Chromophobe Renal Cell Carcinoma: Multiphase MDCT Enhancement Patterns and Morphologic Features

Genitourinary Imaging Original Research Raman et al. Enhancement Patterns and Morphologic Features of Chromophobe Renal Cell Carcinoma Genitourinary Imaging Original Research Siva P. Raman 1 Pamela T. Johnson 1 Mohamad E. Allaf 2 George Netto 3 Elliot K. Fishman 1 Raman SP, Johnson PT, Allaf ME, Netto G, Fishman EK Keywords: chromophobe, CT, enhancement, morphology, renal cell carcinoma DOI:10.2214/AJR.13.10813 Received February 23, 2013; accepted after revision March 26, 2013. 1 Department of Radiology, Johns Hopkins University, JHOC 3251, 601 N Caroline St, Baltimore, MD 21287. Address correspondence to S. P. Raman (srsraman3@gmail.com). 2 Department of Urology, Johns Hopkins University, Baltimore, MD. 3 Department of Pathology, Johns Hopkins University, Baltimore, MD. AJR 2013; 201:1268 1276 0361 803X/13/2016 1268 American Roentgen Ray Society Chromophobe Renal Cell Carcinoma: Multiphase MDCT Enhancement Patterns and Morphologic Features OBJECTIVE. The purpose of this investigation is to retrospectively describe morphologic features, enhancement characteristics, and clinical outcomes in a series of pathologically proven chromophobe renal cell carcinomas (RCCs). MATERIALS AND METHODS. Thirty-five patients who were imaged at a single institution between 2005 and 2012 with pathologically proven chromophobe RCC were identified, all of whom underwent preoperative renal protocol CT (unenhanced, arterial, venous, and delayed images). The morphologic characteristics of each tumor (e.g., necrosis, tumor composition, and calcification), as well as attenuation values (in Hounsfield units) of the tumor, aorta, inferior vena cava, and kidney were evaluated by a board-certified radiologist. In addition, information regarding patient demographics and survival was obtained by a separate radiologist from the electronic medical record. RESULTS. Sixty percent of the patients were men, with a mean age of 60.2 years. Forty-six percent of cases were incidentally identified, without patient symptoms. None of the patients had evidence of distant metastatic disease, either on initial staging CT or over the course of follow-up (mean, 2.0 years). Mean maximal tumor diameter was 5.24 cm. Forty-six percent of tumors were homogeneous, 85% of lesions were either completely solid or mostly solid, 14% showed calcifications, and 34% showed a central scar or necrosis. Mean maximum attenuation values were 87.9 HU (arterial phase), 83.9 HU (venous phase), and 60.6 HU (delayed phase), with an average delayed washout of 31%. Tumor-to-cortex ratios for the three enhanced phases were 0.59, 0.48, and 0.50, respectively. CONCLUSION. Chromophobe RCCs were found to have a wider variability of CT features than previously reported, although they do have a greater propensity for homogeneity and the presence of a central scar or necrosis. Their enhancement characteristics fall in between those of clear cell and papillary RCC, although there is considerable overlap. C hromophobe renal cell carcinoma (RCC), which accounts for 4 6% of all RCCs, is a rare RCC subtype whose cells are thought to differentiate toward the type B intercalated cells of the cortical collecting duct [1]. Chromophobe RCCs reportedly have the best prognosis of all of the different RCC subtypes, with a 5-year survival rate of over 90%, as opposed to clear cell and papillary RCCs, which have rates of survival of 55 60% and 80 90%, respectively [2 4]. This subtype of RCC is unusual histopathologically, as evidenced by the fact that Fuhrman grading (which is commonly used to histologically grade conventional RCCs) is not used in the histopathologic evaluation of chromophobe RCCs and is not thought to be predictive of ultimate clinical outcomes [5]. Despite their unique histopathologic profile and superior clinical outcomes, the CT characteristics (both in terms of morphologic features and enhancement) of chromophobe RCCs have not been well described in the literature. The few studies in the literature that have examined this topic have either grouped chromophobe RCCs with other nonconventional RCCs or consist of relatively low numbers of subjects [3, 6 12]. In general, chromophobe RCCs have traditionally been thought to present as homogeneous masses that are hypovascular relative to clear cell RCCs, although few studies have attempted to systematically study the appearance of these rare tumors [8]. To our knowledge, this study is the largest radiology series of chromophobe RCCs performed with a consistent CT technique. The purpose 1268 AJR:201, December 2013

