Genetic investigation of nodal melanocytic nevi in cases of giant congenital melanocytic nevus

Abstract

Nodal melanocytic nevi are common incidental findings in lymph nodes that have been removed during sentinel lymph node biopsy for melanoma. They can also occur in the local lymph nodes of the giant congenital nevus (GCN), but very little is known regarding nodal melanocytic nevi in the giant congenital nevus, especially at the genetic level. There are two theories that explain the possible pathogenesis of nodal melanocytic nevi, mechanical transport and arrested migration during embryogenesis. However, there have been few tests of these two theories at the molecular biology level until now. We used whole-exon sequencing to test these two theories at the gene level for the first time. In clonal evolution analysis of patient 1, whose tumor mutation burden (TMB) value was relatively stable, showed that the GCN and nodal nevus had the same initial origin and then diverged into two branches as a result of gene mutations. In contrast, analysis indicated that in the other patient, whose TMB value declined from 68.02/Mb in a GCN to 17.55/Mb in associated nodal nevi, these two samples were from different origins at the beginning, each with its own gene mutation. These results are consistent with the two respective theories at the molecular biological level. We provided the first tests of the two theories of pathogenesis of nodal melanocytic nevi at the gene level, and these findings may provide some clues for further study. In addition, not all nodal nevi should be treated as lymph node metastasis in clinical diagnosis, and we should make a comprehensive assessment and judgment of nodal melanocytic nevi based on morphology, immunological characteristics and fluorescence in situ hybridization (FISH) tests.