MOD 2 more lectures (Pathology of AIDS/HIV, and Intro to Hematolymphoid neoplasia) Flashcards
AIDS facts
mostly africa, then asia
top three cities for AIDS are Miami, NOLA, baton rouge
risk groups are homo/bi men, IV drugs (sometimes transfusion or newborns with HIV mothers)
AIDS routes of transmission
Sexual (75%)
perenteral (IV drug)
mother to infant
which route of transmission has highest rate of transmission of HIV (highest infectivity rate)?
transfusion of blood products bc highest viral load/conc
Key target of HIV virus?
CD4+
also types of macros bc cells with CD4 receptors
What type of viruses are HIV1/2?
nontransforming human retrovirus of LENTIVIRUS family
HIV-1 virion
2 single stranded copies of RNA
uses RT
has p24 capsid, use to ID (also ab’s to surface glycoprots)
HIV viral attachment and entry?
viral glycoprot gp120 binds CD4+ receptor
-interaction with chemokine receptor (co-receptor, eitehr CCR-5 of CXCR-4) exposes viral gp41(which can penetrate host memb bc lipophilic), membranes fuse and release viral contents into cyto
HIV viral replication
HIV can either remain dormant in host cell (hard to target virus infected cells) or cDNA (DNA synth from viral RNA using RT) can inc into host DNA (progressive infection)
What two things are needed for progressive infection?
actively dividing host cell
integrase (enz encoded by virus to integrate cDNA into host DNA)
What are the 3 stages of the HIV virus
Acute prodromal phase
Chronic stage
Crisis
Acute prodromal phase
nonsepc sx, drop in CD4 cells (T cells destroyed by many diff methods), viremia (widespread dissem of virus)
Chronic stage
clinical latency, no sx, immune cells being repl at same rate, enlarged lymph nodes due to lots of cytokine release
Crisis sx
constitutional sx (fever/chills/night sweats/ wasting) neoplasm, neuro disease, atrophic lymph nodes, opportunistic diseases
What happens to immune cells in HIV infection? Lymphoma?
decr T cell immune surveillance, decr B cell stim, abnormal lymphoid prolif due to cytokine stim (can progress into lymphoma which prod abnormal prots)
What is PGL (persistent generalized lymphadenopathy?)
nodal enlargement in extra-inguinal sites that lasts more than 3 months w/ constitutional sx (eg hepatosplenomeg, anema, hyper Igs)
Histo findings of PGL
- follic hyperplasia (expanded irreg germinal ctr, T cell zone compressed, look like “naked follicles”)
- dissolution of cortical germinal centers: follic DCs are infected, and their lysis causes germ ctr to fall apart (specific to HIV)
- Lymphoid depletion: atrophic, w hyalinized germinal ctr
How can HIV cause cancer?
polyclonal to oligoclonal (few cell lines) to MONOCLONAL (one cell line) prolif
What is HIV assoc NHL (non-hodkins lymphoma?)
30% of aids pts get it, less prevalent w HAART use (highly active antiretroviral tx), B cell phenotype
-path: infxn with HIV causes immunosuppr, promotes infxn of EBV virus, potent mitogen causes prolif o fhost cells, mutations (e.g.. dereg of c-myc protooncogene in EBV, 8:__ transloc)
Subtypes of NHL lymphoma?
Diffuse large B cell lymphoma
Burkitt lymphoma
(both aggro)
Cavity based primary effusion lyphoma
What is cavity based lymphoma related to?
Sx?
EBV and HSV-8
early involvement of pleural spaces
Burkitt lymphoma histo?
Dx?
Lymphoid like cells larger than RBC and have cytoplasm vacuoles
Dx: IHC to confirm lymphoid origin
Kaposi sarcoma classic pres
indolent (slow onset, few sx), skin lesions
AIDS assoc kaposi sarcoma
STI indep of HIV, men
more aggro
HHV-8 and HIV synergise to affect cells of endoth origin, not just skin can inv any organ (lesions are epidermal mucocutaneous, and visceral)
What disease is kaposi sarcoma often associated with?
