Chronic Lymphocytic Leukemia Infiltrating in the Brain

Abstract

While earlier post-mortem studies show involvement of the central nervous system in 71% of patients with chronic lymphocytic leukemia (CLL), involvement intravitam is rare. A 72-year-old man with untreated, minimally symptomatic CLL developed subacute-onset encephalopathy and presented with severe hyponatremia and stress-induced cardiomyopathy. His initial head computed tomography scan was unremarkable. His mental status did not improve with careful sodium correction. Magnetic resonance imaging of the brain eventually revealed widespread T2 hyperintensities throughout the cerebral hemispheres, brainstem, and cerebellum. A cerebrospinal fluid analysis demonstrated elevated total nucleated cells (31/mcL, 89% lymphocytes), protein of 75 mg/dL, positive human herpesvirus 6 by polymerase chain reaction, and the presence of malignant CD5+ B cells, consistent with CLL. Brain biopsy confirmed direct infiltration of CLL cells in the brain parenchyma. He was started on zanubrutinib, which led to clinical and radiologic improvement. His neurologic recovery remained slow, and his family elected to transition to comfort-focused care. Our patient's case exemplifies a rare neurologic manifestation affecting <1% of patients with CLL. Despite partial clinical and radiologic response to zanubrutinib, he had a poor outcome, likely due to the extensive brain areas involved by CLL.

Keywords: brain biopsy; chronic lymphocytic leukemia (cll); encephalopathy; neuro-oncology; radiology.

Figure 1. Initial head CT scan

A) Head CT scan without IV contrast demonstrating no acute intracranial abnormality. B) Head CT scan showing left frontal metal artifact (yellow arrow).

Figure 2. Initial brain MRI

A) Diffusion-weighted brain MRI with increased signal in the splenium of the corpus callosum on the left (blue arrow). B-D) FLAIR sequences demonstrating patchy T2 hyperintensities in the brainstem (orange arrows) and cerebral white matter (pink arrows). There was no associated contrast enhancement.

Figure 3. Left parietal lobe brain biopsy pathology

A) Hematoxylin and eosin-stained section of the left parietal lobe brain biopsy shows a predominantly perivascular infiltrate of small lymphocytes. B) CD3 stain demonstrating total T-cells. C) CD5 stain showing T-cells that express CD5 and B-cells of CLL, which also express CD5. D) CD20 stain demonstrating B-cells, which characteristically have lower expression of CD20 compared to normal B-cells.  All images were taken at 200x magnification. Concurrently performed flow cytometry identified a kappa light chain restricted B-cell population with the expression of CD5 and CD23.

Figure 4. Follow-up brain MRI

Fluid-attenuated inversion recovery (FLAIR) magnetic resonance imaging (MRI) obtained after zanubrutinib treatment showing improvement in T2 hyperintensities in the brainstem (A, orange arrow) and cerebral hemispheres (B, pink arrows).