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Dermal Backflow Correlates with Inflammatory Responses and Epidermal Changes in Secondary Lymphedema
Benjamin D. Wagner
*, Sarit Pal, Stav Brown, Xizhao Chen, Adana-Christine Campbell, Joseph Dayan, Geoffrey Hespe, Raghu Kataru, Babak J. Mehrara
Plastic and Reconstructive Surgery Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY
Background: Lymphatic dysfunction in secondary lymphedema is characterized by impaired lymphatic pumping, retrograde flow from collectors to superficial lymphatics, and accumulation of lymphatic fluid in the skin, termed dermal backflow (DBF). DBF can be visualized using indocyanine green (ICG) lymphography and represents an early clinical finding. However, its biological significance in lymphedema pathophysiology remains unclear. This study evaluated pathologic skin changes in patients with breast cancer-related lymphedema (BCRL) in regions with and without DBF.
Methods: Thirty-one patients with unilateral BCRL underwent ICG lymphography, arm volume measurements, and bioimpedance. Areas of the affected arm with and without DBF were identified, and transepidermal water loss (TEWL), percentage water content (PWC), and tonometry were measured in these regions and corresponding sites in the unaffected arm. Eight patients underwent matched full-thickness skin biopsies from the unaffected arm, affected arm with DBF, and affected arm without DBF for histologic analysis.
Results: DBF intensity correlated with PWC (r = 0.77,
P < 0.0001) and TEWL (r = 0.42,
P = 0.002). Patient-reported localization of swelling correlated with DBF intensity (r = 0.79,
P < 0.0001) and PWC (r = 0.63,
P < 0.0001). Compared with normal skin and affected regions without DBF, areas with DBF demonstrated epidermal hyperplasia, rete ridge formation, keratinocyte dedifferentiation, markers of epithelial-mesenchymal transition, and increased CD4+ T-cell infiltration.
Conclusion: DBF identified by ICG lymphography correlates closely with objective and patient-reported measures of BCRL. Skin regions with DBF exhibit pathologic changes characteristic of lymphedema, suggesting DBF may represent an early and biologically significant manifestation of disease and a potential target for early diagnosis and intervention.
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