Which stains would be positive for this lesion?

• A. CK7 and CK20
• B. P63 and CK5/6
• C. Uroplakins II & III, CK20
• D. Uroplakins I & II, CK7

Answer: (C)

Immunohistochemical profiling for urothelial differentiation is being tested here. Uroplakins are urothelium-specific proteins, with II and III being highly characteristic of urothelial cells, especially when found together with CK20. If the lesion stains positive for uroplakins II & III and CK20, it strongly indicates a urothelial origin, such as urothelial carcinoma. This pattern is more definitive than patterns like CK7/CK20 alone, which can occur in many tumors, or P63 with CK5/6, which points toward basal or squamous differentiation rather than urothelial lineage. Uroplakins I & II with CK7 would be less specific than including II & III, so the combination of uroplakins II & III and CK20 is the best fit.