R.
      • Silverman S.G.
      • Hindman N.M.
      • Uzzo R.G.
      • Hartman R.P.
      • Israel G.M.
      • Baumgarten D.A.
      • Berland L.L.
      • Pandharipande P.V.
      Management of the Incidental Renal Mass on CT: A White Paper of the ACR Incidental Findings Committee.
      ,
      • Expert Panel on Urologic Imaging
      • Wang Z.J.
      • Nikolaidis P.
      • Khatri G.
      • Dogra V.S.
      • Ganeshan D.
      • Goldfarb S.
      • Gore J.L.
      • Gupta R.T.
      • Hartman R.P.
      • Heilbrun M.E.
      • Lyshchik A.
      • Purysko A.S.
      • Savage S.J.
      • Smith A.D.
      • Wolfman D.J.
      • Wong-You-Cheong J.J.
      • Lockhart M.E.
      ACR appropriateness criteria® indeterminate renal mass.
      ,
      • Kay F.U.
      • Pedrosa I.
      Imaging of solid renal masses.
      ,
      • Silverman S.G.
      • Pedrosa I.
      • Ellis J.H.
      • Hindman N.M.
      • Schieda N.
      • Smith A.D.
      • Remer E.M.
      • Shinagare A.B.
      • Curci N.E.
      • Raman S.S.
      • Wells S.A.
      • Kaffenberger S.D.
      • Wang Z.J.
      • Chandarana H.
      • Davenport M.S.
      Bosniak classification of cystic renal masses, version 2019: an update proposal and needs assessment.
      ,
      • Krishna S.
      • Schieda N.
      • Pedrosa I.
      • Hindman N.
      • Baroni R.H.
      • Silverman S.G.
      • Davenport M.S.
      Update on MRI of cystic renal masses including bosniak version 2019.
      ,
      • Vikram R.
      • Beland M.D.
      • Blaufox M.D.
      • Moreno C.C.
      • Gore J.L.
      • Harvin H.J.
      • Heilbrun M.E.
      • Liauw S.L.
      • Nguyen P.L.
      • Nikolaidis P.
      • Preminger G.M.
      • Purysko A.S.
      • Raman S.S.
      • Taffel M.T.
      • Wang Z.J.
      • Weinfeld R.M.
      • Remer E.M.
      • Lockhart M.E.
      ACR appropriateness criteria renal cell carcinoma staging.
      ,
      • Expert Panel on Urological Imaging
      • Purysko A.S.
      • Nikolaidis P.
      • Dogra V.S.
      • Ganeshan D.
      • Gore J.L.
      • Gupta R.T.
      • Heilbrun M.E.
      • Khatri G.
      • Kishan A.U.
      • Lyshchik A.
      • Savage S.J.
      • Smith A.D.
      • Wang Z.J.
      • Wolfman D.J.
      • Wong-You-Cheong J.J.
      • Yoo D.C.
      • Lockhart M.E.
      ACR appropriateness criteria post-treatment follow-up and active surveillance of clinically localized renal cell Cancer.
      ,
      • Lopes Vendrami C.
      • Villavicencio C.P.
      • DeJulio T.J.
      • Chatterjee A.
      • Casalino D.D.
      • Horowitz J.M.
      • Oberlin D.T.
      • Yang G.
      • Nikolaidis P.
      • Miller F.H.
      Differentiation of solid renal tumors with Multiparametric MR imaging.
      ,
      • Cornelis F.
      • Grenier N.
      Multiparametric magnetic resonance imaging of solid renal tumors: a practical algorithm.
      ]. MRI is mainly recommended when optimal CT cannot be performed (severe allergy to iodinated CT contrast or high risk for contrast-induced nephropathy) or when radiation exposure is contraindicated (young age or pregnant women) [
      • Herts B.R.
      • Silverman S.G.
      • Hindman N.M.
      • Uzzo R.G.
      • Hartman R.P.
      • Israel G.M.
      • Baumgarten D.A.
      • Berland L.L.
      • Pandharipande P.V.
      Management of the Incidental Renal Mass on CT: A White Paper of the ACR Incidental Findings Committee.
      ,
      • Expert Panel on Urologic Imaging
      • Wang Z.J.
      • Nikolaidis P.
      • Khatri G.
      • Dogra V.S.
      • Ganeshan D.
      • Goldfarb S.
      • Gore J.L.
      • Gupta R.T.
      • Hartman R.P.
      • Heilbrun M.E.
      • Lyshchik A.
      • Purysko A.S.
      • Savage S.J.
      • Smith A.D.
      • Wolfman D.J.
      • Wong-You-Cheong J.J.
      • Lockhart M.E.
      ACR appropriateness criteria® indeterminate renal mass.
      ,
      • Kay F.U.
      • Pedrosa I.
      Imaging of solid renal masses.
      ,
      • Silverman S.G.
      • Pedrosa I.
      • Ellis J.H.
      • Hindman N.M.
      • Schieda N.
      • Smith A.D.
      • Remer E.M.
      • Shinagare A.B.
      • Curci N.E.
      • Raman S.S.
      • Wells S.A.
      • Kaffenberger S.D.
      • Wang Z.J.
      • Chandarana H.
      • Davenport M.S.
      Bosniak classification of cystic renal masses, version 2019: an update proposal and needs assessment.
      ,
      • Krishna S.
      • Schieda N.
      • Pedrosa I.
      • Hindman N.
      • Baroni R.H.
      • Silverman S.G.
      • Davenport M.S.
      Update on MRI of cystic renal masses including bosniak version 2019.
      ,
      • Vikram R.
      • Beland M.D.
      • Blaufox M.D.
      • Moreno C.C.
      • Gore J.L.
      • Harvin H.J.
      • Heilbrun M.E.
      • Liauw S.L.
      • Nguyen P.L.
      • Nikolaidis P.
      • Preminger G.M.
      • Purysko A.S.
      • Raman S.S.
      • Taffel M.T.
      • Wang Z.J.
      • Weinfeld R.M.
      • Remer E.M.
      • Lockhart M.E.
      ACR appropriateness criteria renal cell carcinoma staging.
      ,
      • Expert Panel on Urological Imaging
      • Purysko A.S.
      • Nikolaidis P.
      • Dogra V.S.
      • Ganeshan D.
      • Gore J.L.
      • Gupta R.T.
      • Heilbrun M.E.
      • Khatri G.
      • Kishan A.U.
      • Lyshchik A.
      • Savage S.J.
      • Smith A.D.
      • Wang Z.J.
      • Wolfman D.J.
      • Wong-You-Cheong J.J.
      • Yoo D.C.
      • Lockhart M.E.
      ACR appropriateness criteria post-treatment follow-up and active surveillance of clinically localized renal cell Cancer.