Published online before print June 20, 2003, 10.1148/radiol.2282020922
(Radiology 2003;228:330-334.)
© RSNA, 2003
Distinction of Renal Cell Carcinomas from High-Attenuation Renal Cysts at Portal Venous Phase Contrast-enhanced CT1
Michael Suh, MD,
Fergus V. Coakley, MD,
Aliya Qayyum, MD,
Benjamin M. Yeh, MD,
Richard S. Breiman, MD and
Ying Lu, PhD
1 From the Department of Radiology, Box 0628, M-372, University of California San Francisco, 505 Parnassus Ave, San Francisco, CA 94143-0628. Received July 26, 2002; revision requested September 30; revision received October 8; accepted December 19. Address correspondence to F.V.C. (e-mail: fergus.coakley@radiology.ucsf.edu).
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ABSTRACT
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PURPOSE: To determine if renal cell carcinomas can be distinguished from high-attenuation renal cysts on portal venous phase contrast material–enhanced computed tomographic (CT) scans.
MATERIALS AND METHODS: Fifty-seven renal cell carcinomas and 37 high-attenuation (>20 HU) renal cysts that were at least 1 cm in diameter were retrospectively identified in 90 patients who underwent portal venous phase contrast-enhanced CT. Two independent readers recorded the CT number and degree of internal heterogeneity (uniform or mildly, moderately, or markedly heterogeneous) of all lesions. Logistic regression analysis with adjustment for the two readers was used to examine the association between clinical and CT parameters and the final diagnosis. Stepwise logistic regression analysis was used to identify independent distinguishing variables, which were then incorporated in a classification and regression tree analysis to construct the most efficient classification algorithm.
RESULTS: Renal cell carcinomas were of significantly greater size (5.10 cm vs 2.84 cm, P < .001), mean attenuation (101.2 HU vs 55.3 HU, P < .001), and internal heterogeneity (P < .001) than high-attenuation renal cysts. Stepwise logistic regression showed attenuation and internal heterogeneity were both independent variables associated with final diagnosis, but lesion size was not an independent distinguishing variable after adjustment for internal heterogeneity. Classification and regression tree analysis demonstrated that an attenuation greater than 70 HU or the presence of moderate or marked internal heterogeneity was an accurate sign of renal cell carcinoma, with a sensitivity of 91% (52 of 57) for both readers and a specificity of 92% (34 of 37) for reader 1 and 84% (31 of 37) for reader 2.
CONCLUSION: On portal venous phase contrast-enhanced CT scans, attenuation greater than 70 HU or moderate or marked internal heterogeneity favor a diagnosis of renal cell carcinoma over a diagnosis of high-attenuation renal cyst.
© RSNA, 2003
Index terms: Kidney, cysts 81.311 • Kidney neoplasms, CT, 81.12112, 81.324
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INTRODUCTION
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Up to 61% of renal cell carcinomas are asymptomatic and are discovered incidentally during abdominal computed tomography (CT) or other imaging performed for unrelated reasons (1). Such CT examinations are frequently performed only in the portal venous phase of contrast material enhancement because renal abnormalities are unsuspected and nonenhanced images are not acquired. The incidental discovery of a renal lesion that has an attenuation greater than that of simple fluid (ie, -20 to +20 HU) (2,3) at CT with only a single phase of enhancement is a common diagnostic dilemma, since considerations include both renal cell carcinoma and high-attenuation (hyperdense or hemorrhagic) renal cyst (4,5). Renal cell carcinoma can generally be distinguished from high-attenuation renal cysts with additional imaging studies, including multiphase CT, ultrasonography (US), or magnetic resonance (MR) imaging (3,4,6). However, such additional imaging is burdensome for the patient, and, in our experience, recommendations for additional imaging studies of high-attenuation renal lesions are not always followed. For such reasons, findings at portal venous phase contrast material–enhanced CT that might distinguish renal cell carcinomas from high-attenuation renal cysts would be of clinical benefit. We therefore undertook this study to determine if renal cell carcinomas can be distinguished from high-attenuation renal cysts at portal venous phase contrast-enhanced CT.
