Lymph Node Transfer and Neolymphangiogenesis: From Theory to Evidence

Background: Vascularized lymph node transfer (VLNT) has proven to be a valuable treatment for patients affected by advanced stages of lymphedema. Although a spontaneous neo-lymphangiogenesis has been advocated to explain the positive effects of VLNT, there is still a lack of supportive biological evidence. The aim of the paper was to demonstrate the post-operative formation of new lymphatic vessels using histological skin sections from the lymphedematous limb. Materials and methods: All patients diagnosed with extremities' lymphedema who had undergone gastroepiploic vascularized lymph node flap (GE-VLN) between January 2016 and December 2018 were identified. Full thickness 6-mm skin punch biopsies were obtained from all voluntary patients at identical sites of the lymphedematous limb (during the surgical procedure of VLNT (T0) and 1 year later (T1). The histological samples were prepared to be immunostained with Anti-Podoplanin / gp36 antibody. Results: The study analyzed the results of 14 lymph node transfer voluntary patients. At 12 months of follow-up, the mean circumference reduction rate was 44.3 ± 4.4 at above elbow/above knee level (AE/AK) and 60.9 ± 7 at below elbow/below knee level (BE/BK) Podoplanin expression values were on average 7.92 ± 1.77 (vessels/mm2) at time 0 and 11.79 ± 3.38 (vessels/mm2) at T1. The difference was statistically significant between pre-operative and post-operative values (p=0.0008). Conclusion: The present study provides anatomic evidence that a neo-lymphangiogenetic process is induced by the VLNT procedure as new functional lymphatic vessels can be detected in close proximity to the transferred lymph nodes.