CPC #2: 38 year old woman with HIV/AIDS and altered mental status October 9, 2007
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
Pulmonary edema
Necrotizing nodules – no AFB or fungi ID’d CD20 – B-cells CD3 – T-cells
Bronchopneumonia
Bronchopneumonia – and CMV infection
CMV in alveoli and around necrotizing masses
Disseminated CMV Kidney Adrenal Pancreas
Disseminated CMV Spleen Ovary
Brain: multiple poorly defined masses Right frontal lobe Left striatum * Right striatum * Left insula Left cerebellum
Primary CNS lymphoma
Tumor cells in vessel walls Diffuse parenchymal invasion
Primary CNS lymphoma - EBV CD20 – B-cells CD3 – T-cells EBV
Cause of death Part I a)B-cell lymphoma, brain b)Acquired immunodeficiency syndrome Part II a) Disseminated CMV infection
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
CNS infections in AIDS Fungi Cryptococcus Aspergillus Coccidioides VFCE%20OLD/jpg/ jpg
CNS infections in AIDS Fungi Cryptococcus Aspergillus Coccidioides Parasites Toxoplasma
CNS infections in AIDS Fungi Cryptococcus Aspergillus Coccidioides Parasites Toxoplasma Viruses (encephalitis) Cytomegalovirus (CMV) HIV Ellison & Love: Neuropathology 2e © 2004 Elsevier Ltd.
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
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
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
References Burger et al. Surgical Pathology of the Nervous System and Its Coverings. Fourth Edition Churchill Livingston. Ellison et al. Neuropathology. A reference text of CNS pathology. Second Edition