hg

1. Received February 23, 1990; accepted after revision May 20, 1990.
I Both authors: Department of Radiology, Box 3808, Duke University Medical Center, Durham, NC 27710. Address reprint requests to A. A. Leder.
AJR 155:713-722, October 1990 0361-803X/90/1554-0713 C American Roentgen Ray Society
713
Review Article
‘‘. I
Transitional Cell Carcinoma of the Pelvicalices and Ureter
Richard A. Leder1 and N. Reed Dunnick
Transitional cell carcinoma accounts for about 90% of all can-cers
of the renal pelvis and more than 90% of all cancers of the
ureter. Its clinical presentation is nonspecific. Radiology plays a
critical role in detection, evaluation, and disease monitoring. We
reviewed the pathologic and clinical features of transitional cell
carcinoma of the upper urinary tract, with attention to its radio-logic
appearance, staging, and treatment.
Primary tumors of the renal pelvis and collecting system
are relatively uncommon. They are less common than renal
adenocarcinomas by a ratio of 1 :4 to 1 :5. They are two to
three times more common than ureteral neoplasms. Bladder
carcinomas are 50 times more common than renal pelvic
tumors, reflecting the larger surface area of the bladder
mucosa. Transitional cell carcinoma accounts for approxi-mately
9O% of all cancers of the renal pelvis and over 90%
of all cancers of the ureter [1]. The clinical presentation of
transitional cell carcinoma of the pelvicaliceal system and
ureter is nonspecific. The radiologic evaluation is critical for
both initial detection and subsequent evaluation and disease
monitoring. The pathologic and clinical features of transitional
cell carcinoma of the upper urinary tract are reviewed, with
attention to its radiologic appearance, staging, and treatment.
Pelvicaliceal Transitional Cell Carcinoma
Pathology
Transitional cell mucosa can differentiate into either squa-mous
or glandular tissue. Eighty-five percent to 95% of uro-epithelial
carcinomas are transitional cell tumors, approxi-mately
10% are squamous cell carcinomas, and less than 1%
are adenocarcinomas. Of the transitional cell carcinomas,
85% or more are papillary; the rest are nonpapillary.
Grabstald et al. [2] divide the renal pelvic tumors into four
groups on the basis ofhistologic stage and degree of invasion.
Group I tumors are histologically benign papillomas. They are
composed of delicate fronds, each with a central fibrovascular
core and usually five to 1 0 cell layers of epithelium. The
individual epithelial cells are cytologically benign. These cells
closely resemble normal epithelial cells except for a spindling
tendency. Group II tumors are noninvasive or focally invasive
papillary carcinomas. Group Ill tumors are fully invasive, but
confined to the kidney. Invasion outside the kidney or renal
pelvis constitutes a group IV tumor. Each group is further
subclassified into those without (A) and those with (B) other
tumors in the bladder and/or ureter. Modifications to this
staging system have been made that are analogous to the
Jewett-Marshall-Strong system for bladder cancer. Higher
stage reflects greater depth of tumor invasion [1].
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2. 714 LEDER AND DUNNICK AJA:155, October 1990
Papillary transitional cell carcinomas are exophytic polypoid
lesions that are attached by a stalk to the mucosa. The
papillary type of carcinoma tends to be a low-grade malignant
lesion that is slow to infiltrate, is late to metastasize, and
follows a relatively benign course. Nonpapillary carcinomas
present as nodular or flat tumors. The noninfiltrating, non-papillary
tumors may show only slight thickening of the renal
pelvis. Nonpapillary tumors do not produce well-defined filling
defects. They are typically high-grade malignant tumors and
are infiltrative [1-3].
Histologic grading of transitional cell neoplasms is based
on the degree of cellular anaplasia. Grade I tumor cells display
some anaplasia but are well differentiated and closely resem-ble
normal epithelial tissue. Grade II cells are still recognizable
as being of transitional origin, however, the number of cell
layers is increased, as are the number of mitoses. Tumor cells
of grade III are barely recognizable as being of transitional
origin, and there are exaggerated layers of cells and more
frequent mitoses. The cells are disarrayed, and superficial cell
layers are loosened and fragmented [4].
Etiology
A number of chemical agents may play an important role in
the development of urothelial neoplasms. Occupational ex-posure
to beta-naphthylamine, 4-aminobiphenyl, 4-nitrobi-phenyl,
or 4,4-diaminobiphenyl is carcinogenic. These com-pounds
are used in the synthesis of azo dyes and pigments
used in the textile, printing, and plastic industries. N-hydrox-ylation
produces even more carcinogenic compounds. Blad-der
tumors are more common than upper tract transitional
cell carcinomas because of the time required for hydrolyzing
enzymes to become activated. Stasis in the upper tracts may
provide increased exposure time and therefore upper tract
tumors [5]. For example, renal pelvic tumors occur in horse-shoe
kidneys at least three times as often as in nonfused
kidneys. The urine stasis present in the horseshoe kidney
prolongs the contact of carcinogens with the collecting sys-tem.
