Tumors With GNAQ Mutations: A Review With a Focus on Possible Shared Neural Crest Origins

Mutations in the guanosine nucleotide-binding protein Q gene (GNAQ) lead to complex pathologies involving both vascular and melanocytic components, which may seem surprising at first glance. Traditionally, melanocytes have been considered cells derived from the neural crest, while blood vessels are derived from mesodermal mesenchyme. However, in recent years, the understanding of ectomesenchyme, a mesenchymal derivative originating from the neural crest, has revealed how this embryonic layer gives rise not only to structures of the head and neck but also to those of the trunk. This discovery has allowed the contextualization of GNAQ mutations within a new ontogenetic interpretation, wherein neural crest cells, capable of differentiating into both ectodermal and mesodermal derivatives, can lead to a variety of dermatological lesions. In this article, we review the major pathological entities observed in dermatopathology associated with GNAQ mutations and place them within this new understanding of ectomesenchyme. In doing so, we explain how a single gene can influence the development of various vascular and melanocytic pathologies, while also challenging the traditional relationship between melanocytes and endothelial cells and their common origin in the neural crest.