Objective Lymphatic malformations (LM) are common congenital vascular lesions, most often diagnosed at birth. They deform local anatomy and can be life-threatening if they compress the aerodigestive tract or other vital structures. Significant progress has been made in the treatment of LMs in the past 20 years. We conducted a systematic review of the literature on the management of LMs. Methods On September 21, 2020, we searched PubMed/MEDLINE for studies published from 2000 to 2020 reporting outcomes of invasive and pharmacologic treatment of LMs. Results A total of 251 studies met the eligibility criteria. Surgery has continued to be a mainstay in the management of LMs, especially in the treatment of microcystic and mixed lesions. Sclerotherapy has emerged as a first-line treatment of macrocystic LMs and as an adjunctive therapy used in combination with surgery for other lesions. Sirolimus, a strong inhibitor of mTOR (mechanistic target of rapamycin), has shown tremendous promise in the treatment of LMs, as both an oral and a topical agent. Recent investigations have shown the potential of targeted small molecule modulators of cellular pathways in the treatment of LMs. Conclusions Multiple invasive and pharmacologic therapies have been shown to be effective in the treatment of LMs. Future research should focus on rigorous, prospective comparisons of these treatment modalities.
