AUTHOR AND EDITOR INFORMATION

Section 1 of 11  

• Authors and Editors
• Introduction
• Differentials
• Radiograph
• CT SCAN
• MRI
• Ultrasound
• Nuclear Medicine
• Intervention
• Multimedia
• References

INTRODUCTION

Section 2 of 11  

• Authors and Editors
• Introduction
• Differentials
• Radiograph
• CT SCAN
• MRI
• Ultrasound
• Nuclear Medicine
• Intervention
• Multimedia
• References

Background

Embryologic derivation of the collecting system of the urinary tract occurs from the fetal mesonephros. As a result of this development, tumors of the renal collecting system have cell origins different from those of the renal parenchyma. These tumors are classified on the basis of their respective mesodermal or epithelial tissue origin. Primary neoplasms of the renal collecting system represent 10% of renal tumors, of which approximately 80% are malignant. Most are transitional cell carcinomas (TCCs).

Bladder TCC is 50 times more common than renal pelvic tumors. Often, TCCs are multiple, involving any part or all of the collecting system. The tumors are traditionally classified into papillary and nonpapillary types. Nonpapillary tumors are considered malignant.

For excellent patient education resources, visit eMedicine's Kidneys and Urinary System Center. Also, see eMedicine's patient education article Blood in the Urine.

Related Medscape topics:
Specialty Site Radiology
Specialty Site Oncology
Resource Center Bladder Cancer Resource Center
Resource Center Renal Cell Carcinoma Resource Center
CME/CE Screening for Bladder Cancer in Primary Care: A Comprehensive Review
CME Treating Non-muscle-invasive Bladder Cancer: The AUA 2007 Update

Pathophysiology

Causative agents

Exposure to a large variety of noxious stimuli is thought to play a major role in the etiology of TCC, although many of these stimuli have no known direct link. A variety of chemical carcinogens have been linked to the development of TCC. These include tobacco; aniline dyes; benzidine; aromatic amines; rubber; and azo dyes used in textiles, printing, and plastic manufacturing. These carcinogens have essentially been removed from the workplace (by the US Environmental Protection Agency).

The underlying pathophysiology is thought to involve hyperplastic metaplastic changes secondary to chronic irritation, particularly within the ureter. Chemical carcinogens act locally on the epithelium, causing a field change; their action is enhanced by the contact time (exacerbated by urinary stasis or diverticula). Bladder tumors are thought to be more common partly because of the time required for the agents to be activated by hydrolyzing enzymes to produce their carcinogenic effect. Partial obstruction may account for increased exposure to the upper tracts (eg, increased incidence of TCC in horseshoe kidney).

Risk factors and causative agents include tobacco use (which is postulated to increase the risk 2-3 times); occupational exposure; abuse of analgesics (eg, phenacetin, which increases the risk 8 times); cyclophosphamide therapy (6-y lag time), particularly after drug-induced hemorrhagic cystitis; Balkan nephritis, with progressive renal failure; multiple bilateral tumors (etiology unknown); recurrent or chronic infection; and urinary calculi (squamous cell carcinoma [SCC] is the most common entity in such cases).

Of great importance is the multiplicity of TCCs of both synchronous and metachronous natures.¹ There is a frequent association of papillomas in patients with TCCs. Almost 25% of patients with renal pelvic papillomas develop a carcinoma. Of those with multiple papillomas, 50% develop carcinomas.

When both renal pelves are involved, synchronous tumors occur with a prevalence of 1-2%.¹ With both ureters, the prevalence is 2-9%. The bladder is affected in 24% of cases with primary pelvic involvement, in 39% of cases with primary ureteral involvement, and in 2% of cases with primary bladder involvement.

Ureteric TCC may be solitary, but TCC has a marked propensity for unilateral multicentricity. The reason is unknown, but this distribution may result from antegrade and/or retrograde seeding or the fact that the entire ureteral mucosa is exposed to the carcinogen.

Within the upper renal tracts, metachronous TCC appears in 12% of pelvic and ureteric primary tumors within 25 months and in 4% of bladder primary tumors (two thirds within 2 years, the others as long as 20 years later). Within the bladder, metachronous TCC occurs in 23-40% of primary renal TCCs after 15-48 months and in 20-50% of primary ureteral TCCs after 10-24 months.

Zhou and associates have reported a 10-fold increase in urologic malignancies, especially TCC, in renal allograft recipients.²

Pathology/histology

TCCs usually have the following broad classification: (1) exophytic papillary lesion (85%) with a frondlike structure and central fibrovascular core lined by an epithelial layer (broad based and pedunculated); (2) nonpapillary, noninfiltrating; (3) infiltrating, usually of higher grade and less common; and (4) carcinoma in situ.