In addition, calculi in horseshoe kidneys have been
reported in 21 -60% of cases, and an association may exist
between hydronephrosis, renal calculi, renal infection, and
renal pelvic tumors [6, 7]. No clear interrelationship has been
established between these factors, although it could be pos-tulated
that metaplasia as a response to inflammation or
calculi may then progress to carcinoma [3].
Other chemical agents have been associated with urothelial
malignant neoplasms. Cyclophosphamide is a biologically in-active
nitrogen mustard that is metabolized by liver micro-somes
to several biproducts, at least two of which are cyto-toxic.
The upper tract urothelial malignant tumors associated
with cyclophosphamide therapy are high-grade and extremely
aggressive. It is unclear whether these tumors are due to the
immunosuppressive character of cyclophosphamide or to in-herent
carcinogenic properties. Additional urologic effects of
cyclophosphamide include hemorrhagic cystitis and bladder
fibrosis with contracture [8, 9].
Thorotrast, a 25% colloidal thorium dioxide suspension,
also has been associated with transitional cell carcinoma. The
compound can spread subepithelially because of pyelointer-stitial
backflow during retrograde pyelography. This results in
permanent retention in the wall of the renal pelvis and in the
renal sinus surrounding fornices and intrarenal vessels. The
frequency of tumor induction after Thorotrast retrograde pye-lography
is 50%, with a latent period ranging from 21 to 35
years [10].
Numerous reports have described the association of highly
invasive transitional cell carcinomas and phenacetin abuse.
Phenacetin is an aniline derivative and its major metabolite,
N-acetyl-para-aminophenol, is excreted in the urine [1 1]. The
vast majority of these neoplasms have been in the renal pelvis
[1 2]. Patients with analgesic nephropathy have widespread
urothelial dysplasia, which predisposes to neoplasia [13].
Ureteral pseudodiverticulosis is associated with epithelial
carcinoma of the urinary tract. Although this may be coinci-dental,
it suggests that patients with ureteral pseudodiverti-culosis
are predisposed to the development of malignant
epithelial tumors. It is unlikely that pseudodiverticula are pre-malignant
by themselves. The presence of pseudodiverticula
may increase the susceptibility of the ureteral mucosa to
carcinogenesis, perhaps by serving as multiple small pools of
stagnant urine [14].
Transitional cell carcinoma is more prevalent in patients
from the Balkan states (Yugoslavia, Greece, Rumania, Bul-garia).
In these areas, an endemic nephropathy develops
slowly (approximately 20 years) and there is no acute phase.
In the later phases of the disease, renal failure develops and
is accompanied by high urine output. The cause of this form
of the disease is obscure, although it may be related to
drinking water. It is part of a degenerative interstitial disease.
The renal pelvic and ureteral tumors that develop are usually
of low grade, and of relatively slow evolution. Bilateral tumors
are found in 1 0%, and multiplicity is common [15].
Clinical Findings
The average age at diagnosis of patients with transitional
cell carcinoma is 65 years; approximately 70% of patients are
more than 60 years old at presentation (range, 32-88 years).
Males predominate by a ratio of4:1 [1 6]. Gross or microscopic
hematuria is the most common symptom in patients with
renal pelvic or ureteral tumors. It is present in more than 75%
of patients. Flank pain, precipitated by ureteral or ureteropel-vic
junction obstruction caused by a tumor mass, occurs in
approximately one fourth of patients. Approximately 10% of
patients have lost weight and less than 5% have other symp-toms.
A tumor will be discovered incidentally in less than 5%
of patients [17].
Urine Cytology
Urine cytology can be used in the diagnosis of transitional
cell carcinomas, although the technique is inaccurate and has
a high false-negative rate. Nocks et al. [1 8] reported positive
findings on urine cytology in no patients with grade I tumors,
29% with grade II tumors, and 79% with grade Ill tumors.
