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

Anthony P. Fernandez, Maria Mitiva, Brenda Roberts, Carlos Ricotti, Panta Rouhani, Paolo Romanelli

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

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.

Original languageEnglish
JournalJournal of the American Academy of Dermatology
Volume64
Issue number6
DOIs
StatePublished - Jun 1 2011

Fingerprint

Varicose Ulcer
Venous Insufficiency
Lymphatic Vessels
Skin
Blood Vessels
Lymphatic Abnormalities
Sample Size
Edema
Leg
Glycoproteins
Endothelial Cells

Keywords

  • chronic venous insufficiency
  • D2-40
  • dermal lymphatics
  • edema
  • light microscopy
  • ulcer

ASJC Scopus subject areas

  • Dermatology

Cite this

Histopathologic analysis of dermal lymphatic alterations in chronic venous insufficiency ulcers using D2-40. / Fernandez, Anthony P.; Mitiva, Maria; Roberts, Brenda; Ricotti, Carlos; Rouhani, Panta; Romanelli, Paolo.

In: Journal of the American Academy of Dermatology, Vol. 64, No. 6, 01.06.2011.

Research output: Contribution to journalArticle

Fernandez, Anthony P. ; Mitiva, Maria ; Roberts, Brenda ; Ricotti, Carlos ; Rouhani, Panta ; Romanelli, Paolo. / Histopathologic analysis of dermal lymphatic alterations in chronic venous insufficiency ulcers using D2-40. In: Journal of the American Academy of Dermatology. 2011 ; Vol. 64, No. 6.
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abstract = "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.",
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