1609 Transitional Cell Carci- RadioGraphics noma of the Upper Uri … · 2019. 4. 11. · ances of...

EDUCATION EXHIBIT 1609

Transitional Cell Carci-noma of the Upper Uri-nary Tract: Spectrumof Imaging Findings1

LEARNINGOBJECTIVESFOR TEST 5After reading thisarticle and takingthe test, the reader

will be able to:

� Identify the typicaland atypical appear-ances of upper uri-nary tract TCC withconventional imagingmodalities (EU, RP,US) and emergingCT and MR imagingtechniques.

� Describe the com-prehensive, mul-tiphasic CT and MRimaging techniquesfor one-stop evalua-tion of upper urinarytract TCC.

� Discuss the com-bined radiologic andendourologic ap-proach to staging andfollow-up of upperurinary tract TCC.

Ronan F. J. Browne, MB, BCh, MSc, FFRRCSI ● Conor P. Meehan,MB, BCh, MRCPI ● Jane Colville, MB, BCh ● Raymond Power, MB,BCh, FRCSI ● William C. Torreggiani, MB, BCh, MRCPI, FRCR,FFRRCSI

Transitional cell carcinoma (TCC) accounts for up to 10% of neo-plasms of the upper urinary tract and usually manifests as hematuria.Imaging plays an important role in assessment of upper tract disease,unlike in bladder TCC, diagnosis of which is usually made at cystos-copy. Traditional imaging modalities, such as excretory urography,retrograde pyelography, and ultrasonography, still play pivotal roles indiagnosis of upper tract TCC, in combination with endourologic tech-niques. The multicentric nature of TCC makes assessment of the en-tire urothelium essential before treatment. The advent of minimallyinvasive surgery, which allows renal preservation in selected patients,makes accurate tumor staging mandatory to determine the appropriatetherapy; staging is usually performed with computed tomography (CT)or magnetic resonance (MR) imaging. Vigilant urologic and radiologicfollow-up is warranted to assess for metachronous lesions and recur-rence. The emerging technique of CT urography allows detection ofurinary tract tumors and calculi, assessment of perirenal tissues, andstaging of lesions; it may offer the opportunity for one-stop evaluationin the initial assessment of hematuria and in follow-up of TCC. SimilarMR imaging protocols can be used in patients who are not candidatesfor CT urography, although detection of urinary tract calcificationsmay be suboptimal.©RSNA, 2005

Abbreviations: EU � excretory urography, MIP � maximum intensity projection, RP � retrograde pyelography, TCC � transitional cell carci-noma, 3D � three-dimensional

RadioGraphics 2005; 25:1609–1627 ● Published online 10.1148/rg.256045517 ● Content Code:

1From the Departments of Radiology (R.F.J.B., C.P.M., J.C., W.C.T.) and Urology (R.P.), Adelaide and Meath Hospital, Tallaght, Dublin 24, Ire-land. Presented as an education exhibit at the 2003 RSNA Annual Meeting. Received March 30, 2004; revision requested May 12; final revision re-ceived April 21, 2005; accepted April 22. All authors have no financial relationships to disclose. Address correspondence to W.C.T. (e-mail:[email protected]).

©RSNA, 2005

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CME FEATURESee accompanying

test at http://www.rsna.org

/education/rg_cme.html

IntroductionTransitional cell carcinoma (TCC) is commonlyencountered in the urinary bladder and is usuallydiagnosed at cystoscopy. Five percent of urothe-lial tumors arise from the ureter or the renal pelvisor calices, accounting for approximately 10% ofupper tract neoplasms (1,2). Patients with TCCtypically present with hematuria, which may befrank or microscopic. Up to one-third of patientspresent with flank pain or acute renal colic, symp-toms more typically associated with calculi. Occa-sionally, tumors may manifest with distant metas-tases or be discovered incidentally at radiologicexamination.

Renal TCC most frequently arises in the extra-renal part of the pelvis, followed by the infun-dibulocaliceal region (3). The distribution isequal between the left and right kidneys, with2%–4% of cases occurring bilaterally. Twenty-five percent of upper tract tumors occur in theureter, where 60%–75% of cases are found in thelower third, with no side predominance (2). Tu-mor spread occurs by mucosal extension or local,hematogenous, or lymphatic invasion. The mostcommon sites for metastases are the liver, bone,and lungs. The tumor stage at diagnosis influ-ences the development of local recurrence andmetastases and hence overall survival (1,4). Mul-ticentric TCC is common and is associated withpoor survival (4). Synchronous or metachronoustumor of the ipsilateral or contralateral collectingsystem is also common, necessitating vigilant uro-logic and radiologic follow-up.