Positive urine cytology was found in 14% of patients with
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3. AJR:155, October 1990 URINARY TRANSITIONAL CELL CARCINOMA 715
Fig. 1.-Low-grade, low-stage transitional cell carcinoma of left renal pelvis. Fig. 2.-Infiltrating renal pelvic transitional cell
A, Excretory urogram shows small, smooth filling defect in renal pelvis (arrowhead). carcinoma. Excretory urogram shows large nodu-
B, CT scan shows intrapelvic soft-tissue mass (arrow). lar filling defect in renal pelvis with multiple infun-dibular
extensions (arrowheads).
lesions confined to the renal pelvis, mucosa, or submucosa
(stage A); 33% with tumor extending into the renal paren-chyma
or invading the renal pelvis wall but still confined to
the kidney (stage B); 80% with tumor penetrating into the
peripelvic or perirenal fat (stage C); and 89% with metastatic
tumor (stage D). Cytologic samples obtained by barbotage
(repeated washings) provide a more reliable sampling of the
upper tract when neoplasia is present. In these instances, the
accuracy of cytologic diagnosis increases from 35% to 60%
with voided urine, from 60% to 70% with urine collected
passively by catheter, and from 80% to 90% with lavaged
samples [19].
An improved technique in the diagnosis of upper urinary
tract transitional cell carcinomas is fluoroscopically guided
retrograde brush biopsy. Appropriate catheter placement is
confirmed by injecting a small amount of contrast material,
and the area of abnormality is brushed vigorously. Maximal
sensitivity of the procedure is achieved by using fluoroscopic
guidance and dilute contrast material. Water-soluble contrast
material may cause changes in the cellular structure of the
epithelium on routine cytologic techniques. This appears to
be concentration dependent and is probably related to the
hypertonic nature of the contrast media. Because of the
possibility of cellular distortion, the contrast material should
be washed away with saline. Alternatively, low-osmolar, non-ionic
contrast material or dilute standard 60% diatrizoate may
be used. Contact smears on glass slides are made immedi-ately
after withdrawal of the brush guidewire, placed in 95%
ethyl alcohol, and sent for subsequent Papanicolaou staining.
Brush tips are cut off and sent in carboxymethylcellulose
fixative solution for cell-block analysis. A recently reported
schema grading cells from grade I (normal transitional epithe-hum)
to grade V (conclusive evidence of malignancy) showed
a brush biopsy diagnosis of atypical cells to be strongly
suggestive of malignancy (75% positive predictive value)
[20].
Although retrograde brush biopsy has a high diagnostic
accuracy compared with urine cytology, it is not without risk.
This consists mainly of flank pain, infection, and gross he-matuna.
Mechanical trauma has been reported as a cause of
spread of a ureteral transitional cell tumor. However, this is
unusual and seldom pertinent because therapy usually in-cludes
nephroureterectomy [21].
When cytology or brush biopsy is inconclusive, uretero-scopic
techniques are available to the urologist. Under anes-thesia,
the ureteral ostium is dilated and a 12-French, 50-cm-long
ureterorenoscope is inserted. Five-French biopsy forceps
and an electroresectoscope can be inserted. This technique
allows the unequivocal diagnosis of urothelial carcinoma en-doscopically
with the ability to obtain biopsy specimens [22].
Plain Films
Plain abdominal radiographs are seldom useful in making
the diagnosis of transitional cell carcinoma. Rarely, a renal
mass may be detected. Renal calculi or tumoral calcification
can be present, although it is uncommon. The prevalence of
calcification in transitional cell tumor ranges from less than
1% to approximately 7% [23]. Detection of calcification is
improved greatly on CT examination.
Excretory Urography
Excretory urography is the most commonly performed initial
examination in patients with transitional cell carcinomas. Five
categories of abnormality were described by Lowe and Roy-lance
[24]: (1) a discrete filling defect within the renal collecting
structures (35%) (Fig. 1); (2) filling defects within distended
calices (26%) (Fig. 2); (3) caliceal obliteration and caliceal
amputation (19%); (4) hydronephrosis with renal enlargement
and a “soap-bubble” nephrogram (6%); and (5) reduced func-
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4. 716 LEDER AND DUNNICK AJR:155, October 1990
tion without renal enlargement (1 3%). In this category, no
pyelogram is evident. Although transitional cell carcinoma can
present in any of these fashions, multiple other disorders can
cause each of these urographic appearances (Table 1) [24].
The surface of a pelvicaliceal or ureteral filling defect may
be smooth, irregular, or stippled. The “stipple sign” refers to
trapping of contrast material within the interstices of a papil-lary
lesion. The vast majority of urothelial tumors are papillary
transitional cell carcinomas; these tumors exist as multiple
branching fronds emanating from a central core. This sign
may be seen anywhere in the urinary tract and is helpful in
differentiating a tumor from inflammation or blood clot. Blood
clots within the collecting system may trap contrast material
irregularly; however, the pattern is much coarser than that of
tumors. Contrast material trapped in a fungus ball has a
lamellar pattern [25].