Enhancement Patterns and Morphologic Features of Chromophobe Renal Cell Carcinoma of our study was, therefore, to describe the morphologic features, enhancement characteristics, and clinical outcomes in a series of pathologically proven chromophobe RCCs. Materials and Methods Study Population and Clinical Parameters This study was approved by our institutional review board with a waiver of informed consent for record and CT review. A search of the pathology database for all cases of chromophobe RCCs at our institution from 1995 to 2013 yielded a total of 172 patients who had undergone either surgical resection or imaging-guided biopsy. A total of 35 patients who underwent imaging at our institution with a dedicated renal protocol CT (all between 2005 and 2012) were identified. Correlation with the electronic medical record was conducted to determine clinical and demographic information, including age, sex, presenting symptoms, the presence or absence of microscopic hematuria, the type of surgery or intervention performed for treatment of the tumor, and postsurgical follow-up. Pathology Review Pathology reports for each patient were retrospectively reviewed by a board-certified radiologist (separate from the radiologist who reviewed the imaging studies), and each patient who had undergone surgical resection was assigned a TNM category according to the World Health Organization criteria [4]. Notably, only patients who had undergone lymph node dissection (n = 3) could be assigned an N category, whereas all patients who had undergone surgery with curative intent could be assigned a T category. The M category was assigned on the basis of the patient s initial CT examination, rather than the pathology results. TABLE 1: Patient Demographics, Clinical Information, and Pathologic Findings for 35 Patients With Chromophobe Renal Cell Carcinoma Characteristic Value Age (y), mean (median) [range] 60.2 (61) [29 80] Sex, no. (%) of patients Male 21 (60) Female 14 (40) Type of intervention Partial nephrectomy 17 Radical nephrectomy 16 Percutaneous cryoablation 2 Presenting symptoms Flank pain 12 Gross hematuria 6 Urinary tract infection 1 Back pain 1 Dysuria 1 None (incidental finding) 16 Presence of microscopic hematuria 8 Duration of follow-up (y), mean (range) 2.0 (0.02 6.43) Evidence of recurrence or metastases 0 Note Except where noted otherwise, data are number of patients. MDCT Imaging Review If more than one renal protocol CT was available for review, the CT study performed closest in time to the patient s surgery or cryoablation was chosen for review. Most patients underwent definitive surgery or cryoablation within 6 weeks of their CT acquisition (range, 0.14 50.84 weeks; average, 7.6 weeks). All reviewed MDCT examinations were performed on one of three different MDCT scanners, all from Siemens Healthcare, in use at our institution during the time course of the study: Somatom Sensation 16 (detector collimation, 16 0.75 mm; reconstruction at 3-mm slice thickness and 3-mm slice interval for diagnostic interpretation; reconstruction at 0.75-mm slice thickness and 0.5-mm intervals for multiplanar reformation [MPR] and interactive 3D rendering; 120 kvp; and 150 200 mas), Somatom Sensation 64 (detector collimation, 64 0.6 mm; reconstruction at 3-mm slice thickness and 3-mm slice interval for diagnostic interpretation; reconstruction at 0.75-mm slice thickness and 0.5-mm intervals for MPR and interactive 3D rendering; 120 TABLE 2: Pathologic Findings and Tumor Staging kvp; and 150 200 mas), and Somatom Definition Flash dual-source (detector collimation, 128 0.6 mm; reconstruction at slice thickness of 3 mm and 3-mm slice interval for diagnostic interpretation; Finding No. of Patients T category T1 21 T2 6 T3 6 T4 0 N category N0 2 N1 1 M category (at presentation) M0 35 Mx 0 Staging at initial CT Suspicious lymphadenopathy 3 Tumor thrombus 0 Distant metastatic disease 0 Note T category could not be determined for two patients who underwent percutaneous cryoablation (following biopsy), rather than surgical resection. N category could be formally determined for only three patients who had a lymph node sampled at surgery. M category is based on the presence or absence of distant metastatic disease on initial CT. AJR:201, December 2013 1269

