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

Nguyen, Van Anh; Fürhapter, Christina; Romani, Nikolaus; Weber, Florian; Sepp, Norbert

doi:10.1016/j.humpath.2004.02.005

Cited by 53 publications

(39 citation statements)

References 24 publications

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“…3 To help to distinguish the growth phases of infantile hemangiomas at the cellular level, several biomolecular markers have been introduced, including b4 integrin by our group. 4,18,19 Specifically, we found expression of b4 integrin only in involuting infantile hemangiomas. This led us to suggest an antiangiogenic effect of b4 integrin with induction of arrest of endothelial cell proliferation, presumably via integrin-mediated signal transduction pathways.…”

Section: Discussionmentioning

confidence: 62%

“…As described earlier in detail, the staining pattern of these cells, that is, HLA-DR, CD68 and DC-SIGN positive, CD1a, DC-LAMP and BDCA-2 negative, is most compatible with monocytes/ macrophages or dendritic cells. 4 At the present time, we do not know their function. Evidently, their presence alone does not imply that they are involved in growth or regression of infantile hemangiomas because they were found during both proliferative and involutional phases.…”

Section: Discussionmentioning

confidence: 89%

“…A number of distinct hypotheses have been put forth to account for hemangiogenesis, including genetic predisposition, imbalance of angiogenic factors, dysregulated vasculogenesis, clonality and placental origin of hemangioma endothelial cells. [4][5][6][7][8][9] Owing to the exclusive expression of LYVE-1 by proliferating hemangioma endothelial cells, recent studies suggested an intrinsic defect in hemangioma endothelial cell maturation. 11 This prompted us to study the expression of the lymphatic endothelial cell-specific markers LYVE-1, Prox-1, podoplanin and D2-40 in a large number of infantile hemangiomas the growth status of which was categorized to a part by the staining with b4 integrin.…”

Section: Discussionmentioning

confidence: 99%

“…3 Using immunohistochemistry on frozen sections, we recently identified b4 integrin as a novel marker for staging infantile hemangiomas, showing that b4 integrin was exclusively expressed in regressing and involuting infantile hemangiomas, but was lacking in proliferating infantile hemangiomas. 4 Although infantile hemangiomas are well-known vascular lesions, the cellular and molecular mechanisms that cause the abnormal excessive endothelial cell proliferation are still poorly understood. Many theories have been proposed concerning the pathogenesis of infantile hemangiomas, including hormonal influences and growth factors that are released by adjacent hyperplastic epidermis, neighboring stromal cells and/or hemangioma endothelial cells.…”

mentioning

confidence: 99%

“…8,9 Equally important was our finding that hemangioma vessels are closely surrounded by densely packed HLA-DR-positive cells with dendritic cell morphology. 4 This close anatomic relationship to each other prompted us to suggest that infantile hemangiomas are the result of inappropriate vasculogenesis rather than of angiogenesis. 10 The latter is currently regarded as the critical inductive mechanism for the abnormal vessel formation.…”

mentioning

confidence: 99%

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Infantile hemangioma is a proliferation of LYVE-1-negative blood endothelial cells without lymphatic competence

et al. 2006

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Infantile hemangiomas are common benign vascular tumors that exhibit a characteristic history of rapid proliferation in the first year of life and slow spontaneous involution during early childhood. The causative pathogenic event responsible for the abnormal endothelial proliferation remains elusive. The recent discovery of an immature phenotype of proliferating hemangioma endothelial cells due to the exclusive expression of the lymphatic endothelial hyaluronan receptor LYVE-1 led to the proposal that infantile hemangiomas are the result of a primary defect in endothelial cell maturation. To test this hypothesis, we looked for the expression of the lymphatic endothelial cell-specific markers LYVE-1, Prox-1, podoplanin and D2-40 in b4 integrin-negative proliferating and b4 integrin-positive involuting infantile hemangiomas. As b4 integrin proved to be a suitable marker for staging infantile hemangiomas, we used it in combination with clinical and histological criteria to objectively determine the proliferative and involutional phases. In immunohistochemical and immunofluorescent stains, hemangioma vessels were negative for all lymphatic endothelial cell-specific markers tested during both proliferation and involution. LYVE-1 immunoreactivity, however, was found in the dense network of perivascular HLA-DR-positive cells with dendritic cell morphology that are supposed to play a role in hemangiogenesis by releasing pro-and antiangiogenic factors. Notably, this LYVE-1 staining failed to correlate with the growth status of infantile hemangiomas. Our results do not support the notion that LYVE-1 expression was restricted to the proliferative phase and downregulated during involution. Thus, LYVE-1 does not seem to be a reliable marker for proliferating infantile hemangiomas. We conclude that the suggested intrinsic defect in endothelial cell maturation is unlikely the cause for the post-natal rapid growth in infantile hemangiomas. In addition, the lack of lymphatic endothelial cell-specific markers implies that infantile hemangiomas are tumors of blood vessels without lymphatic competence.

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Section: Discussionmentioning

confidence: 62%

Section: Discussionmentioning

confidence: 89%