Answer: Melanoma

Histology: The biopsy shows a tumor with atypical epithelioid cells with abundant eosinophilic cytoplasm and some with prominent cherry red nucleoli. Some of the cells show angulated hyperchromatic nuclei. Binucleate cells are also seen. The tumor shows brisk mitotic activity. The tumor is sheet-like and, in some areas, it appears discohesive. Melanin pigment can be seen in some of the cells. Pagetoid spread of the tumor cells is seen in the overlying epithelium.

Discussion: The large epithelioid cells raise the question of a poorly differentiated urothelial carcinoma. However, the usual nesting pattern seen in urothelial carcinoma is not present. Binucleate cells are also unusual for urothelial carcinoma. A poorly differentiated adenocarcinoma can also show pagetoid spread in the epithelium. A mucin stain can help in the diagnosis of adenocarcinoma. Plasmacytoma would have a discohesive appearance similar to areas in this tumor, but would not show pagetoid spread. An immunohistochemical panel can be helpful in resolving the differential diagnosis. A panel that includes cytokeratin, kappa, lambda, S100, HMB-45 and Melan-A can be used to distinguish the lesions, as melanomas are positive for S100, HMB-45 and Melan-A.

Primary melanoma of the urethra is rare. However, other than carcinoma, melanoma accounts for the greatest number of malignant urethral tumors. Primary melanoma is more common in the female urethra than in the male urethra. The diagnosis of a primary urethral melanoma should be made only after the possibility of a metastasis from another primary site has been excluded.