Background: The incidence rate of prostate adenocarcinoma in the United States was 112 per 100,000 in 2019. Men aged 65 to 74 years had a higher incidence rate (638 per 100,000), and 70% of the cases were detected locally (confined to the primary site) per the United States Cancer Statistics. While rare, prostate adenocarcinoma metastasis to the penis has variable presentation and potentially atypical histology that may require immunohistochemical, biomarker, and genetic analysis for confident diagnosis. Case Description: We present a 56-year-old patient with advanced prostate cancer post-chemoradiation and androgen deprivation therapy with an uncommon site of metastasis to the penis. The clinical presentation and progression of the disease led to surgical removal and frozen section analysis. Initial pathologic assessment proved equivocal in the distinction between metastatic prostatic carcinoma versus primary penile squamous cell carcinoma. Diagnostic difficulty due to ambiguous histomorphological features was attributed to the loss of intrinsic prostatic protein markers in metastatic post-treatment cases. Immunohistochemistry and detailed biomarker analysis eventually aided diagnosis. Conclusions: This report illustrates some of the gross and microscopic histological ambiguity that can obfuscate immediate diagnostic certainty of origin of rapidly growing cutaneous penile lesion in the context of existing prostate cancer, while elaborating on immunohistochemical and genetic markers that can increase otherwise elusive diagnostic certainty. Early patient education and intervention represent sites of potential improvement in management of similar cases.
Narasimhan et al. (2026) studied this question.