Small Cell Carcinoma of the Urinary Bladder—Histogenesis, Genetics, Diagnosis, Biomarkers, Treatment, and Prognosis

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Small cell carcinoma of the urinary bladder is a rare but highly aggressive malignancy with a dismal prognosis. Most patients present with advanced disease at the time of diagnosis. Hematuria is the most frequent presenting symptom. Histologically, small cell carcinoma of the urinary bladder is indistinguishable from its pulmonary counterpart. Coexistence with other types of carcinoma is common. Histogenesis is uncertain; there are several competing theories, including origin from stem cells, from urothelial cells, and from neuroendocrine cells in normal or metaplastic urothelium. The molecular pathogenesis remains unclear. Immunohistochemical staining can be extremely helpful in establishing the diagnosis, and in investigating the use of potential therapeutic strategies. Currently, combinations of surgical resection, chemotherapy, and radiation therapy represent the main treatment options. The recent observation of c-kit and epidermal growth factor receptor expression in more than 25% of patients with urinary bladder small cell carcinoma opens new avenues for further investigation. Improvement in survival may depend upon the identification of new molecular markers to facilitate earlier diagnosis and the development of novel targeted therapies. In this paper, we review general aspects of small cell carcinoma of the urinary bladder, focusing on the ways in which our understanding of this entity has been positively influenced by studies of the histopathologic and immunohistochemical findings, and by investigations of genetic alterations in this disease.

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