Raman et al. reconstruction at 0.75-mm slice thickness and 0.5- mm intervals for MPR and interactive 3D rendering; 120 kvp; and quality reference 290 mas for online dose modulation system [CareDose 4D, Siemens Healthcare]). The current renal protocol includes acquisition of unenhanced images through the kidneys, followed by arterial, venous, and delayed phase images at 25 30 seconds, 50 60 seconds, and 5 minutes, respectively, after the administration of IV contrast agent. In this series, 10 of the 35 patients (mostly imaged before 2008) did not have venous phase imaging performed. The contrast agent used was either iohexol (Omnipaque 350, GE Healthcare) or iodixanol (Visipaque 320, GE Healthcare) infused rapidly through a peripheral IV at 3 5 ml/s and water as an oral contrast agent. At present, axial images as well as MPRs (coronal and sagittal) are generated at the CT scanner and sent to the PACS. For older cases, MPRs were created at the PACS by the interpreting radiologist. Image Analysis All available CT studies were reviewed by a board-certified attending radiologist with subspecialty training in abdominal imaging and 8 years of TABLE 3: Morphologic Features of 35 Chromophobe Renal Cell Carcinomas at CT Analysis Feature Value Size (cm), mean (range) 5.24 (1.6 17.1) Location Upper pole 7 (20) Interpolar 15 (43) Lower pole 12 (34) Entire kidney 1 (3) Distance from collecting system < 4 mm 30 (86) 4 7 mm 1 (3) > 7 mm 4 (11) Tumor configuration 100% solid 18 (51) Mostly solid with small cystic components 12 (34) Equally solid and cystic 4 (11) Mostly cystic with small solid components 1 (3) Tumor heterogeneity Homogeneous 16 (46) Heterogeneous 19 (54) Central scar or necrosis 12 (34) Calcification 5 (14) Well circumscribed 28 (80) Note Except where noted otherwise, data are no. (%) of tumors. postfellowship experience. The following tumor parameters were evaluated for each CT scan: location (right vs left kidney; upper pole, interpolar, or lower pole), distance from the collecting system (< 4, 4 7, or > 7 mm), composition (100% solid, mostly solid with a small cystic component, equally cystic and solid, mostly cystic with a small solid component, or 100% cystic), maximum diameter (in any dimension), presence or absence of central scar or necrosis, presence or absence of calcification, wellcircumscribed shape versus poorly circumscribed (i.e., irregular margins, lobulation, and so forth), and heterogeneous versus homogeneous tumor. The presence of distant metastatic disease, suspicious lymphadenopathy, or tumor thrombus was noted. Additionally, the following Hounsfield unit measurements were conducted: aorta and inferior vena cava on all four phases; tumor on all four phases, with maximum and minimum density measured for heterogeneous masses; kidney cortex and medulla on arterial and venous phase images; and kidney parenchyma on the unenhanced and delayed images. Notably, for tumors deemed to be homogeneous, a region of interest was selected that encompassed roughly 50% of the tumor area on the selected image. For tumors deemed to be heterogeneous, a region of interest was selected that encompassed the majority of the maximally or minimally attenuating portions of the tumor. Results Patient Demographics, Clinical Information, and Pathology Patient age, sex, presenting symptoms, presence of hematuria, type of intervention performed, and clinical follow-up are summarized in Table 1. The majority of patients were male (60%) and most patients (94%) underwent surgery with curative intent (except for two patients who underwent percutaneous biopsy followed by cryoablation). Notably, 16 of the 35 (45.7%) patients were incidentally discovered to have a tumor on imaging performed for other reasons (subsequently confirmed on a formal renal mass protocol CT performed at our institution), whereas the most common symptom was flank pain (34%). Only six patients presented with gross hematuria, and an additional eight patients were discovered to have microscopic hematuria. Review of the imaging and clinical records for patients after their surgeries revealed no instances of recurrent or metastatic disease (mean follow-up, 2.0 years). Pathologic and Imaging-Based Staging Table 2 summarizes the T and N staging for each of the tumors based on retrospective review of postoperative pathology reports. Initial staging of each patient (distant metastatic disease, suspicious lymphadenopathy, and presence of tumor thrombus) based on the patient s initial staging CT examination is also detailed. Notably, none of the patients had evidence of metastatic disease at presentation (M0), and only one patient was found to have positive lymph node spread after lymph node dissection. Tumor Morphologic Features on CT Table 3 summarizes the morphologic features for each of the 35 patients tumors. The vast majority (85%) of lesions were either completely solid (51%) or mostly solid (34%). Fourteen percent had a sizeable cystic component, whereas an additional 35% had at least a tiny cystic component (Figs. 1 3). Calcification was uncommon (14%), whereas necrosis or a central scar was seen in 34% (Figs. 4 and 5). A roughly equivalent number of lesions were deemed to be homogeneous (46%) and heterogeneous (54%). Tumor Location Tumors were identified in upper pole, mid pole, and lower pole. The vast majority (86%) 1270 AJR:201, December 2013

