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Simultaneous progressive multifocal leukoencephalopathy, Epstein-Barr virus (EBV) latent infection and cerebral
1Department of Internal Medicine, Saint Louis Hospital, Paris VII University, France.
Abstract:
We report a non-HIV patient who had B chronic lymphocytic leukemia (CLL) with progressive multifocal leukoencephalopathy (PML) and diffuse cerebral leukemic parenchymal infiltration in the presence of JC virus and Epstein-Barr virus (EBV) cerebral co-infection. Multiple subcortical hypodensities lining the cortico-subcortical junction were present within the white matter on computerized tomography (CT) scan, with large areas of high signal intensity on T2-weighted sequences on magnetic resonance imaging (MRI). JCV DNA was identified in peripheral blood nuclear cells and cerebrospinal fluid polymerase chain reaction (PCR) DNA/DNA hybridization plus Southern blot analysis. Frontal stereotactic biopsy confirmed the diagnosis of PML by immunocytochemistry, in situ hybridization (ISH) with JC Enzo probe and electron microscopy. Leukemic B cells with the same phenotype as leukemic blood cells were disseminated in the demyelinated areas. They were labeled by anti-latent membrane protein and by BamHl W EBV probe after ISH. Adhesion and activation molecules were positive for CD23. Autopsy showed diffuse visceral leukemic infiltration without acutization. EBV-transformed B lymphocytes would favour JCV penetration and/or intracerebral reactivation of previously latent JCV infection with further development of simultaneous PML and cerebral CLL infiltration in an immunosuppressed patient.
Insights
In an immunocompromised patient without HIV, concurrent progressive multifocal leukoencephalopathy (PML) and B chronic lymphocytic leukemia (CLL) brain infiltration occurred. This case highlights EBV-associated B-cell transformation potentially facilitating JC virus reactivation and co-infection.
Area of Science:
- Neurovirology
- Hematology
- Immunology
Background:
- Progressive multifocal leukoencephalopathy (PML) is a rare demyelinating disease caused by the JC virus (JCV).
- Chronic lymphocytic leukemia (CLL) is a B-cell malignancy often associated with immunosuppression.
- Cerebral co-infections with multiple viruses can complicate diagnosis and treatment in immunocompromised individuals.
Observation:
- A non-HIV patient presented with neurological symptoms and imaging findings suggestive of white matter lesions.
- Computerized tomography (CT) revealed subcortical hypodensities, while magnetic resonance imaging (MRI) showed extensive T2-weighted signal hyperintensities.
- JC virus (JCV) DNA was detected in peripheral blood and cerebrospinal fluid (CSF).
Findings:
- Stereotactic brain biopsy confirmed PML, with leukemic B cells infiltrating demyelinated areas.
- In situ hybridization (ISH) identified both JCV and Epstein-Barr virus (EBV) within the cerebral lesions.
- Leukemic B cells expressed latent membrane protein and EBV, along with CD23 adhesion molecules.
Implications:
- Epstein-Barr virus (EBV)-transformed B lymphocytes may promote JC virus (JCV) entry or reactivation in the brain.
- This case demonstrates simultaneous PML and cerebral CLL infiltration in an immunosuppressed patient.
- Understanding viral co-pathogenesis is crucial for managing complex neurological complications in hematological malignancies.