Urothelial Tumors of the Renal Pelvis and Ureters 

  • Author: Daniel M Kaplon, MD; Chief Editor: Bradley Fields Schwartz, DO, FACS   more...
 
Updated: Oct 27, 2011
 

Problem

Urothelial tumors of the renal pelvis and ureters (upper urinary tract) are relatively rare. Tumors of the renal pelvis account for approximately 10% of all renal tumors and approximately 5% of all urothelial tumors. Ureteral tumors are even more uncommon, occurring with one quarter the frequency of renal pelvis tumors. Transitional cell carcinoma (TCC) accounts for more than 90% of urothelial tumors of the upper urinary tract.

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Epidemiology

Frequency

  • The mean age in persons who develop upper urinary tract urothelial tumors is 65 years.
  • The incidence of TCC increases with age. Moreover, TCC tumors are rarely found at autopsy.
  • Upper tract urothelial tumors are more common in men, with a male-to-female ratio of 3:1.
  • Upper tract urothelial tumors are twice as common in white people as in black people.
  • Upper tract TCC is associated with Balkan nephropathy, which is a degenerative interstitial nephritis of unknown etiology that predisposes to upper tract TCC in individuals from rural Balkan areas by a factor of 100-200 greater than that in individuals residing in neighboring communities. Tumors associated with Balkan nephropathy are generally low-grade, multiple, and bilateral, in contrast to TCC of other etiologies.
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Etiology

Tobacco smoking is the factor most strongly associated with upper tract TCC and increases the risk more than 3-fold. Estimates point to smoking as the cause of 70% of upper tract tumors in men and 40% in women.

Drinking coffee slightly increases the risk of upper tract TCC; this risk factor is typically observed in people who consume more than 7 cups of coffee per day.

Analgesic abuse is also a risk factor for urothelial malignancy. It is independent from and synergistic with renal papillary necrosis. Long-term exposure to analgesics, notably phenacetin, induces a nephropathy that raises the risk of upper tract TCC to as high as 70%. Capillarosclerosis, which is characterized by a thickening of the basement membrane, is the pathognomonic finding of analgesic abuse and is found in 15% of patients with upper urinary tract tumors.

Occupational exposure to agents used in the petrochemical, plastic, and tar industries has been linked to an increased risk of TCC.

Chronic infections, irritation, and calculi may also predispose to squamous cell carcinoma and, less commonly, adenocarcinoma of the upper urinary tract.

Cyclophosphamide has been linked to the development of urothelial tumors. More specifically, a breakdown metabolite called acrolein is thought to be the causative agent. Tumors associated with cyclophosphamide tend to be high-grade.

Finally, heredity may play a part in the development of TCC. TCC is associated with Lynch syndrome type II, which is a syndrome that is characterized by early onset of proximal colonic nonpolyposis tumors, numerous synchronous and metachronous colonic tumors, and extracolonic tumors.

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Pathophysiology

Types of upper urinary tract tumors

TCC is the most common histology observed, accounting for greater than 90% of upper urinary tract urothelial tumors. TCCs are strongly associated with smoking.

Squamous cell carcinoma comprises 1-7% of upper tract urothelial tumors. Squamous cell carcinoma is frequently associated with longstanding infected staghorn calculi. Affected patients frequently present with moderately to poorly differentiated tumors and advanced disease.

Adenocarcinoma accounts for less than 1% of upper tract tumors. Patients with adenocarcinoma of the upper urinary tract may also have associated calculi and long-term obstruction, suggesting an etiologic origin for these processes.

Inverted papilloma is an unusual lesion that is generally considered a benign histologic lesion; however, it may harbor foci of malignant change.

Molecular mechanisms

Several molecular mechanisms have been associated with the development of upper urinary tract TCC. Tumor suppressor genes p19, p16, RB1, and TP53 have all been associated with upper tract TCC.[1] Losses of TP53, p19, and p16 are associated with low-grade cancers, while a loss of RB1 has been associated with higher-grade, more aggressive tumors.[1]

Tumor microsatellite instability (MSI) has been studied as a prognostic indicator for upper tract tumors. In general, high levels of MSI seem to correlate with a more favorable prognosis, particularly in younger patients with T2 or T3/N0 disease (see Staging).[2, 3]

