Ultrastructural pathological features of cerebrovascular malformations: a preliminary report
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Updated: Sep 16, 2026

Longitudinal In Vivo Imaging of the Cerebrovasculature: Relevance to CNS Diseases
Published on: December 6, 2016
1Department of Neurosurgery, Yale University School of Medicine, New Haven, Connecticut 06520, USA.
Objective:
Although cerebrovascular malformations have been characterized histologically, a systematic examination of such lesions by transmission electron microscopy has not been previously published. In this preliminary study, we describe the ultrastructural pathological features of cerebral arteriovenous malformations (AVMs) and cavernous malformations (CMs).
Methods:
Using transmission electron microscopy, we examined three CMs and three AVMs microsurgically harvested from patients, for conventional indications. Normal control cerebral tissue was obtained from two patients undergoing surgery for epilepsy. Specific attention was directed at components of the vascular wall, endothelial cell (EC) morphology, intercellular tight junctions, and the subendothelial layer.
Results:
In embolized AVM vessels, ECs were disrupted, with preservation of the underlying subendothelial vessel wall. Nidal vessel walls of AVMs showed disorganized collagen bundles. In CM specimens, ECs lined attenuated cavern walls that were composed of an amorphous material lacking organized collagen. Peripheral to the CMs, capillaries were often surrounded by rings of hemosiderin. Tight junctions between ECs were present in AVMs and control specimens, but substantial inter-EC gaps were found in CMs. Subendothelial smooth muscle cells were present in AVM and control specimens, but they were sparse or poorly characterized in CMs.
Conclusion:
Surgically resected vascular malformations demonstrate abnormal ultrastructural pathological features. The preoperative embolization of AVMs results in EC denudation, with preservation of vessel wall structural integrity. The thin walls of CMs, lacking significant subendothelial support, along with the rarity of intact tight junctions between ECs, may contribute to the known propensity of CMs for recurrent microhemorrhage.
Insights
Transmission electron microscopy revealed distinct ultrastructural differences in cerebral arteriovenous malformations (AVMs) and cavernous malformations (CMs). CMs exhibit thin, fragile walls and gaps between endothelial cells, potentially explaining their tendency for hemorrhage.
Area of Science:
- Neuropathology
- Vascular Biology
- Electron Microscopy
Background:
- Cerebrovascular malformations (CVMs) like AVMs and CMs require detailed pathological understanding.
- Previous ultrastructural studies using transmission electron microscopy (TEM) on these lesions are limited.
Purpose of the Study:
- To systematically examine and describe the ultrastructural pathological features of cerebral arteriovenous malformations (AVMs) and cavernous malformations (CMs) using TEM.
- To compare the ultrastructure of AVMs and CMs with normal cerebral tissue.
Main Methods:
- TEM analysis of three surgically harvested AVMs and three CMs.
- Examination of normal control cerebral tissue from two epilepsy surgery patients.
- Focused analysis on vascular wall components, endothelial cell (EC) morphology, intercellular tight junctions, and the subendothelial layer.
Main Results:
- AVM vessels showed disrupted ECs but preserved subendothelial walls; nidal walls had disorganized collagen.
- CM cavern walls were attenuated, lined by ECs, and composed of amorphous material lacking organized collagen.
- CMs displayed significant inter-EC gaps and sparse subendothelial smooth muscle cells, unlike AVMs and controls.
Conclusions:
- Surgically resected AVMs and CMs present unique abnormal ultrastructural features.
- Preoperative embolization of AVMs causes EC denudation but preserves vessel wall integrity.
- CMs' thin, poorly supported walls and defective tight junctions may underlie their propensity for recurrent microhemorrhage.
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