AIDS
Kaposi sarcoma pathology
rel of cytokines and GFs from infected cells, prolif of endoth cells and angiogen, vascualrize KS lesions
Kaposi sarcoma pathway
PATCH (flat red/purp macula) –> PLAQUE (thickning of patch) –> TUMOR (nodule)
What will biopsy of kaposi sarcoma lesion show>
spindle to epith atypical endoth cells, dilated vasc spaces, leaked or degraded RBCs which can lead to hemosiderin (brown) granules and hyaline bodies, inflam infiltrate
How can HIV promote squamous cell carcinoma of uterine cervix and anal canal?
synergy between HIV and HPV promotes neoplastic changes
HIV squamous cell carcinoma histo?
characterized by KOLIOCYTES (binucleated raisin nuclei with halo)
What do koliocytes on slides mean?
HPV infection
Viral infections common in AIDS patients (list)
CMV (wtih low CD4 count, owl's eye inclusions) HSV varicela EBV KSHV (HHV-8) etc
Protozoal infections common in AIDS
Toxoplasma gondii (brain)
crytospor
microspor
isospor (latter 3 GI)
bacterial infections common in AIDS
mycobacterium TB and avium
bartonella
fungal infections common in AIDS
PCP (lung eosin material, pneumonia sx)
candida (dissem inv solid organ abcesses)
histoplasma capsulatum (in macros)
coccidiodes (large cyst)
cryptococcus neoformans: asymp infects resp, spreads to CNS as meningitis (mucicarmien stain, india ink for capsule)
HIV/AIDS and CNS infections
- many CNS issues
- pathogens include cryptococcus, CMV, toxoplasma
- AIDS dementia complex
- HIV encephalitis carried across BBB by infected monos/macros, infects a bunch of cells in brain, causes perivascular microglial nodules (aroudn bv’s)
- Progressive Multifocal leukoencephalopathy: patchy areas of WM destruction, demylelination (on microscope: spaghetti and meatballs form of papovavirus/polyomavirus)
- Toxoplasma encephalitis (protozoal infxn that resembles TB, lymphoma, intracranial mass with ring enhancement, non-spec; acute is necrotizing microabcesses in brain, chronic is microcysts)
Diff between complete blood cell count (CBC) and differential blood count?
Differential gives percentages of WBCs, and CBC gives actual values of many diff blood cells.
“penia”= deficiency
“cytosis”= extra
How do you measure “cellularity” of patient? (eg in bone marrow histology(?)
Normal cellularity is 100 minus age of patient
So 40 y.o. pt would have 100-40= 60% cellularity (40% fat)
So cellularity decreases, and fat increases, as u get older
What progenitor cell gives rise to lymphocytes, and what gives rise to all other blood cells?
Myeloid stem cells give rise to myeloblasts (baso/eosin/neutro), monocytes, megakaryocytes, and pronormoblasts (RBCs)
Lymphoid stem cells give rise to lymphocytes (T, B, NK)
What are 3 types of myeloid lineage diseases?
- Acute Myeloid Leukemia (AML)
- Myelodysplastic Syndrome (MDS)
- Myeloproliferative Neoplasms (MPN)
AML (Acute myeloid leukemia)–which cells prolif?
Characteristics of these cells?
What main structural feature do only they have?
IMMATURE MYELOID BLAST CELLS in bone marrow:
int sized, round, blue cells, high N:C ratio, finely dispersed chromatin, nucleoli (white areas)
-Have AUER RODS: crystal aggregates of MPO (red lines) means abnormal mitosis
AML
pop
dx
sx
slight male >65
DX BY MORE THAN 20% BLASTS IN PERIPH BLOOD OR MARROW
sx: anemia (fatigue, pallor), neutropenia, thrombocytopenia (bleeding)
What’s an important type of AML?
Presentation? translocation?
ACUTE PROMYELOCYTIC LEUKEMIA (APL)
presents with dissem vascular coag (DIC, too much clotting, but can also bleed)
15;17 translocation
MDS (myelodysplastic syndrome)
Cx
Risk of dev?
Diff w/ AML
CYTOPENIAS, dysplasia in myeloid line(s), ineffective hematopoeisis
- incr risk of dev AML
- must have LESS than 20% blasts (AML would be more than 20%)
MDS
pop
sx
- older ~male med age 70
- same 3 as AML
MDS histology
high cellularity and incr megakaryocytes
- left shift (incr monolobed neutros)
- RING SIDEROBLASTS (iron Fe3+ stain allows us to see accum of stored iron, blue rings around pinkish cells)
Cytopenia plus what genetic abnormalities may indicate MDS?
cytopenia + deletion of chrom 5q
(MPN) Myeloproliferative Neoplasms
mutation
pop
marrow cells
Chronic prolif of MATURE cells (effective hematopoeisis–aka just too many)
- Tyrosine kinase mutations can cause oncogenic growth
- adults
- hyper-cellular bone marrow with increased periph counts
What can MPN develop into
Spent phase: hyper-prolif exhausts bone marrow, so dev cytopenia and marrow fibrosis
-can also transform into AML
Which two myeloid diseases can become AML?
