Progressive multifocal leukoencephalopathy associated with isolated CD8+ T-lymphocyte deficiency mimicking tumefactive MS

Abstract

Progressive multifocal leukoencephalopathy (PML) is a severe demyelinating disease of the central nervous system (CNS) caused by lytic infection of oligodendrocytes by the polyomavirus JC (JCV). PML has classically been described in individuals with profound cellular immunosuppression. While some case reports have documented PML in individuals with minimal or occult immunosuppression, such cases are very rare and their pathogenesis is not well understood. We report a unique case of a 74 year-old woman who developed PML clinically mimicking tumefactive multiple sclerosis in the context of an idiopathic isolated CD8+ T-lymphocytopenia. Her course subsequently stabilized, concomitant to the development of a cellular immune response directed against JCV. We review the current literature of related cases and discuss the pathogenesis and implications of this rare presentation.

Figure 1

MRI brain. Initial Presentation (top row): axial FLAIR showing tumefactive lesion in the right frontal lobe white matter extending to the subcortical white matter of the temporal lobe (A and B), axial T1 + gadolinium showing ring enhancement of the lesions (C and D). 10-month follow-up (bottom row): axial FLAIR showed residual lesions in the right frontal and temporal lobe white matter and left periventricular area, associated with atrophy (E and F), axial T1+ gadolinium demonstrating absence of enhancement in the lesions (G and H).

Figure 2

Right frontal lobe pathology. A: Hematoxylin and eosin stain of biopsied lesion showing extensive inflammatory infiltrate. B: JCV in situ hybridization demonstrating JCV+ cells. C: Double Immunohistostaining showing equal numbers of CD8+ (brown) and CD4+ T cells (blue, CD3+/CD8−). Antibodies: Vector VP-C325 CD8 (1A5) & Novocastra NCL-L-CD3-PS1.