Which marker pattern supports melanoma over a benign nevus?

• A. S100 negativity rules out melanoma.
• B. S100 positivity with concomitant positivity for HMB-45 or Melan-A supports melanoma; S100 alone is not specific.
• C. S100 positivity alone
• D. Melan-A negativity excludes melanoma.

Answer: (D)

Immunohistochemical profiling relies on combining a highly sensitive marker with more specific melanocytic markers. S100 is excellent at identifying melanocytic cells, but it’s not specific and can be positive in benign nevi as well. To distinguish melanoma from a benign nevus, you look for S100 positivity plus concomitant positivity for a more specific marker such as HMB-45 or Melan-A. When both S100 and one of these specific markers are positive, it supports melanoma more strongly than S100 positivity alone, which by itself cannot reliably discriminate between nevus and melanoma. Melan-A negativity does not exclude melanoma, since some melanomas may lack Melan-A expression.