Although no staging method is universally recommended, the following tumor, nodes, metastases (TNM) system of the American Joint Committee on Cancer (AJCC) is useful for upper-tract and ureteral lesions: Tis 0 indicates an in situ lesion; Ta, noninvasive papillary carcinoma; T1 I, invasion of the subepithelial connective tissue; T2 II, tumor confined to the muscularis layer; T3 III, invasion of the renal parenchyma and/or peripelvic soft tissues; and T4 IV, extension beyond the renal capsule.

The grade is usually correlated with the stage, as follows: 1 indicates that the cells are slightly anaplastic; 2, that intermediate features are present; and 3, that marked cellular pleomorphism is present.

Within the upper tracts, grade I papillary lesions remain controversial because some believe that these lesions represent nonmalignant neoplastic proliferation of transitional epithelial cells, which are often associated with independent TCCs. Transitional cell mucosa has the capacity for both benign and malignant squamous and/or glandular differentiation. TCC occurs with a frequency of approximately 90% in the renal pelvis, although care must be taken in its identification because pure cell types are rare.³

Nonpapillary, noninfiltrating TCC of the renal pelvis may show no gross changes other than slight planar thickening and occasional mild hyperemia and/or hemorrhage. Invasion may occur en bloc or in a tentacle-like fashion. Within the ureter, papillary tumors are attached by a broad pedicle, with surrounding edema if the infiltration is deep. Infiltration by ureteral papillary tumors is less common (40%) than infiltration by tumors in the renal pelvis. However, multiplicity is more common. Approximately 40% of tumors are nonpapillary. Surface ulceration is common; it is associated with early invasion and metastases.

The stage of tumors in the bladder, as assessed by the depth of infiltration, is the single most important prognostic parameter when treatment is initiated. Clinical staging has an accuracy of 50%; by way of comparison, CT has an accuracy of 32-80%, and MRI has an accuracy of 73%. Overstaging commonly occurs as a result of edema after endoscopy and/or endoscopic resection and as a result of fibrosis from radiation therapy.^{4, 5, 6, 7, 8}

A staging classification that incorporates the TMN and Jewett-Strong-Marshall (JSM) systems is useful. The stages are as follows: T1 A indicates lesions involving the mucosa and submucosa; T2 B1, invasion of the superficial muscle layer; T3a B2, invasion of the deep muscular wall; T3b C, invasion of perivesical fat; T4a D1, extension to perivesical organs; T4b, invasion of the pelvic and/or abdominal wall; and D2, distant metastases.

TCC in situ is a term used to describe full-thickness dysplastic changes present in flat, nonpapillary urothelium. This is consistently seen in the bladders of patients with invasive TCC, and it is thought to be a precursor of this lesion. About 80% of all bladder TCCs are low-stage superficial papillary neoplasms (multifocal in a third); these become invasive in 10-20% of cases. These invasive tumors are almost always solitary. Nonpapillary or sessile bladder tumors are typically more invasive than the exophytic types, although both may coexist. Early lymphatic invasion and bladder wall infiltration are associated with a poor prognosis.

Metastases

Hematogenous spread is less frequent with renal pelvic tumors than with hypernephromas. Lymphatic supply is extensive, and lymphogenous involvement occurs early in the disease process. Metastases occur to the lung, lymph nodes, and liver; direct extension into the retroperitoneum is common.

Frequency

United States

Primary renal pelvis neoplasms account for less than 10% of all renal tumors. Of these, approximately 75% are considered malignant; most are TCCs. TCCs involving the extrarenal part of the renal pelvis are more common than those in the infundibulocaliceal region. They are far less common than hypernephromas (ratio, 1:5) and 3 times more common than ureteric neoplasms. Conversely, bladder tumors are 50 times more common than renal pelvis tumors, which are thought to stem from the relatively larger surface area of bladder mucosa. The incidence of ureteric TCC, determined on the basis of combined autopsy reports, is 1 per 1000-3600; these account for 1 in every 25 upper-tract tumors. The lower third is usually most affected (70%).

Bladder TCC accounts for approximately 5% of all new malignant neoplasms; as such, it is the most common tumor of the genitourinary tract, accounting for approximately 2% of all cancer deaths in the United States. The lateral wall of the bladder and bladder diverticula are more frequently involved. An increased incidence of TCC of the bladder and ureter has been seen in patients with multiple ureteral diverticula; these patients should be closely screened for TCC.

International

The true incidence of TCC internationally is not known; however, the incidence of TCC is expected to be higher in regions of the world where schistosomiasis is endemic.

Mortality/Morbidity

Approximately 90% of TCCs are curable in patients with superficial, confined tumors. Those with deeply invasive tumors that are still confined to the renal pelvis and ureter have a 10-15% likelihood of cure. Usually, distant metastases that penetrate the urothelial wall cannot be cured with current forms of treatment.

