Which statement about S100 staining in melanoma is true?

Which statement about S100 staining in melanoma is true?

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

Answer: (A)

S100 is a highly sensitive marker for melanocytic cells, but it is not specific to melanoma. In practice, melanoma is best supported when S100 positivity is combined with staining for more specific melanocytic markers such as HMB-45 or Melan-A (MART-1). These latter markers reflect melanosome-associated proteins and add diagnostic specificity for melanocytic differentiation. Therefore, S100 positivity alone cannot confirm melanoma, and S100 positivity with concurrent HMB-45 or Melan-A strongly favors melanoma. Conversely, S100 negativity does not reliably exclude melanoma because some melanomas can show weak or absent S100 staining.

S100 is a highly sensitive marker for melanocytic cells, but it is not specific to melanoma. In practice, melanoma is best supported when S100 positivity is combined with staining for more specific melanocytic markers such as HMB-45 or Melan-A (MART-1). These latter markers reflect melanosome-associated proteins and add diagnostic specificity for melanocytic differentiation. Therefore, S100 positivity alone cannot confirm melanoma, and S100 positivity with concurrent HMB-45 or Melan-A strongly favors melanoma. Conversely, S100 negativity does not reliably exclude melanoma because some melanomas can show weak or absent S100 staining.