MDS and MPN
What are 4 types of MPNs?
Chronic myelogenous leukemia (CML) Polycythemia Vera (PV) Essential Thrombocytopenia (ET) Primary Myelofibrosis (PMF)
What mutation do the latter 3 (PV, ET, and PMF) all have?
JAK2 kinase mutation
CML prolif mut tx can become
GRANULOCYTE/BASO PROLIF, 9;22 bcr-abl fusion
Tx with imatinib
-can become AML or ALL
PV
prolif
mut
sx
RBC PROLIF (and granulo/platelets) (EPO dep erythrocytosis) JAK2 kinase, hyperviscosity of blood, blurry vision, flushed face, itching, decr EPO, normal SaO2
ET
prolif
PLATELET PROLIF (also RBCs/gran) jak2 kinase
PMF
prolif
histo
MEGKARYOCYTE PROLIF
Jak2 kinase
PDGF leads to marrow fibrosis
TEAR DROP SHAPE OF RBCs on histo (darocyte) from distortion of memb from fibrosis
other causes of neutrophilia (for differential dx)
bacteria, GF tx, stress
other causes of thrombocytosis
iron def anemia, infxn, stress
other causes of erythrocytosis
tumor (pheo, hepatic, ut leiomyo, cerebell hemangioblast, kidney), high alt, smoking, hypoxia, high O2 aff hb, blood doping or high T, INCR EPO LEVELS
Diff between erythrocytosis due to PV vs other factors
PV shows DECREASED EPO, others show incr
Which tumors causes erythrocytosis? (mnemonic)
PHUCK
What can thymic mass indicate
T cell leukemia/lymphoma
The two lymphoid neoplasia types are?
LEUKEMIAS and LYMPHOMAS
Acute lymphoblastic leukemia (ALL)
pop
histo
Neoplasm of IMMATURE lymphoid precursors
- often in kids
- similar histo to AML but no Auer rods
B-cell vs T-cell ALL?
- B-cell ALL is more common (presents as acute leukemia inv marrow)
- ALL presents as lymphoma inv anterior mediastinum
Lymphomas in general
neoplasm of MATURE lymphoid cells
-most inv B cell
Diff between leukemia and lymphoma
Leukemia is IMMATURE neoplasm, lymphoma is MATURE
2 types of lymphomas?
Hodgkins and Non-Hodgkins
Hodgkins lymphoma
- cell dist feature
- tx
presence of REED-STERNBERG CELLS (multinuclear giant cells), aggro
- curable w/ combo tx
- many types
What are some classical types of hodgkins lymphoma
Nodular sclerosis
Mixed cellularity
Lymphocyte rich
Lymphocyte depleted
Non-Hodgkin lymphoma B cell types
B cell types:
small: slow, noncurable;
large: aggro, curable, localized (TYPES include DIFFUSE LARGE B CELL AND BURKITT)
Non-hodgkin lymphoma T cell and NK cell types
aggro, curable, localized,
-types incl periph T cell, anaplastic large cell, adult t, mycosis fungoides, large gran, extranodal
What 2 types o fmarkers are used to distinguish cell types in immunophenotypic analysis in lymphoid neoplasias?
Pan markers and Maturity markers
Pan marker examples>
for B cells: CD19, CD20 (obv)
For T and NK cells: CD3
Maturity marker examples
immature blast: TdT
myeloblast specifically: CD34
What does lots of CD19 and CD20 indicate
B cells
What does lots of CD34 indiccate
myeloblasts
Genetic analysis methods in lymphoid issues?
Karyotyping, FISH, PCR
Which lymphoid issue has greater than 20% blasts
AML!
Which lymphoid issue has auer rods?
AML!
Which lymphoid issue has ring sideroblasts w/ iron stain?
MDS (meylodysplastic syndrome, a myeloid neoplasia)
Which lymphoid issue has reed-sternberg cells (multinuclear giant cells)
HODGKINS LYMPHOMA!
