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Exp Mol Pathol. 2014 Apr;96(2):162-7. doi: 10.1016/j.yexmp.2013.12.011. Epub 2014 Jan 4.

VHL-deficient vasculogenesis in hemangioblastoma.

Author information

  • 1Department of Neurosurgery, Freiburg University Medical Center, Germany.
  • 2Department of Neurology, Mayo Clinic, Rochester, MN, USA.
  • 3Laboratory of Pathology, National Cancer Institute, Bethesda, MD, USA.
  • 4Department of Pathology, Yale University School of Medicine, New Haven, CT, USA.
  • 5Surgical Neurology Branch, NINDS, National Institutes of Health, Bethesda, MD, USA.
  • 6Department of Pathology, Yale University School of Medicine, New Haven, CT, USA. Electronic address:


Hemangioblasts are capable of differentiation into vascular structures and blood. Patients with von Hippel-Lindau (VHL) disease develop hemangioblastomas which are composed of VHL-deficient tumor cells with protracted hemangioblastic differentiation potential. In a subset of these tumors, hemangioblastic differentiation is characterized by different stages of red blood cell formation. It has remained controversial, however, whether VHL-deficient hemangioblastic cells are similarly capable of differentiating into vascular cells and functioning vascular structures in vivo. By histologic, immunohistologic and microdissection-based genetic analysis of 60 VHL disease-associated hemangioblastomas, we re-examined the controversial question whether VHL-deficient neoplastic hemangioblastic cells are capable of vascular differentiation (vasculogenesis). In most tumors (n=47), there was no evidence of either vasculogenesis or hematopoiesis; tumor cells were either scattered between reactive angiogenetic vascular structures or arranged in solid clusters. A subset of tumors (n=13), however, revealed vaculogenetic structures that were composed of cuboidal or flat cells and frequently contained red blood cell precursors or mature red blood cells. Microdissection-based deletion analysis of epithelial cells confirmed them to be VHL-deficient tumor cells. Immunohistochemistry for CD31 was consistently negative in these structures, and no evidence could be obtained for connectivity with reactive vasculature. We demonstrate that hemangioblastic differentiation capacity of VHL-deficient hemangioblastic cells includes not only erythropoiesis, but also differentiation into primitive vasculogenetic structures. Tumor cells, however, do not appear to have the potential of terminal differentiation into mature and functional vascular structures.

Copyright © 2014 Elsevier Inc. All rights reserved.


Angiogenesis; Hemangioblastoma; Vasculogenesis; von Hippel–Lindau disease

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