FLT4 and lymphatic malformation: Later experiments in 2020 by Martinez-Corral et al suggest that elevated lymphangiogenesis seen in PIK3CAH1047R-driven microcystic lymphatic malformations requires intact upstream VEGFC-VEGFR3 signaling, with maximal regression of lymphatic overgrowth phenotypes following in vivo treatment with both VEGFC trap and sirolimus, suggesting the need for a multi-pronged therapeutic approach in the management of these disorders (Martinez-Corral et al., 2020).