Transitional cell tumors also may appear as a distended
tumor-filled calix (oncocalix) or tumor obstructing a caliceal
infundibulum (phantom calix). In the ureter, a transitional cell
carcinoma may appear as a goblet or “champagne glass”
(Fig. 3). In this situation, the ureter is dilated distal to the filling
defect. This may be caused by accommodation of the ureter
to the intraluminal tumor growth or by repeated tumoral
prolapse during ureteral peristalsis [26]. This is distinct from
ureteral calculi that cause proximal ureteral dilatation and
distal ureteral narrowing due to spasm and/or edema.
The hallmark of analgesic nephropathy is necrosis of the
renal papillae. Changes on excretory urography are variable
and can be subtle. Parenchymal scarring characterized by a
“wavy” renal outline may be found. Cortical depressions may
be located directly over a calix or between calices. With
continued use of analgesics, indentations develop and result
in discrete renal cortical depressions. This scarring pattern
may be unilateral, but frequently is bilateral. When transitional
cell carcinoma is associated with analgesic abuse, 5% have
demonstrated simultaneous bilateral renal pelvic tumors [27].
Retrograde Pyelography
Retrograde pyelography can be used to show morphologic
features of tumors found on excretory urography. In particu-lar,
a fixed filling defect suggests neoplasm rather than blood
clots and mycetoma, which move with change in position of
the patient. Tumors arising from the anterior wall of the renal
pelvis may be missed if only radiographs of the supine patient
are obtained [28]. Retrograde examination allows evaluation
of a nonfunctioning kidney, which occurs when the kidney is
extensively invaded by tumor without associated hydrone-phrosis
or renal vein involvement [29]. A change in orientation
of a ureteral filling defect demonstrated first with retrograde
injection of contrast material, and subsequently with ante-grade
flow of contrast material, is diagnostic of an intraluminal
lesion rather than a vascular impression [30]. Other intralu-minal
lesions, such as a fibroepithelial polyp of the ureter,
also may demonstrate this pyelographic sign.
Son ography
Sonography is useful in differentiating nonopaque calculi
from blood clots, tumors, and other soft-tissue masses. The
most common appearance of a renal transitional cell carci-noma
is a discrete, solid, hypoechoic mass separating the
central echo complex (Fig. 4). Less common presentations
are disruption of a portion of the central echo complex with
normal surrounding parenchyma or an appearance resembling
hydronephrosis [31]. A centrally located mass in the renal
sinus may resemble mild hydronephrosis, but the solid nature
of the lesion is discernible on careful examination [32]. When
tumor resides within a kidney that is obstructed by some
other process, the sonographic appearance may be confus-ing.
Tumor may be discovered coincidentally in an obstructed
system, rather than causing the obstruction itself.
The sonographic characteristics of a renal mass are not
sufficiently specific to allow confident differentiation of tran-sitional
cell carcinoma from adenocarcinoma, metastasis, lym-phoma,
or inflammatory disease. Transitional cell carcinoma,
however, can be suggested when a mass is seen in a central
location; focal enlargement of the adjacent renal cortex sug-gests
cortical infiltration. Hypernephromas cause more corti-cal
disruption associated with a renal mass. Inflammatory
masses usually do not involve the central echo complex [31].
Pyelocaliceal mucosal thickening is nonspecific and may be
caused by infection or chronic obstruction; potentially it could
mimic a nonpapillary transitional cell carcinoma on sonogra-phy.
In this setting, appropriate clinical history and retrograde
pyelography with cytology would be necessary.
Transitional cell carcinoma occasionally mimics a renal
stone on sonography. High-grade transitional cell carcinomas
can exhibit areas of squamous metaplasia. These metaplastic
TABLE 1: Differential Diagnoses in Transitional Cell Carcinoma on Excretory Urography
Type of Abnormality Differential Diagnosis
Discrete filling defect within renal Stone, clot, pyelitis/uretentis cystica, intramural hemorrhage
collecting structures
Filling defects within distended cal- Tuberculosis, papillary necrosis
ices
Caliceal obliteration and caliceal Hypernephrorna, abscess, focal xanthogranulornatous pyelonephritis, metastasis, tuberculosis
amputation
Hydronephrosis with renal enlarge- Hydronephrosis, pyonephrosis
ment and soap-bubble appear-ance
on nephrogram
Reduced function without renal en- Ureteral/bladder carcinoma, renal artery stenosis, diffuse xanthogranulomatous pyelonephritis
largement
Note-Adapted from Lowe and Roylance [24].
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5. AJR:1 55, October1990 URINARY TRANSITIONAL CELL CARCINOMA 717
A B
Fig. 3.-Ureteral transitional cell carcinoma.
A, Excretory urogram shows hydroureter with
obstruction by mass In mid ureter.
B, Retrograde pyelogram shows intraluminal fill-ing
defect with distal ureteral widening, the cham-pagne-
glass sign.
