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Educational paper: pathogenesis of infantile haemangioma, an update 2014 (part I)

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Abstract

Infantile haemangioma (IH) is the most frequent childhood tumour. Although it is benign and self-limiting, severe complications can arise due to localisation and fast tumour growth. Management and therapy of IH has changed greatly after 2008 with propranolol. However, the pathogenesis remains elusive. This update provides an overview of all possible mechanisms currently considered. We discuss the possibility that several mechanisms act together, although local hypoxia seems to be important. Clinically, in about half of the cases, an IH is preceded by an anaemic macula (local ischaemia) or a so-called precursor lesion. Laboratory findings indicate stabilisation and an increased transcription activity of hypoxia-inducible factor 1 alpha (HIF1α), leading to up-regulation of its downstream target genes (such as vascular endothelial growth factor (VEGF)), which normally occurs in cases of hypoxia.

Conclusion: Three main hypotheses have been proposed, namely (1) the theory of tissue hypoxia, (2) the theory of embolization of placental endothelial cells and (3) the theory of increased angiogenic and vasculogenic activity.

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Abbreviations

BNIP3:

Bcl-2/adenovirus E1B kilodalton-interacting protein (BNIP) family member 3

CA-IX:

Carbon anhydrase IX

GLUT-1:

Glucose transporter 1

HIF1α:

Hypoxia-inducible factor 1 alpha

HIF2α:

Hypoxia-inducible factor 2 alpha

IDO:

Indoleamine 2,3-dioxygenase

IGF:

Insulin-like growth factor

IH:

Infantile haemangioma

MMP9:

Matrix metallopeptidase 9

mTOR:

Mammalian target of rapamycin

mTORC1:

mTOR complex 1

pAKT:

Phosphorylated v-akt murine thymoma viral oncogene homolog 1

pS6:

Phosphorylated S6 protein

ROP:

Retinopathy of prematurity

SDF1α:

Stromal cell-derived factor 1 alpha

TNF-α:

Tumour necrosis factor alpha

VEGF:

Vascular endothelial growth factor

VEGF-A:

Vascular endothelial growth factor A

VEGFR:

Vascular endothelial growth factor receptor

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Acknowledgments

We thank Ko Hagoort for language revision. This study was funded by project Aardbeesie (www.aardbeesie.nl) and the Foundation for Paediatric Dermatology Rotterdam.

Conflict of interest

The authors declare that they have no conflict of interest

Author information

Authors and Affiliations

  1. Department of Paediatric Surgery, Erasmus University Medical Centre, Dr. Molewaterplein 60, 3015 GJ, Rotterdam, The Netherlands

    Sherief R. Janmohamed & Gerard C. Madern

  2. Department of Paediatrics, Erasmus University Medical Centre, Rotterdam, The Netherlands

    Peter C. J. de Laat

  3. Department of Dermatology, Maasstad Hospital, Rotterdam, The Netherlands

    Arnold P. Oranje

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  1. Sherief R. Janmohamed
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  2. Gerard C. Madern
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  3. Peter C. J. de Laat
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Correspondence to Sherief R. Janmohamed.

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Communicated by Beat Steinmann

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Janmohamed, S.R., Madern, G.C., de Laat, P.C.J. et al. Educational paper: pathogenesis of infantile haemangioma, an update 2014 (part I). Eur J Pediatr 174, 97–103 (2015). https://doi.org/10.1007/s00431-014-2403-6

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  • DOI: https://doi.org/10.1007/s00431-014-2403-6

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