Squamous Cell Carcinoma of the Bladder: A Clinicopathologic Analysis of 45 Cases

Abstract

Squamous cell carcinoma of the bladder comprises less than 5% of all bladder cancers in the United States and its long-term prognosis has remained controversial. We examined a large series of patients who underwent radical and partial cystectomies for squamous cell carcinoma to identify associated histopathologic findings and clinical outcomes associated with these tumors. Patient age ranged from 46 to 83 years (average 68.5 y) with a male:female ratio of 3:2. Forty-three patients were white and 2 patients were African-American. No patient had a history of schistosomal infection and only 1 patient had a history of condyloma acuminatum. The majority of patients with reported signs and symptoms presented with hematuria (n=29/34), with the remainder presenting with lower urinary tract symptoms. Tumor size ranged from 0.8 to 6.4 cm (average 3.8 cm). Invasion was identified into the lamina propria (pT1, n=1/45), muscularis propria (pT2, n=14/45), perivesical fat (pT3, n=27/45), and adjacent structures (pT4, n=3/45). Concurrent metastases were identified in 11 of 45 patients (24%) to pelvic lymph nodes (n=9), perivesical lymph nodes (n=3), obturator lymph nodes (n=1), and bowel wall (n=1). Most tumors were moderately (n=29/45) or poorly (n=13/45) differentiated, whereas only 3 tumors were well differentiated (n=3/45). Keratinization was present in all cases within the invasive component and ranged from 5% to 95% of tumor bulk. Necrosis ranged from 0% to 60% and inversely correlated with tumor differentiation. Eighteen cases demonstrated a prominent giant cell reaction to keratin, and 30 tumors were associated with a desmoplastic reaction. Extensive perineural (n=11/45) and angiolymphatic invasion (n=7/45) were identified in a subset of tumors. The majority of cases demonstrated associated superficial lesions including keratinizing squamous metaplasia (n=28/45), nonkeratinizing squamous metaplasia (n=20/45), squamous cell carcinoma in situ (n=16/45), squamous metaplasia with dysplasia (n=4/45), verrucous squamous hyperplasia (n=3/45), and extensive condyloma acuminatum (n=1/45). Seven cases additionally demonstrated separate small foci of focal flat urothelial carcinoma in situ. Three cases demonstrated a markedly atypical squamous lining of the prostatic ducts at the prostatic urethra. Clinical follow-up was available on 35 patients (78%) and ranged from 1 to 175 months (average 33 mo, median 15 mo). Two patients developed recurrent local disease (n=2/35, 6%) and 13 patients developed subsequent metastatic disease (n=13/35, 37%). Ten patients were dead of disease (29%), with a time to death for most patients of less than 2 years (range 2 to 21 mo, average 10.5 mo). Thirty-seven percent of patients (n=13/35) were alive without disease. In conclusion, squamous cell carcinoma often presents at an advanced stage; however, radical cystectomy with lymph node dissection appears to offer a significant benefit in survival in a subset of patients.

The 2016 WHO Classification of Tumours of the Urinary System and Male Genital Organs—Part B: Prostate and Bladder Tumours

“…Squamous cell carcinoma is defined by the presence of intercellular bridges or keratinization and may be present in up to 40% of invasive urothelial carcinomas [63][64][65][66]. It is almost never associated with human papillomavirus infection, with the rare exception of some cases with a basaloid morphology [67,68].…”

The use of Urovysion™ fluorescence in situ hybridization in the diagnosis and surveillance of non-urothelial carcinoma of the bladder

“…These include keratinizing squamous metaplasia, non-invasive squamous lesions, smoking and chronic mucosal irritants such as calculi and indwelling catheters. [4][5][6] In Africa, however, chronic infection with Schistosoma hematobium (bilharziasis) is the most common cause. 4,6 Although these tumors are derived from urothelium, they show pure squamous morphology and at the time of diagnosis have often infiltrated the muscularis propria and are thus associated with a poor clinical outcome.…”

Urothelial carcinoma with prominent squamous differentiation in the setting of neurogenic bladder: role of human papillomavirus infection

“…Although these are rare and generally regarded as benign lesions, several studies have shown squamous cell carcinoma arising in the background of condylomata. 11,16,17,35 It is important to note that patients in these studies were either chronically immunosuppressed 11,17 or showed persistent condylomatous infection with 11 or without 16 associated extensive vaginal condylomata. Inverted papillomas of the bladder have also been examined for HPV with variable results.…”

“…1 HPV is a small circular double-stranded DNA virus with more than 100 different types described to date. 2 The potential of the virus to cause malignant or benign lesions dictates its classification into low-risk (6,11,40,42, and so on) or high-risk (16,18,31,33,45,51, and so on) types. The prototypical model for carcinogenesis is squamous cell carcinoma of the uterine cervix, in which nearly all such carcinomas are associated with HPV infection.…”

“…The few published studies [11][12][13][14] on this relationship have shown a low frequency of HPV detection, implying that HPV is not likely to have a major role in the development of bladder squamous cell carcinoma. However, the positive cases identified in the literature suggest that under certain circumstances, such as immunosuppression 12 and persistent condylomatous infection, 11,15,16 the virus may exert its oncogenic activity in the bladder.…”