This article reviews the characteristic imagingfeatures of upper tract TCC and outlines the roleof imaging in diagnosis, preoperative staging, andfollow-up. The appearances at excretory urogra-phy (EU), retrograde pyelography (RP), and re-nal ultrasonography (US) are reviewed. Emphasisis placed on cross-sectional imaging modalitiessuch as computed tomographic (CT) urography,which is fast becoming the investigation of choicein the assessment of patients with suspectedTCC. The emerging role of magnetic resonance

(MR) imaging techniques such as gadolinium-enhanced three-dimensional (3D) MR angiogra-phy and urography is also discussed.

PathogenesisUpper tract TCC typically occurs in the 6th and7th decades of life, with males affected threetimes more often than females (3). Besides in-creasing age and male gender, the most importantrisk factor is smoking, with smokers being two tothree times more likely to develop TCC thannonsmokers (3). Chemical carcinogens (ani-line, benzidine, aromatic amine, azo dyes), cyclo-phosphamide therapy, and heavy caffeine con-sumption are also associated with TCC, and allpredispose to synchronous and metachronoustumor development (2). These substances aremetabolized and excreted in the urine as carcino-genic substances that act locally on the urothe-lium. Stasis of urine and structural abnormalitiessuch as horseshoe kidney are also associated withincreased prevalence (5).

Upper tract TCC is common in families af-fected with “Balkan endemic nephropathy.” Fa-milial metabolic abnormalities in these patientslead to tubulointerstitial nephritis, renal failure,carcinogenic glomerulotubular toxins, and mul-tiple tumors (2). Analgesic abuse, particularlylong-term use of phenacetin, produces capillo-sclerosis and predisposes to a highly invasive typeof TCC that preferentially involves the renal pel-vis (5). Human papilloma virus and hereditarynonpolyposis colon cancer have also been sug-gested as risk factors for TCC of the upper tract,and the prevalence is significantly higher in areaswhere endemic “blackfoot disease” is seen (2).

Pathologic FeaturesUpper tract TCC is histologically and cytologi-cally similar to bladder TCC (6). Eighty-five per-cent of upper tract TCCs are low-stage, superfi-cial, papillary neoplasms with a broad base andfrondlike morphologic structure (7). These tu-mors are usually small at diagnosis, grow slowly,and follow a relatively benign course (8). Pedun-culated or diffusely infiltrating tumor is less com-mon, accounting for approximately 15% of upper

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tract TCCs, but tends to behave more aggres-sively and be more advanced at diagnosis (9). In-filtrating tumors are characterized by thickeningand induration of the ureteric or renal pelvic wall.If the renal pelvis is involved, there is often inva-sion into the renal parenchyma. However, thisinfiltrative growth pattern preserves renal contourand differs from renal cell carcinoma, which istypically expansile.

Synchronous bilateral TCC has been reportedto occur in 1%–2% of cases of renal lesions and2%–9% of cases of ureteric lesions. Eleven per-cent to 13% of patients with upper tract TCCsubsequently develop metachronous upper tracttumors (3). Furthermore, up to 50% of patientsinitially presenting with upper tract TCC will de-velop metachronous tumors in the bladder, typi-cally developing within 2 years of surgical treat-ment and seen more commonly with ureteric tu-mors than with renal tumors (2,10). Two percentof patients with bladder TCC also have synchro-nous upper tract tumors at presentation, and 6%will develop metachronous upper tract disease(11).

DiagnosisThe evaluation of hematuria requires assessmentof the entire urothelium and the renal paren-chyma for tumor and of the urinary tract for cal-culi. The standard work-up for these patients asrecommended by the American Urological Asso-ciation consists of urinalysis and cytologic analy-sis, cystoscopy, and EU (12,13). The initial diag-nosis of TCC is usually made on the basis of find-ings from urine cytology; the diagnostic yield isimproved with selective lavage and collection andwith brush biopsies performed at cystoscopy orRP (14,15). However, these techniques are inva-sive and technically demanding. The limitationsof EU in assessing the renal parenchyma usuallyrequire the supplemental use of US, CT, or MRimaging to evaluate the kidneys for masses (16–18). Furthermore, additional imaging is oftenrequired to clarify indeterminate findings at EU.

Recently, the technique of multiphasic CTurography has emerged as an alternative methodof assessing patients with hematuria, offering su-

perior detection of urinary calculi and renal pa-renchymal masses, and in some studies, improveddetection of urothelial lesions. Because surround-ing structures can also be assessed, CT urographyis rapidly replacing EU as the definitive study forthese patients, potentially shortening the durationof diagnostic evaluation. MR imaging, includingthe newer techniques of MR angiography andMR urography, is also being used, particularly inpatients who cannot tolerate iodinated contrastmaterial and in whom multiplanar, vascular, andcollecting system imaging is required. Because ofthe multifocal and metachronous nature of TCC,thorough assessment of the entire urothelium isrequired before treatment. Therefore, evaluationof the upper tract with EU (or CT urography ifequivalent) is indicated in those with newly diag-nosed bladder TCC; conversely, patients withupper tract TCC should undergo cystoscopicevaluation.

