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PRAME-negativity in sclerosing nevi with pseudomelanomatous features supports classification as an indolent lesion
Haiming Tang1, Jennifer M McNiff1,2, Earl J Glusac1,2
1Department of Pathology, Yale School of Medicine, New Haven, Connecticut, USA.
Background:
Some dysplastic nevi, termed sclerosing nevi with pseudomelanomatous features, may have florid fibroplasia associated with features that cause melanoma to be a prominent consideration in the differential diagnosis. PRAME (PReferentially expressed Antigen in MElanoma) immunohistochemistry (IHC) has been shown to be a useful marker in the distinction of melanoma and nevus. PRAME expression in such sclerosing nevi with pseudomelanomatous features has not been evaluated to our knowledge.
Methods:
Thirty-two sclerosing nevi with pseudomelanomatous features were stained with PRAME IHC, with positive labeling defined as staining of >75% of the cytomorphologically atypical lesional cells.
Results:
All 32 cases had variable cytologic atypia, bridging of elongated rete, fibroplasia, and a vertically oriented trizonal appearance. Some cases (23/32) had centrally located flattening of the rete ridge pattern bilaterally flanked by fibroplasia associated with elongated rete. PRAME labeling was negative (<1% labeling) in 28/32 cases. Four cases, also interpreted as having negative labeling with PRAME, showed only weak nuclear positivity of <50% of the melanocytes within the pseudomelanomatous foci. p16 staining was positive in 28/28 lesions.
Conclusions:
Rare sclerosing nevi with pseudomelanomatous features (4/32; ~13%) had weak PRAME labeling of 25%-50% of atypical foci. Twenty-eight of 32 lesions had virtually no labeling with PRAME. PRAME results support classifying sclerosing nevi with pseudomelanomatous features as indolent lesions.
Insights
PRAME immunohistochemistry (IHC) rarely labels sclerosing nevi with pseudomelanomatous features, suggesting these lesions are indolent. This study evaluated PRAME expression in 32 such nevi.
Area of Science:
- Dermatopathology
- Immunohistochemistry
- Melanoma Diagnosis
Background:
- Sclerosing nevi with pseudomelanomatous features can mimic melanoma.
- PRAME immunohistochemistry (IHC) aids melanoma vs. nevus differentiation.
- PRAME expression in these specific nevi was previously unevaluated.
Purpose of the Study:
- To assess PRAME IHC expression in sclerosing nevi with pseudomelanomatous features.
- To determine if PRAME can help differentiate these nevi from melanoma.
Main Methods:
- 32 sclerosing nevi with pseudomelanomatous features were analyzed.
- PRAME IHC staining was performed, with positivity defined as >75% cell labeling.
- p16 staining was also assessed.
Main Results:
- 28 out of 32 cases (87.5%) showed negative PRAME labeling (<1%).
- Four cases (12.5%) exhibited weak PRAME positivity (<50% of cells).
- p16 staining was positive in all evaluated lesions.
Conclusions:
- Most sclerosing nevi with pseudomelanomatous features lack significant PRAME expression.
- Weak PRAME labeling was observed in a minority of cases (~13%).
- Findings support classifying these nevi as indolent lesions.

