Background: Chronic encapsulated expanding hematoma is a rare, but highly morbid, severe complication after stereotactic radiosurgery for intracerebral arteriovenous malformations (AVMs). The aim of this study was to clarify the clinical features and possible mechanisms of formation and expansion of this type of hematoma based on histopathological findings. Methods: The patients were comprised of three males and one female. Three of these patients had AVMs in the basal ganglia, while the remaining one in the frontal lobe. Results: Cerebral angiograms performed 6 months to 11 years after radiosurgery demonstrated major, but incomplete, obliteration of the nidi. Each patient developed localized enhancing mass lesions at 2, 3, 5, and 11 years after radiosurgery. The lesions expanded slowly, but progressively over time in association with marked perifocal edema. The perifocal edema disappeared immediately after removal of the hematoma; their neurological symptoms improved partially or completely. Histopathologically, the hematomas were well-encapsulated and the capsule walls uniformly consisted of an outer fibrocollagenous layer and an inner granulation layer. Immunohistochemistry revealed vascular endothelial growth factor (VEGF) expression in the endothelium of newly formed blood vessels and myofibroblasts in the hematoma capsule inner layer. Myofibroblasts also expressed VEGFR-1. Conclusions: The activation of VEGF pathway may lead to neovascularization in the granulation layer of the hematoma capsule that serves as a continual source of bleeding and perifocal edema. Thus, radical resection of the capsule and residual nidus is strongly recommended for the management of both bleeding and edema.
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