Distinguishing Epithelioid Blue Nevus From Blue Nevus-like Cutaneous Melanoma Metastasis Using Fluorescence In Situ Hybridization

Abstract

Blue nevus (BN)-like cutaneous melanoma metastasis is a well-recognized variant of melanoma metastasis. These lesions may clinically and histologically simulate benign blue nevi. The histologic changes may be indistinguishable from conventional blue nevi or epithelioid blue nevi (EBN), a benign dermal-based melanocytic neoplasm with epithelioid morphology and heavily pigmented cytoplasm. Distinguishing BN-like cutaneous melanoma metastasis from benign conventional or EBN is important for staging and treatment. We evaluated a fluorescence in situ hybridization (FISH) assay using probes targeting 6p25 (RREB1), 6q23 (MYB), 11q13 (CCND1), and centromere 6 (Cep6) with previously determined criteria, to distinguish EBN and BN-like melanoma metastasis. Ten BN-like cutaneous melanoma metastatic lesions and 10 EBN were blindly evaluated with the above mentioned FISH probes. FISH enumeration and criteria for diagnosis of melanoma was as previously described. Nine of 10 BN-like cutaneous metastatic lesions showed significant aberrations and met previously established criteria for melanoma. None of the EBN cases showed evidence of significant copy number changes or met FISH criteria for a diagnosis of melanoma. FISH is an important diagnostic adjunct for melanocytic neoplasms. In this study, we show that a FISH assay targeting 6p25, 6q23, 11q13, and centromere 6 can distinguish EBN from BN-like metastatic melanoma with high accuracy. The test and the parameters previously established can perform with high sensitivity and specificity when dealing with this differential diagnosis.