Excretory UrographyThe diagnosis of upper tract TCC is most fre-quently made at EU in patients undergoing inves-tigation for hematuria. EU remains the noninva-sive method of choice for imaging the detailedanatomy of the pelvicaliceal system and ureters(15,17–19), although this is likely to change asCT urography becomes more refined and ac-cepted as a primary diagnostic investigation. Theappearances of upper tract lesions at EU are welldescribed. Calcification may be visualized on con-trol radiographs but is uncommon, occurring in2%–7% of tumors, and, when present, maymimic urinary tract calculi (3). Enlargement ofthe kidney may be seen with a large infiltratingtumor or a ureteric tumor causing prolonged ob-struction.

Renal TCC usually manifests as a filling defectwithin the contrast-enhanced collecting system,which may be single or multiple and smooth, ir-regular (Fig 1), or stippled. The stipple sign refersto tracking of contrast material into the intersticesof a papillary lesion (Fig 2) (2,3). However, this

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sign may also be seen with blood clot and fungusballs and should be interpreted with caution.Stricture-like lesions of the pelvicaliceal systemmay be evident and, if multiple, may mimic renaltuberculosis (5). Filling defects within dilatedcalices may occur secondary to tumor obstructionof the infundibulum and may lead to caliceal“amputation” (Fig 3). Tumor-filled, distendedcalices have been called “oncocalices.” If thesefail to opacify with contrast material, they areknown as “phantom calices.”

Ureteric TCC is typically seen as single ormultiple ureteric filling defects with or withoutsurface stippling and proximal ureteric dilatation.It is important to remember that long-standingtumor obstruction of the ureteropelvic junction orureter may lead to generalized hydronephrosisand poor excretion. This is a major disadvantageof EU when compared with CT urography, whichallows assessment of nonfunctioning kidneys. Up-per tract filling defects may be nonspecific at EU,and obstruction of pelvicaliceal drainage may ob-scure distal synchronous ureteric tumors, mean-ing that RP is usually performed to further assessthese patients.

Retrograde PyelographyRP is usually performed during cystoscopy or tofurther characterize abnormalities detected atEU, in inadequately excreting kidneys, or in cases

of contrast material allergy. Although invasive,RP allows confirmation of the radiologic diagno-sis while also facilitating ureterorenoscopy withbiopsy or brushing and cytologic examination oflocalized urine collections. As with EU, renalTCC typically appears as an intraluminal fillingdefect, which may be smooth, irregular, orstippled. Opacification of a tumor-involved calix

Figures 1, 2. (1) TCC of the renal pelvis in a 60-year-old man with painless hematuria. Fifteen-minute EU imageshows a large irregular filling defect (arrow) involving the right renal pelvis and extending into the lower pole calicealsystem. (2) TCC of the renal pelvis in a 65-year-old man. Fifteen-minute EU image shows a large stippled filling de-fect involving the collecting system of the right kidney (arrow).

Figure 3. TCC of the upper pole collecting system in a55-year-old woman. Fifteen-minute EU image showsamputation of the upper pole calix (arrow) secondary toTCC.


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may show irregular papillary or nodular mucosa(Fig 4). If TCC involves an infundibulum, thenan “amputated” calix may be seen with or with-out focal hydronephrosis and calculi secondary tourinary stasis (Fig 5). Tumor-filled, distendedcalices are known as “oncocalices.”

Ureteric TCC classically appears as a solitary,polypoid filling defect with ureteric dilatation

proximal to the lesion (Fig 6). The ureter itselfmay occasionally be fixed by diffuse ureteric wallinfiltration from an intramural lesion. An “applecore” appearance may be observed with eccentricor encircling ureteric lesions (Fig 7). Malignant

Figure 4. Renal TCC in a 67-year-old woman. RPimage shows a diffuse infiltrating TCC involving theright lower pole calix with irregularity of the involvedmucosa (arrow).

Figure 5. Renal TCC in a 67-year-old man with he-maturia. RP image shows amputation of the upper polecalix due to TCC (straight arrow). Multiple calculi arealso seen within the lower pole and interpolar calices(curved arrows).

Figure 6. Ureteric TCC in a 62-year-old man. RPimage shows an irregular stricture (arrow) with hy-droureter proximal to the site of the tumor.

Figure 7. Ureteric TCC in a 68-year-old woman. RPimage shows a long irregular stricture of the left distalureter with proximal hydronephrosis and “shoulder-ing” (arrow).


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ureteric strictures may be circumferential or ec-centric and can occasionally be confused withbenign strictures (Fig 8), although ureteric fixa-tion and nontapering margins are suggestive ofmalignancy (3). At RP, localized ureteric dilata-tion around and distal to the filling defect maygive rise to the “goblet” sign (Fig 9), which oc-curs due to slow tumor growth with resultant lu-men expansion and is not characteristic of moreacute causes of obstruction.

