Bladder Malignancies on CT: The Underrated Role of CT in Diagnosis

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1 Genitourinary Imaging Clinical Perspective Raman and Fishman CT of ladder Malignancies Genitourinary Imaging Clinical Perspective Siva P. Raman 1 Elliot K. Fishman Raman SP, Fishman EK Keywords: bladder cancer, CT urography, transitional cell carcinoma DOI: /JR Received October 1, 2013; accepted after revision October 31, oth authors: Department of Radiology, Johns Hopkins University, JHOC 3251, 601 N Caroline St, altimore, MD ddress correspondence to S. P. Raman (srsraman3@gmail.com). JR 2014; 203: X/14/ merican Roentgen Ray Society ladder Malignancies on CT: The Underrated Role of CT in Diagnosis OJECTIVE. The purpose of this article is to review the utility of CT in diagnosing bladder malignancies, CT protocol options that may improve the conspicuity of bladder tumors, suggestive imaging features, and potential mimics. CONCLUSION. lthough evaluation of the bladder has traditionally been considered purely the realm of cystoscopy, many bladder tumors can be identified with CT. However, diagnosis requires optimization of CT technique and close attention to a number of potentially subtle findings. T he role of CT, CT urography in particular, has been well described in the literature with regard to the diagnosis of upper urinary tract tumors (i.e., tumors of the ureters and pelvicalyceal system) [1]. The role of CT in the imaging of patients with hematuria has become well established, and CT urography is regularly used in both the outpatient and emergency settings. ecause cystoscopy is considered the reference standard examination for evaluation of the bladder and diagnosis of bladder malignancies, the bladder has been a largely ignored and disregarded structure during routine CT interpretation [2]. This is a potentially dangerous perspective on the part of radiologists, because bladder malignancies can often be incidentally appreciated at screening CT examinations in the emergency department, particularly when patients are imaged with a full bladder and arterial phase technique is used [3 5]. Moreover, even in individuals being imaged with CT urography for hematuria, particularly in the emergency setting, it is far from certain that patients will ultimately undergo diagnostic cystoscopy, placing the onus on the radiologist for diagnosis. In this article, we discuss the pathophysiology and background of bladder malignancies, CT urography protocol considerations that may improve the visualization of subtle tumors, the imaging findings that should raise suspicion of these lesions, and some potential imaging mimics. ackground ladder cancer is quite common; 2.7 million patients either receive a diagnosis of or are treated for bladder cancer each year worldwide. ladder cancer is the fourth leading cause of malignant disease in the United States [6, 7]. Transitional cell carcinoma (TCC) of the bladder is approximately 50 times as common as TCC of the upper urinary tract [6]. lthough most of the tumors are TCC, squamous cell carcinoma and adenocarcinoma account for a small minority of lesions [6]. Like those for TCC of the upper urinary tract, the primary risk factors for bladder TCC include male sex, advancing age (typically older than 60 years), smoking, several specific chemical carcinogens, and pelvic radiation [6]. The most common (> 80%) clinical symptom of bladder cancer is gross hematuria, which confers a four times higher risk of malignancy compared with microscopic hematuria. Most patients with macroscopic hematuria, particularly those older than 50 years, should undergo both cystoscopy and CT urography [2]. Microscopic hematuria carries a much lower risk of malignancy and may be present in a sizeable percentage of persons without symptoms, making the decision to perform further investigation (CT urography or cystoscopy) largely dependent on a patient s underlying risk factors [8]. Other than hematuria, potential patient symptoms include urinary frequency, urgency, repeated urinary tract infections, and urinary obstruction secondary to an advanced mass [2]. JR:203, ugust

Raman and Fishman Protocol Considerations and Technique Three primary CT urography protocols have been described, including the single-bolus technique, split-bolus technique, and triple-bolus

The single-bolus technique, the most commonly used of the three options, involves administration of a fullstrength bolus of contrast material, followed by the acquisition of separate arterial,

In the splitbolus technique, the total contrast material dose is divided into two separate administrations, and images are acquired in a combined excretory and nephrographic phase [9, 10].

