Abstract
Background
The pathophysiology of lymphedema is poorly understood. Current treatment options include compression therapy, resection, liposuction, and lymphatic microsurgery, but determining the optimal treatment approach for each patient remains challenging.
Objectives
We characterized skin and adipose tissue alterations in the setting of secondary lymphedema.
Methods
Morphologic and histopathologic evaluations were conducted for 70 specimens collected from 26 female patients with lower extremity secondary lymphedema following surgical intervention for gynecologic cancers. Indocyanine green lymphography was performed for each patient to assess lymphedema severity.
Results
Macroscopic and ultrasound findings revealed that lymphedema adipose tissue had larger lobules of adipose tissue, with these lobules surrounded by thick collagen fibers and interstitial lymphatic fluid. In lymphedema specimens, adipocytes displayed hypertrophic changes and more collagen fiber deposits when examined using electromicroscopy, whole mount staining, and immunohistochemistry. The number of capillary lymphatic channels was also found to be increased in the dermis of lymphedema limbs. Crown-like structures (dead adipocytes surrounded by M1 macrophages) were less frequently seen in lymphedema samples. Flow cytometry revealed that, among the cellular components of adipose tissue, adipose-derived stem/stromal cells (ASCs) and M2 macrophages were decreased in number in lymphedema adipose tissue compared to normal controls.
Conclusions
These findings suggest that long-term lymphatic volume overload can induce chronic tissue inflammation, progressive fibrosis, impaired homeostasis, altered remodeling of adipose tissue, impaired regenerative capacity, and immunologic dysfunction. Further elucidation of the pathophysiologic mechanisms underlying lymphedema will lead to more reliable therapeutic strategies.
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