Lymph Node Transfer and Neolymphangiogenesis: From Theory to Evidence

Background: Vascularized lymph node transfer (VLNT) has proven to be a valuable treatment for patients with advanced stages of lymphedema. Although spontaneous neolymphangiogenesis has been advocated to explain the positive effects of VLNT, there is still a lack of supportive biological evidence. The aim of this study was to demonstrate the postoperative formation of new lymphatic vessels using histologic skin sections from the lymphedematous limb. Methods: Patients with lymphedema of the extremities who had undergone gastroepiploic vascularized lymph node flap surgery between January of 2016 and December of 2018 were identified. Full-thickness 6-mm skin-punch biopsy specimens were obtained from patients at identical sites of the lymphedematous limb during the VLNT surgical procedure (T0) and 1 year later (T1). The histologic samples were immunostained with anti-podoplanin/gp36 antibody. Results: A total of 14 patients with lymph node transfer were included. At the 12-month follow-up, the mean circumference reduction rate was 44.3 ± 4.4 at the above-elbow/above-knee level and 60.9 ± 7 at the below-elbow/below-knee level. Podoplanin expression values were, on average, 7.92 ± 1.77 vessels/mm² at T0 and 11.79 ± 3.38 vessels/mm² at T1. The difference between preoperative and postoperative values was statistically significant (P = 0.0008). Conclusion: This study provides anatomic evidence that a neolymphangiogenic process is induced by the VLNT procedure because new functional lymphatic vessels can be detected in close proximity to the transferred lymph nodes. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.