UltrasonographyCurrently, renal US is frequently requested in theevaluation of patients with hematuria to assess forrenal parenchymal masses. However, US is not assensitive as CT in identifying or characterizingrenal masses (16,20–22); as CT urographyemerges as an initial imaging investigation for he-maturia, US will likely play a limited diagnosticrole in the future. US can be useful in patientswith renal functional impairment or allergy toiodinated contrast material, although MR imag-ing is becoming established as the investigation ofchoice in these patients. US can also allow assess-

ment of the degree of hydronephrosis and guideinterventional procedures in the setting of acuteobstruction.

At US, renal pelvic TCC typically appears as acentral soft-tissue mass in the echogenic renalsinus, with or without hydronephrosis (Figs 10,11) (2). TCC is usually slightly hyperechoic rela-tive to surrounding renal parenchyma; occasion-ally, high-grade TCC may show areas of mixedechogenicity (Fig 12). Infundibular tumors maycause focal hydronephrosis. Although lesions mayextend into the renal cortex and cause focal con-tour distortion, typically TCC is infiltrative anddoes not distort the renal contour (3).

US has a limited role in the evaluation of ure-teric TCC as the ureters are rarely visualized intheir entirety, even if dilated. If visualized, thesetumors are typically intraluminal soft-tissuemasses with proximal distention of the ureter(23). US also allows limited assessment of peri-ureteric tissues. Recent developments in high-resolution endoluminal US performed duringureterorenoscopy have shown promise in theevaluation of upper tract TCC, offering potentialadvantages over other imaging techniques, andmay assume a more prominent role in future di-agnosis (2,24).

Figure 8. TCC of the pelviureteric junction in a 76-year-old man with painless hematuria. RP image showsconcentric narrowing of the pelviureteric junction (ar-row) with hydronephrosis. This appearance simulatesbenign disease but was shown to represent TCC at his-tologic analysis.

Figure 9. Ureteric TCC in a 58-year-old man. RPimage shows a duplex right collecting system. TCC inthe midportion of the ureter draining the upper polemoiety produces the characteristic goblet sign (straightarrow). Another tumor is identified in the ureter drain-ing the lower pole moiety (curved arrow).


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Computed TomographyCT is well established in the preoperative stagingand assessment of upper tract TCC. CT has alsobeen shown to be more sensitive than either USor EU in the detection of small renal mass lesions

and urinary tract calculi (15,25–30). The recentadvent of CT urography, offering single breath-hold coverage of the entire urinary tract, im-proved resolution, and the ability to capture mul-tiple phases of contrast material excretion, offersimproved diagnostic potential over EU and US inthe assessment of patients with hematuria due tocalculi or tumor (16,18,29,30). Recent studieshave also shown higher detection rates for upperand lower tract urothelial malignancies with CTurography over EU (17,31). Although the Ameri-can College of Radiology still recommends EU inthe investigation of hematuria, as CT urographybecomes more prevalent it is likely to become theinvestigation of choice, as the urothelium, renalparenchyma, and perirenal tissues can be assessedat a single examination.

Typically, CT urography consists of a mul-tiphasic helical CT protocol (Fig 13). A preen-hancement scan is initially performed from theupper pole of the kidney to the lower edge of thesymphysis pubis to exclude urinary tract calculi.A late arterial, early corticomedullary phase scanof the kidney and lower pelvis, beginning 15–25seconds after contrast material infusion, allows

Figures 10, 11. (10) Renal TCC in a 59-year-old woman. Sagittal US scan shows a tumor (arrows) in the echogenicrenal sinus. Tumor tissue is more echogenic than the surrounding renal cortex but less echogenic than renal sinus fat.(11) Renal TCC in a 55-year-old man. Sagittal US scan of the left kidney shows a tumor in the upper pole (arrow).

Figure 12. Renal TCC in a 65-year-old woman. Sag-ittal US scan shows a large mass of mixed echogenicity(arrows) involving the upper pole calix and overlyingrenal parenchyma. At histologic analysis, the mass wasshown to represent high-grade TCC.


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evaluation for vascular abnormalities. In the inter-est of decreasing radiation exposure and time ofexamination, however, this scan may be omittedunless a vascular abnormality is suspected. Anephrographic phase scan of the kidney, per-formed 80–140 seconds after contrast materialinfusion, allows assessment of the renal paren-chyma. An excretory phase scan from the upperpole of the kidney to the symphysis pubis, per-formed 4–8 minutes after contrast material infu-sion, allows assessment of the urothelium. Someauthors advocate a two-phase hematuria protocolwhere a nephropyelographic phase is performedonly if the initial nonenhanced scan does notdemonstrate a satisfactory cause for the patient’shematuria (18).

Three-dimensional reformations typically in-clude thick and thin slab coronal and sagittalMIPs for the kidneys, ureters, and bladder, al-

though other 3D reformation techniques can beused. Coronal reformation in particular demon-strates the longitudinal extent of a lesion, allowsassessment for multicentric tumors, and providesurologists with a familiar imaging format (Fig 13).Viewing the opacified system at wider windowsettings such as bone windows can also aid inidentifying and differentiating subtle lesions(Fig 13).

