Squamous Cell Carcinoma
Variants: pure squamous cell carcinoma, verrucous carcinoma, and squamous cell papilloma. Epidemiology: 2–5% of US bladder-cancer histology; in regions where Schistosoma is endemic, squamous cell carcinoma may account for up to 75% of cases. More common in women, spinal-cord-injured patients, and chronic irritation (UTI, stones). Diagnosis requires keratinization on the pathologic specimen and is morphologically indistinguishable from squamous cell carcinoma elsewhere; it generally presents at an advanced stage.
Management — no proven role for neoadjuvant/adjuvant chemotherapy for pure SCC (2022 NCCN); treat with cystectomy, radiotherapy, or agents used for SCC elsewhere (5-FU, taxanes). There is no survival difference at cystectomy between pure SCC and urothelial carcinoma with squamous differentiation. For T1 squamous bladder cancer without pure SCC or LVI on the initial TURB, consider intravesical BCG; with pure SCC or LVI, consider immediate RC. (Lonati 2022, n=188 T1 HG squamous, immediate RC vs BCG: no significant difference in 5-year cancer-specific mortality [29% vs 16%] or overall mortality [34% vs 26%]; among BCG patients, pure SCC was associated with increased progression [HR 2.40] and LVI with increased recurrence and progression.)
Adenocarcinoma
Accounts for 2% of histology; the majority represent metastases from other primaries (colon, breast, lung), so investigate other sites (e.g. colonoscopy). Risk factors for primary bladder adenocarcinoma (4): nonfunctioning bladder, obstruction, chronic irritation, and bladder exstrophy. Patients undergoing bladder augmentation with bowel are at risk (~1.5–2.5% per decade); screening is not recommended, but follow-up includes annual renal/bladder ultrasound, electrolytes, creatinine, serum B12, and urinalysis. Urachal adenocarcinoma arises from the urachus.
Small Cell Carcinoma
A type of neuroendocrine histology, <1% of bladder cancer. Should be considered and treated as metastatic disease even without radiologic evidence of spread, and even small components within urothelial carcinoma should be managed as small cell. It is very chemosensitive: treat with initial chemotherapy followed by radiation or cystectomy as consolidation (even if non-metastatic). The primary mode is chemoradiation; chemotherapy + radical cystectomy is an option with similar survival (5-year cancer-specific survival 16% chemoradiation vs 18% chemotherapy + RC).
Primary Signet Ring Cell Carcinoma
Can be of urachal origin and directly extend into the bladder; extremely rare (<1% of epithelial bladder neoplasms). Generally presents as high-grade, high-stage disease with a uniformly poor prognosis — regional or distant metastases are usually present at diagnosis and mean survival is <20 months. CEA may be elevated. Primary treatment is radical cystectomy; understaging is very common, with peritoneal studding often found at exploration.
Sarcoma
Subclassified by malignant cell type. Leiomyosarcoma is the most common subtype, followed by rhabdomyosarcoma and then, rarely, angiosarcoma, osteosarcoma, and carcinosarcoma.
Self-Test
1. Which patients are at risk of bladder adenocarcinoma? Patients with a nonfunctioning bladder, obstruction, chronic irritation, or bladder exstrophy.
2. Which variant histologies are considered aggressive? Micropapillary, nested, plasmacytoid, and sarcomatoid.