Penile malignancies are uncommon, with the majority being squamous cell carcinoma (SCC). Penile SCC are classified as human papillomavirus- (HPV) associated and HPV-independent. Lymphoepithelioma-like carcinoma (LELC) is one of the rarest HPV-associated subtypes, and resembles lymphoepithelial carcinoma of the nasopharynx. There are only three cases reported in the literature.

A 78-year-old male was found to have an incidental 3cm lesion on the dorsal inner foreskin which involved the glans penis. Punch biopsy demonstrated high grade penile intraepithelial neoplasia (PIN), warty type. Tumour cells expressed p16. He underwent partial glansectomy and circumcision, which demonstrated a 35x17mm lesion on the glans involving the foreskin, but not invading the corpora cavernosum or urethra. Microscopic examination showed poorly differentiated HPV-associated SCC with multiple irregular nests and broad trabeculae of epithelial cells, and features of LELC such as surrounding prominent lymphoplasmacytic infiltrate that obscured cell borders. The lesion was <0.1mm from the deep margin, and demonstrated perineural invasion (TNM stage pT1b). Tumour cells again expressed p16, as well as p40. Staging computed tomography (CT) showed no evidence of metastatic disease. After multidisciplinary consensus, he underwent completion glansectomy, partial penectomy and bilateral sentinel lymph node biopsy three months later. A circumferential subcoronal incision was made with a 1cm margin and a minimal partial penectomy was performed by resecting the corporal tips. Microscopic examination showed a 2mm thick moderately differentiated SCC with irregular nests of pleomorphic squamous cells, but no features of LELC. Surgical margins were clear. No inguinal lymph nodes had metastatic disease.

The patient is now 20 months post-initial biopsy and has no evidence of local recurrence or metastatic disease during his three-monthly physical examination and CT chest/abdomen/pelvis. He is voiding well and has returned to pre-morbid function. To our knowledge, this is only the fourth reported case of penile LELC in the literature. Previous cases were in a 50, 58 and 75 year-old, all of whom were also uncircumcised. One patient was alive and well after three months follow up, and two died of unrelated causes three and 17 years after diagnosis. Histopathology similarly demonstrated p16 expression and was negative for Epstein–Barr virus (EBV). This lack of EBV expression reflects the difference between penile LELC and those arising from the nasopharynx. Lymphoepithelioma-like pattern has also been reported in two cases of penile medullary carcinoma; however, it is unclear if medullary and LELC are distinct entities.

LELC is an extremely rare subtype of penile SCC. It appears to be definitively HPV-associated and expresses p16 but not EBV. Further cases are required to better understand its clinical, pathological and prognostic features, as well as relationships with similar variants.