Enhancement Patterns and Morphologic Features of Chromophobe Renal Cell Carcinoma Fig. 1 45-year-old man with surgically proven 6.7- cm chromophobe renal cell carcinoma discovered in left kidney after he presented with acute left flank pain. A D, Lesion (arrow) is well-circumscribed and homogeneous, with maximum attenuation value measurements of 33, 94, 90, and 57 HU on unenhanced (A), arterial (B), venous (C), and delayed (D) images, respectively. of lesions were located within 4 mm of the collecting system, with only 11% more than 7 mm from the collecting system. Tumor Multiphase Attenuation Values on CT Table 4 summarizes the attenuation values for the 35 patients tumors over the unenhanced, arterial, venous, and delayed phases. For heterogeneous lesions, both the highest attenuation focus (maximum) and lowest attenuation focus (minimum) are reported. The maximum attenuation values for each phase are presented as a scatterplot in Figure 6. The chromophobe RCCs in our series showed maximum attenuation values of 87.9 HU (54.6 HU enhancement), 83.9 HU (51.4 HU enhancement), and 60.6 HU (27.3 HU enhancement) in the arterial, venous, and delayed phases respectively. Sixteen of the 35 lesions had an attenuation over 84 HU in the arterial phase, 15 were over 90 HU, and nine were over 100 HU (Figs. 7 and 8). The tumors had an average washout (arterial [delayed / arterial HU]) of 31%. In addition, the ratios of the maximum tumor attenuation value relative to the renal parenchyma (unenhanced and delayed phases), renal cortex and medulla (arterial and venous phases), aorta, and inferior vena cava are also reported. The tumor-to-cortex ratios for chromophobe RCCs in our series were 0.59, 0.48, and 0.50. Tumor Enhancement Values on Multiphase CT Table 5 summarizes tumor multiphase enhancement (relative to the unenhanced images, calculated as enhanced phase minus unenhanced phase), with both the maximally and minimally attenuating regions of interest in each tumor listed for those with appreciable heterogeneity. Discussion Chromophobe RCCs are the third most common subtype of RCC and account for fewer than 6% of RCCs [1]. In our series, the average patient age was 60.2 years, and 60% of patients were male, comparable to the largest existing series in the pathology literature (which included 185 subjects), to our knowledge, where the average patient age was 57.9 years and 57% of patients were male [5]. Chromophobe RCCs have a significantly better prognosis compared with other RCC variants (clear cell and papillary), with over 85% of patients with chromophobe RCC having stage I or II disease at presentation and fewer than 5% with evidence of tumor thrombus [13, 14]. In the large pathology series by Cheville et al. [5], only eight of 185 patients had evidence of distant metastatic disease, only seven had evidence of locoregional lymphadenopathy, and 85% were found to have stage I or II disease. Similarly, in another large pathology series from the Mayo Clinic [4], only three of 102 cases had evidence of locoregional lymphadenopathy, and only five had distant metastatic disease. Nevertheless, these tumors retain the potential for aggressive behavior, with the liver thought to be the most common site of metastasis [15]. The cases in our series are supportive of a positive prognosis for these patients. None of the 35 patients in our series had evidence of distant metastatic disease or tumor thrombus, and only one patient was found to have locoregional lymph node metastasis on surgical lymph node dissection. Furthermore, available follow-up for an average A C of 2 years showed no evidence of postoperative recurrences or metastases. From a morphologic perspective on CT, although some series have suggested that chromophobe RCCs may have a higher rate of calcification (as high as 38% according to Kim et al. [3]), only 14% of chromophobe RCCs in our series had calcification, comparable to rates previously noted for clear cell RCCs [2, 6]. The vast majority of lesions were either completely solid or mostly solid (85%), whereas only 3% were predominantly cystic (with small solid enhancing components) and 12% were equally cystic and solid (Figs. 1 3). This is broadly concordant with rates reported for RCCs overall (all subtypes), which are thought to present as primary cystic lesions in 4 15% of cases [16]. Prior investigations have reported that homogeneity is a characteristic of chromophobe RCC more than for papillary and clear cell variants, with homogeneous enhancement reported in up to 69 75% of chromophobe RCCs [2, 3, 9]. However, fewer than half (46%) of tumors in our series showed ho- B D AJR:201, December 2013 1271

