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.