Supplementary Material for: Metastatic Prostatic Adenocarcinoma to the Penis with Diffuse P16 Expression: Recognizing a Diagnostic Pitfall

Introduction: Prostate cancer (PCa) is the most common malignant tumor in men, with acinar adenocarcinoma as the predominant subtype. While PCa metastases typically affect bones, penile metastases are exceedingly rare. Penile tumors are generally squamous cell carcinoma (SCC), with p16 overexpression often used as a surrogate marker for oncogenic human papillomavirus (HPV) infection.
Case Presentation: We report the case of an 85-year-old male with a history of PCa (grade group 5) treated with irradiation and hormonal therapy, who presented with a progressive penile lesion initially misdiagnosed as HPV-associated SCC. Immunohistochemistry revealed diffuse panCK, p16, NKX3.1, AR, and ERG positivity, with Rb1 protein loss confirming metastatic PCa. PSA levels remained within the normal range, complicating the diagnosis.
Conclusion: This case emphasizes the importance of thorough clinico-pathological correlation in unusual metastatic presentations and highlights that p16 overexpression, even in penile tumors, may indicate Rb1 inactivation rather than HPV-related SCC.