Melanoma — SCE Dermatology MCQ

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ModerateSkin CancerMelanomaSCE Dermatology

A 70-year-old man with melanoma on his leg has a sentinel lymph node biopsy that is positive. Immunohistochemistry of the sentinel node shows melanoma cells positive for S100 protein, Melan-A, and HMB-45. Which of these markers is most sensitive for melanoma?

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Correct answer: E — S100 protein

S100 protein is the correct answer. It is the classic most sensitive immunohistochemical marker for melanoma because it is expressed in the great majority of melanocytic tumours, including variants such as spindle cell/desmoplastic melanoma that may be negative for Melan-A and HMB-45. Its limitation is poor specificity, so it is interpreted with more specific melanocytic markers. Melan-A/MART-1 and HMB-45 are more specific markers of melanocytic differentiation but are less sensitive, especially in desmoplastic/spindle cell melanoma. SOX10 is also a highly useful nuclear melanocytic marker in modern practice, but for this SBA the tested principle is that S100 protein is the most sensitive melanoma marker. CK20 is an epithelial marker classically associated with Merkel cell carcinoma and gastrointestinal/urothelial tumours, not melanoma.

Reference: Moccia A, et al. Immunohistochemistry for Skin Cancers: New Insights into Diagnosis and Treatment of Melanoma. Cancers (Basel). 2025. https://pmc.ncbi.nlm.nih.gov/articles/PMC12153578/