AbstractCutaneous intermediate melanocytic neoplasms with ambiguous histopathological features are diagnostically challenging. Ancillary cytogenetic techniques to detect genome-wide copy number variations (CNVs) might provide a valuable tool to allow accurate classification as benign (nevus) or malignant (melanoma). However, the CNV cut-off value to distinguish intermediate lesions from melanoma is not well defined. We performed a systematic review and individual patient data meta-analysis to evaluate the use of CNVs to classify intermediate melanocytic lesions. A total of 31 studies and 431 individual lesions were included. The CNV number in intermediate lesions (median 1, interquartile range [IQR] 0–2) was significantly higher (p<0.001) compared to that in benign lesions (median 0, IQR 0–1) and lower (p<0.001) compared to that in malignant lesions (median 6, IQR 4–11). The CNV number displayed excellent ability to differentiate between intermediate and malignant lesions (0.90, 95% CI 0.86–0.94, p<0.001). Two CNV cut-off points demonstrated a sensitivity and specificity higher than 80%. A cut-off of ≥3 CNVs corresponded to 85% sensitivity and 84% specificity, and a cut-off of ≥4 CNVs corresponded to 81% sensitivity and 91% specificity, respectively. This individual patient data meta-analysis provides a comprehensive overview of CNVs in cutaneous intermediate melanocytic lesions, based on the largest pooled cohort of ambiguous melanocytic neoplasms to date. Our meta-analysis suggests that a cut-off of ≥3 CNVs might represent the optimal trade-off between sensitivity and specificity in clinical practice to differentiate intermediate lesions from melanoma.
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