Contribution to the pathogenesis of radiation-induced injury to large arteries

Abstract

We report a case of a 35-year-old man who died of a brain infarct 20 months after radiotherapy for carcinoma of the tonsil with metastases to the cervical lymph nodes. Histology revealed mild atherosclerosis, necrotizing vasculitis, and occlusive thrombosis of the internal carotid artery. Significant changes were observed in the vasa vasorum: swelling and detachment of the endothelium, subendothelial oedema, hyaline change, fibrinoid necrosis of the vessel walls with mononuclear cellular infiltration, accompanied by focal haemorrhages and chronic inflammation in the periadventitial soft tissue. We believe that these changes of the vasa vasorum and necrotizing vasculitis are causally related and that vasculitis represents focal ischaemic necroses with inflammatory reaction. Our findings support the hypothesis, based on experimental studies, that injury to the vasa vasorum is an important mechanism in the development of radiation-induced vasculopathy of large arteries. They also suggest an evolution of the injury to the vasa vasorum and periadventitial tissue from the early lesions described in our patient, to late stages resulting in dense periadventitial fibrosis as reported previously. We suggest that injury to the vasa vasorum and the consequent ischaemic lesions of the arterial wall are morphological features distinguishing radiation-induced arterial injury from spontaneous atherosclerosis.

Ischemic Stroke and Transient Ischemic Attack After Head and Neck Radiotherapy

“…Some authors have argued that chronic occlusive radiation vasculopathy is primarily an accelerated form of atherosclerosis 56,60 -63 ; others have described it as a distinct disease entity shaped by the initial radiation insult to the vasa vasorum. 15,59,64,65 Either way, it is the most radiosensitive mesenchymal cell common to both the artery proper and the vasa vasorum, the endothelial cell, 9 that bears the brunt of any XRT field effect. Fonkalsrud et al 55 used scanning electron microscopy to analyze the evolution of radiation vasculopathy in canine femoral arteries after a net dose of 40 Gray.…”

“…It is this periadventitial scarring, often combined with advanced atheroma of the endothelium, that is most commonly described in surgical case series. 7,56,57,62 Documentation of disease evolution in the manner of Fonkalsrud et al 55 in humans is clearly impossible, but Zidar et al 59 described an autopsy case of a 35-year-old-man who succumbed to metastatic tonsillar carcinoma 20 months after XRT. Extensive focal inflammation and necrosis of the vasa vasorum and adventitium were seen.…”

The effect of halofuginone on radiation-induced cardiovascular injury

“…4,10,11 The sequence of endothelial injury, cell detachment, thrombosis and fibrosis results in significant tissue injury that often limits radiation oncologist in attempting to deliver curative doses to a nearby tumor. The hallmark of radiation-induced injury is extensive fibrosis.…”

“…3 Primary basic mechanisms behind radiation-induced cardiovascular disease appear to be endothelial dysfunction. [4][5][6] The sequence of endothelial injury, cell detachment, thrombosis and fibrosis results in significant tissue injury that often limits radiation oncologist in attempting to deliver curative doses to a nearby tumor. Fajardo and Steward have demonstrated that damage to the myocardium develops through three phases of injury.…”

Moyamoya Syndrome after Radiation Therapy: Case Reports

“…By contrast, radiation-induced vascular injury is a well-known phenomenon, in which small arteries and capillaries are commonly and severely affected. Injuries of large arteries by radiation has been considered relatively rare, but the clinically important damage may be more common than previously thought [5,6]. This report describes 2 pediatric patients with moyamoya syndrome after radiation therapy: optic pathway glioma and medulloblastoma.…”