Answer: Mixed (hybrid) usual-verrucous carcinoma

Histology: The slides 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 extremely well-differentiated and cytological atypia is minimal. There is also a prominent stromal reaction. The second component is a usual SCC showing solid tumor nests composed of polygonal cells with ample, eosinophilic cytoplasm. Histological grade range from 2 (moderately differentiated) to 3 (poorly differentiated). Grade 2 areas are characterized by evident nuclear atypias and retained squamous maturation with keratin pearls formation. In grade 3 areas nuclear atypias are overt with pleomorphism, prominent nucleoli, and irregular nuclear membrane.

Discussion: 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 that of a verrucous carcinoma mingled with an otherwise usual (typical, classical, keratinizing) SCC. 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 usual SCC-verrucous carcinoma the verrucous component depicts an exophytic growth pattern and 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. Distinction 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 ones permitted for a verrucous carcinoma should alert about the possibility of a mixed SCC. The distinction between a verrucous carcinoma and hybrid usual-verrucous carcinoma is of clinical importance since pure verrucous SCC are not associated with inguinal nodal metastases and the prognosis is excellent while in the latter regional involvement may be observed in up to one-quarter of all patients, warranting a more closed follow-up in cN0 individuals and proper evaluation of any clinically palpable inguinal lymph node.