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MATERIALS AND METHODS
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Subjects
This was a retrospective single-institutional study and was approved by our Committee on Human Research. Written informed consent was not required. We identified patients who were suspected of having a high-attenuation renal cyst on the basis of CT findings obtained between January 1997 and December 2001. For this purpose, we used a computerized search of CT reports in our radiology information system (IDXrad, version 9.7.1; IDX Systems, Burlington, Vt). The search terms used were "high density," "hyperdense," or "hyper-attenuating" and "kidney" or "renal." An experienced radiologist (M.S.) reviewed all images of these patients and used the following criteria to identify further those patients with a proven high-attenuation renal cyst. First, the radiologist searched for the presence of a renal mass of at least 1 cm in maximal transverse diameter with a CT attenuation greater than 20 HU. (Lesions less than 1 cm in maximal transverse diameter were excluded because partial volume artifact limits attenuation measurements in these smaller lesions.) Second, the radiologist ensured the cystic nature was confirmed with multiphase CT, US, or MR imaging. Lesions were considered cystic if absence of enhancement was confirmed on nonenhanced and contrast-enhanced CT scans (Fig 1) (4). Enhancement was defined as an increase in attenuation of at least 10 HU (7). Lesions were considered cystic on US images if they were anechoic or minimally echogenic with posterior acoustic enhancement (3,4). Lesions were considered cystic on MR images if the lesion was well demarcated with a smooth thin wall, did not enhance, and had signal intensity similar to that of fluid on T2-weighted images (8).
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Figure 1a. (a) Nonenhanced transverse CT section in a 56-year-old man undergoing multiphase surveillance CT after previously undergoing pancreaticoduodenectomy for pancreatic adenocarcinoma. A 3.0-cm high-attenuation (65-HU) mass (arrow) is visible arising from the lower pole of the right kidney. (b) Portal venous phase contrast-enhanced transverse CT section shows the mass is not enhancing and has a contrast-enhanced attenuation of 62 HU. These findings are characteristic of a high-attenuation renal cyst.
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Figure 1b. (a) Nonenhanced transverse CT section in a 56-year-old man undergoing multiphase surveillance CT after previously undergoing pancreaticoduodenectomy for pancreatic adenocarcinoma. A 3.0-cm high-attenuation (65-HU) mass (arrow) is visible arising from the lower pole of the right kidney. (b) Portal venous phase contrast-enhanced transverse CT section shows the mass is not enhancing and has a contrast-enhanced attenuation of 62 HU. These findings are characteristic of a high-attenuation renal cyst.
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Thirty-seven high-attenuation cysts were identified in 34 patients (one patient had two lesions and another patient had three). Diagnosis was confirmed with multiphase contrast-enhanced CT in 29 cysts, with US in six, and with MR imaging in two. The 34 patients consisted of 23 men and 11 women with a mean age of 65.8 years (range, 36–84 years).
We searched computerized pathology reports for the term "renal cell carcinoma" to identify patients who underwent surgery between January 1997 and December 2001 and who had a diagnosis of renal cell carcinoma. An experienced radiologist (M.S.) reviewed the images of these patients to identify further those who underwent a preoperative contrast-enhanced CT examination and had a tumor of at least 1 cm in maximal transverse diameter. Cystic renal cell carcinomas were also excluded, since they have a distinctive appearance and are unlikely to be confused with high-attenuation renal cysts and since our primary aim was to investigate the distinction of high-attenuation renal cysts from solid renal cell carcinomas. Cavitating tumors were not considered cystic (9) and were included. Fifty-seven solid renal cell carcinomas were identified in 57 patients with a mean patient age of 63.5 years (range, 42–84 years), of whom 35 were men and 22 were women.
There were 90 patients in the study because one patient belonged to both the group of 34 patients with high-attenuation cysts and the group of 57 patients with renal cell carcinoma. Clinical indications for CT scanning were known or suspected renal mass (n = 40), extrarenal malignancy (n = 20), hematuria (n = 16), sepsis (n = 6), urinary calculi (n = 5), or abdominal aortic aneurysm (n = 3).