Metastases from ureteral TCC are far more common than those from bladder cancer, partly because the ureteral wall is thin and acts as a poor barrier. Metastases occur in approximately 11% of cases, in the following sites: retroperitoneal nodes (34%); distant lymph nodes (17%); liver (17%); lumbar vertebrae (13%); lungs (9%); kidneys (8%); adrenals (4%); spleen (2%); sacral vertebrae (2%); brain (2%); pancreas (2%); and skin (2%). In addition, isolated metastases occur in the colon, broad ligament, diaphragm, humerus, omentum, pericardium, pleura, prostate, and vagina.

Race

No particular racial prevalence has been demonstrated.

Sex

The male-to-female ratio is 3-4:1, except when tumors occur in people who abuse analgesics or when the tumors occur in association with Balkan nephropathy, which affects both sexes equally.

Age

The mean age of onset is 50-70 years.⁹

Anatomy

Embryologic derivation of the urinary tract collecting system occurs from the fetal mesonephros. As a result of this development, tumors of the collecting system of the renal tract have cell origins different from those of the renal parenchyma. These tumors are classified on basis of their respective mesodermal or epithelial tissue origin.

The uroepithelium is the mucosal lining of the calyces, infundibula, ureters, urinary bladder, and portions of the urethra. The uroepithelium has a characteristic microscopic appearance that is midway between glandular and squamous tissue—hence its name, transitional epithelium. With regard to distribution, in addition to the uroepithelium, TCC can develop anywhere from the calyces to parts of the urethra with uroepithelial lining.

Clinical Details

Hematuria is a common symptom that occurs in as many as 80% of patients; it may be frank or microscopic. Hematuria may occur early or late in the development of the disease. In cases of TCC of the upper tract, pain, abdominal mass, and pyuria occur with approximately the same frequency as they do in cases involving other renal tumors. Dysuria and frequency are more commonly reported with ureteral tumors. Pain is usually dull and colicky and results from obstruction, although a second type of pain results from direct tumoral extension. This second type of pain is frequently severe, constant, and penetrating.

Rare instances of spontaneous urinary extravasation caused by rupture have been reported; this often results in an acute abdomen. Other rare findings include hypercalcemia, secondary amyloidosis, and elevated chorionic gonadotropin levels.

Preferred Examination

Elevated urinary lactate dehydrogenase (LDH) levels have been reported, but this finding is nonspecific. However, cytology can play a significant role, with a 60% accuracy rate in the diagnosis of renal pelvic and ureteral TCC. Cytology is particularly useful in cases involving tumors of more advanced stage; in such cases, the accuracy rate improves to 80%. Selective lavage, ureteral urine collection, brush biopsy, or ureteroscopy may be performed to obtain specimens.

Plain radiographic findings, such as calcifications, are not specific in the diagnosis of urothelial tumors, and they usually contribute little to the diagnosis. Intravenous urography (IVU) is a common diagnostic test in patients with hematuria, although the early detection of small urothelial tumors may be difficult. A meticulous IVU technique is required. Multidetector-row CT with postprocessing image manipulation (contour imaging) is increasingly coming to challenge IVU.

Retrograde pyelography is useful when the kidney cannot be visualized by means of IVU or when IVU cannot be performed because of renal disease or an adverse response to the contrast agent. Retrograde pyelography also has the advantage of being able to be combined with various biopsy techniques.¹⁰

CT is becoming increasingly sensitive for the staging of early TCC. Developments such as virtual cystoscopy and postmicturition scanning should improve the overall accuracy of staging by the use of CT.^{6, 11, 12}

MRI has the advantages of high intrinsic soft tissue contrast, direct multiplanar capability, and the availability of nontoxic renally excreted contrast agents. MRI appears to be at least as useful as CT in the evaluation of perivesical fat involvement, and it may be superior to CT in the detection of invasion of the adjacent organs. However, MRI cannot depict well the superficial invasion by TCC of the upper urinary tract.^{6, 7, 8, 13, 14, 15, 16, 17}

Both CT and MRI have been shown to perform better than cystography in the diagnosis of tumors in the bladder diverticula that are not depicted on cystograms because of obstruction at the diverticular orifice.

Ultrasonography is inaccurate for diagnosing early TCC; it is useful in the diagnosis of obstructive uropathy.^{18, 19, 20} Ureteric lesions are particularly difficult to visualize unless they cause hydronephrosis and hydroureter. Other limitations of ultrasonography are that it is inaccurate in the staging of bladder TCC, particularly Ta and T1 tumors, and in the detection of pelvic lymph node involvement.

Isotope renography is an extremely sensitive means of assessing relative renal function and obstructive uropathy before surgery. Isotope bone scanning is a useful technique in the investigation of skeletal metastases.²¹

Limitations of Techniques

Elevated urinary LDH levels are nonspecific. Urine cytologic results may be negative in as many as 40% of cases of TCC; this finding is useful in only advanced-stage tumors.

