The neuroendocrine component in bladder tumors

Neoplastic urothelium has the capacity to display enormous plasticity and divergent differentiation. Neuroendocrine tumors arise as a result of such capacity. Neuroendocrine tumors of the bladder represent a limited number of neoplasms characterized by neuroendocrine hormone secretion and a poor outcome. These tumors can be displayed as pure neuroendocrine neoplasms or more frequently as a neuroendocrine counterpart mixed with classical urothelial bladder cell carcinomas, adenocarcinoma, sarcomatoid carcinoma or mixtures of these components. Their heterogeneous character and clinical aggressiveness remain a challenge for clinical, pathological diagnosis and for therapy selection. Several types have been described, although small cell carcinoma represents the major subgroup of neuroendocrine tumors as compared to large cell carcinoma and carcinoid subtypes. In this review, epidemiology, presentation, macroscopic and microscopic features, and clinical prognostic and therapeutic implications of the major subgroups are described. Special focus is given to discuss how immunohistochemistry protein patterns and laboratory determinations may aid to characterize this type of tumors and to improve the clinical management of this highly aggressive type of bladder cancer patients.