8.2.1

Imaging Diagnosis

Radiological explorations represent the main diagnostic modality. Approximately 50–70% of patients with TCC have lacunar images on intravenous urography (IVU) ( Figs 8.3 and 8.4 ).

Filling defect of the right renal pelvis (IVU).

Right pyelocaliceal lacunar images (IVU).

However, less than half of the filling defects seen on IVU prove to be malignant ( ). The urographic differential diagnosis is made with benign conditions: radiolucent stones, blood clots, fibroepithelial ureteral polyps ( Fig. 8.5 ), irregular renal papillae, nephrogenic adenomas, subepithelial hematomas, extrinsic vascular compressions, cystic pyelitis or ureteritis, tuberculosis, endometriosis, and amyloidosis.

Voluminous right distal ureteral polyp (IVU).

Retrograde pyelography is indicated if there is a poor visualization of the upper urinary tract or when the contrast agent cannot be administered intravenously (allergic patients, renal failure, or urographic nonfunctioning kidney) ( Fig. 8.6 ). Although this method provides a diagnostic accuracy of approximately 75% ( ), false-negative results are described with an incidence of 25% (Keeley, 1997a). It is generally recommended to use a diluted contrast agent for retrograde ureteropyelography (1/2–1/3 compared to the initial concentration) in order to allow the visualization of the filling defects ( Fig. 8.7 ).

Urographic nonfunctioning right kidney in a patient with total hematuria (a), retrograde ureteropyelogram showing right hydronephrosis (b), and a filling defect of the middle ureter (c).

Left pyelocaliceal filling defect (retrograde pyelogram).

Antegrade pyelography is not recommended in patients with suspicion of TCC because of the risk of secondary tumor seeding along the percutaneous tract.

Ultrasonography can detect kidney stones, being useful for the differential diagnosis of filling defects visualized on urography, but its accuracy is reduced regarding the detection of tumors developed in the upper urinary tract.

Computed tomography (CT) is used especially for the differential diagnosis of a filling defect discovered on urography. This method can differentiate a radiolucent stone (80–250 Hounsfield units – HU) from tumoral tissue (10–70 HU) ( Fig. 8.8 ).

Right ureteral tumor detected on computed tomography in a patient with total hematuria.

The sensitivity of CT is approximately 90%, but it cannot differentiate between a T1 and a T2 tumor. The percentage of false-negative results regarding the assessment of local tumoral invasion is 59%. Still, the CT exam is very useful for identifying the locoregional extension ( Fig. 8.9 ) or lymph node masses ( ).

Right pyelocaliceal tumor with perihilar adenopathy (CT aspect).

Nuclear magnetic resonance shows similar results to the CT exam regarding the diagnosis of TCC ( ), proving to be useful in certain patients with nonfunctioning kidneys or with severe allergies to contrast agents.

8.2.2

Urinary Cytology

Urinary cytology has a limited role in the diagnosis of TCC due to the increased frequency of false-positive and false-negative results ( Fig. 8.10 ). There is a direct correlation between the cytological exam’s sensitivity and the TCC grade ( Fig. 8.11 ). The sensitivity ranges from 10% for grade 1 lesions to 80% for grade 4 lesions, with a specificity of approximately 60% ( ) ( Fig. 8.12 ). According to some authors, urinary cytology may be useful for the diagnosis of CIS, with an accuracy of approximately 80% ( ). However, urinary cytology for low-grade TCC can have false-negative results in 96% of cases ( ).

Negative cytology in a patient with T1 ureteral tumor (false-negative result).

Urinary cytology – moderate atypia which cannot exclude a neoplastic lesion (patient with a pT2G3 renal pelvis tumor).

Positive cytology with severe atypia (patient with pT3G3 ureteral tumor).

The use of molecular biology techniques (p53 protein immunophoresis, flow cytometry for DNA ploidy analysis) can determine an increase in the sensitivity of the diagnosis of low-grade TCC ( ; Keeley, 1997b).

Selective urinary cytology obtained by ureteral catheterization (although disputed by some authors who prefer to perform a diagnostic ureteroscopy) can increase the diagnostic accuracy, having a 65–78% sensitivity ( ). The exam is indicated in patients with positive cytology, without significant radiographic changes and with normal cystoscopy and bladder biopsy. The urinary cytological examination obtained by sparging with saline solution (after ureteral catheterization) has a superior diagnostic accuracy compared to simple cytology ( ).

Many authors ( ) have demonstrated the superiority of filling defects biopsy by fluoroscopically guided brushing (brush biopsy). The technique is performed by successive movements of the biopsy brush on the filling defect that was detected fluoroscopically after the introduction of 1/2–1/3 diluted contrast agent. The sensitivity and specificity of the method ranges between 72–91% and 88–94%, respectively ( ; ). To avoid false-positive results due to contamination, potential bladder tumors should be treated before performing the procedure. However, this technique is not recommended if performing a diagnostic ureteroscopy is intended.

