What causes urothelial tumors of the renal pelvis and ureters?

Updated: Aug 07, 2020
  • Author: Kyle A Richards, MD, FACS; Chief Editor: Bradley Fields Schwartz, DO, FACS  more...
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Answer

Tobacco smoking is the factor most strongly associated with upper tract transitional cell carcinoma (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 seven 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. In contrast, Shih et al demonstrated a risk reduction in upper tract TCC with use of nonaspirin nonsteroidal anti-inflammatory drugs (NSAID)s in those patients who quit smoking at least 10 years ago. [2]

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.

Upper tract TCC is associated with Balkan nephropathy, which is a degenerative interstitial nephritis linked to the consumption of aristolochic acid (contained in some plants in the Balkans). Tumors associated with Balkan nephropathy are generally low-grade, multiple, and bilateral, in contrast to TCC of other etiologies.

Finally, heredity can play a part in the development of TCC. TCC is associated with Lynch syndrome type II (hereditary nonpolyposis colorectal carcinoma), which is a syndrome characterized by an early onset of proximal colonic nonpolyposis tumors, numerous synchronous and metachronous colonic tumors, and extracolonic tumors. If patients younger than 60 years old are diagnosed with upper tract TCC, a thorough family history should be taken and they should be counseled about genetic testing and Lynch syndrome.


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