Plain radiographic findings are nonspecific, particularly the presence of calcification, which has a wide differential diagnosis. Filling defects in the renal collecting system and the bladder, as seen with IVU, CT, and retrograde pyelography, are present in a number of other pathologies. These findings are not specific to TCC.

On CT scans, a hyperattenuating TCC may be confused with a blood clot, particularly in the early stages of the disease. Also, inhomogeneous renal fatty attenuation of any cause in a patient with undiagnosed early-stage TCC may hinder accurate diagnosis.

MRI is expensive and has limited availability. False-positive diagnoses have been reported. In staging bladder TCC, tumor extension is overstaged according to the TNM classification in 7.5% of patients; it is understaged in 32.5% of patients.

On sonograms, calculi may be confused with high-grade TCCs, which can be densely echogenic. No sonographic features are specific for TCC, and many filling defects within the renal collecting system and bladder have a nonspecific appearance. It is also difficult to discern nondilated ureters on ultrasonography.

DIFFERENTIALS

Section 3 of 11  

• Authors and Editors
• Introduction
• Differentials
• Radiograph
• CT SCAN
• MRI
• Ultrasound
• Nuclear Medicine
• Intervention
• Multimedia
• References

Other Problems to Be Considered

Nonneoplastic lesions — Lucent calculi, blood clot, fungus balls, pus, sloughed papillae, pyeloureteritis cystica
Primary epithelial tumors — Papilloma, SCC, adenocarcinoma, carcinosarcoma, undifferentiated tumors
Mesodermal smooth muscle tumors — Leiomyoma, leiomyoblastoma, leiomyosarcoma
Mesodermal neural tumors — Neurofibroma, neurilemoma
Other sarcomas - Spindle cell, osteosarcoma
Mesodermal vascular tumors — Hemangioma, lymphangioma, hemangiosarcoma
Mesodermal fibrous tumors — Fibroepithelial polyp, renal medullary fibroma
Mesodermal mixed tumors — Fibromyoma, fibrolipoma, fibromyxoma
Lymphoma
Metastases or direct invasion of the uroepithelial by tumors

RADIOGRAPH

Section 4 of 11  

• Authors and Editors
• Introduction
• Differentials
• Radiograph
• CT SCAN
• MRI
• Ultrasound
• Nuclear Medicine
• Intervention
• Multimedia
• References

Findings

Plain radiography

Plain radiographs may first alert the radiologist to presence of a renal mass or a bladder mass. Occasionally, a large renal outline may be seen in a completely obstructed kidney. Uncommonly, radiographically discernible areas of punctate calcification may be seen in TCC. The calcification is on the surface of the tumor and not within the mass duct. Intrinsic calcifications suggest an adenocarcinoma or an unusual cell type.

TCC is associated with analgesic nephropathy. Plain radiographic findings of displacement of renal calcifications, which occur in analgesic nephropathy, may be the first sign of TCC. Surface calcification of a bladder tumor may be seen on plain radiographs in 1% of cases. Osseous expansive destruction or lung metastases may be seen in the presence of renal malignancy.

Intravenous urography

The most common findings in TCC of the kidney are single or multiple filling defects in the renal pelvis, as seen in 35% of cases. In about 26% of patients with renal TCC, the calyx is dilated; such dilation is caused by partial or complete obstruction of the infundibulum. Amputation of the calyx may be seen in 19% of cases. In 13-31% of cases, the affected kidney is not visualized. Such failure to visualize the kidney is usually secondary to hydronephrosis but can be the result of tumor infiltrating and replacing functioning kidney or of occlusion of the renal vein. Hydronephrosis with renal enlargement caused by tumoral obstruction of the ureteropelvic junction may be seen in 6% of cases (see Images 1, 4-6, 12-13).

Various signs have been described in renal TCC. The stipple sign is a rare sign that occurs when contrast material is trapped within the interstices of a papillary tumor. When this is seen en face, the tumor appears to contain multiple stipples. This sign is highly suggestive of TCC. When this sign is seen, blood clots and radiolucent calculi are excluded, and further investigations are superfluous. Punctate calcification on a TCC may mimic the stipple sign.

Punctate calcification is unusual in TCC; such calcification is apparent on the scout image before the intravenous contrast material is delivered. Occasionally, contrast material may be trapped within a blood clot formed in the ureter and then extruded into the bladder as a stringy mass that may trap contrast material in an irregular fashion. However, this entrapment is coarser than that seen with neoplastic stippling.

Fungus balls or mycetoma may also occasionally entrap contrast material. The pattern of entrapment is lamellar; such entrapment is frequently associated with gas formation (frequently, patients have poorly controlled diabetes with urinary tract infections). Rarely, stippling may be observed in tubular ectasia when papillae containing dilated ducts of Bellini are seen en face. Inspection of the other papillae may make the diagnosis obvious.

Phantom calyx represents the failure of a calyx to opacify because of obstruction. Oncocalyx represents calyceal distension caused by the tumor.