2 Raman and Fishman Protocol Considerations and Technique Three primary CT urography protocols have been described, including the single-bolus technique, split-bolus technique, and triple-bolus technique. The single-bolus technique, the most commonly used of the three options, involves administration of a fullstrength bolus of contrast material, followed by the acquisition of separate arterial, venous, and excretory phase images [1]. In the splitbolus technique, the total contrast material dose is divided into two separate administrations, and images are acquired in a combined excretory and nephrographic phase [9, 10]. The triple-bolus technique splits a full dose of contrast material into three separate small boluses, and acquisition is a combined corticomedullary-nephrographic-excretory phase [1]. Given that a smaller amount of IV contrast material is ultimately excreted in the latter two protocol options, it is not surprising that use of the split-bolus and triple-bolus techniques ultimately reduces the degree of urinary bladder distention on delayed phase images and may limit identification of a subtle filling defect. However and most important, both the split-bolus and the triple-bolus techniques were designed primarily to reduce radiation dose by combining the different phases of acquisition. s a result, each of these two protocols may markedly limit sensitivity for bladder malignancies if early phase images with unopacified urine distending the bladder are not acquired [1, 10 12]. In the performance of CT urography, a number of ancillary techniques have been described, including oral hydration, IV hydration, IV administration of diuretics, abdominal compression, and prone positioning [11, 13 16]. For the most part, these techniques have been described in the literature with regard to improving the efficacy of upper urinary tract distention, and their effect on the detection of bladder malignancies has not been specifically discussed. lthough some of these techniques are unlikely to have a substantial effect on bladder distention, three of these techniques are likely to improve detection of a bladder malignancy: oral hydration, IV hydration, and IV administration of diuretics. These techniques can improve excretion into and distention of the collecting system and ultimately improve bladder distention. Moreover, all three result in dilution of the excreted contrast material, potentially improving the ability to identify subtle lesions. t our institution, we use oral hydration as a component of our standard CT urography protocol to improve distention not only of the upper urinary tract but also of the bladder. Moreover, we routinely ask patients not Fig year-old man undergoing CT in preparation for transcatheter aortic valve replacement. xial arterial phase image shows hypervascular wall thickening (arrow) along right bladder wall, confirmed at cystoscopy to represent transitional cell carcinoma. to urinate for at least 1 hour before the study so as to improve bladder distention. Notably, all three of these techniques increase not only the excretion of opacified contrast medium into the collecting system and bladder on delayed phase images but also the excretion of unopacified, low-density urine into the collecting system and bladder on early phase images. The result is improved juxtaposition of subtle bladder wall thickening or hyperenhancement compared with low-density fluid within the bladder lumen [11, 14]. Diagnostic Performance lthough there is little doubt that cystoscopy is the most sensitive, specific, and reproducible method for identification of bladder malignancies, the diagnostic performance of CT is better than is commonly thought: In a study by Turney et al. [8], 200 patients with hematuria underwent both cystoscopy Fig year-old woman with gross hematuria. and, rterial phase CT image () shows nodular hypervascular wall thickening along posterior bladder wall (arrow) more clearly than does delayed phase image (). Finding was found to represent transitional cell carcinoma. 348 JR:203, ugust 2014

CT of ladder Malignancies and CT urography. ladder malignancy was found in 24% of the patients, and the sensitivity and specificity of CT urography were 0.93 and 0.99 (positive predictive value, 0.

[17] conducted a study that included 838 patients who had undergone CT urography and cystoscopy within 6 months of each another and found that CT urography had a sensitivity and specificity of 79%

xial arterial phase CT image shows nodular wall thickening (arrow) along right anterior bladder that was proved at subsequent cystoscopy to represent transitional cell carcinoma. Fig.

and, xial () and coronal () volumerendered CT images show extensive polyploid nodular thickening (arrow, ) of bladder wall, in keeping with multifocal transitional cell carcinoma.