CT Technique and Image Interpretation
CT examinations were performed with spiral CT scanners (HiSpeed, n = 68; LightSpeed, n = 22; GE Medical Systems, Milwaukee, Wis). All patients received 150 mL of intravenous iohexol (Omnipaque 350; Nycomed Amersham, Princeton, NJ), and 68 patients received 800 mL of oral diatrizoate meglumine (Hypaque; Nycomed Amersham). Portal venous phase images were acquired after a scan delay of 70 seconds. Section collimation was either 2.5 mm (n = 3), 3 mm (n = 2), 5 mm (n = 40), 7 mm (n = 44), or 10 mm (n = 1). All images were contiguous. Imaging was performed in only the portal venous phase of enhancement in 15 patients. Imaging prior to the administration of contrast material and portal venous phase imaging were performed in 64 patients. Multiphase postcontrast imaging was performed in 11 patients.
Two attending radiologists with at least 5 years of subspecialist experience in abdominal imaging (F.V.C., A.Q.) independently reviewed only the randomized portal venous phase CT images of all 94 lesions on a picture archiving and communication system workstation (Impax; Agfa, Mortsel, Belgium). For those patients who underwent multiphase CT, the readers did not review the non–portal venous phase images. To prevent confusion with other incidental lesions such as simple cysts, readers were made aware of the location of the lesions of interest. Readers were unaware of all other clinical and radiologic information. Both readers recorded the maximal transverse diameter, CT attenuation, and degree of internal heterogeneity of each lesion. CT attenuation was measured by placing a region of interest in the center of uniform lesions or in the portion of higher attenuation in heterogeneous lesions. The region of interest was chosen to include as much of the lesion as possible while excluding any visible blood vessels. Internal heterogeneity was rated on a four-point scale of 1 (uniform), 2 (mildly heterogeneous, characterized by slight mottling), 3 (moderately heterogeneous, characterized by small foci of high and low attenuation), or 4 (markedly heterogeneous, characterized by large foci of mixed attenuation, including cavitation). The presence of visible calcification was also recorded.
Statistical Analysis
Statistical analysis was performed by using software packages of SAS version 8.2 (SAS Institute, Cary, NC) and S-plus 2000 (Insightful, Seattle, Wash). Logistic regression analysis with adjustment for two readers was used to examine the association between clinical and CT parameters and the final diagnosis of either high-attenuation renal cyst or renal cell carcinoma. Means were obtained with the least squares method and 95% CIs were calculated by using random-effects models to adjust for the use of two readers. Reader agreement for measurement of lesion size and attenuation (continuous variables) was evaluated by using intraclass correlation coefficients and Bland-Altman regression analysis (10). Reader agreement for the degree of internal heterogeneity (categorical variable) was evaluated with the weighted 
statistic. The degree of observer agreement, as indicated by values, was interpreted as follows: 0–0.20 = slight agreement, 0.21–0.40 = fair agreement, 0.41–0.60 = moderate agreement, 0.61–0.80 = substantial agreement, and 0.81–1.00 = almost perfect agreement (11). Stepwise logistic regression analysis was used to identify the most accurate linear combinations of distinguishing variables (patient age, patient sex, lesion size, lesion attenuation, and lesion heterogeneity). Classification and regression tree analysis (12) were used for construction of the most efficient classification algorithm combining attenuation and heterogeneity. Three patients had multiple lesions; one had three high-attenuation renal cysts, one had two high-attenuation renal cysts, and one had a high-attenuation renal cyst and a renal cell carcinoma. These lesions were treated as independent observations, because the number of patients with multiple lesions was insufficient for use of generalized estimation equation methods (algorithm failed to converge). This approach was considered reasonable because a separate analysis that used a weighting factor of one divided by the number of lesions yielded results of the same significance.
