Abstract
Our knowledge in vascular anomalies has grown tremendously in the past decade with the identification of key molecular pathways and genetic mutations that drive the development of vascular tumors and vascular malformations. This has led us to better understand the pathogenesis of vascular lesions, refine their diagnosis and update their classification while also exploring the opportunity for a targeted molecular treatment. This paper aims to provide an overview of venous malformations (VM) in childhood. Specific entities include common VMs, cutaneo-mucosal VM, blue rubber bleb nevus syndrome or Bean syndrome, glomuvenous malformation, cerebral cavernous malformation, familial intraosseous vascular malformation and verrucous venous malformation. The clinicopathological features and the molecular basis of each entity are reviewed.
Highlights
venous malformations (VM) are considered the most frequent vascular malformation referred to multidisciplinary centers that specialize in vascular anomalies, with an estimated incidence of 1 to 5 in 10,000 births [1,2]
Study of Vascular Anomalies (ISSVA) classification for vascular anomalies, we provide an outline of the sporadic and inherited conditions that encompass VMs (Table 1), discussing the clinicohistopathological features and molecular basis for each entity
Lymphatic malformations can show varying degrees of hyperkeratosis and acanthosis, but they lack the lobular arrangement of the vessels seen in most verrucous venous malformation (VVM) and are negative for glucose transporter 1 protein (GLUT1) and Wilms tumour 1 protein (WT1) [58]
Summary
Venous malformations (VMs) are slow-flow vascular lesions that occur due to a defect in vascular morphogenesis during early embryonic life, sometime between 4 and 10 weeks of gestation. Somatic activating mutations in TEK/TIE2 cause more than half of sporadic unifocal VMs [3,4], and somatic mutations in PIK3CA are responsible for around 20% of cases [5] Mutations in both genes activate the PI3K/AKT/mTOR signalling pathway, underscoring the importance of this pathway in the pathogenesis and the opportunity of targeted molecular inhibitors for the treatment of VMs. TEK-mediated venous anomalies include a spectrum of phenotypes of varying severity and models of mutation acquisition that are distinctive to sporadic unifocal VM, inherited cutaneo-mucosal VM, sporadic multifocal VM and blue rubber bleb nevus syndrome [6]. Available at https://www.issva.org/classification (accessed on 28 March 2021)
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
