# Analysis of the Occurrence of PIK3CA Gene Mutation in Children with Lymphatic Malformation—Single Center Study

## TL;DR

This study found that half of children with lymphatic malformations have PIK3CA gene mutations, suggesting a role for targeted therapies in treatment.

## Contribution

The study confirms the high prevalence of PIK3CA mutations in isolated lymphatic malformations and supports the use of molecular diagnostics for targeted treatment.

## Key findings

- PIK3CA mutations were detected in 50% of children with lymphatic malformations.
- The p.E542K mutation was the most common hotspot mutation found in the study.
- Mutations were more frequent in isolated lymphatic malformations compared to complex forms.

## Abstract

What are the main findings?

PIK3CA mutations were detected in 50% of children with lymphatic malformations, with the p.E542K variant being the most prevalent hotspot mutation.

PIK3CA mutations were more frequently detected in isolated lymphatic malformations (63%) than in complex forms and were most commonly associated with truncal lesions.

What is the implication of the main finding?

The results confirm the key role of PIK3CA mutations in lymphatic malformation pathogenesis and highlights the clinical importance of incorporating molecular diagnostics into routine evaluation.

These findings provide a rationale for targeted therapies acting on the PI3K/AKT/mTOR pathway.

Background: Lymphatic malformations (LM) are rare congenital vascular anomalies caused by abnormal development and growth of lymphatic vessels. These malformations can lead to a wide range of symptoms, from mild swelling to more severe complications. Treatment options remain limited, especially for complex cases. Recent research has suggested that PIK3CA mutations play a key role in the pathogenesis of LM, potentially offering new possibilities for targeted treatment strategies. Methods: In this study, a cohort of 36 patients diagnosed with LM, Klippel-Trenaunay syndrome (KTS), and Proteus syndrome was analyzed. PIK3CA mutations were assessed in tissue samples obtained from the LM during clinically indicated procedures using digital droplet polymerase chain reaction (ddPCR), targeting five hotspots. Results: PIK3CA mutations were found in 18 patients (50%). The most frequent mutation was p.E542K (c.1624G>A), found in 19.44% of patients, followed by p.H1047R (c.3149A>G), p.E545K (c.1633G>A), and p.H1047L (c.3140A>T) each occurring in 11.11% of the cases. Mutations were more common in isolated LMs, with 63.16% of patients exhibiting PIK3CA mutations. Conclusions: PIK3CA mutations are common in LM, supporting the potential for targeted therapies like PI3K inhibitors in treating complex cases. This research highlights the importance of genetic analysis in the management of LM and offers a new therapeutic approach.