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AIDS pathology
cmbm exam V
57
Chemistry
Graduate
02/13/2010

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Term
what is common target for HIV?
Definition
the lymph nodes where changes occur to T cells, some malignant/some benign
Term
what is a lymphoma?
Definition
a malignant neoplasm visible in lymphoid tissue (nodes) or extra-nodular lesions (GI tract, brain)
Term
how does the process of HIV-related lymph node pathology start? what is the manifestation of this?
Definition
T cells are infected by HIV leading to lymph node enlargement/follicular hyperplasia, which is seen clinically as lymphadenopathy (often bilateral, can be either painless (usually neoplasm associated) or painful (usually due to an infection)
Term
how do germinal centers behave in lymph nodes of AIDs pts? does this affect B cells?
Definition
the germinal centers of lymph nodes usually merge with the interfollicular area (change in microscopic architecture of the lymph node), usually effecting the B cell areas of the node
Term
are B cells activated by HIV action in lymph nodes?
Definition
yes, and this causes hypergammaglobulinema
Term
as AIDs progresses, what happens to the follicles?
Definition
the follicles involute and break down, disrupting the organized network of dendritic cells
Term
as AIDs progresses, what happens to the germinal centers?
Definition
the germinal centers are hyalinized/scarred
Term
what is persistent generalized lymphadenopathy (PGL)? is there a differential diagnosis for PGL? how is it diagnosed?
Definition
2 or more non-inguinal sites (cervical, submandibular, occipital, axillary, epitrochlear) expressing non-tender follicular hyperplasia. retroperionteal, mesenteric, and mediastinal involvement is seen, hilar is NOT typical. differentials include neoplastic changes, lymphomas (hodgkin's/non-hodgkins), TB, and castleman's disease HHV-8. diagnosis consists of a needle bx or sx incision
Term
what might be seen on a salivary gland bx?
Definition
epithelial hyperplasia and lymphocytic infiltration -> seen often
Term
do AIDS pts develop lymphoma? what is the main predisposing factor? what types are there?
Definition
6% of AIDS pts develop lymphoma, for which immunodeficiency is the main predisposing factor. AIDS lymphomas can present differently and are divided according to location: systemic, CNS (brain lymphoma should make you think HIV), body cavity lymphomas
Term
how do AIDS lymphomas form? are other viruses implicated in their formation?
Definition
AIDS lymphomas are the result of polyclonal B cell activation followed by monoclonal/oligoclonal B cell population, stimulated by viruses like EBV which are able to proliferate b/c of HIV infection. HIV doesn't directly cause lymphomas, but allows them to form. the EBV genome is seen in many AIDS lymphomas and is likely the cause of the high level of cytokines, IL-6 and growth factors -> neoplastic B cells will have many neoplastic clone B cells eventually leading to cancer
Term
what kind of lymphoma is seen more often with AIDS pts? where in the body are they commonly seen?
Definition
non-hodgkin's which is 75-80% systemic, 20% CNS (immunoblastic), and 5% primary effusion lymphoma
Term
what is the histology of AIDS NHLs?
Definition
AIDS non-hodgkins lymphomas are 40% large cells and immunoblastic and 40% are burkitt/burkitt-like
Term
how has HAART affected the median time between HIV and NHL diagnoses? NHL survival time from diagnosis?
Definition
the median time as tripled, and the median survival time has doubled
Term
what is the mechanism of EBV-induced non-hodgkins lymphoma?
Definition
the EBV latent membrane protein-1 (LMP-1) protects B cells from apoptosis by inhibition of BAX (apoptotic) and upregulation of BCL2 (anti-apoptotic). LMP-1 also contains 2 C-terminal activation regions which bind to the TNF associated receptors w/activation of the NFkB signaling pathway
Term
what are some characteristics consistent with malignancy in lymphocytes?
Definition
prominent nucleoli, prominent nuclear membrane and large size
Term
what are angiocentric lymphocytes?
Definition
blood vessels with various neoplastic lymphocytes surrounding them, they are associated with EBV
Term
if an HIV patient presents with mental status changes, seizure activity, what should be in the differential?