3 CT of ladder Malignancies and CT urography. ladder malignancy was found in 24% of the patients, and the sensitivity and specificity of CT urography were 0.93 and 0.99 (positive predictive value, 0.98; negative predictive value, 0.97). Similarly, Sadow et al. [17] conducted a study that included 838 patients who had undergone CT urography and cystoscopy within 6 months of each another and found that CT urography had a sensitivity and specificity of 79% and Fig year-old man with hematuria. xial arterial phase CT image shows nodular wall thickening (arrow) along right anterior bladder that was proved at subsequent cystoscopy to represent transitional cell carcinoma. Fig year-old man with dysuria and suprapubic pain. and, xial () and coronal () volumerendered CT images show extensive polyploid nodular thickening (arrow, ) of bladder wall, in keeping with multifocal transitional cell carcinoma. Coronal image nicely shows extensive vascularity and enhancement associated with malignancy. 94% (positive predictive value, 75%; negative predictive value, 95%). In another study, Kim et al. [18] found CT urography effective in the diagnosis of recurrent tumors in patients who had previously undergone transurethral resection of a bladder tumor. It is undoubtedly true that the diagnostic performance of CT will vary dramatically depending on the technique used and degree of bladder distention, thus explaining the variable diagnostic performance from one study to another. dedicated CT urography technique with multiphase protocol will clearly be more sensitive for a subtle tumor than a routine screening examination performed in the emergency department for suspected abdominal pain. Nevertheless, the results of these studies suggest that if technique is optimized, subtle malignancies can be identified reasonably accurately at imaging. Fig year-old woman with hematuria and incontinence. xial arterial phase axial CT image shows multiple sites of focal urothelial thickening (arrows) and abnormal hyperenhancement, ultimately proven to represent multifocal transitional cell carcinoma. JR:203, ugust

Raman and Fishman Fig. 6 30-year-old man with history of multiple sclerosis.

Given young age of patient and presence of multiple sclerosis and multifocal thickening of bladder,

proved to represent diffuse infiltrating transitional cell carcinoma. Fig.

and, rterial () and delayed () phase CT images show focal nodular thickening (arrow) along posterior

Given vascularity and enhancement of this nodularity, abnormality is more apparent on arterial phase

4 Raman and Fishman Fig year-old man with history of multiple sclerosis. CT image shows multifocal bladder wall thickening and hyperenhancement. Given young age of patient and presence of multiple sclerosis and multifocal thickening of bladder, finding was originally thought to represent either cystitis or neurogenic bladder but was ultimately proved to represent diffuse infiltrating transitional cell carcinoma. Fig year-old man with abdominal pain. and, rterial () and delayed () phase CT images show focal nodular thickening (arrow) along posterior bladder wall. Given vascularity and enhancement of this nodularity, abnormality is more apparent on arterial phase images and was proved to represent transitional cell carcinoma. Fig year-old man with 2-year history of hematuria. and, rterial phase CT image () shows nodular thickening (arrow) along posterior bladder wall more clearly than does delayed image (). Finding was ultimately proved to represent transitional cell carcinoma. 350 JR:203, ugust 2014

CT of ladder Malignancies Imaging Findings ladder Wall Thickening In a well-distended bladder, focal bladder wall thickening, particularly when nodular or irregular, should be considered suspicious

Nevertheless, one should be hesitant to overinterpret bladder abnormalities in an underdistended bladder, because the anterior bladder can often look spuriously thickened in such cases [19].

[20], in which bladder wall thickening was further evaluated with cystoscopy, there were no cases of malignancy in patients with diffuse wall thickening.

