Penile warty mucoepidermoid carcinoma with features of stratified mucin-producing intra-epithelial lesion and invasive stratified mucin-producing carcinoma.

Aims: Stratified mucin-producing intra-epithelial lesion (SMILE) and invasive stratified mucin-producing carcinoma (ISMC) are recently described cervical and penile lesions. We report an unusual case of mixed variant of penile squamous cell carcinomas with warty, usual and mucoepidermoid SMILE/ISMC features.

Methods And Results: A 62-year-old Japanese man had a glans penis lesion of one-and-a-half years' duration, suggesting malignancy. Partial penectomy and left inguinal lymphadenectomy were performed. Pathological evaluation revealed a mixed squamous cell carcinoma with warty, mucinous and usual features. The mucinous component resembled mucoepidermoid carcinoma (MEC) and SMILE/ISMC. Glandular differentiation was absent. All the diverse tumour components were negative for p16, which was confirmed by negative human papillomavirus (HPV) genotyping. The mucinous component was diffusely positive for cytokeratin 7 and largely negative for cytokeratin 5 and p63. Fluorescence in-situ hybridisation did not detect rearrangement in the MAML2 or EWSR1 genes. The tumour was pathological stage pT2, pN1 (AJCC prognostic stage group IIIA) and was disease-free 26 months after surgery.

Conclusions: The lack of glands in the mucinous areas suggested that MEC should be separated from adenosquamous carcinoma (ASC). Penile SMILE/ISMC may occur without dependence upon HPV status. Further studies will be necessary to determine the pathogenesis and definition of penile SMILE/ISMC, the presence of true MEC arising from the glans penis and the clinicopathological differences of penile ASC, MEC and SMILE/ISMC. Herein, we refer to the SMILE-like penile lesion as 'mucinous penile intra-epithelial neoplasia'.