Vascular malformations syndromes: an update

Abstract

Purpose of review To provide an update of vascular malformation syndromes by reviewing the most recent articles on the topic and following the new International Society for the Study of Vascular Anomalies (ISSVA) 2018 classification. Recent findings This review discusses the main features and diagnostic approaches of the vascular malformation syndromes, the new genetic findings and the new therapeutic strategies developed in recent months. Summary Some vascular malformations can be associated with other anomalies, such as tissue overgrowth. PIK3CA-related overgrowth spectrum (PROS) is a group of rare genetic disorders with asymmetric overgrowth caused by somatic mosaic mutations in PI3K-AKT-mTOR pathway that encompass a heterogeneous group of rare disorder that are associated with the appearance of overgrowth. CLOVES syndrome and Klippel–Trénaunay syndrome are PROS disease. Proteus syndrome is an overgrowth syndrome caused by a somatic activating mutation in AKT1. CLOVES, Klippel–Trénaunay and Proteus syndromes are associated with high risk of thrombosis and pulmonary embolism. Hereditary hemorrhagic telangiectasia is an autosomic dominant disorder characterized by the presence of arteriovenous malformations. New therapeutic strategies with bevacizumab and thalidomide have been employed with promising results.

Update on infantile hemangioma

“…The International Society for the Study of Vascular Anomalies (ISSVA; https://www.issva.org) published the ISSVA classification for VA in 2014 and revised version in 2018, which classifies VA into two large categories of vascular tumors and vascular malformations. [1][2][3][4][5][6][7] Vascular tumors are defined as vascular neoplasms caused by the proliferation and hyperplasia of abnormal endothelial and other vascular cells, while vascular malformations are defined as congenital developmental disorders consisting of capillary, lymphatic, venous, and arterial vessel formation. [2][3][4][5][6][7][8][9][10] Vascular tumors feature increased endothelial turnover (mitosis), while vascular malformations do not.…”

An Investigation of Clinical Features and Exploration of Comprehensive Treatments for Colorectal Vascular Malformation in Children

“…Other reported, but rare, symptoms include abdominal discomfort, abdominal pain, diarrhea, and perianal discomfort (2,8). CRVM may manifest as intestinal lesions in syndromic diseases, such as KTS, which is characterized by CRVM, skin capillary malformation, and asymmetric limb hypertrophy (13,14). In this study, two children showed multiple wine-like skin spots all over the body, complicated with asymmetric hypertrophy of both lower limbs, which was considered to be KTS.…”

Frequent activating PIK3CA mutations in sporadic angiolipoma

“…7,31 The proliferative effect of PIK3CA mutations in PROS syndromes exhibits an apparent skewing in the pattern of affected tissues, with mesoderm-derived tissues (including vasculature and adipose tissue) being markedly affected. 32 Importantly, mosaic activating mutations in PIK3CA are also known to cause the majority of isolated lymphatic malformations (>90%) as well as a significant proportion of isolated venous malformations (25%-30%) in the nonsyndromic population 5,6,25 ; unrestrained activation of p110α in endothelial cells leads to a hyperproliferative phenotype and formation of vascular developmental tumors responsive to therapeutic PI3K inhibition. 25 Intermediate PROS phenotypes, characterized by capillary malformations with overgrowth and lipomatous neoformations, are often caused by PIK3CA mutations with intermediate oncogenic potency, including the p.E545A mutation that was detected in our study.…”

“…The currently prevailing view is that, in contrast to other lipoma variants, ALs possess a normal karyotype and lack any distinctive chromosomal aberrations 3 . An association between sporadic AL and an overlying cutaneous capillary malformation has been reported 4 ; according to recent evidence, the pathogenesis of capillary malformations appears to be tightly linked to abnormal activation of the PI3K/AKT signaling pathway 5,6 . Interestingly, patients suffering from overgrowth syndromes caused by mosaic activating PIK3CA mutations (thus belonging to the PIK3CA‐related overgrowth spectrum, PROS) show a predisposition for the development of not only cutaneous vascular malformations but also benign proliferations of mature adipose tissue 7,8 …”

“…3 An association between sporadic AL and an overlying cutaneous capillary malformation has been reported 4 ; according to recent evidence, the pathogenesis of capillary malformations appears to be tightly linked to abnormal activation of the PI3K/AKT signaling pathway. 5,6 Interestingly, patients suffering from overgrowth syndromes caused by mosaic activating PIK3CA mutations (thus belonging to the PIK3CA-related overgrowth spectrum, PROS)…”