Unlike EU, imaging is not dependent on afunctioning kidney and the tract distal to a lesioncan be evaluated. CT urography may revealcauses of hematuria other than tumor or calculi,such as papillary necrosis, inflammatory lesions,or infarcts. Precontrast scans are necessary to de-tect calculi and obtain accurate attenuation valuesfor nonopaque filling defects, whereas postcon-trast scans aid in confirming lesion location andextent. On precontrast images, TCC is typicallyhyperattenuating (5–30 HU) to urine and renalparenchyma (Fig 13) but less attenuating thanother pelvic filling defects such as clot (40–80HU) or calculus (�100 HU).

Renal TCC is typically seen as a sessile fillingdefect in the excretory phase, which expands cen-trifugally with compression of the renal sinus fat(Fig 14). Other appearances include pelvicalicealirregularity, focal or diffuse mural thickening, on-cocalix, and focally obstructed calices. Early tu-mors confined to the muscularis are separatedfrom the renal parenchyma by renal sinus fat orexcreted contrast material and have normal-ap-pearing peripelvic fat (Fig 13). Advanced TCCextends into the renal parenchyma in an infiltrat-ing pattern that distorts normal architecture (Figs15, 16). However, reniform shape is typically pre-served (Figs 17, 18), unlike in renal cell carci-noma.

Figure 14. TCC of the renal pelvis in a 66-year-oldman with hematuria. Axial nephrographic phase CTscan shows a sessile filling defect (arrow), which is typi-cal of renal pelvic TCC.

Š Figure 13. TCC of the renal pelvis in a 43-year-old man with flank pain and hematuria. (a) Axial nonenhancedCT scan shows a mass (arrow) in the right renal pelvis. The mass is slightly hyperattenuating relative to the urine andrenal parenchyma. (b) Axial nephrographic phase CT scan shows that the mass (arrow) has characteristic early en-hancement, which is less than that of the surrounding renal parenchyma. (c) Axial excretory phase CT scan showsthe mass within the renal pelvis with surrounding excreted contrast medium. (d) Axial excretory phase CT scan(bone window) shows the lesion more clearly (arrow). (e) Coronal maximum intensity projection (MIP) image showsthe tumor (arrow) in EU format. (f) Detail of a coronal MIP image shows the lesion more clearly (arrow).


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Both TCC and renal cell carcinoma can showearly enhancement and de-enhancement aftercontrast material administration (30). Renal cellcarcinoma, being hypervascular, tends to enhancemore, although the two tumors often cannot be

differentiated. Parenchymal invasion may be seenas a focal delay in all or part of the cortical nephro-gram, although superimposed pyelonephritis orobstruction alone can also have these appear-ances. A large infiltrating renal TCC may occa-sionally manifest with areas of necrosis and mustbe differentiated from lymphoma, metastases,

Figure 15. TCC of the upper renal pole in a 61-year-old woman. (a) Axial nonenhanced CT scan shows a mass(arrow) in the upper pole calix of the left kidney. (b) Axial nephrographic phase CT scan shows characteristicearly enhancement of the tumor with extension into the surrounding upper pole parenchyma (arrow). (c) Axial ex-cretory phase CT scan shows the diffuse tumor with a small amount of excreted contrast medium centrally (arrow).(d) Coronal MIP image shows the extent of the tumor (arrow) in EU format.

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and xanthogranulomatous pyelonephritis, whichcan have a similar appearance (3,5).

Hydronephrosis is the most frequent finding inureteric TCC and hydroureter can often be seento the point of obstruction, where Hounsfield unitvalues for attenuation and enhancement usually

allow differentiation of TCC from calculus andclot. Ureteric wall thickening (eccentric or cir-cumferential), luminal narrowing, or an infiltrat-ing mass are other features of disease (29). Athickened enhancing ureteric wall with peri-ureteric fat stranding is suggestive of extramuralspread (Fig 19).

Figure 16. Renal TCC in a 54-year-old man. Axialexcretory phase CT scan shows TCC expanding cen-trifugally from the right renal pelvis. Note the paren-chymal invasion with a delay in the cortical nephro-gram (arrow).

Figure 17. Renal TCC in a 53-year-old man. Axialnephrographic phase CT scan shows diffuse tumor in-filtration of the left kidney with preservation of its reni-form contour.

Figure 18. Renal and ureteric TCC in a 76-year-oldwoman with gross hematuria and flank pain. Axialnephrographic phase CT scan shows extensive involve-ment of the left kidney and proximal ureter with TCCand perinephric extension of the tumor (arrow). Notethe preservation of the reniform contour.

Figure 19. Ureteric TCC in a 62-year-old man withright flank pain. Axial nephrographic phase CT scanshows enhancing TCC in the wall of the right ureter(arrow) with periureteric stranding and tumor exten-sion.

