Squamous cell carcinogenesis and squamous cell carcinoma of the urinary bladder: A contemporary review with focus on nonbilharzial squamous cell carcinoma

Bladder squamous cell carcinoma, squamous metaplasia, and transitional cell carcinoma with squamous differentiation are infrequent findings in Western countries. A common risk factor for their development consists of chronic bladder irritation and inflammation. The prognostic and clinical relevance and natural history of squamous cell lesions has been under investigation, revealing individual premalignant characteristics. Recent developments in molecular characterization of squamous alterations of the urinary tract indicate pathogenetic similarities and interrelations and might lead to more precise tumor classification and risk stratification in the future. Nevertheless, current clinical management of patients with premalignant and malignant bladder squamous cell lesions remains challenging, as high evidence level studies are not available and prognosis of invasive squamous carcinoma is poor. Our review summarizes the available data on clinical presentation, treatment, and outcome of bladder squamous cell carcinoma, metaplastic lesions, and transitional cell carcinoma with squamous differentiation and discusses implementable current advances in the understanding of bladder cancer tumorigenesis.