Answer: Papillary squamous cell carcinoma

Histology: In areas the tumor shows a papillomatous process with well-established fibrovascular cores surrounded by squamous epithelium. The squamous epithelium lining the fibrovascular cores shows mild to moderate atypia. At the base of the lesion there are foci of irregular nests of squamous epithelium extending into the underlying connective tissue. These nests show moderate to severe cytologic atypia with large nuclei, prominent nucleoli, and occasional mitotic figures. The nests have abundant eosinophilic cytoplasm at their advancing fronts and are associated with prominent acute inflammation.

Discussion: There is a broad differential diagnosis for papillomatous squamous lesions involving the penis. Verrucous carcinomas differ from papillary squamous cell carcinoma, in that verrucous carcinomas show no cytologic atypia. Verrucous carcinomas at their invasive front are characterized by broad, bulbous squamous projections into the underlying connective tissue rather than irregular, ragged, small nests of squamous epithelium as seen in the current case. In addition, the superficial component of a verrucous carcinoma shows a spiky papillomatous proliferation in contrast to the rounded papillary fronds seen in papillary squamous cell carcinoma, analogous to what is seen in squamous papilloma of the larynx. Usual squamous cell carcinoma shows as its surface component either flat in situ squamous cell carcinoma or ulceration where there may not be an in situ component identified. Warty carcinomas have long papillae with central fibrovascular cores not seen in the current case. More distinctively, in addition to prominent hyperkeratosis and parakeratosis, warty carcinomas have obvious nuclear pleomorphism with prominent koilocytosis.

Despite its name, verrucous carcinoma is not specifically associated with HPV. Similarly, papillary squamous cell carcinoma along with usual squamous cell carcinoma are not strongly HPV related. The two forms of squamous cell carcinoma of the penis that are strongly related to HPV are warty carcinoma and basaloid squamous cell carcinoma. Whereas basaloid squamous cell carcinoma is associated with a worse prognosis than usual squamous cell carcinoma, papillary squamous cell carcinoma and warty carcinoma tend to have a better prognosis than usual squamous cell carcinoma. However, it is important to distinguish papillary and warty carcinoma from verrucous carcinoma in that the latter is not associated with lymph node metastases whereas both papillary squamous cell carcinoma and warty carcinoma may metastasize.