5 CT of ladder Malignancies Imaging Findings ladder Wall Thickening In a well-distended bladder, focal bladder wall thickening, particularly when nodular or irregular, should be considered suspicious for malignancy (Figs. 1 10). Nevertheless, one should be hesitant to overinterpret bladder abnormalities in an underdistended bladder, because the anterior bladder can often look spuriously thickened in such cases [19]. Moreover, diffuse bladder wall thickening rarely represents malignancy, except in cases of irregular or nodular wall thickening: In a study by McPartlin et al. [20], in which bladder wall thickening was further evaluated with cystoscopy, there were no cases of malignancy in patients with diffuse wall thickening. In many cases, subtle focal thickening may be difficult to appreciate on delayed images, particularly along the dependent posterior wall of the bladder, because it can be obscured by contrast Fig year-old man with hematuria. and, lthough bladder is decompressed, arterial phase image () shows subtle foci of urothelial hyperenhancement (arrows), whereas delayed phase image () does not. Finding was proved to represent transitional cell carcinoma. material in the bladder lumen and associated beam-hardening artifact. ladder Nodule or Mass The presence of a discrete bladder mass or nodule should be considered suspicious for malignancy (Fig ). In many cases, such lesions may be better appreciated on early phase images when surrounded by low-attenuation urine, particularly when the lesion is avidly enhancing, although a discrete filling defect may not be difficult to appreciate on delayed images when the nodule is large. bnormal Urothelial Enhancement In a study by Kim et al. [3], the attenuation of 20 bladder tumors was measured on arterial, venous, and delayed images. The investigators found that the enhancement of bladder TCC peaked at approximately 105 HU, usually at approximately 60 seconds, before washing out slowly over time. In other words, although TCC has typically been regarded as a hypovascular tumor, these lesions have considerable urothelial hypervascularity and are typically most conspicuous on early phase images. s a result, any focal hyperenhancement of the bladder urothelium must be considered suspicious for malignancy. This also emphasizes the point that although the delayed phase has typically been considered the most important for identifying bladder tumors, early phase images (whether arterial or venous) are likely more important for lesion conspicuity, particularly because subtle lesion enhancement may be more difficult to appreciate once contrast material has been excreted into the bladder (as a result of beam hardening artifact and washout of enhancement) (Figs. 1, 2, 4 11). s a result, for any patient presenting with hematuria, it is critical to obtain at least one early phase image (arterial or venous) through the bladder before contrast excretion occurs. Fig year-old man with hematuria. CT image shows focal hypervascular thickening along left posterolateral bladder wall (arrow) that was confirmed to represent transitional cell carcinoma. JR:203, ugust

Raman and Fishman Calcification lthough calcification is seen in rare instances as a sequela of previous infections, schistosomiasis, previously

in association with bladder wall thickening, should prompt further evaluation with cystoscopy [19] (Fig. 13).

manifestation of malignancy and Fig. 11 83-year-old man with 1-year history of macroscopic hematuria.

12 23-year-old woman with incidentally discovered bladder tumor.

() does. Fig. 13 74-year-old man with incidentally diagnosed bladder mass.

6 Raman and Fishman Calcification lthough calcification is seen in rare instances as a sequela of previous infections, schistosomiasis, previously treated malignancy, and even intravesical bacille Calmette- Guérin therapy, the presence of any calcification along the bladder wall, particularly in association with bladder wall thickening, should prompt further evaluation with cystoscopy [19] (Fig. 13). Imaging Mimics Inflammatory or Infectious Cystitis Diffuse bladder wall thickening in the absence of focal nodularity or a discrete mass is rarely a manifestation of malignancy and Fig year-old man with 1-year history of macroscopic hematuria. rterial phase CT image shows multiple hypervascular nodules (arrows) throughout bladder in keeping with multifocal transitional cell carcinoma. Fig year-old woman with incidentally discovered bladder tumor. and, rterial phase image () does not clearly show small tumor nodule (arrow) along left posterior wall of bladder, but delayed excretory phase image () does. Fig year-old man with incidentally diagnosed bladder mass. xial arterial phase CT image shows polyploid lesion (arrow) along right lateral bladder wall with subtle calcification. Finding was confirmed to represent transitional cell carcinoma at cystoscopy. Fig year-old man with gross hematuria. rterial phase CT image shows small hypervascular polyploid nodule (arrow) clearly accentuated by surrounding low-attenuation urine. 352 JR:203, ugust 2014

