Radiosurgical Pathology of Brain Tumors: Metastases, Schwannomas, Meningiomas, Astrocytomas, Hemangioblastomas

Abstract

Systematic human pathological background to brain tumor radiosurgery explaining biological and pathophysiological effects of focused irradiation barely exists. The goal of this study was to explore histopathological changes evoked by single high-dose irradiation in a set of different brain tumors following Gamma Knife radiosurgery (GKRS). Light microscopy revealed that GKRS evokes degenerative and proliferative pathological changes in the parenchyma, stroma and vessels of the irradiated tumors. Three main histological types of gamma radiolesions, that is acute, subacute and chronic variants of tissue reactions were recognized in different neoplasms irrespective of their ontogenetic nature. Acute type gamma radiolesions were characterized mainly with necrotic changes and appeared either early or in a delayed time interval. Subacute type gamma radiolesions expressed resorptive activity also with early or delayed chronology. Chronic type lesions showed a reparative tendency but presented only at the delayed stage. These changes seem to follow each other consecutively. There was no significant relation between morphological characteristics of the generated tissue reaction and the time interval elapsed after GKRS. This relative time and environment autonomy of the developed pathological lesions with similar histological picture in different neoplasms suggests either a vascular mechanism or/and a genetically directed origin presumably induced by the ionizing energy of high-dose irradiation.

Experimental Analysis of Radiation Dose Distribution in Radiosurgery: I. Dose Hot Spot inside Target Volume

“…On histological analysis performed 3 months after irradiation, several histopathological effects of focused irradiation were noticed inside the target volume: spongiosis, microhemorrhages, necrosis, thickening of the wall of microvessels, ischemic neurons, macrophages and calcifications. These findings are in accordance with observations reported in previous studies at this time interval after irradiation [11][12][13][14] . Additional radiobiological effects might develop after the 90-day interval arbitrarily used in this study; other experimental studies using a longer time interval between irradiation and sacrifice could perhaps provide additional histological observations in the different groups of rats.…”

Radiation-induced effects and the immune system in cancer

“…Damage to vascular/stromal elements in tumors has also been observed around 2 weeks after radiation exposure that was less dependent on size of dose per fraction (Chen et al, 2009). Pathological observations show profound changes in vasculature after radiosurgery and from studies on arteriovenous malformations, where obliteration of abnormal vasculature occurs months after irradiation, but is rarely seen below single doses of 12 Gy climbing steeply with increasing doses above this threshold (Szeifert et al, 2007). Although lymphocyte radiosensitivity is well recognized, the effects of different doses and delivery methods on systemic and locoregional naive, effector, or Treg or other immunologically relevant populations is still the subject of debate.…”

The Confluence of Stereotactic Ablative Radiotherapy and Tumor Immunology

“…Pathological observations show profound changes in vasculature after radiosurgery and from studies on arteriovenous malformations [10], where obliteration of abnormal vasculature occurs months after irradiation, but is rarely seen below single doses of 12 Gy climbing steeply with increasing doses above this threshold.…”