Raman et al. A Fig. 2 68-year-old woman with 4.2-cm surgically proven chromophobe renal cell carcinoma in right kidney that was incidentally discovered. A C, Lesion (arrow) is well-circumscribed and homogeneous, with maximum attenuation value measurements of 137, 97, and 62 HU on arterial (A), venous (B), and delayed (C) images, respectively. A A B B B Fig. 3 79-year-old woman with 4-cm cystic chromophobe renal cell carcinoma discovered after she presented with left flank pain and gross hematuria. A and B, Venous (A) and delayed (B) images show predominantly cystic mass (arrow) in left kidney with mural soft tissue. Fig. 4 60-year-old man with 5.6-cm surgically proven chromophobe renal cell carcinoma that was incidentally discovered. A and B, Arterial (A) and venous (B) phase images show well-circumscribed relatively hypovascular mass (arrow) in left kidney with well-defined central scar and necrosis. This mass had maximum attenuation of 83 HU on arterial phase, 66 HU on venous phase, and 63 HU on delayed images (not shown). C mogeneous enhancement, even though the tumors in our series were slightly smaller (mean, 5.2 cm) than the chromophobe RCCs in series by Kim et al. [3] and Sheir et al. [2]. Nevertheless, this was still a considerably higher rate of tumor homogeneity compared with rates reported for clear cell and papillary RCCs (7% and 12%, respectively) [2, 3, 9]. Interestingly, the presence of heterogeneity has long been known to be associated with tumor aggressiveness and poor clinical outcomes [4]. In studies by Zhang et al. [6] and Choi et al. [10], renal 1272 AJR:201, December 2013

Enhancement Patterns and Morphologic Features of Chromophobe Renal Cell Carcinoma lesions with heterogeneous mixed enhancement were more likely to behave aggressively. As a result, given the relatively nonaggressive biologic behavior of these tumors, it is not surprising that chromophobe RCCs are more likely to be homogeneous in appearance. In a series by Sheir et al. [2], 75% of chromophobe lesions had homogeneous enhancement, whereas 70% of clear cell and 69% of papillary lesions had heterogeneous enhancement. Similarly, Jung et al. [8] found that heterogeneous lesions were statistically more likely to represent clear cell RCCs (as opposed to non clear cell subtypes). The rate at which chromophobe tumors exhibit cystic changes has been reported at 4 25% [6]. In our series, 48% showed some cystic component. This higher rate could potentially reflect the improved image quality afforded by the newer CT scanners used in our investigation, compared with the 4- and 16- MDCT scanners used by Zhang et al. [6]. Approximately one third (34%) of the chromophobe lesions in our series had a central scar or necrosis, features traditionally associated with poor clinical outcomes [17]. Specifically, necrosis has been associated with poorer outcomes in chromophobe tumors in at least one account in the literature [4]. Other studies in the literature have also suggested that the presence of central necrosis may actually be more likely with chromophobe RCCs compared with clear cell or papillary variants [18 21]. In other words, although chromophobe RCCs tend to be homogeneous in appearance, those that are heterogeneous are more likely to have frank central necrosis or a scar (Figs. 4 and 5). As a result, it is not surprising that Rosenkrantz et al. [19] were unable to find any difference in morphologic features on MRI be- A B C Fig. 5 60-year-old woman with large 11.5-cm surgically proven chromophobe renal cell carcinoma discovered after she presented with back pain. A C, Axial unenhanced (A), axial arterial (B), and coronal arterial (C) images show large mass (arrow) in right kidney with central scar and calcifications. tween a small group of chromophobe RCCs and oncocytomas (a benign renal lesion associated with a central scar). TABLE 4: Multiphase Attenuation Values for