Histopathologic correlation of recurrent glioblastoma tissue samples obtained from regions with and without reduced diffusion using image-guided stereotactic neurosurgical techniques in a patient demonstrating salt & pepper phenotype following bevacizumab therapy. (a) Intraoperative tissue sampling site superimposed on a post-therapeutic T1-weighted contrast-enhanced image, diffusion-weighted image, and apparent diffusion coefficient (ADC) map demonstrates mass like infiltrative T2 hyperintensity involving the left frontal lobe associated with salt & pepper phenotype reduced diffusion and minimal contrast enhancement. Tissue sampling site from region without reduced diffusion (left) demonstrated ADCmin of 842 and ADCmean of 951. Tissue sampling site from region with reduced diffusion demonstrated ADCmin of 485 and ADCmean of 646 (right). (b) Tissue samples obtained from region of recurrent tumor without reduced diffusion (blue region of interest [ROI]) demonstrated infiltrating cellular tumor (left; H&E stain 200× magnification), cellular proliferation of 1% (middle; Ki-67), with minimal vascular hyperplasia (right; factor VIII = delicate vascular appearance). (c) Tissue samples obtained from region of recurrent tumor with reduced diffusion (red ROI) demonstrated infiltrating cellular tumor (left; H&E stain 10× magnification) with elevated cellular proliferation (middle; Ki-67 = 11%), and predominantly simple vascular hyperplasia (right; factor VIII). No significant necrosis was observed within either tissue specimens. (Color version of figure is available online.)