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A transitional cell epithelium lines the urinary tract from the renal pelvis to the ureter, urinary bladder, and the proximal two-thirds of the urethra. Cancers can occur at any point: 90% of malignancies develop in the bladder, 8% in the renal pelvis, and the remaining 2% in the ureter or urethra. Bladder cancer is the fourth most common cancer in men and the thirteenth in women; an estimated 70,530 new cases and 14,680 deaths in the United States were predicted for the year 2010. The almost 5:1 ratio of incidence to mortality reflects the higher frequency of the less lethal superficial variants compared with the more lethal invasive and metastatic variants. The incidence is three times higher in men than in women and twofold higher in whites than blacks, with a median age at diagnosis of 65 years.
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Once diagnosed, urothelial tumors exhibit polychronotropism—the tendency to recur over time and in new locations in the urothelial tract. As long as urothelium is present, continuous monitoring of the tract is required.
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Cigarette smoking is believed to contribute to up to 50% of the diagnosed urothelial cancers in men and up to 40% in women. The risk of developing a urothelial malignancy in male smokers is increased two- to fourfold relative to nonsmokers and continues for 10 years or longer after cessation. Other implicated agents include the aniline dyes, the drugs phenacetin and chlornaphazine, and external-beam radiation. Chronic cyclophosphamide exposure may also increase risk, whereas vitamin A supplements appear to be protective. Exposure to Schistosoma haematobium, a parasite found in many developing countries, is associated with an increase in both squamous and transitional cell carcinomas of the bladder.
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Clinical subtypes are grouped into three categories: 75% are superficial, 20% invade muscle, and 5% are metastatic at presentation. Staging of the tumor within the bladder is based on the pattern of growth and depth of invasion: Ta lesions grow as exophytic lesions; carcinoma in situ (CIS) lesions start on the surface and tend to invade. The revised tumor, node, metastasis (TNM) staging system is illustrated in Fig. 41-1. About half of invasive tumors presented originally as superficial lesions that later progressed. Tumors are also rated by grade. Grade I lesions (highly differentiated tumors) rarely progress to a higher stage, whereas grade III tumors do.
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More than 95% of urothelial tumors in the United States are transitional cell in origin. Pure squamous cancers with keratinization constitute 3%, adenocarcinomas 2%, and small cell tumors (with paraneoplastic syndromes) <1%. Adenocarcinomas develop primarily in the urachal remnant in the dome of the bladder or in the periurethral tissues; some assume a signet cell histology. Lymphomas and melanomas are rare. Of the transitional cell tumors, low-grade papillary lesions that grow on a central stalk are most common. These tumors are very friable, have a tendency to bleed, are at high risk for recurrence, and yet rarely progress to the more lethal invasive variety. In contrast, CIS is a high-grade tumor that is considered a precursor of the more lethal muscle-invasive disease.
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The multicentric nature of the disease and high rate of recurrence have led to the hypothesis of a field defect in the urothelium that ...