The Association of Nevus-Associated Melanoma with Common or Dysplastic Melanocytic Nevus: A Systematic Review and Meta-Analysis

SIMPLE SUMMARY: Acquired melanocytic nevi are classified as common or dysplastic. Cutaneous melanoma may develop in a pre-existing acquired nevus (nevus-associated melanoma, NAM). We conducted a systematic review and meta-analysis of 22 published articles to investigate whether NAM occurs more frequently within a dysplastic or common nevus. Although our meta-analysis showed a similar proportion of 51% dysplastic nevus (compared with common nevus) in NAM, when including those studies with larger patient numbers, there was a higher proportion of 65% NAM developing in a dysplastic nevus. A separate meta-analysis of invasive and in situ NAMs showed that the proportion of dysplastic nevus were 56% and 71%, respectively. The larger proportion of dysplastic nevus in in situ NAMs should be interpreted with caution due to the low numbers and possible misclassification bias of in situ NAM developing in dysplastic nevus that may be challenging to differentiate from a dysplastic nevus. Our meta-analysis had considerable uncertainty and high heterogeneity, highlighting the need for future well-designed studies with uniform histopathological definitions for dysplastic nevus remnants which report the type of nevus in NAM separately for invasive and in situ melanomas, thin tumors, and by histological subtype. ABSTRACT: Background: Cutaneous melanoma has an adjacent nevus remnant upon histological examination in 30% of cases (nevus-associated melanoma, NAM), while it appears de novo for 70% of tumors. Regarding NAM arising in acquired melanocytic nevus, currently there is no evidence on whether NAM more frequently develops in association with a dysplastic or common melanocytic nevus. Objectives: To conduct a systematic review and meta-analysis to investigate the proportion of dysplastic or common melanocytic nevus in NAM associated with acquired nevus. Methods: A systematic literature search is conducted using PubMed, Scopus, and the Cochrane Library. The PRISMA checklist is used. Studies reporting patients diagnosed with NAM arising in an acquired common or dysplastic melanocytic nevus are included. A meta-analysis of proportions is performed using the random-effects model. The magnitude of heterogeneity is assessed with the I(2) statistic. Results: A total of 22 studies with 2174 NAMs with an acquired nevus (dysplastic or common) are included. The proportion of dysplastic nevus in NAM varies considerably in the included studies, ranging from 0% to 100%. In the meta-analysis, the overall estimate of the proportion of having a dysplastic nevus in NAM is 51% (95% CI: 39–63%) with high heterogeneity at I(2): 95.8% (p < 0.01). A sensitivity meta-analysis of 12 studies that included 30 or more acquired nevus-NAMs (2023 cases) shows that 65% of the NAMs developed in a dysplastic nevus (95% CI: 51–77%). In a meta-analysis of 4 studies reporting invasive-only acquired nevus-NAMs (764 cases), the proportion of dysplastic nevus is 56% (95% CI: 36–75%). Only 2 studies are found reporting in situ NAMs with an acquired nevus, and the pooled estimated proportion of dysplastic nevus is 71% (95% CI: 63–78%). Conclusions: The results of this meta-analysis suggest a higher proportion of dysplastic nevus in acquired nevus-NAM; however, there is considerable uncertainty and high heterogeneity, highlighting the need for future well-designed studies with uniform histopathological definitions for dysplastic nevus remnants which report the type of nevus in NAM separately for invasive melanomas, thin tumors, and by histological subtype.