Histological images of precancerous lesions and penile cancer in situ.

The majority of malignant tumours of penis are squamous cell carcinomas (SCC) and they chiefly occur in the squamous epithelium of the glans, coronal sulcus and foreskin. SCC develops via human papillomavirus (HPV) – associated precursor lesions (penile intraepithelial neoplasia; PIN) that are graded I-III depending on the epithelial thickness occupied by transformed basaloid cells. These cells vary in size and shape, with the nuclei being pleomorphic, hyperchromatic; they lose polarity. In grade I, PIN occupies the lower one third, in grade II the lower two thirds, and in grade III full epithelial thickness. PIN III is in other words called Bowen’s atypia or in situ SCC. HPV is present in a subset of penile SCC, with HPV 16 being the most frequent type. HPV DNA is preferentially found in cancers with either basaloid and/or varrucous character, and is rarely correlated with typical keratinizing SCC. Penile intraepithelial neoplasia is consistently HPV DNA positive in 70-100% of cases. The HPV negative invasive cancers do not arise from the HPV positive PIN, but from unrecognized HPV-negative precursor lesions.