Bevacizumab (
Avastin, Genetech/Roche) is an
anti-angiogenic drug approved for treating patients with
malignant gliomas that reduces
edema and mass effect, but has been suggested to promote multifocal
tumor spread within the brain. Patients with systemic
malignancies are also treated with
bevacizumab, but there is limited information regarding effects of the
drug on the neuroimaging or neuropathological features of metastatic
CNS disease. We report 2 patients with
non-small cell lung carcinomas who had received
bevacizumab for their systemic
cancers and then developed cognitive deficits consistent with white matter
dementia. Diagnosis of
leptomeningeal carcinomatosis (LC) was confounded and delayed by the finding of atypical neuroimaging features, including minimal to absent leptomeningeal enhancement and unusual perivascular and punctate hemorrhagic lesions and multifocal subgyral signal abnormalities suspicious for
vasculitis or small vessel vasculopathy. Neuropathological assessment confirmed LC but, in the autopsy case also disclosed extraordinary perivascular spread of individual metastatic
tumor cells to the depth of capillaries. The pattern was reminiscent of vascular "cooption" by
tumor seen in experimental animals in preclinical trials of
bevacizumab. Small
infarctions were associated with perivascular
tumor and vasculopathy, unusual features of LC in patients who do not receive
bevacizumab. In the biopsied patient, multiple perivascular
tumor nodules were identified in superficial cortex. In these two patients,
bevacizumab appeared to alter neuroimaging characteristics of LC, confounded diagnosis and possibly also influenced the pattern of
tumor spread of LC. More cases will need to be studied to confirm this latter finding.