FINAL DIAGNOSIS: PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY
The diagnostic stain was a JC virus in situ hybridization which showed many positive nuclei. The initial HSV immunostains were thought to be due to high background or other artifact and were repeated. The repeat HSV immunostains again showed scattered poitive nuclei. These nuclei did not have the Cowdrey A inclusions typical of herepes simplex, but resembled the oligodendroglial inclusions of PML. In situ hybridization for HSV was also negative and it was concluded that the HSV immunostaining was probably an unusual cross-reactivity. Immunostains for VZV were negative. Viral cultures of the brain biopsy were negative. Electron microscopy showed cells with typical papova virus structures in the nucleus. No herpes viral particles were seen.
PML has only rarely been described as the presenting sign of AIDS, and then usually in high risk populations. This patient had no history of immunocompromise and no previous opportunistic infections. She gave no history of needle-stick injuries and was not an IV drug abuser. Her husband was also not known to be HIV-infected and had no known risk factors for HIV.
Subsequent to this biopsy, she was shown to be infected with HIV and was diagnosed with AIDS. Her husband has since tested negative. She has an 18-month old child and had been tested for HIV during the pregnancy and was negative. The child is also currently negative. Her CD4 count at the time of the biopsy was 63 (nl: 288-1736). An MRI 10 days after the biopsy showed progression of the lesions as seen in these axial and coronal scans with contrast. A Roche quantitative RT-PCR test for plasma HIV-1 RNA showed a HIV-1 genomic titer of 106,000 per milliliter of blood.
Acknowledgements: The contributors would like to thank Dr. Oscar Lopez for the clinical history and Ms. Patricia A. Snyder, B.S., for the EM micrographs.
Contributed by Ronald L. Hamilton, MD and A. Julio Martinez, MD