Pigmented Nodule on the Sole With Ambiguous Immunohistochemistry
A 62-year-old man has a 1.4 cm asymmetric, irregularly pigmented nodule on the plantar arch present for 8 months; he reports recent enlargement and bleeding. Shave biopsy shows a dermal proliferation of epithelioid cells with melanin, 6 mitoses/mm2, and no clear maturation. Immunohistochemistry: S100 positive, SOX10 positive, Melan-A patchy, HMB-45 negative, PRAME diffusely positive in the dermal component. Ki-67 labels ~25%. The lesion is 1.1 mm from the deep margin and the base is transected. The clinician asks whether this is a benign nevus or melanoma and whether re-excision is needed.
1. How should the immunohistochemical profile and margin status be integrated into the diagnosis and next step?
Read the worked answer
The profile is not benign-nevus-like: diffuse PRAME in the dermal component, loss of HMB-45 with retained SOX10, high Ki-67, and epithelioid morphology with mitoses favor melanoma. PRAME is a useful adjunct but not standalone; combine with morphology and proliferation. Because the base is transected, Breslow thickness cannot be measured and the diagnosis of a clearly benign process cannot be made. The appropriate action is to recommend complete excision/re-excision for definitive measurement and staging rather than signing out as a nevus. Document that margin assessment is limited by transection and state the suspicion of melanoma so the surgeon plans adequate margins.
2. What additional studies or stains would you consider, and what are their limits?
Read the worked answer
Consider a melanocytic cocktail (SOX10/Melan-A), p16 (loss in some melanomas but also nevi), and BAP1 if concerned about a BAP1-inactivated tumor. FISH or RNA-based expression profiling can support malignancy in ambiguous melanocytic tumors but has imperfect sensitivity/specificity and should not replace morphologic judgment. In this case the combination of diffuse PRAME, high Ki-67, and epithelioid dermal cells already supports melanoma; ancillary testing should be used to resolve genuine ambiguity, not to override a transected base. The key limitation is that no stain reliably distinguishes all nevi from melanoma, and the transected base must be addressed surgically.
3. If the re-excision shows residual melanoma with a Breslow thickness of 1.8 mm and no ulceration, what staging and margin considerations follow?
Read the worked answer
Breslow 1.8 mm without ulceration is pT2a. For T2 melanoma, wide local excision with 1-2 cm margins is generally recommended, and sentinel lymph node biopsy should be discussed (typically offered for tumors >1.0 mm or thinner with adverse features). The pathology report should include Breslow thickness, ulceration, mitotic rate (for thin melanomas), and margins. The initial shave's transected base explains why the first specimen could not be staged; the re-excision provides the definitive thickness and margin status.