Evolving concepts in prostatic neuroendocrine manifestations: from focal divergent differentiation to amphicrine carcinoma.

Prostatic neuroendocrine manifestations encompass a heterogeneous spectrum of morphologic entities. In the era of evidence-based and precision-led treatment, distinction of biologically relevant clinical manifestations expanded the evolving clinical role of pathologists. Recent observations on the occurrence of hormone therapy-induced aggressive prostatic cancers with neuroendocrine features have triggered the need to refine the spectrum and nomenclature of prostatic neuroendocrine manifestations. Although the morphologic assessment still remains the basis of the diagnostic workup of prostatic neoplasms, the application of ancillary biomarkers is crucial in the accurate classification of such presentations. This review provides a diagnostic roadmap for the practicing pathologist by reviewing the characteristic morphologic, immunohistochemical, and molecular correlates of various faces of prostatic neuroendocrine manifestations.