Definition
lymphoma
Term
what are HIV related factors that lead to the decline in CD4+ lymphocyte level?
Definition
apoptosis of infected cells (cytopathic effect), CD8+ attack, colonization of GALT, spleen, loss of CD4+ T cell progenitor stem cells, syncytial fusion, apoptosis of uninfected CD4+ cells (via binding of gp 120 to the receptor)
Term
what is seen pathologically the first stage of HIV?
Definition
asymptomatic, persistent generalized lymphadenopathy
Term
what is seen pathologically the second stage of HIV?
Definition
weight loss, predisposed to infections such as HSV, HPV, VZV, neoplasms
Term
what is seen pathologically the third stage of HIV?
Definition
candidiasis, dysphasia, difficulty swallowing, hairy leukoplakia, pts possibly bedridden
Term
what is seen pathologically the fourth stage of HIV?
Definition
defining opportunistic infections, pneumocystis carinii, neoplasms, kaposis sarcoma (HHV 8), bedridden
Term
what are some skin & oral lesions seen w/HIV?
Definition
hairy leukoplakia, candida albicans, gingivitis, periodontitis, HSV 1&2, molluscum contagiosum, bacillary angiomatosis (bartonella henslae), kaposi's sarcoma (vascular sarcoma, HHV-8)
Term
what can herpes zoster follow on pt's bodies?
Definition
dermatones, L5 is a common presentation
Term
what are base-line tests for HIV?
Definition
CD4 count, plasma HIV-RNA, HIV genotype to determine ARV resistance
Term
why might a CBC be done for newly diagnosed HIV+ pts?
Definition
anemia may contradict use of zidovudine
Term
why might a chem 12 (renal) test be done for newly diagnosed HIV+ pts?
Definition
azotemia contraindicates used of tenofovir, high glucose prevents use of protease inhibitors (insulin resistance)
Term
why might a bilirubin, HCV test be done for newly diagnosed HIV+ pts?
Definition
to make sure the liver can withstand ARV hepatoxicity
Term
why might a lipid profile be done for newly diagnosed HIV+ pts?
Definition
to ensure protease inhibitors aren't contraindicated
Term
should comorbidities such as SCC (women), Hep B,C, CMV, toxoplasmosis, HPV be checked with new HIV+ pts? how
Definition
yes, via serological testing
Term
has more TB been seen since HIV, is it tested for?
Definition
yes and TB is tested for w/new HIV pts
Term
why would an EKG be ordered for a new HIV+ pt?
Definition
to check on vascular effects of protease inhibitors
Term
what diseases can be seen at 500 CD4+ levels?
Definition
kaposi's sarcoma, lymphoma, TB
Term
what diseases can be seen at 250 CD4+ levels?
Definition
pneumonia jiroveci pneumonia, toxoplasmosis, brain, candidial esophagitis
Term
what diseases can be seen at 100 CD4+ levels?
Definition
CMV, cryptoccosis, mycobacterium avium complex infection, microsporidiosis, HIV encephalopathy, progressive multifocal leukoencephalopathy
Term
what % of pts have some degree of CNS involvement at autopsy? how does it present?
Definition
90% CNS involvement may be the sole or initial presenting feature of HIV infection, examples include lymphomas, self limited meningoencephalitis, aseptic meningitis, vacuolar myelopathy, peripheral neuropathy, and AIDs dementia complex
Term
what are the organisms that cause toxoplasmosis and associated pathologies?
Definition
t. gondii has 2 protozoal forms, tachyzoite (causes tissue injury), and bradyzoite (fills cysts/pseudocysts which collect around neurons/perivascular macrophages). toxoplasmosis leads to central necrotic masses surrounded by edema and inflammation. this is accompanied by perivascular infiltration, lymphoid infiltration, aggregates, endothelial swelling, thrombosis, fibrinoid necrosis, and fibrous obliteration of vessels = can lead to ischemia, organ death, seizure
Term
where is toxoplasmosis generalized? how does it present?
