Infantile hemangioma is a proliferation of β4-negative endothelial cells adjacent to HLA-DR-Positive cells with dendritic cell morphology

doi:10.1016/j.humpath.2004.02.005

Human Pathology

Volume 35, Issue 6, June 2004, Pages 739-744

https://doi.org/10.1016/j.humpath.2004.02.005 Get rights and content

Abstract

Although hemangioma is referred as to the most common tumor in infancy, the underlying pathogenetic events and the biologic origin of this benign vascular neoplasm have remained obscure. By using immunohistochemistry on frozen sections of infantile hemangiomas, we show here that proliferating endothelial cells abundantly expressed α_vβ₃ but lacked β₄ integrins. Instead, regressing and involuting infantile hemangiomas due to treatment with IFN-α showed positive staining of β₄ integrin, which might point to the angiogenic significance of β₄ integrin in infantile hemangiomas. Moreover, immunofluorescence analysis revealed the existence of HLA-DR⁺, mostly CD68⁺ and partly DC-SIGN/CD209⁺ cells with dendritic cell morphology in the intimate vicinity of hemangiomatous vessels. Such cells were also detected in the dermal microvascular unit in normal skin. The coupled occurrence of vascular structures and perivascular cells that were stained positive with markers of monocyte or macrophage or dendritic cells might suggest that the development of infantile hemangioma is a result of vasculogenesis, that is, the formation of primitive blood vessels from angioblasts, rather than of angiogenesis, that is, the sprouting of capillaries from preexisting vessels.

Section snippets

Patients

Hemangiomas were removed by plastic surgeons from 18 patients (15 female and 3 male), who ranged in age from 2 months to 22 years. Biopsy material was immediately frozen in liquid nitrogen and kept at −80 °C until sectioning. The hemangiomas were classified histologically as capillary hemangiomas (n = 16) and capillary or cavernous hemangiomas (n = 2). Most (61%) of the hemangiomas were located on the head; 33% were located on trunk, and 6% were located on genitalia. One patient was receiving

Results

The distribution patterns of immunohistochemical and immunofluorescence stainings in the biopsy tissues investigated are detailed in Table 3.

Capillary and cavernous hemangiomas were composed of vessel channels lined by endothelial cells that were stained with CD31 (Fig 1A), CD34, Ulex europaeus agglutinin 1, and von Willebrand factor. The expression of CD36 was predominantly restricted to endothelial cells in the deeper parts of the vascular plexus. In all cases, endothelial cells lining the

Discussion

In this study we focused our interest on the immunophenotype of endothelial and other cells in infantile hemangiomas to gain insight into the pathophysiologic mechanisms of this poorly elucidated vascular tumor.

Of particular relevance was the observation that the α_vβ₃ integrin was selectively expressed on growing vessels (Fig 1C). This finding emphasizes the angiogenic function of the α_vβ₃ integrin. Numerous studies have shown that the α_vβ₃ complex, referred to as the vitronectin receptor, is

Acknowledgements

DC-LAMP/CD208 was a kind gift of Dr. Serge Lebecque, Laboratory for Immunological Research, Schering-Plough, Dardilly, France. Monoclonal antibody Lag, anti-human Birbeck granule-associated Langerin/CD207 was donated by Dr. Kozo Yoneda, Dermatology, Kyoto University, Kyoto, Japan. DC-SIGN/CD209 was a generous gift from Dr. Y. van Kooyk, Nijmegen, Netherlands.

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Original contributionInfantile hemangioma is a proliferation of β4-negative endothelial cells adjacent to HLA-DR-Positive cells with dendritic cell morphology

Abstract

Section snippets

Patients

Results

Discussion

Acknowledgements

Hum Pathol

J Invest Dermatol

Immunol Today

Cell

J Invest Dermatol

Am J Pathol

Hemangiomas in children

N Engl J Med

Vascular tumors and vascular malformations (new issues)

Adv Dermatol

Clonality and altered behavior of endothelial cells from hemangiomas

J Clin Invest

Pathogenesis of hemangioma