Answer: Sarcomatoid carcinoma

Histology: The slides show a high-grade malignant tumor composed of spindle and pleomorphic cells, with extensive areas simulating pseudovascular spaces; however, true malignant endothelial cells are not seen. These pseudovascular spaces are intermingled with other areas showing myxoid, lower grade histology. Mitotic figures, some atypical, are commonly found. No evidence of squamous differentiation is observed.

Discussion: Sarcomatoid carcinoma represents 1-3% of all penile SCC and it is composed of pleomorphic spindle-shaped neoplastic cells resembling those of leiomyosarcoma or fibrosarcoma; however, in some circumstances, as in the present case, areas with pseudovascular or myxoid features may be observed or even predominate. Grossly, most sarcomatoid carcinomas are polypoid and exhibit a vertical pattern of growth with extensive areas of necrosis and hemorrhage. Histologically, the predominant neoplastic population depicts spindle cell morphology; nuclear atypia is overt and mitoses are abundant and often atypical. Evidence of squamous differentiation, with neoplastic nests of an otherwise usual SCC, is found in the majority of cases although it can be very inconspicuous. Conversely, caution should be taken to identify sarcomatoid areas in an otherwise usual SCC; the presence of sarcomatoid differentiation, even if focal, suggests an aggressive biological behavior and should be enough to classify a tumor as a sarcomatoid carcinoma. The main differential diagnosis is with true penile sarcomas. However, penile sarcomas usually originate in the penile shaft, manifesting as a tumor mass or with priapism or Peyronie-like signs and symptoms, while sarcomatoid carcinomas preferentially affects glans. Immunohistochemical stains are helpful in problematic cases and are usually indicated to confirm diagnosis; neoplastic cells are positive for p63 and 34-beta-E12 and negative for muscle-specific actin, smooth muscle actin, desmin and S-100. High-grade usual SCC can grossly simulate a basaloid or a sarcomatoid carcinoma. Histologically, it is composed anaplastic cells with nuclear pleomorphism, irregular nuclear membrane, coarse chromatin, prominent nucleolus, and abundant and atypical mitoses; cytoplasm ranges from scant to ample but usually retains squamous features with an eosinophilic hue, distinctive boundaries and intercellular bridges. The vast majority of high-grade usual SCC also harbors areas of low-grade, mainly grade 2 but also grade 1 in some occasions; this heterogeneity is a typical feature of usual SCC in general. Finally, the angiosarcomatoid variant of penile sarcomatoid carcinoma can simulate the pseudoglands observed in pseudoglandular (acantholytic) carcinoma; however, in the latter solid nests, some with extensive central acantholysis, are observed, filled with keratin debris, desquamated cells, and neutrophils. Intracytoplasmic vacuoles are a constant features in pseudoglandular carcinomas and are absent in sarcomatoid SCC. In addition, spindle cells are not found in the former while they are almost invariably present in the latter.