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CT urography allows identification of lesionsat an early stage, thereby allowing nephron-spar-ing surgery. Axial source images also allow assess-ment of surrounding structures. Adequate disten-tion and opacification are fundamental factors inthe thorough evaluation of the urothelium at CTurography. The increased radiation exposure isestimated at only 50%–80% over a complete EUseries (30). Although reformatting and review ofmultiple images with different window settings istime-consuming, CT urography has the potentialto stand alone as a comprehensive “one-stop”frontline study for hematuria and therefore detec-tion of TCC.

MR ImagingMR imaging is infrequently used in the primaryassessment of upper tract TCC, and the MR im-aging characteristics of this tumor are not welldescribed. In general, MR imaging has not played

a leading role in renal tumor imaging due to limi-tations in image quality, time-consuming se-quences, and susceptibility to artifacts. Recently,however, the development of newer fast se-quences has led to increasing use and MR imag-ing has been shown to equal CT in the detectionand diagnosis of renal masses (32–34).

MR imaging offers inherently high soft-tissuecontrast, is independent of excretory function,and allows multiplanar imaging, which permitsdirect image acquisition in the plane of tumorspread. The coronal plane is often advantageousbecause it allows evaluation of the kidneys, renalvessels, inferior vena cava, and spine in a smallnumber of sections. As with CT, MR imaging can

Figure 20. Bilateral ureteric TCC in a 57-year-oldwoman. (a, b) Coronal T2-weighted MR images (rep-etition time msec/echo time msec � 1655/99.6) showlow-signal-intensity tumors in the distal right (arrow ina) and distal left (arrow in b) ureters. Note the high-signal-intensity urine surrounding the tumors. (c) Axialgadolinium-enhanced T1-weighted MR image (616.7/10) obtained with fat saturation shows enhancement ofthe right ureteric tumor (large arrow). Note the gado-linium contrast material in the left ureter (small arrow)above the tumor.


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demonstrate tumor involvement of the renal pa-renchyma, perinephric tissues, or periureteric tis-sues and distant metastases (35,36).

TCC has lower signal intensity than the nor-mally high-signal-intensity urine on T2-weightedimages, permitting good demonstration of tumorin a dilated collecting system (Fig 20). However,TCC is nearly isointense to renal parenchyma onT1- and T2-weighted images, meaning that gado-linium contrast material is necessary for accurateassessment of tumor extent (3,33). AlthoughTCC is a hypovascular tumor, moderate en-hancement is seen with gadolinium contrast ma-terial, although not to the same degree as renalparenchyma (37). Postcontrast imaging may beperformed by using 3D sequences to allow dy-namic evaluation of the kidney (Fig 21). This al-lows assessment of the renal vasculature in arte-rial and venous phases and of the renal paren-chyma in corticomedullary and nephrographicphases. Vascular invasion of the renal vein or infe-rior vena cava, although rare, may be demon-strated without gadolinium contrast material byusing T2-weighted or gradient-echo flow-sensi-tive sequences (Fig 22).

Figure 21. Renal TCC in a 68-year-old woman.(a, b) Nephrographic phase (a) and excretoryphase (b) coronal gadolinium-enhanced 3D fastlow-angle shot source MR angiograms (3.64/1.37)show a moderately enhancing TCC (arrow) in theupper pole of the right kidney. (c) Gadolinium-en-hanced 3D MIP MR angiogram shows the tumormore clearly. Note the retroaortic segment of the leftrenal vein.

Figure 22. Bilateral renal TCC in a 77-year-old manwith hematuria. Axial T2-weighted fast spin-echo MRimage (8000/104) obtained with fat saturation showsTCC in the upper poles of both kidneys (arrows) withinvasion of the right renal vein and inferior vena cava(arrowhead).


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MR imaging evaluation of upper tract TCCshould include MR urography, which may bestatic or may be dynamic by using gadoliniumcontrast material (36). Static MR urography per-formed by using heavily T2-weighted sequencescan permit accurate localization of ureteric ob-struction (Fig 23), although imaging of undilatedsystems may be suboptimal (19,38) (Fig 24). Dy-namic gadolinium-enhanced T1-weighted MRurography performed with or without a diureticovercomes this problem and allows delayed ac-quisitions at various time intervals depending onthe degree and level of obstruction (Fig 25). Thistechnique is helpful in patients in whom urogra-phy with iodinated contrast material is not pos-sible. Data postprocessing (eg, MIPs) allows 3Drotation and evaluation of suspected areas of dis-ease without superimposition of other structures.This can be performed for both vessels and thecollecting system. The latter images, which re-semble conventional EU images, are readily ac-ceptable to clinicians.

Figure 23. TCC of the renal pelvis in a 65-year-old man. Coronal (a) and sagittal (b) heavilyT2-weighted (half-Fourier rapid acquisition with relaxation enhancement) source MR urograms(1500/116) show focal hydronephrosis and irregularity of the upper pole and interpolar calices ofthe right kidney (arrow).

