Non-urothelial bladder neoplasms: small-cell neuroendocrine cancer

BACKGROUND: Neuroendocrine tumors (NET) are uncommon neoplasms. Small cell carcinoma of the bladder (SCCB) is a rare, poorly differentiated neuroendocrine tumor. It takes origin from cells of nervous and endocrine systems whitin the bladder. Data in literature are limited and still remains under discussion the best therapeutic approach. Treatment may be multimodal. Prognosis remains poor. Here we report the case of old male affected by SCCB. While opportunely describing it, we also reviewed the literature. CASE REPORT: A 85 years old male presented to us for asymtomatic gross hematuria recently occurred. Bladder ultrasound (US) revealed a 4 cm mass on left wall highly suspicious for neoplasm. Total body contrast-enhanced CT confirmed the lesion; no signs of local infiltration, hydronephrosis or visceral-lyph nodes secundarisms were described. A trans urethral resection of the bladder (TURB) was offered. RESULTS: Pathology report revealed a high-grade T1G3 urothelial carcinoma (30% of specimen) associated to small-cell neuroendocrine variant (70% of specimen): microscopic muscle involvement was excuded. In order to better characterize the neuroendocrine differentiation, immunohistochemistry was mandatory: cytokeratin AE1-3, synaptophysin and Ki-67 were used as molecular markers (Fig. 1). Urothelial histotype resulted positive for cytokeratine but negative for synaptophysin while the neuroendocrine variant was positive for both of them. Ki-67, a molecular marker adopted as expression of proliferation rate, was 90% totally suggesting an aggressive mixed bladder neoplasm. The patient was classed as a highest-risk. Radical cystectomy with extended lymp nodes dissection was offered. DISCUSSION AND CONCLUSIONS: Non-urothelial bladder cancers are uncommon neoplasms: they include neuroendocrine tumor (NET), squamous cell carcinoma (SCC), adenocarcinoma, micropapillary (MCP), plasmocitoid (PUC) and sarcoma. Two forms of bladder NET have been described in literature: small- and a large-cell. Small-cell carcinoma of the bladder (SCCB) is a very rare, poorly differentiated neuroendocrine tumor accounting for 0,5-1,0% of all bladder neoplasms3 and characterized by a highly aggressive course. Patients affected are considered at highest-risk of metastatic spreading and poor prognosis. Risk factors are not completely known. SCCB commonly arises from cells of the endocrine and nervous systems differently expressed whitin the human bladder. Neuroendocrine lesions are histologically graded according to markers of cellular proliferation (Ki-67 index) rather than cellular polymorphism2: whenever urothelial hystotipe coexists, the WHO 2004 grading system is used to classify the urothelial variant. On immunoistochemistry, SCCB is reactive for neuroendocrine markers such as synaptophysin, chromogranin and periodically for CK7 and CK20. TNM system is currently used to staging these neoplasms. Clinical presentation is variable depending from location, staging and visceral-lymph nodes involvement. Radical cistectomy represents the gold standard. A multimodal treatment may be also offered differently combining surgery with chemoterapic regimens. The prognosis remains poor.