Specific dermoscopy patterns and amplifications of the cyclin D1 gene to define histopathologically unrecognizable early lesions of acral melanoma in situ

Abstract

Objective: To define early lesions of acral melanoma in situ that cannot be recognized histopathologically.

Design: A retrospective review of the clinical, dermoscopic, and histopathological findings.

Setting: University department of dermatology.

Patients: Thirty-three patients with melanocytic lesions on acral volar skin that were clinically suspected of being early melanomas.

Main outcome measures: Fluorescent in situ hybridization studies to detect the cyclin D1 gene amplification in proliferating melanocytes, which is a characteristic genetic aberration recently found in acral melanoma.

Results: Seventeen of 33 lesions were histopathologically diagnosed as either melanoma in situ (8 lesions) or benign melanocytic nevi (9 lesions). Amplification of the cyclin D1 gene was observed in 2 (25%) of the 8 melanomas in situ. None of the 9 nevi showed the amplification. The remaining 16 lesions were, however, difficult to classify histopathologically because most of them showed only a slight increase of nonatypical melanocytes in the basal cell layer of the epidermis. On dermoscopic examination, 9 of these 16 lesions exhibited the parallel ridge pattern that has been reported to be highly specific to melanoma in situ, and 4 (44%) of them had amplifications of the cyclin D1 gene. Amplifications were not found in any of the remaining 7 lesions that showed dermoscopic patterns suggestive of melanocytic nevi.

Conclusions: Cyclin D1 gene amplification detected by fluorescent in situ hybridization identified a very early progression phase of acral melanoma that precedes histopathologically defined melanoma in situ. The present study also indicates the specificity of the parallel ridge pattern on dermoscopy to detect melanomas on acral volar skin at such a very early developmental phase.