Abstract

Nevoid melanoma is a variant of melanoma characterized by a deceptively benign histopathologic appearance. The diagnosis of nevoid melanoma is challenging: at scanning magnification, these lesions can be highly similar to melanocytic nevi. Detection of copy number variations (CNVs) at certain loci can help distinguish nevi from nevoid melanomas. Droplet digital PCR is an emerging technology for CNV detection in tumor cells. We performed ddPCR on 25 primary melanomas (7 nodular, 6 superficial spreading, 6 nevoid, 3 acral, and 3 lentigo maligna) for absolute quantitation of DNA copy number in RREB1 and MYB, two diagnostically important genes in melanoma. All diagnoses had been confirmed by a board-certified dermatopathologist prior to ddPCR analysis. The average ddPCR-determined RREB1 copy number for nevoid melanomas (2.69) was higher than that of all other melanoma subtypes: lentigo maligna (2.08; p < 0.05), superficial spreading (2.29; p < 0.10), nodular (2.39; not significant), and acral (2.49; not significant). The average ddPCR-determined MYB copy number for nevoid melanomas (1.26) was lower than that of both superficial spreading (1.62; p < 0.10) and nodular (1.77; p < 0.05) melanomas. Due to limited tissue, ddPCR for MYB copy number quantitation was not performed on the acral or lentigo maligna melanomas. Collectively, our results suggest that nevoid melanomas may acquire more chromosomal alterations than other melanoma subtypes. With further validation, ddPCR may prove useful in the notoriously difficult diagnosis of nevoid melanoma, and in this distinction particularly.