Chromophobe Renal Cell Carcinomas CT Phase Attenuation (HU) Unenhanced Overall 33.3 ± 6.1 Tumor-to-kidney ratio 1.2 ± 0.25 Tumor-to-aorta ratio 0.8 ± 0.16 Tumor-to-IVC ratio 0.8 ± 0.16 Arterial phase (25 30 seconds) Maximum 87.9 ± 34.6 Minimum 49.2 ± 30.6 Tumor-to-renal cortex ratio 0.59 ± 0.20 Tumor-to-renal medulla ratio 1.75 ± 0.63 Tumor-to-aorta ratio 0.33 ± 0.17 Tumor-to-IVC ratio 1.9 ± 0.90 Venous phase (60 seconds) Maximum 83.9 ± 22.2 Minimum 53.96 ± 30 Tumor-to-renal cortex ratio 0.48 ± 0.11 Tumor-to-renal medulla ratio 0.80 ± 0.47 Tumor-to-aorta ratio 0.57 ± 0.15 Tumor-to-IVC ratio 0.90 ± 0.28 Delayed phase (5 minutes) Maximum 60.6 ± 13.9 Minimum 42.7 ± 17.9 Tumor-to-kidney ratio 0.5 ± 0.10 Tumor-to-aorta ratio 0.66 ± 0.14 Tumor-to-IVC ratio 0.68 ± 0.14 Note Data are mean ± SD. IVC = inferior vena cava. The enhancement characteristics of both the clear cell and papillary variants of RCC have been well described previously [3, 6 9, AJR:201, December 2013 1273

Raman et al. Attenuation Value (HU) 200 180 160 140 120 100 80 60 40 20 0 Unenhanced Arterial Venous Delayed Fig. 7 58-year-old man with 8.6-cm surgically proven chromophobe renal cell carcinoma (RCC) that was incidentally discovered. Arterial phase image shows large avidly enhancing mass (arrow) in left kidney with attenuation value of 122 HU. Mass was prospectively thought to be clear cell RCC. 22, 23]. Kim et al. [3] reported clear cell variants to have a mean attenuation of 149 HU in the corticomedullary phase (106 HU enhancement) and a mean attenuation of 95 HU in the excretory phase (62 HU enhancement). Values over 84 HU in the arterial phase and 44 HU in the excretory phase were thought to be predictive of clear cell RCC [3]. Bird et al. [23] reported mean attenuation values (for clear cell RCC) of 110, 108, and 82 HU in the arterial, venous, and delayed phases, respectively, with tumor-to-cortex enhancement ratios of 0.63, 0.51, and 0.53, respectively. Jung et al. [8] found mean attenuation values of 127 Fig. 6 Scatterplot showing attenuation values for each of 35 tumors in each phase of enhancement. Trend line shows mean Hounsfield units at each time point. Symbols represent individual tumors. Fig. 8 53-year-old man with surgically proven small 1.7-cm chromophobe renal cell carcinoma (RCC) that was incidentally discovered. Arterial phase image shows small mass (arrow) in right kidney with intense focal enhancement (191 HU). Mass was prospectively thought to be clear cell RCC. and 105 HU for clear cell tumors in the corticomedullary and nephrographic phases, respectively. Shebel et al. [7] reported 44% enhancement washout for clear cell RCCs in the delayed phase, and suggested a cutoff of 90 HU in the arterial phase as being highly predictive of a clear cell tumor. Jinzaki et al. [9] found an attenuation value of greater than 100 HU for every clear cell tumor in their series. In a study focusing on MRI, Kim et al. [11] reported clear cell RCCs to have greater increases in signal intensity in the corticomedullary phase and higher tumor-to-cortex signal ratios in the corticomedullary and nephrographic phases relative to non clear cell RCCs on dynamic contrast-enhanced MRI. In contrast, papillary RCCs have been shown to be hypovascular, with significantly lower attenuation levels and enhancement, as well as lower tumor-to-aorta and tumor-to-kidney ratios in the arterial and delayed phases. Herts et al. [22] suggested that the strongest predictor of a papillary RCC was a tumor-to-kidney attenuation ratio of less than 0.25 in the arterial phase and a tumor-to-kidney attenuation ratio of less than 0.25 in the excretory phase. Jung et al. [8] reported mean attenuation values of 64 HU (enhancement of 36 HU) in the corticomedullary phase and 72 HU (enhancement of 43 HU) in the excretory phase. Jinzaki et al. [9] reported even lower values of 48.6 and 62.5 HU in the corticomedullary and excretory phases, respectively. Bird et al. [23] reported mean attenuation values of 73, 86, and 65 HU in the arterial, venous, and delayed phases, respectively, with tumor-to-cortex ratios of 0.36, 0.34, and 0.35, respectively. Shebel et al. [7] reported no significant contrast agent washout in the venous or excretory phases. In general, the chromophobe RCCs in our series appeared to be hypoenhancing compared with clear cell RCCs in other series, with maximum attenuation values of 87.9 HU (54.6 HU enhancement), 83.9 HU (51.4 HU enhancement), and 60.6 HU (27.3 HU enhancement) in the arterial, venous, and delayed phases, respectively. These values were comparable to