Daniel J. Canter, MD
BASICS
DESCRIPTION
• Squamous cell carcinoma (SCC) of the bladder is a histologic variant of bladder cancer
– Most frequent histologic form of bladder cancer in countries with endemic schistosomiasis
– SCC comprises 2–5% of all bladder cancers—most common histologic variant in Western countries
EPIDEMIOLOGY
Incidence
• 2–5% of bladder cancers in Western countries
• Originally reported that patients with spinal cord injuries (SCIs) had an incidence of SCC of the bladder of 2.3%—more recent data only suggests 0.39% incidence
• Approximately 75–80% of all bladder cancers are SCCs in regions with endemic schistosomiasis
Prevalence
Difficult to assess since so many of these patients will ultimately die of bladder cancer
RISK FACTORS
• Schistosomiasis infection
• Transitional cell carcinoma (TCC) can differentiate into any histology
• Smoking
• Chronic bladder infection/irritation
– Patients with SCIs
– Chronic indwelling Foley catheter/CIC
– Chronic infection
– Bladder stones
– Leukoplakia
– Squamous metaplasia
• HPV infection
• Industrial exposures for workers involved in the production of rubber, leather, textiles, and paint (traditionally more associated with the development of pure urothelial carcinoma)
Genetics
• Association with variations in inflammatory genes
• Epidermal growth factor receptor and p53 overexpression implicated as well as p16 abnormalities
• Keratin 10 and caveolin-1 identified as potential markers of differentiation from TCC to SCC
PATHOPHYSIOLOGY (1)
• Schistosomiasis infection
• Transitional cell dedifferentiation
– Transitional cells possess unique ability to dedifferentiate into any cell type
• Chronic irritation of bladder mucosa due to a variety of etiologies, especially SCIs
• Most common bladder sites are the lateral wall and trigone
ASSOCIATED CONDITIONS
• Neurogenic bladder/SCIs
• Need for chronic indwelling Foley/CIC
• Smoking history
• Living and travel to areas endemic with schistosomiasis
GENERAL PREVENTION
• No good screening test for bladder cancer in general
• Smoking cessation
• Patients with indwelling catheters (Foley, suprapubic tube, etc.) should be screened with yearly cystoscopy +/– biopsy
– When to start is open to debate
• Treatment of patients infected with schistosomiasis (praziquantel)
DIAGNOSIS
HISTORY
• History of living/travel to countries with endemic schistosomiasis
• In general, in Western countries, patients who have SCC of the bladder present in the same manner as urothelial carcinoma of the bladder
– Hematuria
– Constitutional symptoms
– Flank/back pain due to ureteral obstruction
– History of chronic irritation to bladder mucosa
PHYSICAL EXAM
• Palpable mass on rectal/vaginal exam
• Gross hematuria
DIAGNOSTIC TESTS & INTERPRETATION
Lab
• Urinalysis/urine culture
• Urinary cytology usually not reliable
• CBC
• Comprehensive metabolic panel, including (liver function testing) LFTs, alkaline phosphatase, and albumin
Imaging
• Cross-sectional imaging of the chest, abdomen, and pelvis based on patient’s renal function (CT scan vs. MRI)
• Bone scan if elevated calcium, alkaline phosphatase, or unexplained pain
Diagnostic Procedures/Surgery
• Exam under anesthesia (EUA) and transurethral resection of bladder tumor (TURBT) of primary tumor for histologic diagnosis and clinical staging
• Radical cystectomy with lymph node dissection and urinary diversion is considered 1st-line treatment
Pathologic Findings
• Mixed urothelial and squamous carcinomas are more common than pure SCCs
– The term SCC of the bladder is used only if tumor is solely composed of squamous cell component, with no urothelial carcinoma component
• Grading unreliable. Mostly considered a high-grade neoplasm
• Histologic findings
– Squamous metaplasia
– Keratinized islands
– Squamous pearls
– Intercellular bridges
– Mitotic figures common
DIFFERENTIAL DIAGNOSIS
• Urothelial carcinoma of the bladder
• Squamous metaplasia
• Other histologic variant of bladder (adenocarcinoma, sarcomatoid, etc.)
