# Clinical Utility of Copy Number Abnormality Analysis in the Evaluation of Melanocytic Lesions for Diagnosis and Prognosis: An Evidence-Based Review from the Cancer Genomics Consortium Working Group for Melanocytic Lesions

## TL;DR

This paper reviews how copy number abnormalities can help diagnose and predict outcomes in melanocytic lesions when traditional methods are uncertain.

## Contribution

The study provides evidence-based recommendations for using copy number abnormality testing in ambiguous melanocytic lesion cases.

## Key findings

- Copy number abnormalities are common in melanomas but rare in benign lesions.
- CNA testing helps distinguish between benign and malignant melanocytic lesions.
- CNAs differ between primary and metastatic melanomas and can inform prognosis.

## Abstract

Background/Objective: Although most melanocytic lesions are diagnosed as benign or malignant by histopathologic evaluation, with or without the aid of immunohistochemistry, diagnosis may remain uncertain in a minority of cases. Assessment of copy number abnormalities (CNAs) may provide sufficient additional evidence to favor either a benign or malignant diagnosis in both pediatric and adult cases and in melanocytic lesions of various subtypes, including Spitzoid, mucosal, and acral. CNAs are common in melanomas, while they are rare, with few exceptions, in benign lesions. Detection of CNAs by fluorescence in situ hybridization (FISH) and chromosomal microarray (CMA) has been well established for melanocytic lesions, with advantages and disadvantages for each. The objective of this meta-analysis was to evaluate the utility of CNA testing for the diagnosis of melanoma, across subtypes, when a lesion remains ambiguous after histopathologic and immunohistochemical assessment. In addition, the utility of CNAs to determine prognosis in established diagnoses of melanoma was also evaluated. Methods: The Cancer Genomics Consortium Working Group for Melanocytic Lesions reviewed published data from January 1998 through September 2022 of CNAs in melanocytic lesions detected by either FISH or CMA and conducted a meta-analysis of the findings. Results: Specific abnormalities common in primary cutaneous melanomas of various subtypes and uveal melanomas were enumerated. Differences in CNAs found in primary versus metastatic lesions were also determined, and published evidence for prognosis was summarized. Conclusions: The working group established evidence-based recommendations for the use of CNA testing for evaluation of ambiguous melanocytic lesions.