Treatment-induced leukoencephalopathy in primary CNS lymphoma

Background: Treatment-related leukoencephalopathy is the leading toxicity after successful treatment of primary CNS lymphoma (PCNSL). Its mechanism is poorly understood and there are no autopsy data available on such patients. Methods: From a database of immunocompetent patients with PCNSL diagnosed between 1985 and 2001, the authors identified five autopsied patients who died of leukoencephalopathy. The authors reviewed their clinical records, MRI, and autopsy findings. Results: The median age was 74 years (range 41 to 79) at PCNSL diagnosis. Symptoms of neurotoxicity developed a median of 1 month after treatment completion, and median survival was 30 months (range 22 to 68 months) after neurotoxicity onset. All had white matter hyperintensity on T2-weighted MRI, and two developed enhancing lesions 5 and 14 months following completion of treatment. At autopsy no PCNSL was identified. Myelin and axonal loss, gliosis, pallor, spongiosis, and rarefaction of the white matter were found in all; two patients had tissue necrosis that correlated with the enhancement on MRI, and one had fibrinoid necrosis of vessels. Four of the five patients had atherosclerosis of large cerebral vessels in the circle of Willis and all had small vessel disease; two had recent strokes at autopsy. Conclusions: Treatment-induced leukoencephalopathy is not a late delayed consequence of neurotoxic treatment but can be seen very early in some patients. Vascular disease may be a component of this white matter injury.