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

Gupta, Sounak1; Thompson, R. Houston2; Boorjian, Stephen A.2; Thapa, Prabin3; Hernandez, Loren P. Herrera1; Jimenez, Rafael E.1; Costello, Brian A.4; Frank, Igor2; Cheville, John C.1

Pathology - Journal of the RCPA: October 2015 - Volume 47 - Issue 6 - p 533–542
doi: 10.1097/PAT.0000000000000301

Summary: 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.

1Department of Laboratory Medicine and Pathology

2Department of Urology

3Department of Health Science Research

4Division of Medical Oncology, Mayo Clinic, Rochester, Minnesota, United States

Address for correspondence: John C. Cheville, MD, Department of Laboratory Medicine and Pathology, Mayo Clinic, 200 First Street, Southwest, Rochester, Minnesota 55905, United States. E-mail:

Received 20 March, 2015

Revised 20 May, 2015

Accepted 28 May, 2015

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© 2015 Royal College of Pathologists of Australasia
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