Diana Thomas, MD, PhD and Ronald Hamilton, MD
A middle aged man was admitted to the neurology service for acute onset aphasia and right sided weakness. He received tPA due to clinical concern for stroke, however, subsequent brain MRI was not consistent with ischemic stroke. Scans showed multiple nonenhancing periventricular and subcortical zones of abnormal T2 signal with associated prior hemorrhage (Figure 1). The leading diagnostic consideration was vasculitis and/or vasculopathy. Other considerations were lymphoma or septic emboli, but CSF and flow cytometry studies were negative and lab values did not support an infectious process. The working diagnosis was inflammatory amyloid angiitis based on clinicoradiological criteria. He was treated with steroids and improved sufficiently for discharge.
Over the next several weeks he returned back to the hospital on multiple occasions with fluctuating neurological symptoms including worsening aphasia, confusion, weakness and headache. He was found to have seizures on EEG for which he was treated with antiepileptic medications and steroids, usually with improvement, though never resolution of his symptoms. Throughout these multiple readmissions, brain MRI initially showed stable findings though ultimately showed progression of disease with worsening seizures despite steroid therapy and escalating seizure treatment. A stereotactic needle biopsy of a left frontal lesion was ultimately performed to confirm the diagnosis and rule out other etiologies.
An intraoperative consultation was requested on the needle biopsy and a smear preparation was made.
Whole Slide Image of Smear Prep
The smear preparation revealed lesional tissue involving white matter with marked gliosis, numerous reactive astrocytes and scattered foamy macrophages. No obvious neoplasm was seen.
The permanent H&E sections of the remainder of the core showed fragments of cortex and edematous white matter with mild reactive gliosis and scattered macrophages. The intraparenchymal vessels were mildly thickened and hyalinized (Figures 2 and 3). A few small vessels were associated with lymphocytes and large atypical cells (Figure 4). No acute inflammation was seen.
Whole Slide Image of H&E
A panel of immunostains was performed. A beta-amyloid stain was negative in the vessel walls, arguing against amyloid angiopathy. IDH1, ATRX, p53, and EGFR immunostains showed no evidence of an infiltrating glioma. CD20 and PAX5 highlighted large atypical intraluminal cells in rare vessels (Figure 5). A CD3 stain showed a moderate number of T cells scattered throughout the brain parenchyma and surrounding some small vessels (Figure 6). Nearly all of the intraluminal cells were positive for Ki-67 (Figure 7).
Whole Slide Image of CD20/L26
Whole Slide Image of CD3
Whole Slide Image of Ki-67