The most likely diagnosis is:
FIGURE 58-3
a.renal cell carcinoma.
b.urinary obstruction.
c.urothelial carcinoma.
d.lymphoma.
e.metastatic disease.
Answers
1.d. All of the above. Patients with hereditary nonpolyposis colorectal carcinoma (HNPCC) or Lynch syndrome present at a younger age and are more likely to be female. In addition, the presence of either a
personal history or having two first-degree relatives with an HNPCCassociated cancer (particularly colon and endometrial) should raise suspicion for a hereditary component, and these patients should be referred for microsatellite or genetic testing.
2.c. Obesity. Of all the listed environmental insults, obesity has not been associated with upper tract urothelial cancers (UTUCs). Aristolochic acid has been implicated in the etiology of Balkan endemic and Chinese herb nephropathy because of its mutagenic action. The effect of smoking has been linked to generation of aromatic amines, which are metabolized into carcinogenic N-hydroxyalanine. Notably, this risk is dose dependent and can be modified by smoking cessation. Analgesic abuse is a well-documented risk factor, and experimental evidence supports phenacetin-induced papillary necrosis as a cofactor in renal failure and carcinogenesis. Aromatic amines account for carcinogenicity of β-naphthylamine and benzidine, which have been implicated as occupational hazards in the chemical, petroleum, and plastic industries, among others. Similar to smoking, the duration of exposure is important in determining the risk for UTUC development.
3.e. Distal and midureter. Ureteral tumors occur more commonly in the lower than in the upper ureter. Overall, approximately 70% of ureteral tumors occur in the distal ureter, 25% in the midureter, and 5% in the proximal ureter.
4.a. Stage and grade. The most well-established current predictors of survival in patients with upper tract urothelial tumors are stage and grade. The most significant decrease in survival is seen in T3 tumors, and higher-grade tumors are more likely to invade the surrounding tissues, hence presenting with higher stage. Although there have been studies showing differences in prognosis based on the tumor number, location, size, and architecture, these criteria are evolving and warrant further investigation.
5.d. Hematuria. The most common presenting symptom of upper tract urothelial tumors is hematuria, either gross or microscopic; this occurs in 56% to 98% of patients. Flank pain is the second most common symptom, occurring in 30% of patients with tumors. Approximately 15% of patients are asymptomatic at presentation and are diagnosed when an incidental lesion is found on radiologic evaluation.
6.a. True. Although intravenous pyelography has been the traditional means for diagnosis of upper tract lesions, this has largely been replaced by CT urography, which is easier to perform and less labor intensive. With CT
urography, the sensitivity for detecting upper tract malignant disease has been reported to approach 100%, with a specificity of 60% and a negative predictive value of 100%. It also has a higher degree of accuracy in determining the presence of renal parenchymal lesions.
7.b. False. Complete removal of the distal ureter and bladder cuff offers oncologic outcomes superior to those for incomplete resection. The risk of tumor recurrence in a remaining ureteral stump is 30% to 75%. In addition, adequate cystoscopic surveillance of a residual distal ureter stump after nephroureterectomy is virtually impossible, contributing to high rates of local recurrence. Therefore the entire distal ureter, including the intramural portion and the ureteral orifice, must be removed.
8.f. a and c. Ureteroscopy should be reserved for situations in which the diagnosis remains in question after conventional radiographic studies, and for patients in whom the treatment plan may be modified on the basis of the ureteroscopic findings. Although the risks of tumor seeding, extravasation, and dissemination are low in experienced hands, these risks are real and should preclude ureteroscopy when it is unnecessary. Because upper urinary tract tumors are often associated with bladder cancers, cystoscopy is mandatory in the evaluation to exclude coexistent bladder lesions.
9.b. Cisplatin. The largest experience of instillation therapy for UTUC is from use of BCG via a nephrostomy tube for primary treatment of carcinoma in situ (CIS), and favorable responses are seen. Although the experience with thiotepa, MMC, and gemcitabine is limited, a few small retrospective series have described their use in this setting.
