PSMA-negative Widespread Metastases Identified by 18F-FDG PET/CT in Treatment-related Neuroendocrine Prostate Cancer With Squamous Differentiation

A 62-year-old man had prostate cancer treated for 5 years with prostatectomy, radiation, and hormonal therapy. He presented with worsening back pain for 3 months. Serum prostate-specific antigen was very low (<1.0 ng/mL), while neuron-specific enolase was elevated (23.35 ng/mL), raising suspicion of neuroendocrine differentiation. Dual-tracer PET/CT was performed. 68 Ga-PSMA PET/CT showed no recurrence or metastasis, while 18 F-FDG PET/CT revealed widespread hypermetabolic bone lesions and retrocrural nodal disease. Biopsy confirmed treatment-related neuroendocrine prostate cancer with squamous differentiation. This rare phenotype exhibited typical PSMA-negativity and intense FDG uptake. It emphasizes the diagnostic potential of 18 F-FDG PET/CT in dedifferentiated prostate cancers.