Concomitant progressive multifocal leucoencephalopathy and primary central nervous system lymphoma expressing JC virus oncogenic protein, large T antigen

Abstract

This report describes the concomitant occurrence of the JC virus (JCV) induced demyelinating disease progressive multifocal leucoencephalopathy (PML) and a primary central nervous system lymphoma (PCNS-L) in a patient with AIDS. Postmortem neuropathological examination revealed characteristic features of PML including multiple lesions of demyelination, enlarged oligodendrocytes with hyperchromatic nuclei (many containing eosinophilic intranuclear inclusions), and enlarged astrocytes with bizarre hyperchromatic nuclei. Immunohistochemical analysis demonstrated the expression of the JCV capsid protein VP-1 in the nuclei of infected oligodendrocytes and astrocytes. The PCNS-L lesion located in the basal ganglia was highly cellular, distributed perivascularly, and consisted of large atypical plasmacytoid lymphocytes. Immunohistochemical examination of this neoplasm identified it to be of B cell origin. Moreover, expression of the JCV oncogenic protein, T antigen, was detected in the nuclei of the neoplastic lymphocytes. This study provides the first evidence for a possible association between JCV and PCNS-L.

Figure 1

Neuroimaging and macroscopic features. (A) T2 weighted magnetic resonance imaging of the brain showing extensive hyperintense signal abnormalities in the subcortical white matter of the frontal, temporal, and occipital lobes. (B) A coronal section of the brain at necropsy demonstrating demyelinating lesions in the white matter ranging from discolouration to severe cavitation.

Figure 2

Histological and immunohistochemical characteristics of progressive multifocal leucoencephalopathy lesions. Extensive areas of demyelination in the white matter are evident (A, luxol fast blue; B, haematoxylin and eosin; original magnification, ×10). Infected oligodendrocytes with eosinophilic intranuclear inclusions (arrow) and transformed bizarre astrocytes are present in the demyelination areas (C: original magnification, ×40; D: original magnification, ×100; haematoxylin and eosin). Immunohistochemistry using antisera raised against JC virus VP-1 demonstrates expression of the capoid protein VP-1 in the intranuclear viral inclusions of oligodendrocytes (E: original magnification, ×100) and in the nuclei of transformed astrocytes (F: arrows; original magnification, ×40).

Figure 3

Histological and immunohistochemical evaluation of primary central nervous system lymphoma. Neoplastic cells have an angiocentric pattern, forming collars around blood vessels (A; original magnification, ×20; haematoxylin and eosin). At higher magnification the neoplastic cells are round with big nuclei and moderate eosinophilic cytoplasm (B; original magnification, ×100; haematoxylin and eosin). Immunohistochemical staining with anti-CD20 and anti-CD79α antibodies shows intense cytoplasmic and membrane associated reactivity in the neoplastic perivascular cells (C; original magnification, ×20; D, original magnification, ×100). Immunohistochemical staining with an antibody detecting JC virus T antigen shows expression in the nuclei of approximately 60% of the neoplastic lymphocytes (E; original magnification, ×40; F; original magnification, ×100).