Fig. 4.-Renal pelvic transitional cell tumor.
A, Sonogram shows mass separating central
echo complex of left kidney.
B, CT scan shows soft-tissue mass (arrow)
within renal pelvis.
areas are characterized by the abundant formation of keratin
pearls. This hard and smooth surface produces dense echoes
similar to those seen in calculi. This rare pitfall has been
reported in a high-grade transitional cell tumor and serves as
a reminder that tumor may be mimicked by renal stones [33].
CT
CT provides excellent detail of the kidney and urinary tract.
Transitional cell carcinomas have CT densities ranging from
8 to 30 H, in comparison with fat in the renal sinus (-60 to
1 20 H), renal cysts (-1 0 to +1 0 H), and calculi (1 00 to 250
H) (Fig. 5). The density of sinus fat remains in the negative
range on contrast-enhanced CT; renal cysts remain un-changed.
Transitional cell carcinomas can be detected as
masses of density greater than that of urine, but less than
that of the renal parenchyma. After injection of contrast
material, these tumors increase in density to 1 8-55 H [34].
The density of a transitional cell carcinoma on CT is suffi-ciently
different from other causes of pelvicaliceal filling de-fects
(renal calculi, blood clot) to make CT scans useful [35].
The attenuation value of a blood clot, which ranges from 50
to 65 H, is higher than that of a soft-tissue tumor and lower
than that of a renal calculus (Fig. 6). Blood clots do not show
contrast enhancement. When it is difficult to differentiate
between a blood clot and a neoplasm, a second study can
be performed. At that time, a blood clot most likely will have
lysed, changed configuration, or decreased in attenuation
[36].
CT is also useful in determining the site of origin of a lesion.
Finely collimated images may allow distinction between pel-vicaliceal,
extracaliceal, or parenchymal lesions.
CT patterns in transitional cell tumors include a caliceal or
renal pelvic filling defect, pelvicaliceal irregularity, infundibular
stenosis, caliceal cutoff, caliceal expansion, and focal or global
nonvisualization [34]. Differentiation of transitional cell carci-noma
from renal cell carcinoma is aided by the lesser enhance-ment
of a transitional cell tumor as opposed to the hypervas-cular,
nonnecrotic, noncystic, and noncalcified renal cell tu-mor.
The typical transitional cell tumor is centrally located,
and its centrifugal expansion and/or invasion of the kidney is
different from the eccentric origin and invasion of the renal
sinus seen in hypernephromas. Transitional cell tumors do
not distort the shape of the kidney. A central mass that is
slightly less dense than normal renal parenchyma and shows
minimal tumor enhancement strongly suggests a transitional
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6. 718 LEDER AND DUNNICK AJR:155, October 1990
.4
‘9’.
A
cell tumor. A delayed nephrogram with accentuated late pa-renchymal
opacification occasionally exhibiting a striated
nephrogram also may be seen. The centrifugal expansion
pattern of transitional carcinoma can result in any combination
of findings including compression, displacement, and/or dis-appearance
of the renal sinus fat; trapping of contrast material
in narrowed and compressed caliceal spaces or obstructed
and slightly dilated calices; or thinning of the surrounding
renal parenchyma with focal enlargement of the kidney and
centrifugal, uneven invasion of the renal parenchyma. A mass
that preserves the uniform contour of the kidney and shows
extrarenal spread at and through the renal hilum are all
possible findings on the CT examination of transitional cell
carcinoma [37].
The hydronephrotic form of transitional cell tumor is due to
ureteropelvic junction obstruction and may present a diag-nostic
dilemma. Although urography and/or pyelography may
be used to make the diagnosis, CT occasionally may provide
a definitive diagnosis. An enhancing soft-tissue mass at the
apex of a dilated renal pelvis on CT indicates a tumor causing
ureteropelvic junction obstruction. Nodular thickening of the
wall of the renal pelvis may occur (Fig. 7), or the mass may
be bulky and grow to fill the renal pelvis and extend into
dilated calices. The proximal ureter may be thickened and
filled from invasion by the neoplasm. This is in distinction to
patients with congenital ureteropelvic junction obstruction,
where CT examination will show an enlarged fluid-filled renal
pelvis. The wall in this case will be thin, smooth, and uniform;
the renal pelvis is dilated to a greater degree than the calices.
The pelvic walls are stretched and are barely discernible on
CT. An abrupt transition from the engorged pelvis to the
collapsed proximal ureter will be noted [38].
Carcinoma of the renal pelvis can be mimicked on CT by
other conditions including chronic xanthogranulomatous pye-lonephritis,
chronic ureteropelvic junction obstruction with
superimposed infection, eosinophilic ureteritis, and pyelitis.