In contrast to renal TCC, ureteric tumors show single or multiple filling defects in only 19% of cases. This observation is associated with hydronephrosis and hydroureter in 34% of cases; in advanced cases, it may be associated with a nonfunctioning kidney.

Bladder TCC also shows an irregular filling defect with broad base and fronds. Increased thickness of the bladder wall in the region of the tumor should indicate infiltration.

Retrograde pyelography

Retrograde pyelography in ureteric TCC may show focal expansion of ureters around and distal to the mass; such a finding is called the champagne, or goblet, sign. This finding is helpful in differentiating TCC from focal lesions of other causes, such as calculi or blood clots. Typically, calculi and blood clots do not demonstrate a goblet sign because they do not progressively stretch the ureteral wall from slow growth. Occasionally, the catheter coils below the mass during retrograde catheterization; this is called the Bergman sign (see Image 9).

Degree of Confidence

Plain radiographic findings, such as calcifications, are not specific in the diagnosis of urothelial tumors. Discernible areas of a coarse, punctate pattern of calcification with a mucosal lesion on excretory urography or retrograde pyelography may suggest TCC. An important role for plain radiography is in searching for evidence of osseous metastases that may herald renal malignancy.

Multidetector-row CT is replacing IVU in the evaluation of hematuria, although IVU is still being used. The early detection of small urothelial tumors demands a meticulous IVU technique. Accurate demonstration of the pelvocaliceal system requires abdominal compression to distend the collecting systems, and oblique imaging or tomography may also be necessary. Diuresis multidetector-row CT with contour reformatting of the axial records may be useful. This technique does not require abdominal compression. Early experience with this method has been most positive because the CT technique demonstrates not only the opacified lumen but also the surrounding soft tissue anatomy.

Filling defects with dilated calyces are easily seen and are readily diagnosed. Hydronephrosis with renal enlargement is easily confused with uncomplicated primary pelvic hydronephrosis; antegrade/retrograde pyelography is usually required for diagnosis.

Adequate depiction of the ureters is difficult, and prone, oblique, or even spot images obtained during fluoroscopy may be required at urography. If an area of constant narrowing of the ureters is seen on more than 1 image and if it cannot be explained by the presence of a crossing vessel or a peristaltic wave, a tumor must be suspected. A meticulous urographic examination (radiographic or multidetector-row CT) can prevent unnecessary pyelography/ureterography in the majority of cases.

Importantly, if the demonstration of the pelvicaliceal system at excretion urography or CT is poor, an upper-tract tumor may be missed, particularly when a decoy of a bladder tumor is present. The coexistence of upper- and lower-tract tumors is not rare.

The sensitivity and specificity with regard to the upper urinary tract pathology are 67% and 91%, respectively, for IVU and 56% and 94%, respectively, for ultrasonography. For both techniques combined, the sensitivity and specificity are 79% and 88%, respectively. IVU has a 70% accuracy rate in the diagnosis of bladder TCC. The role of radiology is in demonstrating the upper urinary tract, both at the time of the initial diagnosis and during the follow-up of urothelial cancer. The statistics for multidetector-row CT are now under investigation.

Retrograde pyelography is useful when the kidney cannot be visualized with IVU or when an intravenous approach cannot be performed because of renal disease or an adverse reaction to contrast agents. Retrograde pyelography in combination with brush biopsy is a highly reliable method for making a definitive diagnosis of TCC. The results are considered diagnostic in 85% of cases.

If spot filming is the imaging technique, this should be performed in an appropriate fluoroscopic digital unit where serial images can be obtained. This may be done during diuresis urography (infusion IVU with 300 mL of 30% contrast media) or during antegrade/retrograde pyelography.

Approximately 5% of ureteric TCCs grow intramurally, resulting in a stricture rather than a filling defect. Radiologically, distinguishing this type of tumor from stricture is impossible. However, at CT, a thickened ureteric wall with stranding may be seen.

False Positives/Negatives

Calcification is seen in 10% of renal cell carcinomas. Retroperitoneal tumors, infections, or inflammation; pelvic tumors; pelvic lipomatosis; and gynecologic and gastrointestinal pathologies may cause extrinsic ureteric obstruction. Other causes of ureteric obstruction or bladder abnormalities include irradiation, surgery, trauma, or infections such as tuberculosis or schistosomiasis. These conditions may result in telltale signs on plain radiographs.

Other causes of filling defects may mimic a TCC, such as radiolucent or uric acid stones; blood clots; sloughed papilla caused by papillary necrosis; or fungal balls in patients with diabetes. Vessel crossing may cause a linear extrinsic impression; in these cases, oblique or compression images may help in differentiating TCCs from urothelial tumors. Tuberculosis can cause narrowing of the infundibulum and irregular calices. With regard to imaging, tuberculosis is the major disorder in the differential diagnosis.

