Malignant Melanoma of the Nail Apparatus: A Fluorescence In Situ Hybridization Analysis of 7 Cases

Background. Malignant melanoma of the nail apparatus is exceedingly rare. Increasingly, genetic studies have been employed to aid in distinguishing between malignant melanoma and benign melanocytic nevi. Methods. Archived nail apparatus melanomas were analyzed by fluorescence in situ hybridization (FISH) using probes targeting the genes at 6p25 (RREB1), 11q13 (CCND1), 8q24.1 (MYC), 6q23 (MYB), 9p21 (CDKN2A) and the centromeres of chromosomes 8 (D8Z2) and 6 (D6Z1). The results were correlated with clinical and demographic information. Results. Mean patient age was 57.8 years (range 23-92 years). In all, 5 of 7 (71%) cases involved the upper extremity digits. RREB1 gain was seen in all cases. CCND1 gain was seen in 6 of 7 (86%) cases, 3 of which were amplified. MYB loss and MYC gain were both seen in 5 of 7 (71%) cases. Homozygous loss of CDKN2A was not observed in any case. Two of 7 (28.6%) patients had lymph node metastasis and died of widely metastatic disease. These 2 patients harbored the most genetic aberrations: gains of RREB1, CCND1, and MYC, and MYB loss. Both benign melanocytic nevi controls showed normal FISH results. Conclusions. RREB1 and CCND1 gains are common in nail apparatus melanoma as in most melanomas, and an increased number of genetic aberrations may be associated with a poorer prognosis, though the limited number of cases precludes definitive correlation. FISH appears to be a useful adjunct in the diagnosis of nail apparatus melanomas and improves diagnostic confidence even in the setting of unambiguous histomorphology.