Urothelial neoplasms and inflammation can coexist in the
same kidney. CT is useful in these confusing cases, as
disease-such as liver metastases, regional lymphadenop-athy,
or synchronous contralateral or ipsilateral tumor-may
be found elsewhere, which aids in diagnosis.
Fig. 5.-Uric acid stone.
A, Excretory urogram shows triangular filling
defect (arrow) in collecting system of left kidney.
B, Unenhanced CT scan shows high-density
calculus (arrowhead) in left renal pelvis.
CT can provide valuable information in staging disease in
patients with transitional cell carcinoma. Baron et al. [39]
described three patterns of transitional cell carcinoma. Half of
their patients had a sessile mass, approximately one fifth had
ureteral wall thickening, and about a third had an infiltrating
renal mass. Of 24 lesions, 1 6 had localized disease (stage I
or II), four had stage Ill disease, and four had stage IV disease.
CT correctly characterized the extent of disease in 20 of 24
cases. CT was successful in differentiating tumors confined
to the wall from those with local extension or distant metas-tasis.
In their experience, CT was not useful for differentiating
tumors limited to the uroepithelial mucosa (stage l)from those
with muscle wall invasion (stage II). In this region of the body,
as elsewhere, CT may underestimate the extent of disease
by failing to detect metastases in normal-sized lymph nodes.
The pathologic staging (Table 2) is paralleled by a preoperative
staging system based on CT examination that divides staging
into (A) tumor confined to the pelvicaliceal system, (B) exten-sion
to the renal parenchyma but still confined to the kidney,
(C) transpelvic or transparenchymal invasion into the peripel-vic
and perirenal fat without gross extension and without
nodal involvement, and (D) gross local extrarenal extension
and/or nodal metastases [36]. CT can document metastatic
disease to the lungs, retroperitoneal and distant lymph nodes,
and liver. Bone metastases may be found but are best eval-uated
on radionuclide bone scans or plain films.
MR Imaging
MR imaging is not used frequently in the diagnosis and
management of transitional cell tumors. Detection of tumor is
better accomplished with other techniques. Small lesions may
be missed on MR imaging because of motion artifacts. On
Ti -weighted images, the tumor has similar or slightly less
signal intensity than normal renal parenchyma. T2-weighted
images show a slight increase in signal intensity [40]. MR is
useful in its ability to detect vascular extension [41].
Angiography
Most urothelial neoplasms are hypovascular on arteriog-raphy.
In cases of small, noninvasive tumor, no angiographic
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7. AJR:155, October1990 URINARY TRANSITIONAL CELL CARCINOMA 719
Fig. 6.-Blood clot.
A, CT scan after IV administration of contrast material shows filling defect (arrowhead) in renal
pelvis.
B, Unenhanced CT scan reveals high-density mass (arrow) due to recent blood clot.
Fig. 7.-Hydronephrosis of right kidney due to
transitional cell carcinoma of renal pelvis. Right
kidney is enlarged and renal pelvis is markedly
thickened (arrow). Renal pelvis and calices are
dilated.
TABLE 2: Staging of Transitional Cell Carcinoma
Stage Description
A or I Limited to uroepithelial mucosa and lamina
propria
B or II Invasion to, but not beyond, pelvic/ureteral
muscularis
C or Ill Invasion beyond muscularis into adventitial
fat or renal parenchyma
D or IV Distant metastasis
abnormality can be identified. Invasive tumors may show
arterial encasement and occlusion. Neovascularity with en-larged
pelvic and ureteric arteries can be seen in the region
of a tumor. Arteriography does not allow urothelial tumors to
be differentiated from xanthogranulomatous pyelonephritis,
which may show similar venous encasement, occlusion, and
fine neovascularity [42]. Arteriography is seldom used for
diagnosis or staging of transitional cell carcinoma.
Invasion of transitional cell carcinoma into the renal vein is
an uncommon, late finding [43-45]. Hartman et al. [46] re-ported
a 7% prevalence of venous involvement in cases seen
at the Armed Forces Institute of Pathology. Patients with
renal vein involvement and carcinoma of the renal pelvis have
a reduced 5-year survival rate (5% vs 43% without renal vein
invasion). Venous invasion of transitional cell carcinoma is not
a contraindication to surgery. If tumor completely fills the renal
vein or extends into the inferior vena cava, the surgical
approach will be altered to avoid transecting tumor [47].
