Radiation-Induced Cerebral Vascular “Malformations” at Biopsy

Abstract

Radiation-induced vascular “malformations”, designated cavernous hemangiomas/cavernomas (“RICHs”), are seldom biopsied and are usually diagnosed based on neuroimaging features. They are an increasingly recognized complication of both CNS external beam radiation therapy and stereotactic radiosurgery. We identified 13 patients with radiation-induced vascular “malformations” in our surgical neuropathology databases searched from 2000 to 2016; 4 had received their therapy during childhood; 5 had received radiosurgery. Inclusion required identifiable vascular abnormalities on neuroimaging and/or, if recurrent tumor was additionally present, the vascular lesion had been a separately submitted specimen at the time of resection. Trichrome, and elastic stains and immunohistochemistry (IHC) for CD31, CD34, and smooth muscle actin (SMA) were performed. Five RICHs showed histological and IHC overlap with 12 non-radiation-induced cavernomas; 8/13 had organizing coagulum containing recanalized vasculature and fibrinous deposits. Markedly altered vasculature in these 8 lacked the back-to-back caverns typical of cavernomas; there was near absence of SMA immunopositivity in their ill-defined vessel walls. These coagulum-like lesions likely represented organized fibrinous exudates caused by subacute/remote radiation-induced fibrinoid vascular necrosis and vascular leakage. Thus, RICHs occur as 2 distinct histological types, without direct correlation between histological type and age at receipt, or type, of radiation. Two different etiological mechanisms likely underlie their pathogenesis.