Background: Extensive lymphatic malformations are low-flow vascular malformations that can cause devastating complications. Treatment of these malformations is challenging. This systematic review presents current use of sirolimus in patients with extensive lymphatic malformations.

Methods: MEDLINE and Google scholar search was conducted for studies on sirolimus treatment of lymphatic malformations up to July 2017. Search items included “lymphatic malformation,” “lymphangioma,” “cystic hygroma,” “vascular malformation,” “low-flow malformation,” “sirolimus,” “rapamycin,” and “mTOR inhibitor.”

Results: Twenty studies, including 71 patients receiving sirolimus, were included into this review. Forty-five patients had lymphatic malformations, eight patients venolymphatic malformations, and 19 patients capillary-lymphatico-venous malformations. Sirolimus led to a partial remission of disease in 60 patients, three patients had a progressive disease, and the outcome of eight patients was not reported. Dosing, target trough level, and duration of treatment differed between the studies. Common adverse effects were hyperlipidemia and neutropenia.

Conclusions: Available literature indicated that sirolimus therapy might be effective for lymphatic malformations. However, further randomized controlled studies are required to analyze the efficacy and long-term adverse events and to clarify the potential role for sirolimus in the management of lymphatic malformations.