those from a study by Young et al. [12], who reported attenuation values of 78.5, 89.5, and 63.0 HU in the corticomedullary, nephrographic, and excretory phases, respectively. Unlike their series, however, the attenuation values for the tumors in our study peaked in the arterial phase, rather than the nephrographic phase [12]. Notably, however, although values of 84, 90, and 100 HU have variously been used in the literature as potential predictive cut-offs for clear cell RCCs, 16 of the 35 lesions in our series had an attenuation over 84 HU in the arterial phase, 15 were over 90 HU, and nine were over 100 HU, despite using comparable contrast media and infusion rates. Moreover, although the tumor-to-cortex ratios for chromophobe RCCs were 0.59, 0.48, and 0.50, slightly lower than those reported by Bird et al. [23], there was significant overlap, with several lesions showing higher values (Figs. 7 and 8). Overall, using the mean values, chromophobe RCCs had an average washout (arterial [delayed / arterial HU]) of 31%. On the other hand, the absolute tumor attenuation values for the chromophobe RCCs in our series 1274 AJR:201, December 2013

Enhancement Patterns and Morphologic Features of Chromophobe Renal Cell Carcinoma TABLE 5: Multiphase Tumor Enhancement Values CT Phase Enhancement Relative to Unenhanced Images (HU) Unenhanced N/A Arterial phase (25 30 seconds) Maximum 54.6 ± 32.8 Minimum 15.97 ± 30.9 Venous phase (60 seconds) Maximum 51.4 ± 22.1 Minimum 21.4 ± 30.9 Delayed phase (5 minutes) Maximum 27.3 ± 12.8 Minimum 5.9 ± 14.4 Note Data are mean ± SD. N/A = not applicable. were perhaps slightly higher than those reported for papillary RCCs in the literature, and the tumor-to-cortex ratios were higher than those reported by Bird et al. Ultimately, from an enhancement perspective, although these lesions have traditionally been broadly grouped together with papillary RCCs, there is significant overlap of individual tumors with the enhancement characteristics of clear cell RCCs, and, on the whole, these lesions are likely slightly more vascular than the values reported for papillary RCCs (especially when taking into account their tumor-to-cortex enhancement ratios). It should be acknowledged, however, that there are several limitations to our study: First, given the rarity of chromophobe RCCs, our series is limited by a relatively small sample size, as well as the retrospective nature of our study. Second, in terms of evaluating the long-term prognosis for this group of patients, our follow-up is nonuniform, because a few patients were lost to follow-up relatively soon after surgery. Moreover, given that the patients in our series all received their diagnoses after 2005, long-term follow-up data are not available. Although these patients have done very well in the short term, long-term follow-up would be helpful to evaluate for late recurrences. Conclusion Although there is a greater variability in the morphologic appearance and enhancement characteristics of chromophobe RCCs than previously described in the literature, with substantial overlap in the tumor s appearance compared with clear cell and papillary variants, certain features in a lesion s appearance should at least raise the possibility of a chromophobe RCC. Our retrospective study of 35 patients imaged with 16-, 64-, or 128-MDCT suggests that chromophobe RCCs are most likely to present as a well-circumscribed relatively homogeneous mass, often with a central scar and an enhancement pattern that is hypovascular relative to clear cell RCC and mildly hypervascular relative to papillary variants. In some cases, raising the possibility of this diagnosis prospectively may be clinically useful, because nephron-sparing surgery should certainly be considered for these tumors given their almost universally positive prognosis. Although none of the tumors in our series had evidence of distant metastatic disease at presentation or during the average 2-year follow-up period, longer-term follow-up studies are warranted to determine whether features such as necrosis and cystic components on IV contrast-enhanced CT are associated with disease recurrence, given the propensity of RCC for late presentation of metastatic disease or recurrence. References 1. Prasad SR, Humphrey PA, Catena JR, et al. Common and uncommon histologic subtypes of renal cell carcinoma: imaging spectrum with pathologic correlation. RadioGraphics 2006; 26:1795 1806; discussion, 1806 1810 2. Sheir KZ, El-Azab M, Mosbah A, El-Baz M, Shaaban AA. 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