{Reference Type}: Case Reports {Title}: Primary Prostatic Carcinoma With De Novo Diffuse Neuroendocrine Differentiation. {Author}: Galea LA;Mow C;Fine SW;Manohar P; {Journal}: Int J Surg Pathol {Volume}: 30 {Issue}: 2 {Year}: Apr 2022 {Factor}: 1.358 {DOI}: 10.1177/10668969211035844 {Abstract}: The 2016 World Health Organization classification of prostate cancer with neuroendocrine (NE) differentiation includes NE cells in usual prostate cancer, adenocarcinoma with Paneth cell-like NE differentiation, well-differentiated NE tumor (carcinoid), small cell NE carcinoma, and large cell NE carcinoma. In this article, we report a rare case of primary prostatic carcinoma with de novo diffuse NE differentiation presenting with bilateral hydronephrosis in a 79-year-old man. This case did not fit into any of the existing classifications. The clinical, radiological, morphological, and immunohistochemical findings and response to androgen deprivation therapy (ADT) are presented. The proposed pathogenesis of NE differentiation via transdifferentiation from conventional prostatic adenocarcinoma whereby genomic alterations, coupled with ADT can induce lineage plasticity resulting in NE differentiation is described.