Objectives
To test the hypothesis that somatic PIK3CA mutations would be found in patients with more common disorders including isolated lymphatic malformation (LM) and Klippel-Trenaunay syndrome (KTS).
Study design
We used next generation sequencing, droplet digital PCR (ddPCR), and single molecule molecular inversion probes (smMIPs) to search for somatic PIK3CA mutations in affected tissue from patients seen at Boston Children’s Hospital who had an isolated LM (n=17), KTS (n=21), fibro-adipose vascular anomaly (FAVA; n=8), or congenital lipomatous overgrowth with vascular, epidermal, and skeletal anomalies syndrome (CLOVES; n = 33), the disorder for which we first identified somatic PIK3CA mutations. We also screened 5 of the more common PIK3CA mutations in a second cohort of patients with LM (n=31) from Seattle Children’s Hospital.
Results
Most individuals from Boston Children’s Hospital who had isolated LM (16/17) or LM as part of a syndrome, such as KTS (19/21), FAVA (4/8), and CLOVES (30/32) were somatic mosaic for PIK3CA mutations, with 5 specific PIK3CA mutations accounting for ~ 80% of cases. Seventy-four percent of patients with LM from Seattle Children’s Hospital also were somatic mosaic for 1 of 5 specific PIK3CA mutations. Many affected tissue specimens from both cohorts contained fewer than 10% mutant cells.
Conclusions
Somatic PIK3CA mutations are the most common cause of isolated lymphatic malformations and disorders in which lymphatic malformation is a component feature. Five PIK3CA mutations account for most cases. The search for causal mutations requires sampling of affected tissues and techniques that are capable of detecting low-level somatic mosaicism, because the abundance of mutant cells in a malformed tissue can be low.
Arteriovenous malformations (AVMs) are fast-flow vascular malformations composed of a complex vessel network directly connecting feeding arteries to draining veins. The intervening normal capillary network is absent. Proper diagnosis and treatment of AVMs is challenging and in need of an interdisciplinary team of experienced physicians. Careful analysis of the clinical features and evaluation of therapeutic options represent the basis for successful management of AVMs. This article will focus on the clinical and radiological findings and in particular on interdisciplinary management strategies of AVMs including minimally invasive endovascular and surgical treatment.
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