Association of adipocyte hypertrophy and ultrasound severity score in lymphedematous limb: a cross-sectional study

Lymphedema causes progressive remodeling of subcutaneous adipose tissue, but noninvasive assessment of early adipocyte changes remains limited. This cross-sectional study investigated whether subcutaneous tissue ultrasonography, assessed using subcutaneous echogenicity grade (SEG) and subcutaneous echo-free space grade (SEF), is associated with adipocyte size in lymphedematous limbs. Thirty-two patients undergoing lymphaticovenular anastomosis contributed 78 surgical sites and 515 tissue biopsies. Adipocyte area was quantified from 118,432 cells using Fiji with the Adiposoft plugin. Generalized estimating equation analysis showed that SEG and SEF were independently associated with adipocyte area. Compared with SEF0, adipocyte area was larger in SEF1 (+ 783.5 μm²) and SEF2 (+ 1,123.1 μm²), whereas compared with SEG0, adipocyte area was smaller in SEG1 (− 486 μm²) and SEG2 (− 896 μm²). Adipocyte area was not significantly associated with ISL stage, affected extremity, or surgical level. These findings suggest that SEF and SEG reflect different aspects of adipose tissue remodeling, with higher SEF associated with adipocyte hypertrophy and higher SEG potentially reflecting more advanced remodeling.