Pathogenic variants in PIK3CA are associated with clinical phenotypes of kaposiform lymphangiomatosis, generalized lymphatic anomaly, and central conducting lymphatic anomaly

Complex lymphatic anomalies are debilitating conditions characterized by aberrant development of the lymphatic vasculature (lymphangiogenesis). Diagnosis is typically made by history, examination, radiology, and histologic findings. However, there is significant overlap between conditions, making accurate diagnosis difficult. Recently, genetic analysis has been offered as an additional diagnostic modality. Here, we describe four cases of complex lymphatic anomalies, all with PIK3CA variants but with varying clinical phenotypes. Identification of PIK3CA resulted in transition to a targeted inhibitor, alpelisib. These cases highlight the genetic overlap between phenotypically diverse lymphatic anomalies.

Automated summary

Complex lymphatic anomalies are challenging to diagnose due to significant overlap among conditions. Genetic analysis has emerged as an additional diagnostic tool, as demonstrated in four cases with PIK3CA variants. The identification of PIK3CA led to targeted treatment with alpelisib, highlighting the genetic overlap among phenotypically diverse lymphatic anomalies.