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PRAME Expression in Challenging Dermal Melanocytic Neoplasms and Soft Tissue Tumors With Melanocytic Differentiation

Abstract: Preferentially expressed antigen in melanoma (PRAME) is an immunohistochemical biomarker that is diffusely expressed in most cutaneous melanomas and is negative in most benign nevi. Histologically challenging dermal melanocytic neoplasms, such as cellular blue nevi (CBN) and deep penetrating nevi (DPN), and soft tissue tumors with melanocytic differentiation, such as clear cell sarcoma and perivascular epithelioid cell tumor, may resemble primary or metastatic melanoma. PRAME immunohistochemistry (IHC) was applied to archived formalin-fixed, paraffin-embedded specimens of various dermal melanocytic neoplasms and soft tissue neoplasms with melanocytic differentiation. Staining was graded based on the percentage of melanocytes labeled (0–4+ as previously reported). The gold standard was final pathologic diagnosis using histologic, immunophenotypic, and in some cases molecular findings. Fifty-four cases were evaluated. 62.5% (5/8) of blue nevus-like melanomas and 50% (1/2) of DPN-like melanomas were PRAME positive (4+). Of the other tumors, 100% (20/20) of CBN (including 1 atypical CBN with borderline features); 100% (12/12) of DPN, combined DPN, or borderline DPN; 88.9% (8/9) of perivascular epithelioid cell tumors; and 100% (3/3) of clear cell sarcoma were PRAME negative (0–2+). Within the borderline categories specifically, all 8 tumors (1 borderline CBN and 7 borderline DPN) showed low (0–2+) PRAME expression. Overall, the sensitivity for melanoma in this context was 60%, with a specificity of 97.7%. Although our sample size is limited, the results suggest that IHC staining for PRAME may be useful in supporting a diagnosis of melanoma in the setting of challenging dermal melanocytic neoplasms and other epithelioid neoplasms with melanocytic differentiation. However, PRAME IHC lacks sensitivity in this context.