Figure 24. Ureteric TCC in a 56-year-old woman.Coronal MIP half-Fourier rapid acquisition with relax-ation enhancement MR urogram (1500/116) showshydronephrosis and a filling defect due to a tumor inthe mid left ureter (arrow). Note the poor demonstra-tion of the nondilated right collecting system.


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Ureteric TCC is isointense to muscle on T1-weighted images and slightly hyperintense on T2-weighted images (39). At MR urography, uretericTCC typically appears as an irregular mass,whereas calculi appear as sharply delineated fill-ing defects, although differentiation betweensmall calculi and tumor may be difficult (19). Tu-mor enhancement after administration of gadolin-ium contrast material can also help distinguish itfrom calculi (Fig 20). Soft-tissue stranding in theperiureteric fat is suggestive of periureteric exten-sion, although prior surgery, radiation, and in-flammation can also give these appearances. MRimaging may help differentiate these entities,however, as fibrosis will appear hypointense onT2-weighted images, particularly in long-standingcases (39).

These comprehensive MR protocols can imageall the anatomic components of the urinary tractin a single test and offer advantages over othertechniques, including lack of iodinated contrastmedium and radiation exposure. Although MRimaging remains second line to CT, it offers fur-ther noninvasive imaging of masses that are notadequately characterized with other imaging mo-

dalities (36). The main disadvantage of MR im-aging is the inability to reliably detect urinarytract calcifications, calculi, and air, which limitsits use as a first-line test in the investigation ofhematuria. Although the sensitivity of renal pa-renchymal MR imaging with gadolinium for as-sessing renal masses and abnormalities of thenephrogram is considered similar to that of CT,spatial resolution is poor compared with that ofintravenous urography or CT urography, makingdetection of subtle urothelial malignancies lesslikely (17). Furthermore, complete characteriza-tion of renal masses may require multiple time-consuming sequences before and after adminis-tration of gadolinium contrast material (17,18).

Staging and TreatmentThe tumor stage at diagnosis influences the devel-opment of local recurrence and metastases andhence overall survival (1,4). Furthermore, treat-ment and prognosis are largely determined by thedepth of tumor infiltration, the degree of lymph

Figure 25. Ureteric TCC in a 68-year-old man with hematuria. (a) Coronal gadolinium-enhanced 3D fast low-angle shot MR urogram (3.64/1.37) obtained at 15 minutes shows hydronephrosis and proximal hydroureter to thelevel of the mid ureter. An enhancing tumor is seen in the ureteric wall at this level (thick arrow). No gadolinium con-trast material is seen in the left collecting system. Deep vein thrombosis of the left femoral vein is incidentally noted(thin arrow). (b) Coronal gadolinium-enhanced 3D fast low-angle shot MR urogram (3.64/1.37) obtained at 2 hoursshows the site of ureteric obstruction due to TCC (arrow).


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node and distant metastases, and the histologictumor type, making exact staging imperative(Tables 1, 2).

Conventional imaging methods such as EUand RP cannot demonstrate extension into theperipelvic or periureteric fat or metastases. Cross-sectional imaging with CT or MR is now rou-tinely employed in the presurgical work-up ofthese patients. These techniques can demonstrateintra- and extrarenal local extension of tumor andthe presence of nodal or distant metastases with ahigh degree of accuracy. They are used in con-junction with ureterorenoscopy and biopsy forstaging before surgery.

CT has become routine in the further charac-terization of upper tract lesions demonstratedwith other modalities and, despite varying reportson staging accuracy, is currently the preoperativeimaging modality of choice (9,15,40) (Table 1).As studies show higher detection rates for urothe-lial malignancies with CT urography than withEU (29,31), this technique is being advocated asa one-stop diagnostic and staging assessment ofsuspected urothelial malignancy. Although CTdoes not allow distinction between stage 0–II tu-

mors, it does allow differentiation of early-stageTCC confined to the collecting system wall fromadvanced disease with local extension or distantmetastases, which is important for defining surgi-cal management (8,41). Early-stage tumors (stage0–II) confined to the muscularis are separatedfrom the renal parenchyma by renal sinus fat orexcreted contrast material and have normal-ap-pearing peripelvic fat (Fig 13).

More-advanced tumors infiltrating beyond themuscularis into the peripelvic fat typically showincreased, inhomogeneous peripelvic attenuation(Fig 18), although this finding may also be seenwith superimposed infection, hemorrhage, or in-flammation and should be interpreted with cau-tion to avoid overstaging (39). Metastatic spread

Table 1TNM Classification of Renal TCC

Stage Histopathologic Findings

Tx Primary tumor cannot be assessedT0 No evidence of a primary tumorTa Papillary noninvasive carcinomaTis Carcinoma in situT1 Tumor invades subepithelial connective tissueT2 Tumor invades the muscularisT3 Tumor invades beyond the muscularis into the periureteric fat or renal parenchymaT4 Tumor invades adjacent organs, the pelvic or abdominal wall, or through the kidney into perinephric fatNx Regional lymph nodes cannot be assessedN0 No regional lymph node metastasisN1 Metastasis in a single lymph node �2 cm in greatest dimensionN2 Metastasis in a single lymph node �2 cm but �5 cm in greatest dimension or in multiple lymph nodes