Definition
toxoplasma gondii is often seen as a space-occupying lesion in the cerebral cortex, basal ganglia, brain stem (neuron rich areas) of AIDs pts and may appear as a tumor on an MRI. it presents as seizures, hemiparesis, cranial nerve deficits (should be picked up on in H&P), but some pts may only present with H/A, fever and lethargy
Term
what is seen on toxoplasmosis MRIs?
Definition
ring enhancing lesions that mimic tumors
Term
what is the most common CNS mycosis? how does it present?
Definition
cryptococcus neoformans, which presents in the brain as choroid plexus based masses (cryptococcomas), that often consist of gelatinous material due to capsular mucopolysaccharides
Term
is cryptococcus neoformans found in other organs than the brain?
Definition
yes, but the brain is most common (either in brain or on meninges)
Term
what is progressive multifocal leukoencephalopathy?
Definition
a demyelinating disease seen with defective cell mediated immunity, caused by some DNA viruses such as JC and HIV-1
Term
what are symptoms of progressive multifocal leukoencephalopathy?
Definition
motor deficits, cognitive decline, visual loss (pt may first present to opthamologist), gradual cognitive decline
Term
where is progressive multifocal leukoencephalopathy found?
Definition
usually in the cerebral hemispheric white matter, usually attracted to oligodendrolions - causing enlargement of nuclei, dissolution of chromatin and replacement by basophilic "ground glass" material
Term
what is seen with progression of progressive multifocal leukoencephalopathy?
Definition
progressive multifocal leukoencephalopathy develops into an expanding zone of oligodendroglial loss and infiltration of macrophages ingesting myelin. it appears as yellowish gray discoloration of white matter which may progress to white matter cavitation. florid astrogliosis with bizarre nuclei replace destroyed tissue (no scar tissue in brain)
Term
what kinds of trophic changes are seen with virally (JC/HIV-1) infected cells?
Definition
inlusion bodies and multinucleated cells
Term
what is AIDS dementia complex associated with? who is it seen in?
Definition
encephalitis w/multinucleated microglial cells, CD4 < 500. it is seen in 15% of HIV+ adults, but 30% of HIV + children.
Term
what are clinical symptoms of AIDS dementia complex? what can it mimic? what would be seen on an MRI?
Definition
memory loss, impaired comprehension, apathy, tremor, gait disturbance, hyperreflexia, and apraxia - it can mimic other CNS disorders. an MRI would show diffuse or total cerebral atrophy, T2 white matter and hyper intensity
Term
what are some common AIDS-related carcinomas?
Definition
aggressive SCC in uterine, anal areas. HPV prevalence is also high due to immunosuppression
Term
why might AIDS pts have more GI problems?
Definition
some due to tx: protease inhibitors (nelfinavir, ritonavir), but also due to opportunisitic infections from CMV, cryptosporidium, c. dif, enterobacteriaceae, salmonella, mycobacterium avium complex (AIDS defining illness - aggressive TB form), and giardia
Term
what are some pulmonary manifestations of AIDS-related pathology?
Definition
often opportunistic infections, pneumocystis carinii pneumonia, other pneumonias. lymphocytic interstitial pneumonitis and nonspecific interstitial pneumonitis. pulm. HTN is also seen
Term
how does pneumocystis jirovecii pneumonia present?
Definition
cuplike cysts in the alveoli
Term
what is a common AIDS-related kidney problem?
Definition
*focal segmental golmerulonephritis* seen in heroin using/HIV pts
Term
what are some cardiac manifestations of HIV?
Definition
myocarditis, infectious endocarditis, pleural effusions from tumors/lymphomas, premature atherosclerosis, action of rx protease inhibitors, pulm HTN
Term
how is the biliary system affected by HIV?
Definition
CMV/cryptosporidium can cause acalculous cholecystitis, duct problems, pancreatitis, NHL
Term
what is commonly seen with HIV pts' skin? what does it form? what can it resemble?
Definition
kaposi's sarcoma, very aggressive, involves blood vessels and can form plaques/patches, poorly formed vascular channels. bacillary angiomatosis can look like kaposi's, but is caused by baronella henslae
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