transitional cell carcinoma

Urothelial (transitional cell) carcinoma arises from the multilayered transitional epithelium that lines the urinary tract from the renal calyces to the proximal urethra, allowing for distension without cell damage. It accounts for >90% of bladder cancers and is the most common cancer of the renal pelvis and ureters. Major risk factors include cigarette smoking (most important modifiable risk factor), occupational exposure to aromatic amines (aniline dyes used in rubber, dye, and textile industries), phenacetin abuse, cyclophosphamide exposure, and chronic cystitis. Presents classically with painless gross or microscopic hematuria; other symptoms include irritative voiding symptoms (dysuria, frequency, urgency) and, if advanced, flank pain from ureteral obstruction. Diagnosis involves cystoscopy with biopsy, urine cytology, and imaging (CT urography) to evaluate the entire urothelial tract due to its propensity for multifocality and 'field cancerization.' Histologically, tumors range from low-grade papillary lesions to high-grade invasive carcinomas; morphologic patterns include papillary, sessile/flat (carcinoma in situ), and invasive forms. Molecular pathways differ: papillary low-grade tumors often show FGFR3 mutations, while flat high-grade tumors more often involve TP53 mutations. Staging (TNM) is critical for prognosis and treatment planning—non-muscle-invasive tumors are managed with transurethral resection (TURBT) and intravesical BCG or chemotherapy, whereas muscle-invasive disease often requires radical cystectomy with neoadjuvant cisplatin-based chemotherapy. Squamous cell carcinoma of the bladder is a differential in patients with chronic irritation (e.g., Schistosoma haematobium infection, chronic catheterization), and adenocarcinoma of the bladder is associated with urachal remnants or extensive glandular metaplasia. Prognosis depends on grade, stage, and presence of muscle invasion at diagnosis.