New Insights into the Pathophysiology of Primary and Secondary Lymphedema: Histopathological Studies on Human Lymphatic Collecting Vessels

Background:Lymphedema is characterized by an accumulation of interstitial fluids due to inefficient lymphatic drainage. Primary lymphedema is a rare condition, including congenital and idiopathic forms. Secondary lymphedema is a common complication of lymph node ablation in cancer treatment. Previous studies on secondary lymphedema lymphatic vessels have shown that after an initial phase of ectasia, worsening of the disease is associated with wall thickening accompanied by a progressive loss of the endothelial marker podoplanin. Methods and Results:We enrolled 17 patients with primary and 29 patients with secondary lymphedema who underwent lymphaticovenous anastomoses surgery. Histological sections were stained with Masson's trichrome, and immunohistochemistry was performed with antibodies to podoplanin, smooth muscle alpha-actin (alpha-SMA), and myosin heavy chain 11 (MyH11). In secondary lymphedema, we found ectasis, contraction, and sclerosis vessel types. In primary lymphedema, the majority of vessels were of the sclerosis type, with no contraction vessels. In both primary and secondary lymphedema, not all alpha-SMA-positive cells were also positive for MyH11, suggesting transformation into myofibroblasts. The endothelial marker podoplanin had a variable expression unrelatedly with the morphological vessel type. Conclusions:Secondary lymphedema collecting vessels included all the three types described in literature, that is, ectasis, contraction, and sclerosis, whereas in primary lymphedema, we found the ectasis and the sclerosis but not the contraction type. Some cells in the media stained positively for alpha-SMA but not for MyH11. These cells, possibly myofibroblasts, may contribute to collagen deposition.