Neuroendocrine Tumors of the Prostate: Emerging Insights from Molecular Data and Updates to the 2016 World Health Organization Classification

David S. Priemer, Rodolfo Montironi, Lisha Wang, Sean R. Williamson, Antonio Lopez-Beltran, Liang Cheng

Research output: Contribution to journalReview articlepeer-review


Neuroendocrine neoplasms of the prostate represent a multifarious group of tumors that exist both in pure forms and associated with prostatic adenocarcinoma. Morphologically, neuroendocrine cells in prostate neoplasms can range from being indistinguishable from surrounding prostate adenocarcinoma cells to having high-grade neuroendocrine appearances similar to neuroendocrine malignancies of other organs. On the molecular level, neuroendocrine malignancies arising in the setting of prostate adenocarcinoma have been the subject of a large amount of recent research, most of which has supported the conclusion that neuroendocrine malignancy within the prostate develops as a transdifferentiation from prostate adenocarcinoma. There has not, however, been substantial investigation into rare, pure neuroendocrine malignancies and the possibility that these tumors may have a different cell of origin and molecular genesis. Here, we discuss the morphologic spectrum of malignant neuroendocrine prostate neoplasms and review the most recent molecular data on the subject of malignant neuroendocrine differentiation in prostatic adenocarcinoma. In reflection of the most recent data, we also discuss diagnostic classification of prostate neuroendocrine tumors with reference to the 2016 World Health Organization (WHO) classification. We discuss the reporting of these tumors, placing emphasis on the differentiation between pure and mixed neuroendocrine malignancies so that, in the least, they can be easily identified for the purposes of future clinical and laboratory-based investigation. Finally, we suggest a designation for an unclassifiable (or not otherwise specified) high-grade neuroendocrine prostate malignancy whose features do not easily place it into one of the WHO diagnostic entities.

Original languageEnglish (US)
Pages (from-to)123-135
Number of pages13
JournalEndocrine Pathology
Issue number2
StatePublished - Jun 1 2016
Externally publishedYes


  • Castration-resistant prostate cancer (CRPC)
  • Large cell neuroendocrine carcinoma
  • Molecular cytogenetics
  • Neuroendocrine differentiation
  • Prostate cancer
  • Small cell carcinoma

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Endocrinology, Diabetes and Metabolism
  • Endocrinology

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