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

CPC #2: 38 year old woman with HIV/AIDS and altered mental status

October 9, 2007

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 massesRight 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 CNSInfected monocytes enter, differentiate into perivascular

macrophagesInfected CD4+ T cellsDirect entrance of virusTranscytosis of virus across endothelial cells

Productive infection of macrophages and microgliaRestricted infection of astrocytesInfection of oligodendrocytes and especially neurons is

questionable

Ghafouri et al. Retrovirology 2006; 3:28

CNS infections in AIDS Fungi

Cryptococcus AspergillusCoccidioides

http://www.vfce.arizona.edu/VFCE%20OLD/jpg/2330034.jpg

CNS infections in AIDS

FungiCryptococcus

Aspergillus

Coccidioides

ParasitesToxoplasma

Viruses (encephalitis)Cytomegalovirus (CMV)HIV

ParasitesToxoplasma

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 years6-20% 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. 2002. Churchill Livingston.

Ellison et al. Neuropathology. A reference text of CNS pathology. Second Edition. 2004.

http://www.emedicine.com/neuro/topic519.htm

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

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