Abstract:

Preferentially expressed Antigen in MElanoma (PRAME) is a cancer testis antigen (CTA) that is expressed in melanoma. Diffuse PRAME expression has previously been reported in the majority of primary and metastatic melanomas, whereas melanocytic nevi have demonstrated low PRAME expression levels. The purpose of this study is to elucidate expression levels of PRAME in previously diagnosed lesions that resemble melanoma, including cellular blue nevi (CBN), deep penetrating nevi (DPN), combined DPN, DPN-like borderline tumors not fully diagnostic of melanoma, benign and malignant perivascular epithelioid cell tumors (“PEComas”) from a range of anatomic sites, and clear cell sarcomas (CCS), in comparison to blue nevus-like melanomas (BNLM) and DPN-like melanomas (DPNLM). In this retrospective analysis, PRAME immunohistochemistry (IHC) was applied to archived formalin-fixed, paraffin-embedded specimens. Staining was graded based on percentage of melanocytes labeled (0-4+ as previously reported). The gold standard was final pathologic diagnosis using a combination of histologic, other immunophenotypic, and in some cases molecular diagnostic findings. Fifty-four (54) cases were reviewed. Of the ten (10) melanomas, 62.5% (5/8) of BNLM and 50% (1/2) of DPNLM were PRAME positive (4+). Of the other tumors, 100% (20/20) of CBN, 100% (12/12) of DPN, combined DPN, or DPN-like borderline tumors, 88.9% (8/9) of PEComas, and 100% (3/3) of CCS were PRAME negative (0-2+). Overall, the sensitivity for melanoma in this context was 60%, with a specificity of 97.7%. Although the sample size is limited, our results suggest that IHC staining for PRAME expression may be useful in supporting a diagnosis of melanoma in the setting of challenging predominantly intradermal melanocytic neoplasms and other epithelioid neoplasms with melanocytic differentiation. However, PRAME IHC lacks sensitivity in this context.

Financial Disclosure: No current or relevant financial relationships exist.

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Scott Bresler, MD, PhD