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RESULTS
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Univariate analysis showed no significant difference between patients with high-attenuation renal cysts and patients with renal cell carcinoma with respect to age and sex, but it did show that renal cell carcinomas were of significantly greater size, attenuation, and internal heterogeneity (Table 1). All lesions with an attenuation greater than 110 HU, as measured by either reader, were renal cell carcinomas (Fig 2). None of the lesions contained visible calcification. Readers demonstrated a high degree of agreement for the assessment of lesion size, attenuation, and heterogeneity. The intraclass correlation coefficients for reader agreement in measurement of lesion size and attenuation were 0.96 (95% CI: 0.87, 0.99) and 0.90 (95% CI: 0.56, 0.96), respectively. The weighted value for reader agreement in evaluation of internal lesion heterogeneity was 0.75 (95% CI: 0.67, 0.82). Stepwise logistic regression indicated that attenuation and internal heterogeneity were both independent variables associated with final diagnosis. Lesion size was not an independent distinguishing variable after adjustment for internal heterogeneity.
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Figure 2. Graph shows CT numbers of high-attenuation renal cysts and renal cell carcinomas (RCC) on portal venous phase contrast-enhanced CT scans, as measured by readers 1 and 2. All lesions with an attenuation greater than 110 HU, as measured by either reader, were renal cell carcinomas.
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Classification and regression tree analysis demonstrated that an attenuation greater than 70 HU (Fig 3) or the presence of moderate or marked internal heterogeneity (Fig 4) was the most efficient algorithm for distinguishing renal cell carcinoma from high-attenuation renal cyst (Table 2). Using this algorithm for the diagnosis of renal cell carcinoma, reader 1 had a sensitivity of 91% (52 of 57), a specificity of 92% (34 of 37), a positive predictive value of 95% (52 of 55), and a negative predictive value of 86% (31 of 36). The corresponding values for sensitivity, specificity, positive predictive value, and negative predictive values for reader 2 were 91% (52 of 57), 84% (31 of 37), 90% (52 of 58), and 85% (28 of 33), respectively.
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Figure 3. Portal venous phase contrast-enhanced transverse CT section in a 62-year-old man who underwent staging evaluation of recently diagnosed prostate cancer. A 1.5-cm high-attenuation (104-HU) mass (arrow) is visible arising from the lower pole of the left kidney. Both readers interpreted this lesion as being of uniform heterogeneity. Subsequent US showed the lesion was solid, and renal cell carcinoma was confirmed at surgery.
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Figure 4. Portal venous phase contrast-enhanced transverse CT section in a 72-year-old man with a history of gastric carcinoma. A 2.5-cm high-attenuation (65-HU) mass (arrow) is visible arising from the upper pole of the right kidney. The lesion has a heterogeneous appearance. Renal cell carcinoma was confirmed at surgery.
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DISCUSSION
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Our study suggests that lesion CT attenuation and internal heterogeneity are useful ancillary signs in the distinction of high-attenuation renal cysts from renal cell carcinomas on portal venous phase contrast-enhanced CT scans. This may contribute to reader confidence in lesion characterization in the common clinical setting of a high-attenuation renal mass seen incidentally on a routine portal venous phase contrast-enhanced CT scan. It is important to note that we are not suggesting these signs should serve as a substitute for the standard practice of advising definitive evaluation of such high-attenuation masses with multiphase CT, US, or MR imaging. Likewise, when such lesions are recognized while the patient is still in the scanner or otherwise available to undergo scanning, these signs should not serve as a substitute for obtaining a delayed scan to evaluate the lesion for de-enhancement (13); however, when only portal venous phase images are available and a high-attenuation mass is found to have an attenuation greater than 70 HU or demonstrates moderate or marked internal heterogeneity, additional imaging can be recommended with the added information that malignancy is likely. This may increase the probability that the referring physician will request the appropriate additional studies, potentially resulting in improved diagnosis and treatment of incidental renal cell carcinomas. These ancillary signs may also be helpful when results of multiphase CT or other corroborative imaging studies are inconclusive.