CT of ladder Malignancies Fig. 15 79-year-old man with incidentally diagnosed transitional cell carcinoma.

Coronal phase CT image shows bladder appears thickened and hyperemic with surrounding fat stranding. usually reflects either underdistention or cystitis.

ladder Hematoma or lood Clot In many cases, hematoma can be difficult to differentiate from an underlying malignancy, appearing as a discrete mass (Fig. 18).

difficult to make reliably, and the presence of an underlying tumor can be difficult to exclude. Ultimately, cystoscopy may be necessary for a definitive diagnosis [19].

7 CT of ladder Malignancies Fig year-old man with incidentally diagnosed transitional cell carcinoma. xial arterial phase CT image shows polyploid mass (arrow) in right posterior aspect of bladder. Fig year-old man with cystitis based on positive urinalysis result. Coronal phase CT image shows bladder appears thickened and hyperemic with surrounding fat stranding. usually reflects either underdistention or cystitis. In most cases, it is secondary to bladder infection, although hemorrhagic and radiation cystitis are other possibilities (Fig. 17). ladder Hematoma or lood Clot In many cases, hematoma can be difficult to differentiate from an underlying malignancy, appearing as a discrete mass (Fig. 18). Whereas a hematoma would be expected to have no change in attenuation over the different phases of the study and no clear attachment to the mucosa of the bladder, such subtle distinctions can be difficult to make reliably, and the presence of an underlying tumor can be difficult to exclude. Ultimately, cystoscopy may be necessary for a definitive diagnosis [19]. Enlarged Prostate n enlarged prostate, whether secondary to benign prostatic hypertrophy or to prostate cancer, does not infrequently have a focal nodular component that extends upward to abut the base of the bladder. In most cases, careful appraisal of the sagittal multiplanar reformatted images can help differentiate an enlarged prostate from a true polyploid bladder mass, although in the most concerning cases, cystoscopy may ultimately be necessary [19]. Fig year-old man undergoing evaluation of liver mass. CT image shows incidentally identified bladder mass (arrow) that was ultimately proved to represent transitional cell carcinoma. Fig year-old man with hematuria after renal biopsy. CT image shows large mass (arrow) in bladder that was concluded to represent large hematoma because of its morphologic features and patient s history. ladder Leiomyoma benign bladder mass arising from the smooth muscle layer of the bladder wall, leiomyoma is the most common of a number of benign bladder neoplasms (e.g., adenoma, leiomyoma, hemangiomas, neurofibroma) [2]. lthough the presence of any bladder mass on images should prompt cystoscopy, these lesions are characteristically very well circumscribed and smoothly marginated, in keeping with their mural smooth muscle origin. ladder Lymphoma lthough extraordinarily rare, lymphomatous involvement of the bladder is much more often secondary rather than primary, and evidence of extensive lymphadenopathy is typically found in the abdomen and pelvis. From an imaging standpoint alone, bladder lymphoma cannot be differentiated from other primary bladder masses [2]. JR:203, ugust

