Vascular Anomalies: From A Clinicohistologic to a Genetic Framework

BACKGROUND: Vascular anomalies currently are classified according to their clinical and histological characteristics. Recent advances in molecular genetics have enabled the identification of somatic mutations in most types of vascular anomalies. The purpose of this study was to collate information regarding the genetic basis of vascular anomalies. METHODS: The PubMed literature was reviewed for all citations that identified a mutation in a vascular anomaly between 1994-2017. Search words included "vascular anomaly", "mutation", "gene", "hemangioma", "pyogenic granuloma", "kaposiform hemangioendothelioma", "capillary malformation", "venous malformation", lymphatic malformation", "arteriovenous malformation", and "syndrome". Articles that identified both germline as well as somatic mutations in vascular anomalies were analyzed. Mutations were categorized by type (germline or somatic), gene, signaling pathway, and cell(s) enriched for the mutation. RESULTS: The majority of vascular anomalies had associated mutations that commonly affected tyrosine kinase receptor signaling through the RAS or PIK3CA pathways. Mutations in PIK3CA and G-protein coupled receptors were most frequently identified. Specific types of vascular anomalies usually were associated with a single gene. However, mutations in the same gene occasionally were found in different vascular lesions, and some anomalies had a mutation in >1 gene. Mutations were most commonly enriched in endothelial cells. CONCLUSIONS: Identification of somatic mutations in vascular anomalies is changing the paradigm by which lesions are diagnosed and understood. Mutations and their pathways are providing potential targets for the development of novel pharmacotherapy. In the future, vascular anomalies will be managed based on clinical characteristics as well as molecular pathophysiology. Presented at: 2017 New England Society for Plastic and Reconstructive Surgery (NESPRS) meeting in Falmouth, MA. Disclosures: None of the authors has a financial interest in any of the products, devices, or drugs mentioned in this manuscript. AUTHOR ROLE AND PARTICIPATION: AKG and J.A.G. contributed to overall design, data analysis, writing manuscript, and revising manuscript. Both authors gave final approval. ACKNOWLEDGEMENTS: This manuscript was supported by the National Institutes of Health Awards NICHD-081004 (AKG), NICHD-082606 (AKG), NHLBI-127030 (AKG), and the Translational Research Program Boston Children's Hospital (AKG). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Corresponding Author: Arin K. Greene MD, MMSc, Department of Plastic and Oral Surgery, Boston Children's Hospital, 300 Longwood Ave., Boston, MA 02115, Phone: 617.355.2306, Fax: 617.738.1657, arin.greene@childrens.harvard.edu ©2018American Society of Plastic Surgeons