Ureteral Transitional Cell Carcinoma
Primary carcinoma of the ureter is rare; it accounts for only
1% of all cancers of the upper urinary tract. The peak preva-lence
of these tumors is between the fifth and seventh de-cades
and males predominate in a ratio of 3:1 . Ureteral tumors
are more common on the left side (63%) and are found most
frequently in the lower third of the ureter (70%). Most patients
present with hematuria or flank pain [48]. Metastases from
ureteral transitional cell carcinoma include retroperitoneal
lymph nodes (34%), distant lymph nodes (1 7%), liver (1 7%),
lumbar vertebrae (1 3%), lungs (9%), kidneys (8%), and infre-quently
other sites [26].
Pathologic staging of ureteral tumors includes grades 0,
papilloma; A, submucosal infiltration; B, muscular invasion; C,
periureteral fat invasion; and D, tumor outside the ureter,
regional lymphadenopathy, and distant metastasis. Patients
with stage 0 lesions have an excellent prognosis. Eighty
percent of patients with stage A disease live more than 5
years after diagnosis. The overall 5-year survival rate with
stage B lesions is 50% and with stage C disease is 33.3%;
stage D disease has a dismal prognosis [49]. Most ureteral
carcinomas are superficial; 93% are transitional cell types,
5% are squamous cell, and 2% are glandular cell types [50].
Most are papillary; approximately 40% are nonpapillary.
Excretory urography is the primary tool used in diagnosing
ureteral neoplasms. Excretory urography may show a non-functioning
kidney (46%), hydronephrosis with or without
hydroureter (34%), or a ureteral filling defect with or without
hydronephrosis or hydroureter (1 9%) (Fig. 8) [50]. In approx-imately
70% of cases, hydronephrosis or nonvisualization is
associated with invasive ureteral tumor. When chronic ob-struction
causes nonfunction of the kidney, urography is not
diagnostic. In these cases, pyelography, either retrograde or
antegrade, may be used. However, antegrade pyelography is
an invasive procedure, and occasionally retrograde pyelog-raphy
is impossible because of inability to catheterize the
ureter. CT is able to visualize the entire ureter and can
distinguish between renal calculus and tumor. CT is useful
for identification of both the intraluminal mass and extraure-teral
tumor extension, thereby helping to stage disease. Ure-teral
neoplasms may appear as soft-tissue filling defects
within the ureter or thickening of the ureteral wall [51 ]. The
finding of a soft-tissue filling defect or thickening of the wall
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8. Fig. 8.-Transitional cell carcinoma of ureter
draining lower-pole moiety in patient with complete
duplication of collecting system of right kidney.
A, Retrograde pyelogram shows bibbed mass
(arrow) in ureter.
B, CT scan shows intraluminal soft-tissue mass
(arrowhead).
is nonspecific and can be mimicked by inflammatory condi-tions
(including inspissated pus) [52] or ureteral metastases
[53].
Multiplicity
An important feature of transitional cell carcinoma is its
propensity for multicentricity, both synchronous and metach-ronous
lesions (Fig. 9). Metachronous bladder carcinoma
occurs in 20-37% of patients with transitional cell carcinoma
of the ureter. Transitional cell carcinoma of the upper tract is
multicentric in 20-44% of patients (Fig. 1 0). Unsuspected
renal pelvic tumors have been found in patients with ureteral
tumors. This fact emphasizes the need for complete evalua-tion
of the entire urinary tract when a lesion is discovered.
Furthermore, there is a high prevalence, 1 0-40%, of ipsilateral
recurrence after partial ureterectomy for transitional cell tumor
(Fig. 1 1) [54]. Additionally, tumor may be found in the upper
urinary tract in patients with a history of transitional cell tumor
of the bladder (Fig. 1 2). The upper tract recurrence rate has
been reported to be less than lOb in patients treated by
transurethral resection for transitional cell carcinoma of the
bladder [55].
Since metachronous transitional cell carcinoma of the blad-der
occurs after renal and ureteral transitional cell carcinoma
in 20-55% of patients, close follow-up evaluation of the lower
urinary tracts is necessary. Bladder lesions typically occur
1 5-48 months (renal transitional cell carcinoma) and 10-24
months (ureteral transitional cell carcinoma) after initial diag-nosis
[56]. In these patients, cystoscopic evaluation of the
bladder should be done at 3-month intervals for a period of 2
years, just as it is done in the follow-up of primary bladder
cancer [1 9]. The reported prevalence of bilateral synchronous
and/or metachronous upper tract transitional cell carcinoma
ranges from 1% to 1 0%. Therefore, annual follow-up excre-tory
urography and, if necessary, retrograde pyelography,
performed at the time of cystoscopy, is recommended. Me-tachronous
upper tract lesions develop in 0-6#{176}h of patients,
at an average delay of 77 months, after diagnosis of a primary
transitional cell carcinoma of the bladder. Urine cytologic
examinations should be performed semiannually for 2 years
in these patients and at least annually thereafter. Annual
excretory or retrograde urography, or both, for the first 2
years after diagnosis of transitional cell Carcinoma of the
bladder, followed by biennial examinations, is recommended.
