Genetically-targeted medications are emerging as important therapies for lymphatic malformations (LMs) unresponsive to sirolimus. We describe two patients with EML4::ALK positive LMs, one with Gorham Stout Disease and one with a large genitourinary (GU) LM, who were successfully treated with ALK inhibitors. This report adds ALK inhibitors to the growing toolbox of molecularly-targeted therapies for LMs.

Gorham-Stout disease (GSD) and generalized lymphatic anomaly (GLA) are subtypes of complex lymphatic malformations (CLMs) with osseous involvement that cause significant complications in children, including pain and pathologic fractures. Mutations in cellular growth pathways are common, and the mTOR inhibitor sirolimus alleviates symptoms in some, but not all, patients. We describe two patients, one with GSD and one with GLA, who were found to have EML4::ALK fusions. This report of a targetable, oncogenic fusion in vascular malformations expands our understanding of the genetic basis for CLMs and suggesting additional targeted therapies could be effective.