Background: Penile squamous cell carcinoma (SCC) primarily develops through two distinct etiopathogenic routes: human papillomavirus (HPV)-mediated and non-viral, chronic inflammation-driven pathways. In low-resource settings, long-standing phimosis and recurrent balanoposthitis present significant public health challenges that accelerate tissue transformation. Case Presentation: We report a case of an uncircumcised 75-year-old African man presenting to a tertiary facility in Southwestern Uganda with a 2-year history of a progressive, painful, exophytic penile mass associated with chronic balanoposthitis and a 7-year history of Type 2 Diabetes Mellitus. Clinical examination revealed a 4.0 cm × 5.0 cm ulcerated, necrotic tumor involving the glans penis and distal shaft, along with bilateral 1.5 cm palpable inguinal lymph nodes. Due to resource constraints at our center, molecular screening (p16 immunohistochemistry and HPV DNA PCR) and staging node biopsies were unavailable. Histopathological examination of the partial penectomy specimen confirmed a well-differentiated, keratinizing squamous cell carcinoma (pT2 cN0 M0). The patient experienced an uneventful postoperative recovery and was transitioned to a structured clinical surveillance program. Discussion: This case highlights the role of chronic balanoposthitis, diabetes mellitus, and poor foreskin ventilation in promoting a sustained inflammatory microenvironment that may predispose to malignant transformation of penile epithelium. It underscores the diagnostic challenge posed by inflammatory penile lesions that mimic benign disease and the consequences of delayed medical evaluation. Conclusion: This case provides a descriptive illustration of penile carcinoma emerging in a background of chronic inflammation, highlighting the clinical realities of managing advanced disease in a resource-limited environment. It underscores the critical need for localized screening, early surgical intervention for phimosis, and improved access to molecular diagnostics in sub-Saharan Africa. Keywords: penile squamous cell carcinoma, chronic balanoposthitis, penile cancer, diabetes mellitus, chronic inflammation
Chris-Uchendu et al. (Mon,) studied this question.