Urothelial Tumors of the Renal Pelvis and Ureters Workup
- Author: David F Jarrard, MD; Chief Editor: Bradley Fields Schwartz, DO, FACS more...
Urinalysis should be performed to confirm hematuria and to rule out a coexistent urinary tract infection.
Basic metabolic panel should be ordered to check serum creatinine (assess renal function) and electrolytes.
Activated partial thromboplastin time (aPTT), prothrombin time (PT), and international normalized ratio (INR) should be ordered to check baseline coagulation status.
Excretory urography is commonly referred to as intravenous pyelography (IVP). IVP is used to evaluate the upper urothelial tract. Its use has been primarily replaced with computed tomography (CT). Approximately 50-75% of patients with urothelial tumors of the renal pelvis and ureters have a radiolucent filling defect that is characteristically irregular and in continuity with the wall of the collecting system. See the image below. Approximately 10-30% of such tumors cause obstruction or nonvisualization of the collecting system.
Noncontrast CT scanning can be performed, followed by a contrast study, with particular interest in the excretory phase — a so-called CT urogram. Plain radiography, which demonstrates drainage and anatomy, can also be performed after CT scanning. Transitional cell carcinomas (TCCs) are usually present as an irregular filling defect. They tend to be hypovascular when compared with the rest of the kidney and demonstrate minimal increased attenuation (enhancement) following intravenous contrast injection. See the images below.
CT scanning sensitivities and specificities based on lesion size are as follows:
For lesions 5-10 mm in size - 96% sensitivity and 99% specificity
For lesions smaller than 5 mm in size - 89% sensitivity
For lesions smaller than 3 mm in size - 40% sensitivity
CT scanning has limited value in staging TCC because stage Ta or superficial lesions cannot be differentiated from T2 or invasive lesions (see Staging). However, CT scanning is helpful in demonstrating peripelvic or periureteral tumor extension, thereby assisting with staging of aggressive disease. Hydronephrosis and obstruction are associated with a higher degree of invasiveness.
As with CT scanning, MRI is also of limited use in staging early TCC; however, it may have greater utility in more advanced disease or in patients with limited renal function.
There is interest in fluorodeoxyglucose (18 F-FDG) positron emission tomography (PET)/CT for staging in TCC, but, at present, this study does not appear to have significant advantages over MRI.
Cytopathology of voided urine samples yields low sensitivity, especially for low-grade tumors, which results in normal cytology results in up to 80% of cases. The sensitivity of cytopathology increases for higher-grade tumors, which tend to shed more tumor cells. Cytology yields an accuracy of 83% in patients with high-grade disease. Cytology is less sensitive for upper tract transitional cell carcinoma (TCC) than for bladder cancer. Cytology samples should be taken from as near the suspected lesion as possible (ie, within the calyceal system). Positive cytology has been related to more advanced (invasive) disease. Selective washings of both the upper tracts and the bladder can aid in tumor localization. Cytology plays a role in urothelial tumor surveillance in conjunction with cystoscopy/ureteroscopy.
Fluorescence in situ hybridization (FISH) can be performed using probes for altered genes on chromosomes 3, 7, 17, and 9p21. FISH (UroVysion) is a useful test for detecting urinary tract cancer, as it yields a greater sensitivity for lower-grade tumors than cytology and other tests (as high as 76.6-100% vs 21-24% for cytology).[14, 15] Ureteral cancer has been detected with FISH during evaluation for hematuria. FISH has equal specificity when compared with cytology (as high as 100%).
Ureteroscopy can be used for direct visualization of a tumor. Important to note is that it can be used to obtain tissue for a diagnosis and grade in 90% of cases. Staging information regarding depth of invasion, however, is more difficult to obtain.
