title: Vascular Innervation in Benign Neurofibromas of Patients with Neurofibromatosis Type 1.
abstract: Neurofibroma constitutes a heterogeneous group of solid tumours occurring sporadically or in association with syndromes. The aspect of these peripheral nerve sheath tumours may vary considerably, with disseminated tumours covering various parts of the body or nodular/diffuse plexiform neurofibroma that can grow to an impressive size. Although neurofibromas have vascular density comparable to that of normal tissue, they have tendency to bleed upon surgery which is poorly understood. Herein we investigated whether this finding may result from alterations of peripheral vasculature innervation. Different types of neurofibroma and controls were evaluated with special reference to nerve fibre topography and vessel density.
  
  
  METHODS
  Seventy-six formalin-fixed and paraffin-embedded tissue samples (63 neurofibromas and 13 skin biopsies) were retrieved from the archives of the Institute of Neuropathology, University Medical Center Hamburg-Eppendorf. Nerve fibres and blood vessels were differentiated immunohistochemically on 10-μm-thick tumour slices using antibodies against smooth muscle actin (arteries), protein gene product 9.5 (PGP9.5) and neurofilament (nerve fibres). Skin samples served as controls. Nerve fibre and vessel densities were quantified morphometrically.
  
  
  RESULTS
  Nerve fibre density varied considerably. However, vascular innervation did not statistically significantly differ between the different tumour sub-groups and controls. Vessel density was not significantly increased in tumours compared to skin biopsies. Within the tumour sub-groups, diffuse plexiform neurofibroma presented a significantly higher vascular density than atypical neurofibroma (p=0.006).
  
  
  CONCLUSIONS
  Blood vessel density and vascular innervation in the whole cohort of neurofibromas did not significantly differ from that of controls. Thus, the source of prolonged and intense bleeding of neurofibroma during surgical procedures cannot be explained by increased vessel density or loss of innervation, but may be attributed to other factors such as alterations in the structure of the vascular wall.
authors.affiliation: Department of Oral and Craniomaxillofacial Surgery, University Medical Center Hamburg-Eppendorf, University of Hamburg, Hamburg, Germany rfriedrich@uke.de.
authors.forename: Reinhard E
authors.initials: RE
authors.lastname: Friedrich
authors.affiliation: Institute of Neuropathology, University Medical Center Hamburg-Eppendorf, University of Hamburg, Hamburg, Germany Department of Vascular Medicine, Heart Center, University Medical Center Hamburg-Eppendorf, University of Hamburg, Hamburg, Germany.
authors.forename: Christian-Alexander
authors.initials: CA
authors.lastname: Behrendt
authors.affiliation: Institute of Neuropathology, University Medical Center Hamburg-Eppendorf, University of Hamburg, Hamburg, Germany.
authors.forename: Markus
authors.initials: M
authors.lastname: Glatzel
authors.affiliation: Institute of Neuropathology, University Medical Center Hamburg-Eppendorf, University of Hamburg, Hamburg, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Hagel
mesh_terms: D000328:Adult; D005260:Female; D006801:Humans; D042601:Lymphatic Vessels / Q000098:blood supply*; D008297:Male; D009455:Neurofibroma / Q000098:blood supply* / Q000473:pathology; D009456:Neurofibromatosis 1 / Q000097:blood* / Q000473:pathology
keywords: NF1; Nerve fibre density; blood vessels; lymphatic vessels; neurofibroma; neurofibromatosis; vessel density; vessel innervation