1. CPC #2: 38 year old woman with HIV/AIDS and altered mental status October 9, 2007

2. Lungs  Combined weight 2,200 gm (normal 685-1,050)  Most of weight increase due to pulmonary edema  Multiple discrete nodules with necrotic centers  Bronchopneumonia  CMV infection

3. Pulmonary edema

4. Necrotizing nodules – no AFB or fungi ID’d CD20 – B-cells CD3 – T-cells

5. Bronchopneumonia

6. Bronchopneumonia – and CMV infection

7. CMV in alveoli and around necrotizing masses

8. Disseminated CMV Kidney Adrenal Pancreas

9. Disseminated CMV Spleen Ovary

10. Brain: multiple poorly defined masses Right frontal lobe Left striatum * Right striatum * Left insula Left cerebellum 

11. Primary CNS lymphoma

12. Tumor cells in vessel walls Diffuse parenchymal invasion

13. Primary CNS lymphoma - EBV CD20 – B-cells CD3 – T-cells EBV

14. Cause of death Part I a)B-cell lymphoma, brain b)Acquired immunodeficiency syndrome Part II a) Disseminated CMV infection

15. HIV neuroinvasion: “Trojan Horse hypothesis”  Viral entrance into CNS Infected monocytes enter, differentiate into perivascular macrophages Infected CD4+ T cells Direct entrance of virus Transcytosis of virus across endothelial cells  Productive infection of macrophages and microglia Restricted infection of astrocytes Infection of oligodendrocytes and especially neurons is questionable Ghafouri et al. Retrovirology 2006; 3:28

16. CNS infections in AIDS  Fungi Cryptococcus Aspergillus Coccidioides http://www.vfce.arizona.edu/ VFCE%20OLD/jpg/2330034.jpg

17. CNS infections in AIDS  Fungi Cryptococcus Aspergillus Coccidioides  Parasites Toxoplasma

18. CNS infections in AIDS  Fungi Cryptococcus Aspergillus Coccidioides  Parasites Toxoplasma  Viruses (encephalitis) Cytomegalovirus (CMV) HIV Ellison & Love: Neuropathology 2e © 2004 Elsevier Ltd.

19. CNS infections in AIDS  Fungi Cryptococcus Aspergillus Coccidioides  Parasites Toxoplasma  Viruses (encephalitis) Cytomegalovirus (CMV) HIV  Viruses (other pathology) JC virus (PML, demyelination) Epstein-Barr virus (EBV) - lymphoma

20. Primary CNS lymphoma (PCNSL)  More frequent in both immunocompromised and immunocompetent patients (especially elderly) over last 20 years 6-20% of AIDS patients  EBV implicated in most immunocompromised and some immunocompetent individuals (nearly all AIDS patients)  Usually diffuse large B-cell tumors  Occur anywhere in brain Incidence proportional to volume (i.e., most common in frontal lobe) Often multifocal in AIDS patients Symptoms reflect location

21. Primary CNS lymphoma (PCNSL)  Imaging (without AIDS): homogeneous enhancement  Imaging (with AIDS): “ring-enhancing”, often multifocal  Histology: Solid sheets of tumor cells (often necrotic) blending into less cellular zones Angiocentric and angioinvasive Positive for B-cell markers, EBV (immunocompromised)  Treatment: radiation and / or chemotherapy  Prognosis: Immunocompetent: median survival 18 months Immunocompromised: median survival 4 months

22. References  Burger et al. Surgical Pathology of the Nervous System and Its Coverings. Fourth Edition. 2002. Churchill Livingston.  Ellison et al. Neuropathology. A reference text of CNS pathology. Second Edition. 2004.  http://www.emedicine.com/neuro/topic519.htm