Histopathologic analysis of dermal lymphatic alterations in chronic venous insufficiency ulcers using D2-40

• Published in: Journal of the American Academy of Dermatology 2011-06, Vol.64 (6), p.1123.e1-1123.e12
• Main Authors: Fernandez, Anthony P., MD, PhD, Miteva, Maria, MD, Roberts, Brenda, BS, Ricotti, Carlos, MD, Rouhani, Panta, PhD, MPH, Romanelli, Paolo, MD
• Format: Article
• Language: English
• Subjects: Antibodies, Monoclonal, Murine-Derived; Biological and medical sciences; Biomarkers, Tumor; Blood and lymphatic vessels; Cardiology. Vascular system; chronic venous insufficiency; D2-40; dermal lymphatics; Dermatology; Diseases of the peripheral vessels. Diseases of the vena cava. Miscellaneous; edema; Female; Humans; light microscopy; Lymphatic Vessels - pathology; Lymphatic Vessels - physiopathology; Male; Medical sciences; Middle Aged; Retrospective Studies; Skin - pathology; ulcer; Varicose Ulcer - etiology; Varicose Ulcer - pathology; Varicose Ulcer - physiopathology; Venous Insufficiency - complications; Venous Insufficiency - physiopathology
• ISSN: 0190-9622; 1097-6787
• DOI: 10.1016/j.jaad.2010.05.048

Background Chronic venous insufficiency (CVI) ulcers represent a major medical problem worldwide. Current theories concerning the pathogenesis of CVI ulcers focus on abnormalities in the blood vascular system. Other abnormalities, such as chronic leg edema, may also play pathogenic roles in CVI ulcer development and further understanding of such alterations may lead to better treatments. Objective To gain insight into lymphatic abnormalities occurring in CVI, we compared dermal lymphatics in histologic sections from CVI ulcers and normal controls. Methods We compared global and architectural features of dermal lymphatics in D2-40–stained histologic sections from CVI ulcer tissue and from normal controls. D2-40 recognizes podoplanin, a transmembrane glycoprotein that is constitutively expressed in lymphatic endothelial cells, allowing us to distinguish dermal blood vessels from lymphatic vessels. Results Our analyses reveal that CVI ulcer specimens have more dermal lymphatic vessels per unit area than controls (5.71 vs 4.08 per mm2 , respectively; P  = .0281); a higher percentage of lymphatic vessels with collapsed lumina compared with controls (30.5% vs 8.1%, respectively; P  < .0001); and a higher percentage of competent lymphatic vessels displaying open inter-endothelial junctions compared with controls (5.7% vs 2.9%, respectively; P  < .0369). Limitations Our study is limited by its retrospective nature and relatively small sample size. Conclusions Lymphatic vessels in CVI ulcer specimens display global and architectural differences compared with lymphatic vessels in control specimens. These findings further implicate lymphatic dysfunction in the pathogenesis of CVI ulcers and allow for the formulation of a hypothesis concerning lymphatic changes that may be tested in future studies.