In a 2001 study, survivin, a protein apoptosis inhibitor, was measured in the urine of patients with TCC of the bladder and was found to be highly sensitive and specific for this malignancy.[4] The bladder tumor-associated analytes (BTA) test, CYFRA 21-1, and NMP-22 may have a role in patients at risk for recurrent bladder cancer. Fluorescence in situ hybridization (FISH) may be one of the more useful tests for detecting urinary tract cancer, as it yields a greater sensitivity for lower grade tumors than cytology and other tests. Ureteral cancer has been detected with FISH during evaluation for hematuria.[5]

Patterns of spread

Transitional tumors spread conventionally in a cephalad to caudad direction. For instance, studies have shown a high rate of recurrence in the distal ureteral stump in patients treated with nephrectomy and incomplete ureterectomy. Conversely, TCC rarely recurs proximal to the level of resection of a ureteral lesion. Approximately 30%-75% of patients with upper tract urothelial tumors develop bladder tumors at some point during their cancer course. The risk of upper tract TCC in patients with a bladder malignancy is 2-4% but as high as 21-25% in patients with carcinoma in situ. Thus, higher grade increases the risk of upper tract disease.

Lymphatic extension is another pattern observed in TCC. The most common locations for spread, depending on the site of the primary tumor, include paraaortic, paracaval, ipsilateral common iliac, and the pelvic lymph nodes.

Hematogenous seeding also occurs, with the liver, lung, and bone being common sites for metastases.

Distribution of upper tract transitional cell carcinoma

  • Renal pelvis - 58%
  • Ureter - 35% (73% of which are located in the distal ureter)
  • Both renal pelvis and ureter - 7%
  • Bilateral involvement - 2-5%
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Presentation

  • Gross or microscopic hematuria (75%) is the most common clinical presentation of urothelial tumors of the renal pelvis and ureters.
  • Flank pain (18%) results from gradual obstruction/distention of the collecting system or acute colic due to obstruction by a blood clot.
  • Dysuria (6%): Some patients report irritative lower urinary tract symptomatology such as burning upon urination.
  • Weight loss, anorexia, flank mass, or bone pain are symptoms of advanced disease that manifest in a minority of patients.
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Indications

  • Nephroureterectomy with excision of the bladder cuff is indicated in patients with renal pelvis transitional cell carcinoma (TCC), regionally extensive disease, and high-grade or high-stage lesions.
  • Benefits conferred by laparoscopic nephroureterectomy include decreased patient analgesic requirements, shorter hospitalization, and improved cosmetic results. Short-term follow-up has shown that laparoscopic nephroureterectomy appears to yield cancer control equivalent to that of the open procedure.
  • Segmental ureterectomy coupled with ureteral reimplantation can be used for lower-grade superficial urothelial tumors located in the distal ureter.
  • Renal-sparing surgery, including segmental ureterectomy and endoscopic therapy, is typically used in patients with small, lower-grade superficial lesions. Additionally, patients who would be at risk for dialysis after nephroureterectomy and those who are medically unfit for radical surgery are generally treated with minimally invasive and renal-sparing techniques.
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Relevant Anatomy

Renal pelvis

The renal pelvis is the portion of the urinary collecting system formed by the confluence of 2 or 3 major calices.

Ureter

The ureter is a 20- to 30-cm tubular structure lying on the psoas muscle. It follows an S-shaped curve, passing medially to the sacroiliac joint and then coursing laterally near the ischial spine before passing medially to penetrate the base of the bladder. It passes through a submucosal tunnel to empty into the bladder.

Histology

The renal pelvis and ureter are lined by a transitional epithelium. The next layer is the lamina propria. External to the lamina propria is smooth muscle arranged in a spiral and longitudinal manner. The outermost adventitia is composed of fibrous connective tissue.

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Contraindications

Relative contraindications that must be addressed prior to surgical treatment include the presence of active infection, uncorrected bleeding disorders, renal insufficiency, severe comorbidities, and advanced age. Surgical treatment is generally not warranted in patients with advanced metastatic disease; instead, medical management (ie, chemotherapy) should be instituted.

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Contributor Information and Disclosures
Author

Daniel M Kaplon, MD  Fellow in Endourology, Laparoscopy, and Robotics, Department of Urology, University of Wisconsin Medical School

Daniel M Kaplon, MD is a member of the following medical societies: American Urological Association

Disclosure: Nothing to disclose.