Other mimics include pyeloureteritis cystica, renal cell carcinoma invading the pelvicaliceal system, or choleastoma. SCC is radiographically indistinguishable from TCC; however, SCC is less likely to be a polypoid tumor. Although a diagnosis may be made on the basis of urograms or cystograms, a small bladder tumor, especially one of the infiltrative types, may go undetected. Furthermore, a dense concentration of contrast material may obscure the intraluminal part of the urothelial tumor.

Mimics of ureteric TCC include papilloma or polyp, which commonly produces a long, smooth intraluminal filling defect. This defect may prolapse up and down the ureter on serial images, and it may even intussuscept. Avoiding the introduction of air bubbles is important because these could be mistaken for tumors.

CT SCAN

Section 5 of 11  

• Authors and Editors
• Introduction
• Differentials
• Radiograph
• CT SCAN
• MRI
• Ultrasound
• Nuclear Medicine
• Intervention
• Multimedia
• References

Findings

The workup of patients in whom TCC is suspected includes ultrasonography and IVU. However, CT scanning enables the detection and staging of TCC, usually without the need for additional imaging (see Images 3, 8).^{11, 12, 22}

Features

The commonly recognized presentations of TCC on CT scans include the following: irregular filling defects of the pelvocaliceal system and ureters, which tend to be associated with obstruction and dilatation of the ureter and pelvis proximal to the lesion; ureteral wall thickening; frondlike growths projecting into the bladder from a fixed mural site; and surface calcification of bladder TCC.

On nonenhanced CT scans, the TCC is hypoattenuated or isoattenuated relative to the normal renal parenchyma, and it is hyperattenuated relative to urine. TCCs demonstrate mild to moderate enhancement after the administration of contrast material, and they are hypoattenuated relative to opacified urine.

Staging

The AJCC designates stages in the TNM system. Stages are based on the depth of tumoral invasion, as follows: Ta indicates papillary noninvasive carcinoma; Tis, carcinoma in situ; T1, invasion of the subepithelial connective tissue; T2, invasion of the muscularis propria; T3, invasion beyond the muscularis into the periureteric fat (ureter only), the peripelvic fat (renal pelvis only), or the renal parenchyma; and T4, invasion of adjacent organs or through the kidney into the perinephric fat.

N0 indicates no regional lymph node metastasis; N1, metastasis in a single lymph node 2 cm in diameter or smaller; N2, metastasis in a single lymph node 2-5 cm in diameter or multiple lymph nodes, none larger than 5 cm in diameter; and N3, metastasis in a lymph node larger than 5 cm in diameter.

M0 indicates no distant metastasis, and M1, distant metastasis.

Therefore, the AJCC defines the stages as follows: stage 0, localized disease with Ta or Tis/N0/M0; stage I, mucosal lamina propria involved with T1/N0/M0; stage II, disease into but not beyond the muscularis with T2/N0/M0; stage III, invasion of the renal parenchyma and/or fat with T3/N0/M0; stage IV, metastases with T4/N0/M0, any T/N1-3/M0, or any T/any N/M1.

Degree of Confidence

CT is of limited value in staging low-grade disease because it cannot accurately depict the depths of tumoral invasion. Therefore, stages Ta-T2 cannot be distinguished. The strength of CT lies in the staging of high-grade disease, because of its ability to demonstrate peripelvic, periureteric, and local pelvic extensions, as well as distant metastases.

Inevitably, studies differ with regard to the sensitivity and specificity of preoperative CT scanning in the detection and accurate staging of TCC. The reported range for detection efficiency is 86-100%. The results of most studies suggest a range of 55-64% for correct TNM staging, compared with surgical findings.

Understaging appears to be a limiting factor. However, results with newer scanners and adjunct techniques such as virtual cystoscopy and postmicturition scanning should improve the overall accuracy of staging with CT.

False Positives/Negatives

In stage I or II disease, conditions such as chronic pyelitis, tuberculosis, and xanthogranulomatous pyelonephritis may mimic TCC.

In stage III or IV disease, CT cannot be used to distinguish edema, infection, inflammatory changes, or hemorrhage from tumor. All of these processes may cause inhomogeneous peripelvic attenuation that is indistinguishable from that caused by the infiltration of fat by tumor. Superimposed pyelonephritis can cause inhomogeneous renal enhancement and thus give a false interpretation of invasion by underlying TCC. Occasionally, renal cell carcinoma may simulate TCC with renal parenchymal infiltration.

The characteristic attenuation of a TCC lesion is normally sufficiently different from renal tract filling defects of other causes such as calculi and blood clots to enable the correct diagnosis. However, a blood clot may be confused with a hyperattenuating TCC, particularly in the early stages of the disease. Also, in a patient with undiagnosed early-stage TCC, inhomogeneous renal fat attenuation of any cause may hinder accurate diagnosis.

