Ultrastructural characteristics of hemorrhagic, nonhemorrhagic, and recurrent cavernous malformations

J Neurosurg. 2005 Nov;103(5):903-9. doi: 10.3171/jns.2005.103.5.0903.


Object: Ultrastructural characteristics of hemorrhagic, nonhemorrhagic, primary, and recurrent central nervous system cavernous malformations (CMs) were examined in an attempt to clarify their pathological mechanisms.

Methods: Thirteen specimens (nine from samples of CMs and four from healthy control tissue) were processed for ultrastructural study immediately after surgical or postmortem removal, by fixation in glutaraldehyde/formalin and postfixation in OsO4. Transmission electron microscopy was used to examine the vascular walls, endothelium, subendothelium, and cytoplasmic organelles. The vascular walls in CMs demonstrated abnormal ultrastructure with no basement membranes and astrocytic foot processes. Pericytes were rarely seen. Single-layer lining endothelial cells showed fenestrated luminal surfaces. Large gaps were observed at intercellular junctions between endothelial cells, and large vesicles with extremely thin plasma membranes bordering the lumen were common in the lesions that had previously hemorrhaged. Endothelial cells of recurrent CMs had more Weibel-Palade bodies, filopodia, cytoplasmic processes, micropinocytotic vesicles, and filaments than those in primary lesions and normal control tissues.

Conclusions: The absence of the blood-brain barrier, normal supporting wall structure, and large vesicles bordering the lumen of CM vessels may explain leakage of red blood cells into surrounding brain in the absence of major hemorrhage. Proliferation of residual abnormal endothelial cells may contribute to the recurrence of surgically removed CMs.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Blood-Brain Barrier
  • Brain Neoplasms / pathology*
  • Brain Neoplasms / surgery
  • Capillaries / pathology
  • Capillaries / ultrastructure
  • Cell Differentiation
  • Cerebral Hemorrhage / pathology*
  • Cerebral Hemorrhage / surgery
  • Child
  • Cytoplasmic Vesicles / pathology
  • Endothelial Cells / pathology*
  • Endothelial Cells / ultrastructure
  • Female
  • Hemangioma, Cavernous / pathology*
  • Hemangioma, Cavernous / surgery
  • Humans
  • Intracranial Arteriovenous Malformations / pathology*
  • Intracranial Arteriovenous Malformations / surgery
  • Magnetic Resonance Imaging
  • Male
  • Microscopy, Electron
  • Middle Aged
  • Pseudopodia / pathology
  • Recurrence
  • Vacuoles / pathology
  • Weibel-Palade Bodies / pathology