Delayed radiation-induced vasculitic leukoencephalopathy.
OBJECTIVE
Recently, single-fraction, high-dosed focused radiation therapy such as that administered by Gamma Knife radiosurgery has been used increasingly for the treatment of metastatic brain cancer. Radiation therapy to the brain can cause delayed leukoencephalopathy, which carries its own significant morbidity and mortality. While radiosurgery-induced leukoencephalopathy is known to be clinically different from that following fractionated radiation, pathological differences are not well characterized. In this study, we aimed to integrate novel radiographic and histopathologic observations to gain a conceptual understanding of radiosurgery-induced leukoencephalopathy.


METHODS
We examined resected tissues of 10 patients treated at Yale New Haven Hospital between January 1, 2009, and June 30, 2010, for brain metastases that had been previously treated with Gamma Knife radiosurgery, who subsequently required surgical management of a symptomatic regrowing lesion. None of the patients showed pathological evidence of tumor recurrence. Clinical and magnetic resonance imaging data for each of the 10 patients were then studied retrospectively.


RESULTS
We provide evidence to show that radiosurgery-induced leukoencephalopathy may present as an advancing process that extends beyond the original high-dose radiation field. Neuropathologic examination of the resected tissue revealed traditionally known leukoencephalopathic changes including demyelination, coagulation necrosis, and vascular sclerosis. Unexpectedly, small and medium-sized vessels revealed transmural T-cell infiltration indicative of active vasculitis.


CONCLUSIONS
We propose that the presence of a vasculitic component in association with radiation-induced leukoencephalopathy may facilitate the progressive nature of the condition. It may also explain the resemblance of delayed leukoencephalopathy with recurring tumor on virtually all imaging modalities used for posttreatment follow-up.
Departments of Pathology and Neurosurgery, Yale University School of Medicine, New Haven, Connecticut, USA.
Philipp J
PJ
Rauch
Henry S
HS
Park
Jonathan P S
JP
Knisely
Veronica L
VL
Chiang
Alexander O
AO
Vortmeyer
D000328:Adult; D000368:Aged; D001921:Brain / Q000098:blood supply / Q000528:radiation effects*; D001932:Brain Neoplasms / Q000473:pathology / Q000556:secondary / Q000601:surgery*; D005260:Female; D006801:Humans; D056784:Leukoencephalopathies / Q000209:etiology / Q000473:pathology*; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D008875:Middle Aged; D016634:Radiosurgery / Q000009:adverse effects* / Q000295:instrumentation; D012189:Retrospective Studies; D020293:Vasculitis, Central Nervous System / Q000209:etiology* / Q000473:pathology*