8.2.3

Endoscopic Diagnosis

The endoscopic evaluation of a patient with suspected TCC includes the examination of both the entire bladder and of the upper urinary tract.

Cystoscopy is an essential step in the assessment of a patient with hematuria and/or filling defects detected radiologically, due to the high risk of the coexistence of associated bladder tumors. It also facilitates ureteral access in order to perform a retrograde pyelogram. The upper urinary tract is evaluated only after a complete inspection of the bladder and the biopsy of any suspicious lesions, by performing a retrograde ureteropyelogram, which offers more information regarding the filling defect ( Fig. 8.13 ). It is indicated to use a probe with a conical tip through which the contrast agent is injected, thus efficiently visualizing the entire collecting system without secondary traumatic ureteral injuries.

Filling defect of the right lumbar ureter (multiple ureteral tumor).

Sometimes, in order to define the lesion’s extension as exactly as possible, multiple injections of contrast agent with different concentrations are necessary. However, overfilling of the pyelocaliceal system and the use of an excessively concentrated contrast agent should be avoided because these can create a too-intense opacification and may hide potential filling defects.

Ureteroscopic assessment of filling defects of the upper urinary tract can improve the diagnostic accuracy ( Figs 8.14 and 8.15 ). Moreover, besides the upper urinary tract’s visualization, the method offers the opportunity to biopsy any suspicious lesions, allowing their histological exam. Thus, the tumor grade and sometimes even the tumor stage can be determined. Progress in terms of design, optics, dimensions, and the degree of deflection of flexible ureteroscopes allow the diagnosis of filling defects, in all cases, by direct inspection and tumor biopsy.

Radiological (a) and ureteroscopic (b–e) aspect of multiple pelvic ureteral tumors.

Lumbar ureteral tumor (retrograde ureteroscopy).

In patients with suspected TCC, most authors prefer the no-touch technique for examining the ureter and the pyelocaliceal system. It is recommended to initially insert a 6.9 F semirigid ureteroscope under direct visualization, the dilation of the ureteral orifice being achieved by increasing the pressure of the irrigation fluid. It is usually recommended to avoid using a reinforced metallic guidewire in order to prevent ureteral injuries that can mask a possible tumor ( ).

The assessment using a semirigid ureteroscope can be limited to the distal third of the ureter (in certain cases) or it may also include the renal pelvis (when possible). The exploration is completed with the flexible ureteroscope ( Fig. 8.16 ), which allows for the inspection of all the caliceal groups, using the technique described in the diagnosis chapter.

Flexible ureteroscopy under fluoroscopic control (a, b) showing an upper caliceal tumor (c).

In most cases, visual inspection can diagnose a filling defect that was previously detected radiologically ( ). Thus, a low-grade papillary tumor can be easily differentiated from a stone or from an extrinsic compression. Fluoroscopic control is absolutely necessary in order to demonstrate the positioning of the ureteroscope’s tip at the level of the filling defect, thus confirming the correct identification of the lesion.

TCC can have completely different endoscopic aspects ( Fig. 8.17 ). Low-grade transitional carcinomas can present typical papillary aspects, similar to those located in the bladder. Invasive transitional carcinomas can be more sessile and less papillary, often presenting areas of necrosis. Fibroepithelial polyps located in the renal pelvis and inverted papillomas generally have a soft round surface, giving the impression of an intact epithelial layer (Bagley et al., 1990) ( Fig. 8.18 ). These aspects are not pathognomonic, and both fibroepithelial polyps and inverted papillomas located at the pyeloureteral junction can be elongated with a vermiform aspect.

Particular endoscopic aspects of TCC.

Fibroepithelial ureteral polyp.

In some cases, visual inspection cannot accurately determine the diagnosis of cancer. Thus, high-grade urothelial carcinomas can be mistaken for inflammatory lesions or can be difficult to visualize due to obstructive peritumoral edema.

Sometimes, the tumor can be mistaken for a stone due to the presence of calcifications on its surface. Other tumors, with a necrotic surface, can resemble a soft stone, with infectious etiology, covered by inflammatory detritus.

In these cases, as in many others, visual inspection alone is not enough for the diagnosis, other interventional endoscopic maneuvers being necessary in order to obtain a correct diagnosis.

A technology that improves the detection of malignant lesions is NBI (narrow band imaging), described in the section dedicated to bladder tumors ( Fig. 8.19 ).

Caliceal tumor mass visualized in white light (a) and NBI (b).