Closer surveillance is required in patients at increased risk.
This includes patients with Balkan nephropathy, vesicoure-teral
reflex, multifocal recurrent transitional cell carcinoma of
the bladder, high-grade bladder carcinoma, carcinoma in situ
in the distal ureter resected during cystectomy, history of
analgesic abuse, history of heavy smoking, exposure to car-cinogens,
and treatment with cyclophosphamide [56]. An
additional site of transitional cell carcinoma is in bowel con-duits
used for urinary diversions in patients after cystectomy
for bladder carcinoma (recurrent tumor) or for benign bladder
conditions (primary tumor) [57, 58].
Treatment
Treatment of renal pelvic transitional cell carcinoma con-sists
of total nephroureterectomy with excision of a cuff of
bladder. In selected cases, nephrectomy can be performed
without removal of the entire ureter, either because standard
total nephroureterectomy with removal of a cuff of bladder is
contraindicated by the age or physical debility of the patient
or because the tumor is so extensive that such an addition
to the operation would be futile [59]. Parenchyma-sparing
operations include partial nephrectomy and open pyelotomy
with tumor excision and fulguration. Operative pyeloscopy is
useful for a thorough examination of the entire intrarenal
collecting system. Transurethral ureteropyeloscopy can be
used as an endoscopic method for diagnosis and treatment
of renal pelvic transitional cell carcinoma. There is only very
limited experience in the ureteroscopic treatment of upper
tract tumors. It does appear that low-grade, localized, distal
ureteral tumors can be managed effectively by ureteroscopic
means [60]. In addition to retrograde access to the upper
tracts, antegrade, percutaneous resection techniques are also
available to the urologist. Small, well-localized, superficial
tumors can be removed percutaneously. A cure can be pro-vided
in selected patients, including those with a normal
contralateral kidney and with small (no more than 2 cm),
single, low-grade, papillary tumors that are confined to the
mucosa, who, in addition, have negative cytologic results,
negative results of random biopsies of contiguous mucosa,
and no history of concurrent transitional cell carcinoma else-where
in the urinary tract [61].
Destruction of tumor can be accomplished with either an
argon or neodymium-yttrium aluminum garnet laser placed
through a flexible ureteroscope. Topical use of chemothera-
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9. Fig. 9.-Multifocal transitional cell carcinoma. Fig. 10.-Soft-tissue masses (arrowheads) in renal pel-
A, CT scan shows soft-tissue mass (arrow) at apex of hydronephrotic right kidney. Small vis bilaterally. Selective urine cytologic studies confirmed
calcification is present centrally. bilateral transitional cell carcinoma.
B, Second mass at right ureterovesical junction (black arrowhead). Normal distal left ureter
(whIte arrowhead).
Fig. I 1.-Recurrent transitional cell carcinoma in patient who had had right nephrectomy and
subtotal ureterectomy for transitional cell carcinoma.
A, Retrograde pyebogram shows extreme nodubarity (arrowhead) in right ureteral stump.
B, CT scan shows soft-tissue density (black arrow) in remaining right ureter. Note normal left
ureter (white arrow).
Fig. 12.-Multiple filling defects (arrows) in pel-vis
and collecting system of left kidney seen on
Ioop-o-gram of patient who had prior cystectomy
for transitional cell carcinoma of bladder.
peutic agents, such as bacillus Calmette-Gu#{233}rin instilled di-rectly
into the upper urinary tract, also may be efficacious in
the conservative management of renal pelvic transitional cell
carcinoma [62]. Intracavitary therapy administered through a
nephrostomy tube also may consist of mitomycin C [63].
Thiotepa has been used successfully for low-grade, low-stage
bladder tumors and can be delivered topically for ureteral
carcinoma [64].
Proximal ureteral neoplasms are generally treated with total
nephroureterectomy. Low-grade, noninvasive tumors of the
distal ureter may be treated by partial ureterectomy and
ureteroneocystostomy. Segmental resections can be consid-ered
in cases of solitary kidney with a ureteral tumor, bilateral
synchronous ureteral tumors, patients with poor renal func-tion,
and high-risk patients [65]. Patients who have segmental
resection will require close follow-up surveillance for the pos-sibility
of ipsilateral recurrence. The role of adjuvant radiation
therapy is under investigation. Postoperative radiation may
be used for advanced ureteral carcinomas and in patients
with renal pelvic carcinoma with recurrent or gross disease.
Radiation therapy can be delivered postoperatively to patients
at high risk for local and regional failure [66].
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