Assessing subcutaneous changes in lymphedema by subcutaneous tissue ultrasonography and pathological association

The subcutaneous changes of lymphedema, collectively termed "adipose tissue remodeling", comprises adipocyte hypertrophy, inflammatory cell infiltration, fibrosis, etc. To detect these changes, subcutaneous tissue ultrasonography was developed using conventional high-frequency ultrasound (6-18 MHz) to assess 2 parameters: (1) subcutaneous echogenicity (SEG) and (2) subcutaneous echo-free space (SEF). Despite its potential, research on the histopathological associations and clinical applications of this modality remains limited. This study recruited 22 patients with secondary lymphedema involving upper and lower limbs who were undergoing lymphaticovenular anastomosis (LVA). SEG and SEF were graded at 46 surgical sites. While performing LVA, 46 pieces of skin, 46 aggregates of subcutaneous tissue, and 100 segments of collecting lymph vessels were biopsied for pathological evaluation. The results showed that the presence of adipose tissue remodeling associated with progression of SEG and SEF grades. On the other hand, severity of lymphatic vessels showed no association with progression of SEG and SEF grades but surprisingly showed an inverse trend with the presence of adipose tissue remodeling. SEG grade, SEF grade and clinical stage (ISL) show similarly high sensitivity for detecting adipose tissue remodeling, but none of them show sufficient specificity. The application of subcutaneous tissue ultrasonography is suitable for screening of the adipose tissue remodeling.