8.2.4

Tumor Biopsy

Ureteroscopic biopsy is important for obtaining neoplastic tissue specimens, thus providing the possibility to establish the histological diagnosis. It is a valuable process, not only for determining the malignant nature of the disease, but also for assessing the grade of a transitional carcinoma. The reduced dimensions of the ureteroscope’s working channel limits the insertion of accessory instruments in order to achieve an adequate biopsy.

There are several ways to perform a tumor biopsy. The diagnostic accuracy can be increased by using forceps or basket catheters for biopsy. The main problem of biopsy forceps is the reduced dimensions of the fragment obtained, which can be insufficient for the histological diagnosis.

For example, the tissue fragment obtained with a 3 F biopsy forceps is less than 1 mm in diameter and is usually too small to be prepared for the histological exam using standard techniques. Still, the collected tissue sample is more than enough for the cytological exam. It can be prepared as a cell block, stained and examined as a histological sample, in order to establish a diagnosis and to provide information on the cellular grading.

Some authors have used Piranha forceps (Boston Scientific, Natick, MA) to collect fragments with a reasonable size ( Figs 8.20 and 8.21 ).

Biopsy forceps.

Forceps biopsy of a ureteral tumor.

Even more useful are the basket catheters ( Figs 8.22 and 8.23 ) that are positioned at the level of the lesion, are closed partially under direct visual control, and are then withdrawn en bloc, together with the ureteroscope. Tissue fragments with adequate dimensions (up to 1 cm) can be obtained in this way for histological and cytological exam.

Basket catheter for tumor biopsy.

Device used for handling the basket catheter.

The tissue obtained is introduced into a container with formaldehyde and sent for histological examination. If the dimensions of the tissue are smaller than 1 cm, it is placed in saline solution and sent for cytological exam.

One of the most important factors regarding the accuracy of the histological diagnosis is represented by the close cooperation with the pathologist ( ).

The specificity of the ureteroscopic biopsy regarding the correct diagnosis of TCC varies between 75% and 92% (Keeley, 1997c). When the biopsy cannot be performed under direct visual control, the basket is positioned at the level of the lesion (filling defect) under fluoroscopic control.

A Segura-type basket is usually recommended for friable tumors, while Piranha-type forceps are more commonly used for sessile lesions. Some authors also recommend tumor brushing, especially for flat or sessile lesions, although this procedure is less sensitive in terms of diagnostic accuracy because it fails to collect big enough tissue fragments ( ).

The contralateral renal unit should be assessed before starting treatment for the primary lesion. This is achieved by selective ureteral cytology, intravenous urography, and retrograde pyelography. In case of a suspected contralateral lesion, a flexible ureteroscopy can be performed.

8.2.5

Staging

The correct preoperative staging allows the appropriate selection of cases and the optimal choice of treatment. The presence of metastases or the massive invasion of the renal parenchyma represent important preoperative factors, regardless of the therapeutic method.

CT scan can be useful for determining the local extension, especially to assess the invasion of the renal parenchyma, of regional lymph nodes, of the periureteral tissue, of the renal veins, or of the adjacent structures ( Fig. 8.24 ). This method can also identify hepatic metastases. However, the CT exam cannot differentiate between T1 tumors on the one hand and small T2 or T3 tumors on the other. Also, the sensitivity for identifying multiple tumors is reduced ( ).

Renal pelvis tumor with renal parenchyma invasion (CT aspect).

Endoluminal ultrasonography has been described as a promising technique for staging ureteral tumors ( ). Probes with frequencies between 12.5 MHz and 40 MHz can be used, characterized by a low tissue penetration and a high resolution ( Fig. 8.25 ).

Probes for endoluminal ultrasonography.

The most commonly used are the 3.5–6.2 F probes (Boston Scientific, Natick, MA; Olympus America Inc, NY). These can be inserted into the ureter through a cystoscope or even directly through the ureteroscope.

The maximum resolution of the 20 MHz probes is up to 1.5–2 cm, a distance long enough to visualize the ureteral wall and the periureteral pathological changes ( ) ( Figs 8.26 and 8.27 ). The results of the studies published in the literature show a good correlation between the staging achieved by endoluminal ultrasonography and the histological (final) stage ( ). However, the experience is limited, the technique being conditioned by the availability of instruments.

Endoluminal ultrasonography – ureteral tumor.

Source: With permission from .

Tumor located at the uretero-pelvic junction: 2D (a), respectively 3D (b, c) endoluminal ultrasonography.

Source: With permission from .

Regarding the ureteroscopic biopsy of TCC, some authors have suggested that this can lead to local or systemic dissemination of tumor cells by pyelo-venous or pyelo-lymphatic reflux ( ). However, this mechanism has only been demonstrated in one case, most authors underlining that tumor biopsy does not modify the prognosis or the survival rate of patients with TCC ( ).