Androgen receptor‐neuroendocrine double‐negative tumor with squamous differentiation arising from treatment‐refractory metastatic castration‐resistant prostate cancer

INTRODUCTION: Treatment‐refractory metastatic castration‐resistant prostate cancer is a heterogeneous disease classified into androgen receptor‐high prostate cancer, androgen receptor‐low prostate cancer, amphicrine prostate cancer co‐expressing androgen receptor and neuroendocrine genes, double‐negative prostate cancer lacking androgen receptor and neuroendocrine gene expression, and small cell or neuroendocrine prostate cancer without androgen receptor activity. Double‐negative tumors can convert to the squamous phenotype. CASE PRESENTATION: A 62‐year‐old man was newly diagnosed with prostate cancer (serum prostate‐specific antigen 2613 ng/mL, Gleason score 4 + 5 = 9, cT3aN1M1b) that progressed to castration resistance 4 months after starting abiraterone with androgen deprivation therapy. After enzalutamide and docetaxel failed, a right ilium metastasis newly emerged. Needle biopsy confirmed a metastatic tumor with squamous differentiation that was CK5/6‐positive and chromogranin A‐, synaptophysin‐, and androgen receptor‐negative. CONCLUSION: We encountered a case of double‐negative prostate cancer with squamous differentiation identified by needle biopsy of a right ilium metastasis after abiraterone, enzalutamide, and docetaxel failure.