Significance: Lymphedema is a common disease that affects hundreds of millions of people worldwide with significant financial and social burdens. Despite increasing prevalence and associated morbidities, the mainstay treatment of lymphedema is largely palliative without an effective cure due to incomplete understanding of the disease. Recent Advances: Recent studies have described key histological and pathological processes that contribute to the progression of lymphedema, including lymphatic stasis, inflammation, adipose tissue deposition, and fibrosis. This review aims to highlight cellular and molecular mechanisms involved in each of these pathological processes. Critical Issues: Despite recent advances in the understanding of the pathophysiology of lymphedema, cellular and molecular mechanisms underlying the disease remains elusive due to its complex nature. Future Directions: Additional research is needed to gain a better insight into the cellular and molecular mechanisms underlying the pathophysiology of lymphedema, which will guide the development of therapeutic strategies that target specific pathology of the disease.
Keywords: adipose deposition; fibrosis; inflammation; lymphedema; pathophysiology.