High grade neuroendocrine carcinoma of the urinary bladder treated by radical cystectomy: A series of small cell, mixed neuroendocrine and large cell neuroendocrine carcinoma

Sounak Gupta, R. Houston Thompson, Stephen A. Boorjian, Prabin Thapa, Loren P Herrera Hernandez, Rafael E Jimenez, Brian Costello, Igor Frank, John C. Cheville

Research output: Contribution to journalArticle

10 Scopus citations


High grade neuroendocrine carcinomas (HGNEC) treated by cystectomy often carry an original diagnosis of typical urothelial carcinoma (UC). The correct diagnosis of HGNEC is critical in influencing the decision for early chemotherapy, potentially followed by cystectomy. The objective of this study was to characterise the features of HGNEC treated by radical cystectomy. The study consisted of 79 patients with HGNEC including small cell (68 patients), large cell neuroendocrine (LCNEC) (5 patients) and mixed neuroendocrine (mixed-NEC) carcinoma (6 patients) matched with 122 patients with UC, treated at our institution between 1987 and 2014. Morphometric analysis for cell and nuclear size as well as immunophenotyping for neuroendocrine markers and cell-cycle regulators were applied to tissue microarrays. Small cell, LCNEC and mixed-NEC are a morphological spectrum of high grade neuroendocrine carcinoma with overlapping histological features, identical immunophenotype, Ki-67 proliferative rate and patient outcomes. Finally, the nuclear size criteria is misleading as HGNEC, particularly cases of LCNEC and mixed-NEC, may have enlarged nuclei compared to small cell carcinomas and are more prone to be misdiagnosed as UC, thereby preventing appropriate management.

Original languageEnglish (US)
Pages (from-to)533-542
Number of pages10
Issue number6
StatePublished - Oct 1 2015



  • Cystectomy
  • high grade neuroendocrine carcinoma
  • large cell neuroendocrine carcinoma
  • small cell carcinoma
  • urinary bladder
  • urothelial carcinoma

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

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