�5 cm in greatest dimensionN3 Metastasis in a lymph node �5 cm in greatest dimensionMx Distant metastasis cannot be assessedM0 No distant metastasisM1 Distant metastasis

Table 2Histopathologic Grading of Renal TCC

Grade Histopathologic Findings

Gx Grade of differentiation cannot beassessed

G1 Well-differentiated tumorG2 Moderately differentiated tumorG3, G4 Poorly differentiated or undifferentiated

tumor


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via urinary or hematogenous routes usually mani-fests as multifocal mucosal nodules or wall thick-ening, whereas direct invasion produces a short orlong stricture (22). Extrarenal spread can occur ator through the renal hilum, and common sites ofmetastases include the lungs, retroperitoneum,lymph nodes, and bones (40). Rarely, invasion ofthe renal vein or inferior vena cava is seen and canbe well demonstrated with comprehensive CTurography protocols. The overall accuracy of CTin predicting the pathologic stage ranges from36% to 83% in the literature (2), which meansthat ureterorenoscopy and biopsy remain essen-tial additional tools.

As with CT, MR imaging can demonstratetumor involvement of the renal parenchyma, peri-nephric fat, or periureteric fat and distant metas-tases. It therefore offers an alternative staging mo-dality and has been shown to allow accurate stag-ing of TCC lesions larger than 2 cm (Fig 22)(37). As with CT, however, limitations exist indetecting superficial invasion of the renal paren-chyma and small lesions may be missed becauseof motion artifacts (2,37). It is the preferred stag-ing examination in patients who cannot tolerateiodinated contrast material and in whom multi-planar and vascular imaging is required for preop-erative assessment.

The traditional treatment of upper tract TCCinvolves total nephroureterectomy with excisionof the ipsilateral ureteric orifice and a contiguouscuff of bladder tissue (25). However, the develop-ment of endoscopic and minimally invasive surgi-cal techniques allows renal preservation in se-lected patients, particularly those with a solitarykidney, bilateral tumor, poor renal function, low-grade tumor, or prohibitive surgical risk, with re-sults comparable to those of radical surgery(2,25,42–45). Accurate radiologic detection andstaging of tumor is therefore essential to deter-mine appropriate surgical therapy, especially ifconservative surgery is being considered, or theintensity of chemotherapy for advanced-stage tu-mors (25,40).

Follow-upThere is still no widely accepted protocol for theradiologic follow-up of patients with primaryTCC of the upper urinary tract. Current data

suggest that routine follow-up imaging strategiesshould be individually tailored on the basis of pri-mary tumor characteristics (2). Annual EU is rec-ommended, especially in the first 2 years afterinitial diagnosis (10,19,42). RP should be soughtif EU fails to depict or adequately distend the en-tire upper tract, especially if cystoscopy is beingperformed to assess the bladder. This vigilance isjustified in order to detect early recurrence afterconservative surgery or, in patients who have onlyone remaining kidney, to detect contralateral le-sions at an early stage when local excision may befeasible.

Owing to the high rate of metachronous tumorin the bladder, frequent cystoscopy should also beperformed. At our institution this is performedevery 3 months for the first year, every 6 monthsfor the second year, and yearly thereafter. In thefuture, CT urography will likely become the pri-mary radiologic method of TCC follow-up, al-lowing assessment of the entire urothelium andalso facilitating virtual cystoscopy, although con-ventional cystoscopy is still necessary for directvisualization and biopsy.

ConclusionsConventional imaging modalities such as EU,RP, and US still play a key role in the assessmentof hematuria, in combination with endourologictechniques. However, multiphasic CT urographyoffers superior detection of calculi, urothelial tu-mor, and parenchymal tumor over EU and USand allows accurate staging of detected lesions atthe same examination. MR imaging, includingthe newer techniques of MR angiography andMR urography, offers comparable evaluation inpatients who cannot tolerate iodinated contrastmaterial and in whom multiplanar, vascular, andcollecting system imaging is required. Recogni-tion by the radiologist of the variety of appear-ances of upper tract TCC with all imaging mo-dalities is necessary to detect and stage tumorsaccurately. In addition, atypical appearances, par-ticularly in advanced tumors, should be recog-nized. Synchronous or metachronous tumors of


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the urothelium are common, necessitating vigi-lant urologic and radiologic follow-up. In the fu-ture, CT urography will likely become the defini-tive radiologic examination for diagnosis and fol-low-up in patients with suspected TCC.

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This article meets the criteria for 1.0 credit hour in category 1 of the AMA Physician’s Recognition Award. To obtaincredit, see accompanying test at http://www.rsna.org/education/rg_cme.html.

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