36. Clinical utility of copy number alteration analysis in the evaluation of Melanocytic Lesions for diagnosis and prognosis

Abstract

Melanocytic lesions range from benign to highly aggressive malignancies. Although the diagnosis is often straightforward histologically, ambiguous cases provide a dilemma with critical clinical implications. Copy number alteration (CNA) analysis, from formalin-fixed paraffin-embedded tissue, has emerged over the last two decades as a valuable tool for diagnosis of histologically challenging melanocytic lesions. Numerous studies, with various microarray platforms, demonstrate that the number of CNAs in malignant melanomas is higher than in benign melanocytic nevi with proposed cutoffs for adequate sensitivity and specificity. Targeted fluorescence in situ hybridization panels, utilizing probes to detect the CNAs most commonly seen in melanoma, are sufficient for diagnostic purposes. Furthermore, studies determined that CNAs have prognostic significance. Both the number of CNAs and detection of specific CNAs are helpful for risk stratification. To provide evidence-based recommendations for clinical utility of CNAs in melanocytic lesions, the Cancer Genomics Consortium Working Group for Melanocytic Lesions assessed 410 peer-reviewed articles selected from an extensive Ovid search of publications from 1998 through 2021. The group determined the power of CNAs for 1) aiding diagnosis, 2) stratifying risk, and 3) guiding clinical management. We present the evidence base for the clinical utility of CNA assessment in the workup of melanocytic lesions including ocular, mucosal, and cutaneous melanomas with characteristic findings in various subtypes. This working group has synthesized the findings to establish consensus recommendations for the interpretation of CNAs in melanocytic lesions and incorporation into standard clinical laboratory testing.