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Methods: Skin and subcutaneous adipose tissue (5-μm sections) were collected from one patient (hand, foot, back), fixed in formaldehyde, and stained for inflammatory markers (CD68, CD163) and endothelial cells (CD31). H&E and Masson’s trichrome staining were performed. Images were captured and manually quantified. Results: Cutaneous tissue from the hands and feet demonstrated increased microvascular density (CD31) with thickened walls, perivascular fibrosis, and macrophage infiltration (CD68, CD163). Macrophages were observed along the nerve fibers and outer nerve layers, consistent with localized nerve inflammation alongside vascular remodeling. Conclusion: This study demonstrates concurrent vascular remodeling and nerve-associated inflammation in lipedema adipose tissue of the hand and feet. These findings highlight that pain in lipedema involves both vascular and neurogenic inflammatory mechanisms, extending the understanding of lipedema pathology beyond the lower extremities.