• Invasive cervical cancer: Often squamous cell
TREATMENT
GENERAL MEASURES
• Treatment is related to stage
• In general, SCC of the bladder presents with locally advanced disease, and radical cystectomy with urinary diversion is an integral part of the treatment paradigm
• Although uncommon, noninvasive lesions can be treated with local resection and diligent surveillance
MEDICATION
First Line
• Systemic chemotherapies have been used with limited experience in treating SCC of the bladder
• Small series have reported positive responses to cisplatin-based therapies, similar to pure urothelial carcinoma
• At present, role for neoadjuvant/adjuvant chemotherapy is poorly defined
Second Line
N/A
SURGERY/OTHER PROCEDURES (2)
• After diagnosis is confirmed, radical cystectomy is 1st-line treatment
• Bladder-preserving therapies can be considered if tumor is nonmuscle invasive and completely resected, and patient is willing to commit to intensive surveillance protocol
• Limited experience with chemoradiotherapy as primary treatment modality
ADDITIONAL TREATMENT
Radiation Therapy
Can be used in adjuvant setting for patients with positive surgical margins at time of surgery
Additional Therapies
N/A
Complementary & Alternative Therapies
N/A
ONGOING CARE
PROGNOSIS
• Related to pathologic stage (3)
– Evidence suggests that patients with SCC of the bladder tend to present with higher-stage (pT3/T4) disease at the time of radical cystectomy
• Overall survival has ranged from 4.8 to 50%
• 5-yr cancer-specific survival in contemporary series has ranged from 57 to 64%
COMPLICATIONS
• Related to radical cystectomy and urinary diversion
– Perioperative mortality approaches 2%
– 40–50% of patients will experience a postoperative complication
– Gastrointestinal complication is most common, eg, ileus, small bowel obstruction
FOLLOW-UP
Patient Monitoring
• Related to tumor stage at the time of radical cystectomy
– In general, patients are followed with history, physical exam, laboratory studies (CBC and comprehensive metabolic profile, including liver function tests) and cross-sectional imaging of chest, abdomen, and pelvis every 3–6 mo after surgery for the first 2 yr then semiannually for 2 yr then annually
– Renal function needs to be followed annually as well
Patient Resources
Bladder Cancer Advocacy Network (www.bcan.org)
REFERENCES
1. Kim SP, Frank I, Cheville JC, et al. The impact of squamous and glandular differentiation on survival after radical cystectomy for urothelial carcinoma. J Urol. 2012;188:405–409.
2. Rausch S, Lotan Y, Youssef RF. Squamous cell carcinogenesis and squamous cell carcinoma of the urinary bladder: A contemporary review with focus on nonbilharzial squamous cell carcinoma. Urol Oncol. 2014;32(1):32.e11–6.
3. Xylinas E, Rink M, Robinson BD, et al. Impact of histological variants on oncological outcomes of patients with urothelial carcinoma of the bladder treated with radical cystectomy. Eur J Cancer. 2013;49(8):1889–1897.
ADDITIONAL READING
N/A
See Also (Topic, Algorithm, Media)
• Bladder Cancer, General
• Bladder Cancer, Squamous Cell Carcinoma Image 
• Bladder Cancer, Urothelial, Muscle Invasive (Clinical and Pathologic T2/T3/T4) (MIBC)
CODES
ICD9
188.9 Malignant neoplasm of bladder, part unspecified
ICD10
C67.9 Malignant neoplasm of bladder, unspecified
CLINICAL/SURGICAL PEARLS
• With the control of schistosomiasis in endemic regions, the rate of SCC is dropping relative to the diagnosis of urothelial carcinoma.
• Radical cystectomy is the gold standard for muscle-invasive SCC of the bladder.