Coauthor(s)

David F Jarrard, MD  Professor of Urology and Molecular and Environmental Toxicology, University of Wisconsin School of Medicine and Public Health

David F Jarrard, MD is a member of the following medical societies: American Urological Association

Disclosure: Johnson and Johnson Consulting fee Consulting

John N Papadopoulos, MD  Staff Physician, Department of Urology, Veterans Administration Hospital and Meriter Hospital

Disclosure: Nothing to disclose.

Specialty Editor Board

Leonard Gabriel Gomella, MD, FACS  The Bernard W Godwin Professor of Prostate Cancer Chairman, Department of Urology, Associate Director of Clinical Affairs, Kimmel Cancer Center, Jefferson Medical College of Thomas Jefferson University

Leonard Gabriel Gomella, MD, FACS is a member of the following medical societies: American Association for Cancer Research, American College of Surgeons, American Medical Association, American Society for Laser Medicine and Surgery, American Urological Association, Sigma Xi, Society for Basic Urologic Research, Society of University Urologists, and Society of Urologic Oncology

Disclosure: GSK Consulting fee Consulting; Astra Zeneca Honoraria Speaking and teaching; Watson Pharmaceuticals Consulting fee Consulting

Francisco Talavera, PharmD, PhD  Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Salary Employment

Dan Theodorescu, MD, PhD  Paul A Bunn Professor of Cancer Research, Professor of Surgery and Pharmacology, Director, University of Colorado Comprehensive Cancer Center

Dan Theodorescu, MD, PhD is a member of the following medical societies: American Cancer Society, American College of Surgeons, American Urological Association, Medical Society of Virginia, Society for Basic Urologic Research, and Society of Urologic Oncology

Disclosure: Key Genomics Ownership interest Co-Founder-50% Stock Ownership

J Stuart Wolf Jr, MD, FACS  The David A Bloom Professor of Urology, Director, Division of Endourology and Stone Disease, Department of Urology, University of Michigan Medical School

J Stuart Wolf Jr, MD, FACS is a member of the following medical societies: American College of Surgeons, American Urological Association, Catholic Medical Association, Endourological Society, Society for Urology and Engineering, Society of Laparoendoscopic Surgeons, Society of University Urologists, and Society of Urologic Oncology

Disclosure: Nothing to disclose.

Chief Editor

Bradley Fields Schwartz, DO, FACS  Professor of Urology, Director, Center for Laparoscopy and Endourology, Department of Surgery, Southern Illinois University School of Medicine

Bradley Fields Schwartz, DO, FACS is a member of the following medical societies: American College of Surgeons, American Urological Association, Association of Military Osteopathic Physicians and Surgeons, Endourological Society, Society of Laparoendoscopic Surgeons, and Society of University Urologists

Disclosure: Nothing to disclose.

Additional Contributors

The authors and editors of eMedicine gratefully acknowledge the contributions of previous coauthor Michael N Wilkin, MD, to the development and writing of this article.

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Intravenous pyelogram (IVP) demonstrating an upper calyx filling defect characteristic of transitional cell carcinoma (TCC). Blunting of the involved calyx is noted. Courtesy of Andrew J. Taylor, MD, University of Wisconsin Medical School.
CT scan demonstrating right renal pelvis transitional cell carcinoma (TCC). Contrast in the renal pelvis is displaced by the tumor. Courtesy of Andrew J. Taylor, MD, University of Wisconsin Medical School.
CT scan demonstrating left distal ureteral transitional cell carcinoma (TCC). The left ureter is dilated and a medial filling defect is noted. Courtesy of Andrew J. Taylor, MD, University of Wisconsin Medical School.
Left retrograde ureterogram demonstrating the classic "goblet" sign of ureteral transitional cell carcinoma (TCC). Ureteral dilation distally and proximally to the tumor is present. The narrowed wall of the ureter is irregular. Courtesy of Andrew J. Taylor, MD, University of Wisconsin Medical School.
CT scan demonstrating bulky right renal pelvis transitional cell carcinoma (TCC) replacing the majority of the renal parenchyma. A pericaval lymph node metastasis is noted. Courtesy of Andrew J. Taylor, MD, University of Wisconsin Medical School.
CT scan demonstrating metastatic transitional cell carcinoma (TCC) of the right adrenal gland. A heterogeneous adrenal mass is noted adjacent to the spine. The superior portion of the right kidney is observed. Courtesy of Andrew J. Taylor, MD, University of Wisconsin Medical School.
Treatment algorithm for managing upper-tract transitional cell carcinoma (TCC).
 
 
 
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