Pathogenesis The multicentric nature of the disease and high rate of recurrence has led to the hypothesis of a field defect in the urothelium that results in a predisposition to cancer. Molecular genetic analyses suggest that the superficial and invasive lesions develop along distinct molecular pathways in which primary tumorigenic aberrations precede secondary changes associated with progression to a more advanced stage. Low-grade papillary tumors that do not tend to invade or metastasize harbor constitutive activation of the receptor-tyrosine kinase-Ras signal transduction pathway and a high frequency of fibroblast growth factor receptor 3 (FGFR3) mutations. In contrast, CIS and invasive. | Chapter 090. Bladder and Renal Cell Carcinomas Part 2 Pathogenesis The multicentric nature of the disease and high rate of recurrence has led to the hypothesis of a field defect in the urothelium that results in a predisposition to cancer. Molecular genetic analyses suggest that the superficial and invasive lesions develop along distinct molecular pathways in which primary tumorigenic aberrations precede secondary changes associated with progression to a more advanced stage. Low-grade papillary tumors that do not tend to invade or metastasize harbor constitutive activation of the receptor-tyrosine kinase-Ras signal transduction pathway and a high frequency of fibroblast growth factor receptor 3 FGFR3 mutations. In contrast CIS and invasive tumors have a higher frequency of TP53 and RB gene alternations. Within all clinical stages including Tis T1 and T2 or greater lesions tumors with alterations in p53 p21 and or RB have a higher probability of recurrence metastasis and death from disease. Clinical Presentation Diagnosis and Staging Hematuria occurs in 80-90 of patients and often reflects exophytic tumors. The bladder is the most common source of gross hematuria 40 but benign cystitis 22 is a more common cause than bladder cancer 15 Chap. 45 . Microscopic hematuria is more commonly of prostate origin 25 only 2 of bladder cancers produce microscopic hematuria. Once hematuria is documented a urinary cytology visualization of the urothelial tract by CT or intravenous pyelogram and cystoscopy are recommended if no other etiology is found. Screening asymptomatic individuals for hematuria increases the diagnosis of tumors at an early stage but has not been shown to prolong life. After hematuria irritative symptoms are the next most common presentation which may reflect in situ disease. Obstruction of the ureters may cause flank pain. Symptoms of metastatic disease are rarely the first presenting sign. The endoscopic evaluation includes an examination under anesthesia to
