Answer: D. Hybrid verrucous carcinoma/usual squamous cell carcinoma

Histology: Compared to the thin adjacent normal squamous epithelium, there is a lesion composed of hyperplastic squamous epithelium which has a spiky verruciform surface and broad pushing tongues extending deep into the underlying connective tissue. The verruciform lesion has no cytological atypia. Focally, within the verrucous lesion, there are irregular nests of squamous epithelium with moderate atypia and occasional dyskeratotic cells invading superficially into the underlying tissue.

Discussion: Verrucous carcinoma, despite its name, is not a lesion associated with HPV. Hence it lacks the crinkly viral nuclear atypia and koilocytosis seen in condylomas and warty carcinomas. The diagnosis of verrucous carcinoma cannot be made on superficial biopsies, as the key diagnostic feature is the presence of invasion which typically can only be made on resection specimens. Verrucous carcinomas have broad base bulbous papillae with marked acanthosis, where the papillae extend well beyond the plane of the basal cell layer of adjacent uninvolved squamous epithelium. Cytologically, the tumor is extremely well-differentiated, indistinguishable from normal epithelium. In contrast, the area of usual squamous cell carcinoma has an irregular infiltrative base with jagged edged nests. The cells in the squamous cell carcinoma (SCC) also have a little but more cytologic atypia than verrucous carcinoma. Mixed usual-type SCC/verrucous carcinoma (Hybrid verrucous SCC) is used where typical areas of verrucous carcinoma coexist with foci of an otherwise usual low or high-grade SCC. Generous sampling is advised in verrucous SCC in order to rule out the presence of usual SCC foci. The treatment for verrucous carcinoma is conservative surgical excision. No lymph node metastases have ever been reported in pure verrucous SCC, such that prophylactic inguinal lymphadenectomy is not indicated. There is a higher metastatic and recurrence rates encountered in hybrid verrucous SCC approach that of SCC, usual type. The prognosis of the usual SCC component can be predicted according to penile risk-group stratification systems, taking into account histological grade, anatomical level of maximum tumor infiltration, and the presence of vascular and perineural invasion. Penectomy with adjuvant radiation and chemotherapy is recommended for usual SCC based on depth of invasion, presence of vascular or perineural invasion and grade. In cases where lymph node metastases are clinically suspected, inguinal lymphadenectomy is indicated.