title: Neuroendocrine Tumors of the Prostate: Emerging Insights from Molecular Data and Updates to the 2016 World Health Organization Classification.
abstract: 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.
authors.affiliation: Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, 350 West 11th Street, IU Health Pathology Laboratory Room 4010, Indianapolis, IN, 46202, USA.
authors.forename: David S
authors.initials: DS
authors.lastname: Priemer
authors.affiliation: Institute of Pathological Anatomy and Histopathology, School of Medicine, Polytechnic University of the Marche Region (Ancona), United Hospitals, Ancona, Italy.
authors.forename: Rodolfo
authors.initials: R
authors.lastname: Montironi
authors.affiliation: Michigan Center for Translational Pathology, University of Michigan, Ann Arbor, MI, USA.
authors.forename: Lisha
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Pathology and Laboratory Medicine, Henry Ford Health System, Detroit, MI, USA.|Josephine Ford Cancer Institute, Henry Ford Health System, Detroit, MI, USA.|Wayne State University School of Medicine, Detroit, MI, USA.
authors.forename: Sean R
authors.initials: SR
authors.lastname: Williamson
authors.affiliation: Department of Surgery, Faculty of Medicine, Cordoba University, Cordoba, Spain.|Champalimaud Clinical Center, Lisbon, Portugal.
authors.forename: Antonio
authors.initials: A
authors.lastname: Lopez-Beltran
authors.affiliation: Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, 350 West 11th Street, IU Health Pathology Laboratory Room 4010, Indianapolis, IN, 46202, USA. liang_cheng@yahoo.com.|Department of Urology, Indiana University School of Medicine, Indianapolis, IN, USA. liang_cheng@yahoo.com.
authors.forename: Liang
authors.initials: L
authors.lastname: Cheng
mesh_terms: D014408:Biomarkers, Tumor / Q000235:genetics; D018278:Carcinoma, Neuroendocrine / Q000145:classification* / Q000235:genetics / Q000473:pathology*; D006801:Humans; D008297:Male; D011471:Prostatic Neoplasms / Q000145:classification* / Q000235:genetics / Q000473:pathology*; D014944:World Health Organization
chemical_list: D014408:Biomarkers, Tumor
keywords: Castration-resistant prostate cancer (CRPC); Large cell neuroendocrine carcinoma; Molecular cytogenetics; Neuroendocrine differentiation; Prostate cancer; Small cell carcinoma