The Neuroendocrine Component in Bladder Tumors

Abstract

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.

Primary large cell carcinoma of ureter ： a case report and review of the literature

“…At present, there are four most widely accepted hypotheses about the origin of this tumor. They believe that the tumor originates from (1) pluripotent urothelial stem cells, (2) neuroendocrine cells originally existing in submucosa or normal urothelium, (3) urothelial metaplasia, and (4) transformation of urothelial cancer cells [11][12][13][14]. More than 50% of urinary neuroendocrine cancers are found to be associated with other cell forms, such as urothelial carcinoma and adenocarcinoma.…”

An Approach to Nonurothelial Malignancies of the Urinary Bladder in Urine Cytology

“…This theory is supported by studies highlighting a common clonal origin of SCNC with coexisting CUC components 54. Less frequently, SCNCs have been reported to be associated with SQCs and ADCs of the bladder 53,55–57. Recognition of both pure SCNC and SCNC combined with other UC types is important as it confers a worse prognosis than CUC with frequent lymph node metastasis and higher tumor stage at presentation58 as well as earlier distant metastasis 59,60.…”

“…54 Less frequently, SCNCs have been reported to be associated with SQCs and ADCs of the bladder. 53,[55][56][57] Recognition of both pure SCNC and SCNC combined with other UC types is important as it confers a worse prognosis than CUC with frequent lymph node metastasis and higher tumor stage at presentation 58 as well as earlier distant metastasis. 59,60 Patients with SCNC have reported 5-year survival rates of <30%.…”

“…However, it is important to note that these IHC markers may not always be expressed in SCNC. 10,53,55,56 Another IHC pitfall is that a subset of bladder SCNCs can express thyroid transcription factor-1, 10,53,69 which may lead to misinterpretation of bladder involvement by metastatic lung small cell carcinoma. This highlights the importance of clinicoradiologic correlation to evaluate for potential widespread metastasis from other primary sites and adequately guide patient management.…”

A Case of Bladder Large Cell Carcinoma with Review of the Literature

“…The origin of NE tumor of the bladder is also a matter of debate, and different theories have been proposed, including the multipotent stem cell hypothesis, which could account for the concomitant presence of other tumoral populations in the sample [4][5][6]. Due to its rarity, there are still no guidelines regarding treatment of LCNEC.…”