Other carcinomas
Small cell neuroendocrine carcinoma

Author: Nat Pernick, M.D. (see Authors page)

Revised: 10 August 2016, last major update December 2014

Copyright: (c) 2003-2016,, Inc.

PubMed Search: Bladder [title] small cell carcinoma
Cite this page: Small cell neuroendocrine carcinoma. website. Accessed October 28th, 2016.
Definition / General
  • Rare bladder tumor resembling counterparts in lung and elsewhere
  • A type of poorly differentiated carcinoma
  • A morphologic diagnosis - neuroendocrine differentiation is not required
  • Also called poorly differentiated small cell carcinoma
  • Rare, 0.5 to 1.0% of all bladder malignancies
  • No age, sex or clinical differences from usual type urothelial carcinoma
Clinical Features
  • Pure or with urothelial carcinoma or other carcinomas (diagnose as small cell if any appreciable component, because prognosis is affected by presence of small cell component)
  • Occasionally associated with hypercalcemia and ectopic ACTH production
  • Most cases are advanced at diagnosis; 65% have metastases at or soon after diagnosis
  • Very aggressive with rapid development of metastases to regional nodes, liver, bones and peritoneal cavity
  • Median survival 11 months in recent study (Cancer 2011;117:5325); presence of distant metastases may be most important prognostic factor
  • 5 year survival of 8-16% (Cancer 2004;101:957)
  • Rarely co-exists with tumor cells exhibiting skeletal muscle differentiation (Am J Surg Pathol 2000;24:223)
Case Reports
  • Radical cystectomy unless metastatic disease is present - then need systemic therapy (Cancer 2005;103:1172)
  • High response rate to chemotherapy (similar to that used for lung tumors), but overall prognosis is still poor (BJU Int 2009;103:747)
Gross Description
  • Usually large, polypoid mass anywhere in bladder
Micro Description
  • Tumors with any appreciable small cell component should be classified as small cell carcinoma
  • Resembles small cell carcinoma of lung
  • Loosely cohesive sheets or nests of small to intermediate sized cells with minimal cytoplasm, hyperchromatic nuclei, stippled or coarsely granular chromatin, indistinct nucleoli and no nuclear overlapping
  • Mitotic activity and necrosis are common
  • Often co-exists with other forms of in situ or invasive carcinoma
Micro Images

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(H and E) staining of the biopsy specimen

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Small cell carcinoma of the urinary bladder

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Mixed small cell and classic urothelial carcinoma
shows synaptophysin+ in small cell component

Cytology Description
  • Numerous tumor cells in loose clusters, cells are larger than lymphocytes, have scant cytoplasm, eccentric nuclei with evenly dispersed but coarse chromatin, indistinct nucleoli
Cytology Images

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Mixed small cell and undifferentiated urothelial carcinoma

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Positive Stains
Electron Microscopy Images
  • Few dense core granules
Differential Diagnosis
  • High grade urothelial carcinoma: by definition, should lack any appreciable small cell component; p63+, synaptophysin- (Appl Immunohistochem Mol Morphol 2011;19:395)
  • Lymphoma: tumor cells are smaller, positive for CD45, B or T cell markers
  • Metastatic small cell carcinoma: usually no associated urothelial carcinoma, need clinical information
Additional References