Case report: Hybrid verrucous carcinoma of the penis

58-year-old male with an exo-endophytic tumor mass located in distal penis and involving glans and coronal sulcus.

Microphotographs show two distinctive areas, one corresponding to a verrucous carcinoma (left field) and the other to a usual squamous cell carcinoma (SCC). The verrucous component is characterized by acanthosis, hyperkeratosis, and a broad-based interface between tumor and stroma. Tumor cells are well-differentiated and cytological atypia is minimal, with a prominent stromal reaction. The second component is a usual SCC showing solid tumor nests composed of polygonal cells with wide eosinophilic cytoplasm. Histological grade ranges from 2 (moderately differentiated) to 3 (poorly differentiated). Grade 2 areas are characterized by evident nuclear atypias and retained squamous maturation with keratin pearls. In grade 3 areas nuclear atypias are evident, with pleomorphism, prominent nucleoli, and irregular nuclear membrane.

Mixed penile SCCs are defined as tumors exhibiting two (or rarely three) morphologically distinctive intermingled components. Mixed penile carcinomas represent about one-quarter of all penile primary SCC. The most frequent combination (observed in about one-half of all mixed tumors) is a verrucous carcinoma mingled with an otherwise usual (typical, classical, keratinizing) SCC, the so-called hybrid verrucous carcinoma. The second most frequent combination is a basaloid carcinoma with a warty SCC, observed in about one-third to two-fifths of all mixed cases. Other variants, such as usual-basaloid, usual-warty, usual-papillary, and many more, are rare.

In hybrid verrucous carcinoma the verrucous component depicts an exophytic growth pattern while the usual SCC component typically extends deeper into the penile erectile tissues, underneath this verruciform pattern. Areas of “dedifferentiation” are common but not always present as some hybrid penile carcinomas may be composed of verrucous carcinoma associated with a well-differentiated usual SCC.

The diagnosis is made on morphological grounds and each component should be diagnosed using stringent criteria. The most distinguishing feature is the presence of a broad-based, well-defined tumor-stroma interface in verrucous carcinoma. Regular finger-like projections not exceeding 2 mm in maximum diameter may be present and do not change the diagnosis. However, the presence of irregular, angulated tumor nests, and nuclear atypias beyond the minimal allowed for a verrucous carcinoma should alert about the possibility of a hybrid verrucous carcinoma.

The distinction between a verrucous carcinoma and hybrid verrucous carcinoma is clinically relevant. Pure verrucous SCC are not associated with inguinal nodal metastases and the prognosis is excellent. In hybrid verrucous carcinomas regional involvement may be observed in up to one-quarter of all patients, warranting a more closed follow-up in cN0 individuals, with proper evaluation of any clinically palpable inguinal lymph node.