MRI

Section 6 of 11  

• Authors and Editors
• Introduction
• Differentials
• Radiograph
• CT SCAN
• MRI
• Ultrasound
• Nuclear Medicine
• Intervention
• Multimedia
• References

Findings

The advantages of MRI are its high intrinsic soft tissue contrast, its direct multiplanar capability, and the availability of nontoxic renally excreted contrast agents. MRI appears to be at least as useful as CT in the evaluation of perivesical fat involvement, and it may be superior to CT in the detection of invasion of the adjacent organs. However, MRI cannot depict the superficial invasion of the upper urinary tract by TCC well.^{7, 8, 13, 14, 15, 16, 17}

Gadolinium-based contrast agents (gadopentetate dimeglumine [Magnevist], gadobenate dimeglumine [MultiHance], gadodiamide [Omniscan], gadoversetamide [OptiMARK], gadoteridol [ProHance]) have recently been linked to the development of nephrogenic systemic fibrosis (NSF) or nephrogenic fibrosing dermopathy (NFD). For more information, see the eMedicine topic Nephrogenic Fibrosing Dermopathy. The disease has occurred in patients with moderate to end-stage renal disease after being given a gadolinium-based contrast agent to enhance MRI or MRA scans.

As of late December 2006, the FDA had received reports of 90 such cases of NSF/NFD. Worldwide, over 200 cases have been reported, according to the FDA. NSF/NFD is a debilitating and sometimes fatal disease. Characteristics include red or dark patches on the skin; burning, itching, swelling, hardening, and tightening of the skin; yellow spots on the whites of the eyes; joint stiffness with troublemoving or straightening the arms, hands, legs, or feet; pain deep in the hip bones or ribs; and muscle weakness. For more information, see the FDA Public Health Advisory or Medscape.

Degree of Confidence

Both CT and MRI have been shown to perform better than cystography in the diagnosis of tumors in the bladder diverticula that are not depicted on cystograms because of obstruction at the diverticular orifice.

False Positives/Negatives

False-positive diagnoses have been reported. In staging bladder TCC, tumor extension is overstaged according to the TNM classification in 7.5% of patients and is understaged in 32.5% of patients.

ULTRASOUND

Section 7 of 11  

• Authors and Editors
• Introduction
• Differentials
• Radiograph
• CT SCAN
• MRI
• Ultrasound
• Nuclear Medicine
• Intervention
• Multimedia
• References

Findings

The most common sonographic appearance of TCC is that of a hypoechoic mass in the renal collecting system that splits the central echocomplex with varying degrees of infundibular dilatation. Focal hypoechogenicity of adjacent renal cortex reflects local invasion. Occasionally, the central echocomplex may be only segmentally amputated (see Images 2, 7, 10, 14).^{18, 19, 20}

Degree of Confidence

Ultrasonography is inaccurate for diagnosing early TCC, and it is useful in the diagnosis of obstructive uropathy. Ureteric lesions are particularly difficult to visualize unless they cause hydronephrosis and hydroureter. The other limitation of ultrasonography is that it is inaccurate in the staging of bladder TCC, particularly Ta and T1 tumors, and also in the detecton of pelvic lymph node involvement.

False Positives/Negatives

On sonograms, calculi may be confused with high-grade TCCs, which can be densely echogenic. No sonographic features are specific for TCC, and many filling defects within the renal collecting system and bladder may have a nonspecific appearance. In addition, ultrasonography is limited in its capacity to depict nondilated ureters.

NUCLEAR MEDICINE

Section 8 of 11  

• Authors and Editors
• Introduction
• Differentials
• Radiograph
• CT SCAN
• MRI
• Ultrasound
• Nuclear Medicine
• Intervention
• Multimedia
• References

Findings

Isotope renography is an extremely sensitive means of assessing relative renal function and obstructive uropathy before surgery. Isotope bone scanning is a useful technique in the investigation of skeletal metastases (see Image 11).²¹

INTERVENTION

Section 9 of 11  

• Authors and Editors
• Introduction
• Differentials
• Radiograph
• CT SCAN
• MRI
• Ultrasound
• Nuclear Medicine
• Intervention
• Multimedia
• References

Nephrostomy may be indicated in cases of inoperable renal or ureteric neoplastic obstruction or as a stop-gap procedure before surgery to improve renal function. The conventional, standard technique in the treatment of TCC is a nephroureterectomy with either a standard surgical technique or a laparoscopic approach. Percutaneous renal endoscopy has been used in the diagnosis and treatment of TCC affecting the renal collecting system; however, this approach remains controversial.

