Metastatic castration resistant prostate cancer with squamous cell, small cell, and sarcomatoid elements—a clinicopathologic and genomic sequencing-based discussion

Histologic variants are uncommon but well reported amongst cases of prostatic adenocarcinoma, including those in the setting of hormonal and/or chemoradiation therapy and castration resistance. However, the spectrum of morphologic phenotypes and molecular alterations present in such histologic variants are still incompletely understood. Herein, we describe a case of metastatic prostatic adenocarcinoma with hormonal and chemoradiation therapy-associated differentiation, displaying a combination of squamous cell, small cell, and sarcomatoid elements. The morphologic, immunohistochemical, and molecular observations are discussed with attention given to the gene alterations present, including in TP53, NF1, AR, PTEN , and RB1 . Finally, we will compare our findings with those observed in uncommonly reported similar cases so as to detail the molecular underpinnings of such processes which may carry therapeutic implications.