8 Raman and Fishman Conclusion Evaluation of the bladder has been largely considered the domain of cystoscopy, and the bladder regularly goes ignored by the radiologist. However, several imaging findings should strongly suggest the presence of malignancy whether CT is performed as CT urography for hematuria or routinely in the emergency setting. The cases in this article illustrate the importance of early phase imaging through the bladder, which is often the most sensitive technique for detecting subtle urothelial thickening, nodularity, and hyperenhancement that may suggest the presence of an underlying tumor. References 1. Raman SP, Horton KM, Fishman EK. Transitional cell carcinoma of the upper urinary tract: optimizing image interpretation with 3D reconstructions. bdom Imaging 2012; 37: Dighe MK, hargava P, Wright J. Urinary bladder masses: techniques, imaging spectrum, and staging. J Comput ssist Tomogr 2011; 35: Kim JK, Park SY, hn HJ, Kim CS, Cho KS. ladder cancer: analysis of multi-detector row helical CT enhancement pattern and accuracy in tumor detection and perivesical staging. Radiology 2004; 231: Xie Q, Zhang J, Wu PH, et al. ladder transitional cell carcinoma: correlation of contrast enhancement on computed tomography with histological grade and tumour angiogenesis. Clin Radiol 2005; 60: Gufler H, Schulze CG, Wagner S. Incidental findings in computed tomographic angiography for planning percutaneous aortic valve replacement: advanced age, increased cancer prevalence? cta Radiol 2014; 55: O Connor OJ, McSweeney SE, Maher MM. Imaging of hematuria. Radiol Clin North m 2008; 46: Rouprêt MM. Tumours of the bladder: what does the urologist expect from imaging? Diagn Interv Imaging 2012; 93: Turney W, Willatt JM, Nixon D, Crew JP, Cowan NC. Computed tomography urography for diagnosing bladder cancer. JU Int 2006; 98: Dillman JR, Caoili EM, Cohan RH, et al. Comparison of urinary tract distension and opacification using single-bolus 3-phase vs split-bolus 2-phase multidetector row CT urography. J Comput ssist Tomogr 2007; 31: Chow LC, Kwan SW, Olcott EW, Sommer G. Split-bolus MDCT urography with synchronous nephrographic and excretory phase enhancement. JR 2007; 189: Johnson PT, Horton KM, Fishman EK. Optimizing detectability of renal pathology with MDCT: protocols, pearls, and pitfalls. JR 2010; 194: Maheshwari E, O Malley ME, Ghai S, Staunton M, Massey C. Split-bolus MDCT urography: upper tract opacification and performance for upper tract tumors in patients with hematuria. JR 2010; 194: Caoili EM, Inampudi P, Cohan RH, Ellis JH. Optimization of multi-detector row CT urography: effect of compression, saline administration, and prolongation of acquisition delay. Radiology 2005; 235: Kawamoto S, Horton KM, Fishman EK. Opacification of the collecting system and ureters on excretory-phase CT using oral water as contrast medium. JR 2006; 186: Mueller-Lisse UL, Coppenrath EM, Meindl T, et al. Delineation of upper urinary tract segments at MDCT urography in patients with extra-urinary mass lesions: retrospective comparison of standard and low-dose protocols for the excretory phase of imaging. Eur Radiol 2011; 21: Silverman SG, kbar S, Mortele KJ, Tuncali K, hagwat JG, Seifter JL. Multi-detector row CT urography of normal urinary collecting system: furosemide versus saline as adjunct to contrast medium. Radiology 2006; 240: Sadow C, Silverman SG, O Leary MP, Signorovitch JE. ladder cancer detection with CT urography in an academic medical center. Radiology 2008; 249: Kim CS, Kim SH, Lee HJ, Kim YW. Clinical significance of bladder urothelial thickening and enhancement revealed on MDCT urography after transurethral resection of tumor. J Comput ssist Tomogr 2012; 36: Shinagare, Sadow C, Sahni V, Silverman SG. Urinary bladder: normal appearance and mimics of malignancy at CT urography. Cancer Imaging 2011; 11: McPartlin DS, Klausner P, Nottingham CU, et al. Is cystoscopy indicated for incidentally identified bladder wall thickening? Can J Urol 2013; 20: JR:203, ugust 2014

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