.b. False. There are no randomized trials evaluating the effects of neoadjuvant and adjuvant chemotherapy on patients with UTUC, and the small number of cases treated with adjuvant chemotherapy precludes definitive conclusions of efficacy. However, given the significant influence of renal function on eligibility to receive effective chemotherapy, the focus is shifting toward a neoadjuvant approach, with several trials underway.
Pathology
1.c. Have periodic upper tract imaging. With no symptoms, no further workup is indicated. The patient should be followed for possible development of a ureteral vesicle stricture at the site of the anastomosis.
2.a. Interval cystoscopies and cytology. Patients who have upper tract TCC
have as high as a 30% incidence of bladder tumors and should be followed as for bladder cancer. Moreover, periodic upper tract imaging is necessary.
Imaging
1.c. Urothelial carcinoma. There is an enhancing mass centered in the renal sinus. The appearance is typical for a urothelial neoplasm of the renal pelvis.
Chapter review
1.Upper tract urothelial tumors are rarely diagnosed at autopsy; they present clinically during the patient's lifetime much as bladder tumors do. The peak incidence occurs between ages 70 and 80, and they occur twice as frequently in men as in women.
2.Upper tract recurrence is more likely with high-grade tumors and those associated with carcinoma in situ. Multifocality and the incidence of bilateral disease increases with the presence of CIS.
3.Upper tract tumors develop in 2% to 4% of patients with bladder cancer. Patients with upper tract tumors develop bladder cancer 30% of the time.
4.Bilateral upper tract tumors occur either synchronously or metachronously in 2% to 6% of patients.
5.In renal pelvic tumors, parenchyma invasion is the most significant predictor of metastases.
6.Inverted papillomas may be associated with upper tract tumors; it is not likely that cancers arise from them.
7.Squamous cell carcinoma and adenocarcinoma, although rare in the upper tract, are usually associated with long-term obstruction, inflammation, and occasionally calculi.
8.Tumor stage and grade, lymphovascular invasion, and lymph node spread are predictors of poor prognosis. The single most important predictor of outcome is stage.
9.A significant problem with ureteroscopic biopsy is that grade may be accurate, but accurate staging can be extremely difficult.
10.There is a 30% to 50% recurrence rate in ureteral tissue left distal to an invasive ureteral cancer.
11.Upper tract ureteral tumors after radial cystectomy for bladder cancer occur in 4% to 7% of patients.
12.Patients with Balkan nephropathy, those with analgesic abuse, and those who have ingested arsenic in endemic regions of Taiwan have a higher tendency for multiple and bilateral recurrences than do those with sporadic tumors.
13.Patients with T3 tumors located in the renal pelvis have a better survival than those with T3 tumors located in the ureter. Of renal pelvic tumors, 50% are invasive at diagnosis.
14.An adrenalectomy is not indicated for patients undergoing a nephroureterectomy for upper tract tumors.
15.After percutaneous resection of a tumor of the renal pelvis, the nephrostomy is left indwelling to allow for revisualization several weeks later to be certain that all tumors have been removed.
16.Hydronephrosis in the presence of urothelial carcinoma predicts invasion 80% of the time.
17.Tumor cell implantation has been reported to occur in wounds, port sites, and nephrostomy tracks.
18.Lymphadenectomy has prognostic and possible therapeutic value in patients with T2 to T4 disease.
19.Hereditary TCC should be suspected in patients with hereditary nonpolyposis colorectal carcinoma (HNPCC) or Lynch syndrome. Additionally, the presence of either a prior history of or two first-degree relatives with an HNPCC-associated cancer (particularly colon and endometrial) should raise suspicion for hereditary TCC, and these patients should be referred for microsatellite or genetic testing.
20.Aristolochic acid has been implicated in etiology of Balkan endemic and Chinese herb nephropathy.
21.About 70% of ureteral tumors occur in the distal ureter, 25% in the midureter, and 5% in the proximal ureter.
22.The largest experience of instillation therapy for upper tract urothelial carcinoma is with the use of BCG via a nephrostomy tube for primary treatment of CIS. Favorable responses have been reported.