In high-risk patients and in those with a solitary kidney, a less invasive approach may be considered. A percutaneous nephrostomy tract is created to access the tumor, which is then removed by use of a resectoscope with electrocautery or an Nd:YAG laser.^{23, 24}

Special Concerns

• Although percutaneous nephrostomy is successful for the removal of most tumors of the renal collecting system, the recurrence rate is high, and nearly one third of patients have recurrent tumors within 2 years.
• Because of these serious limitations, the percutaneous method is reserved for high-risk patients with a solitary low-grade lesion of the kidney, a negative history of bladder TCC, and negative preoperative cytologic results in the upper urinary tract.
• Unlike renal cell adenocarcinomas, TCC is prone to spread after percutaneous interventional procedures (eg, nephrostomy).

MULTIMEDIA

Section 10 of 11  

• Authors and Editors
• Introduction
• Differentials
• Radiograph
• CT SCAN
• MRI
• Ultrasound
• Nuclear Medicine
• Intervention
• Multimedia
• References

Media file 1:  A 21-year old man presented with a history of intermittent hematuria of 1-month duration. Three months previously, he had been assaulted and kicked in the right loin. A 30-minute intravenous urogram shows a moderate right hydronephrosis without filling of the renal pelvis, although some contrast material has passed into the upper ureter. Note also a polypoid intraluminal filling defect within the left side of the bladder (arrow).
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Media file 2:  Left, transverse sonogram of the right kidney in the same patient as in Image 1 shows a centrally placed solid mass within the renal pelvis with low-level echoes and with proximal hydronephrosis. Right, transverse sonogram through the bladder shows a polypoid filling defect in the bladder.
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Media type:  Image

Media file 3:  Nonenhanced (top) and enhanced (bottom) CT scans through the kidneys in the same patient as in Images 1-2 show a mass in the right renal pelvis. The histologic diagnosis was a right renal pelvis neurofibroma and a bladder transitional cell carcinoma.
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Media type:  CT

Media file 4:  An intravenous urogram in a 36-year old woman who presented with evidence of a urinary tract infection and gross hematuria. A 10-minute intravenous urogram shows a filling defect in the lower pole calyx on the right. A provisional diagnosis of transitional cell carcinoma was made. Subsequent investigations and the course of events proved that the filling defect was caused by a blood clot related to the hematuria secondary to acute pyelonephritis.
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Media type:  Image

Media file 5:  Localized views of the right vesicoureteric junction obtained after intravenous urography shows a polypoid filling defect in the lower right ureter due to a transitional cell carcinoma.
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Media type:  Image

Media file 6:  A 10-minute intravenous urogram in a 56-year-old man presenting with hematuria. The image shows a mass lesion in the right renal pelvis that bisects the renal sinus and splays the adjacent calyces.
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Media type:  Image

Media file 7:  Longitudinal sonogram obtained through the right kidney of the same patient as in Image 6 shows a hypoechoic mass bisecting the renal sinus fat. The mass is a transitional cell carcinoma.
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Media type:  Image

Media file 8:  Nonenhanced (top) and enhanced (bottom) CT scans obtained through the kidneys in a 73-year-old woman show a mass in the left renal pelvis is a transitional cell carcinoma.
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Media type:  CT

Media file 9:  Left retrograde pyelogram in the same patient as in Image 8 shows marked irregularity of the infundibulum of the upper pole calyx caused by infiltration by transitional cell carcinoma. This information was unavailable on the CT scans.
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Media type:  Image

Media file 10:  Top, Longitudinal sonogram obtained thorough the left kidney in a 58-year-old man presenting with hematuria shows a normal left kidney. Bottom, More medial section through the same kidney shows a vague isoechoic mass in the upper of the kidney. Whether this finding represented an artifact or a genuine lesion was unclear. Technetium-99m dimercaptosuccinate (99mTc DMSA) scanning is good modality for differentiating a renal pseudomass from a genuine mass (see Image 11).
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Media file 11:  Left posterior view of a technetium-99m dimercaptosuccinate (99mTc DMSA) scan in the same patient as in Image 10 shows a photon-deficient mass in the upper pole of the left kidney; this finding indicates a genuine mass in this region. At partial nephrectomy, transitional cell carcinoma was confirmed.
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Media type:  Image

Media file 12:  Scout radiograph in a 53-year-old man presenting with hematuria shows a few small vague opacities in the left renal area; these are suggestive of renal calculi (see Images 13-14).
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Media type:  X-RAY

Media file 13:  Intravenous urogram shows 2 filling defects: 1 in the upper pole and 1 in the lower-pole calyces. Conventional tomographic results (bottom) confirm the findings (see Image 14).
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Media type:  Image

Media file 14:  Longitudinal sonogram through left kidney in the same patient as in Images 12-13 shows that the filling defects are due to calculi. Ultrasonography is an efficient means for differentiating between radiolucent calculi and uroepithelial tumors.
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Media type:  Image

REFERENCES

Section 11 of 11

• Authors and Editors
• Introduction
• Differentials
• Radiograph
• CT SCAN
• MRI
• Ultrasound
• Nuclear Medicine
• Intervention
• Multimedia
• References

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Article Last Updated: Jun 10, 2008