Our finding that a renal mass with an attenuation greater than 70 HU on a portal venous phase contrast-enhanced CT scan is more likely to be a renal cell carcinoma than a high-attenuation renal cyst is somewhat discordant with prior reports of the attenuation of high-attenuation renal cysts. For example, Zirinsky et al (14) found the mean attenuation of 10 high-attenuation renal cysts on contrast-enhanced CT scans to be 68 HU, and all 11 hyperdense cysts reported by Sussman et al (15) were greater than 70 HU in attenuation. There are two probable explanations. First, these prior reports did not explicitly define the attenuation criteria for a hyperdense cyst, although review of the studies suggests Zirinsky et al included patients in whom the cyst was of greater attenuation than the renal parenchyma on nonenhanced images, and Sussman et al included patients in whom the attenuation was greater than 70 HU. These criteria may have resulted in a selection bias to cysts of higher attenuation. We adopted a threshold of 20 HU for the diagnosis of a high-attenuation cyst because this value is independent of any comparison with the renal parenchyma and represents the generally accepted upper limit of attenuation for simple fluid (2,3). Second, these prior studies did not include renal cell carcinomas and did not investigate distinguishing attenuation thresholds.
Our finding that high-attenuation cysts are unlikely to have an attenuation greater than 70 HU is concordant with studies that investigated the CT attenuation of blood. New and Aronow (16) found that blood clots have an attenuation of 60–80 HU, while Wolverson et al (17) reported that the CT attenuation of fresh blood is 60–90 HU. Assuming that the increased attenuation of high-attenuation cysts represents resolving intracystic hemorrhage, one would expect that the cyst attenuation would be less than or, at most, equal to the attenuation of blood or blood clot. This assumption cannot, however, explain the occasional finding of a high-attenuation cyst with an attenuation greater than 90 HU. Presumably, other factors contribute to CT attenuation in these cases.
Our study had a number of limitations. We did not include cases of angiomyolipoma, which could also appear as an incidental high-attenuation mass on portal venous phase contrast-enhanced CT scans. Angiomyolipomas are rare tumors, however, and usually have a distinctive appearance due to the presence of intratumoral macroscopic fat; this makes confusion with renal cell carcinoma or a high-attenuation cyst unlikely (4). Our series of high-attenuation renal cysts and renal cell carcinomas did not include any cases with visible calcification, which might confound the use of lesion CT attenuation measurements as a distinguishing feature. We identified patients with renal cell carcinomas by review of histopathologic findings. This is a possible source of selection bias, since, conceivably, patients with higher attenuation or more heterogeneous lesions may be more likely to undergo surgery. Unfortunately, there is no method that allows us to identify cases of clinically unrecognized or uninvestigated renal cell carcinoma.
In our study, the term "portal venous phase" refers to scans obtained after a standard scan delay of 70 seconds, without adjustment for increased or decreased circulation time, even though the enhancement of solid renal masses is time dependent and enhancement should ideally be evaluated in conjunction with internal standards as controls (7). The assessment of lesion internal heterogeneity is necessarily subjective and poorly defined. Despite the lack of objective definitions for the ratings of internal heterogeneity, both readers showed substantial interobserver agreement, with a weighted value of 0.75. As with any subjective scale, there is the potential for reader disagreement, though our overall results showed very similar sensitivity and specificity for both readers in the distinction of high-attenuation cysts from renal cell carcinoma. Finally, we included lesions with a minimum diameter of 1 cm. It is possible that some of the smaller lesions may have had artificially high attenuation measurements due to partial volume artifact, given that 45 of the 90 patients were examined with a collimation of 7 mm or greater. The phenomenon of pseudoenhancement may also have contributed to falsely high attenuation measurements in small lesions (18); however, our finding that size was not a predictive variable in multivariate analysis suggests this effect was not a major confounding factor.
In conclusion, on portal venous phase contrast-enhanced CT scans, an attenuation greater than 70 HU or moderate or marked internal heterogeneity favor a diagnosis of renal cell carcinoma over a diagnosis of high-attenuation renal cyst; these ancillary signs may be helpful when recommending additional imaging studies or when results of corroborative imaging are inconclusive.
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FOOTNOTES
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Author contributions: Guarantor of integrity of entire study, M.S.; study concepts, F.V.C.; study design, M.S., F.V.C.; literature research, M.S.; clinical studies, F.V.C., A.Q.; data acquisition, M.S., F.V.C., A.Q.; data analysis/interpretation, Y.L.; statistical analysis, Y.L.; manuscript preparation, definition of intellectual content, editing, revision/review, and final version approval, all authors.
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ABSTRACT
INTRODUCTION
