Life-Threatening Lymphovascular Malformation in a 14-Year-Old Girl

Introduction: PIK3CA-related overgrowth spectrum (PROS) is a group of disorders derived from mosaic mutations in the PIK3CA gene. Overactivity of the encoded PI3K enzyme results in uninhibited cellular growth. Alpelisib is the only FDA approved treatment that both decreases and inhibits the hyperactivity of PI3K enzyme specifically for vascular anomaly overgrowth associated with PROS.


Description: A 14 year-old female from Guyana presented with 5 months of abdominal pain and distention with acute hematemesis. She was found to have an infiltrative lymphovascular malformation encasing her left hemithorax with mediastinal shift and abdominal compartment with arteriovenous shunting into abdominal varices, along with micro and macronodular omentum and mesentery involvement. Initial management included variceal banding and lung biopsy. While awaiting results, the patient developed acute hypoxemic respiratory failure requiring intubation, worsening portal hypertension, abdominal compartment syndrome requiring peritoneal drain placement, fluid overload, and hemorrhagic shock as a complication from her lung biopsy requiring product replacement and systemic tranexamic acid therapy. She underwent left pneumonectomy for source-control of bleeding with venovenous extracorporeal support (VV ECMO). She required VV ECMO support for 2 days and was extubated 15 days later. Initial pathology demonstrated vascular/lymphatic malformation prompting treatment with pulse-steroids and an mTOR inhibitor, sirolimus, with improvement in abdominal vascular malformation burden. Ultimately, next-generation sequencing confirmed the presence of a pathogenic variant in PIK3CA, 36 days after receipt of initial biopsy.


Discussion: While most subtypes of PROS have clinical features such as facial asymmetry, visible capillary malformations, or hemihyperplasia and are often diagnosed at birth or early childhood, to our knowledge the subacute presentation of life-threatening lymphovascular malformations is not well described in the literature. Though met by several complications, our experience in managing this rare and extensive malformation was encouraging with the administration of steroids and sirolimus. With symptomatic and radiographic improvement on sirolimus, discussions regarding risk-benefit of Alpelisib remain ongoing.