A preliminary study by Gayed et al concluded that assessment of cell cycle biomarkers obtained from endoscopic biopsy specimens may be useful in individualizing treatment regimens and determining prognosis in patients with upper tract urothelial cancer. In their study of 17 patients, a prognostic score was calculated on the basis of immunohistochemical expression of five biomarkers: p21, p27, p53, cyclin E, and Ki67/pRb, with an unfavorable score defined as more than two altered markers. An overall concordance rate of 60% was seen between biopsy results and findings on subsequent radical nephroureterectomy or segmental ureterectomy.
Each of the following should be obtained in a suspected case of upper tract TCC: cystoscopy to rule out bladder tumor, urinary cytology, and CT urography.
For cystoscopy, a small fiberoptic scope is inserted through the urethra in order to visualize the bladder. This ambulatory/clinical procedure is usually well tolerated by both women and men. A 16F flexible cystoscope is typically used in men, whereas women can undergo either rigid or flexible cystoscopic examination. This procedure is mandatory to rule out coexistent bladder lesions, which occur with a frequency of 8-13%. Cystoscopy is also essential for postoperative surveillance to monitor for bladder tumor development; recurrence in the bladder occurs 15-51% of patients.
In retrograde urography (see image below), contrast is injected into the ureteral orifice with the aid of a cystoscope. This can be performed with fluoroscopic guidance or with standard radiography plates. Retrograde urography allows better visualization of the collecting system than excretory urography by increasing the distention of the urinary collecting system. Retrograde pyelography is preferable in patients with azotemia and/or contrast allergy. Overall, retrograde urography is more than 75% accurate in establishing a diagnosis of urothelial cancer.
Since the advent of rigid and flexible ureteroscopes, ureteropyeloscopy is used increasingly for the diagnosis of upper tract urothelial tumors. Biopsy forceps or cytology brushings can be used to collect tissue. This procedure yields an accuracy of 86% in diagnosing renal pelvis tumors and 90% in diagnosing ureteral tumors. Large size, broad base, and nonpapillary pattern favor tumor invasiveness. Studies have demonstrated that 85% of TCC lesions in the renal pelvis are papillary. The complication rate associated with ureteropyeloscopy is approximately 7%; these include perforation, complete disruption, and ureteral stricture.
Percutaneous nephroscopy is not indicated for the diagnosis of urothelial tumors of the renal pelvis and ureters because of the theoretical risk of tumor cell implantation in the retroperitoneum and nephrostomy tube tract. It is used for treatment in selected situations.
Nevertheless, Huang et al concluded that percutaneous biopsy is safe and effective for diagnosis of upper tract urothelial lesions that are not amenable to endoscopic biopsy. In their study of 26 upper tract lesions in 24 patients, percutaneous biopsy provided tissue diagnosis in 85% of cases; the three recurrences in the nephrectomy bed developed at sites remote from the biopsy site and thus were not attributed to tract seeding.
The distribution of tumor stages and grades differs from study to study. Stage and grade yield the greatest prognostic value.
Grading, based on the 2004 World Health Organization (WHO) classification, is as follows:
Grade 1 - Papillary urothelial neoplasia of low malignant potential
Grade 2 - Low-grade carcinoma
Grade 3 - High-grade carcinoma
Staging, based on the depth of tumor invasion and classified using the tumor, node, metastases (TNM) system (2009), is as follows:
Tis - Carcinoma in situ
Ta - Superficial/papillary, noninvasive
T1 - Lamina propria invasion
T2 - Muscularis propria invasion
T3 – Peripelvic fat/periureteral fat/renal parenchyma invasion
T4 - Contiguous organ involvement
N0 - Negative nodes
N1 - Metastasis in single node less than 2 cm in diameter
N2 - Metastasis in single node 2-5 cm in diameter or metastasis to multiple nodes less than 5 cm in diameter
N3 - Metastasis in lymph node greater than 5 cm in diameter
M0 - No distant metastasis
M1 - Distant metastasis
The location of the tumor can affect the findings. Renal pelvis tumors are more commonly invasive than bladder tumors, possibly because of delayed diagnosis and a less well-developed muscle layer.
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