Reactive and Non-neoplastic Phenomena (CH 11, PFC) Flashcards
Lymphocytosis induced by stress is characterized
by what features ?
- common phenomenon
- occurs in patients with emergency medical conditions such as MI, epilepsy, trauma, bleeding, sickle cell crisis and obstetric complications
- acute onset and usuall resolves in 24-48 hours
- pre-condition lymphocyte count is usually normal, may indicate increased lymphocyte mobilization due to stress
- lymphocyte count varies: 4-10.4 x 10^9
Are there specific morphologic characteristics
to the lymphocytes in stress lymphocytosis ?
- No but usually accompanied by neutrophilia
- occasional see a leukoerythroblastic reaction
- Absolute increase in T cells, B cells and NK cells
- no disturbance of CD4:CD8 ratio
- significant increase in memory T cells
- CD8+ compartment is enriched in CD57+ cytotoxic T cells
- This may serve to enrich the anamnestic immune response
What is the cause of exercise induced lymphocytosis ?
- increased levels of adrenalin and the cell adhesion molecule ICAM-I
- responsible for cell adhesion to the vascular endothelium
- usually this lymphocytosis resolves within a few hours after exercise
- relative increase in CD8+ CD56+ T cells
What type of lymphocytosis is seen
with cigarette smoking?
- polyclonal B cell proliferation is often seen
- peripheral blood lymphocytosis is mild to moderate with a median count of 7.35 x10^9
- isochromosome 3q is a common finding
- but this does not mean it is clonal
- individuals who are HLADR7 positive may be more susceptible to this
What morphology can be seen in
polyclonal B cell lymphocytosis
associated with cigarette smoking ?
- can be binucleate or bilobed nuclei
- polyclonal for light chains and polyclonal increase in serum IgM
- Minority of patients can develop
- mild splenomegaly
- mild lymphadenopathy
- goes away with cessation of smoking
Atypical lymphocytosis due to viral
infection, what are the common features ?
- frequently seen
- EBV is the most well described virus
- but innumerable viruses can cause similar reactions
- EBV also causes a mild thrombocytopenia and /or neutropenia
What other laboratory findings are seen
with EBV lymphocytosis ?
- heterophile antibodies
- virus primarily infects B cell lineage but the lymphocytosis is due to activated cytotoxic T cells
- morphologically these cells are medium to large with lots of convoluted cytoplasm and pleomorphic nuclei
- some of the larger cells show a deep blue cytoplasm
What are the flow cytometry findings of
the lymphocytosis due to EBV infection ?
- lymphocytes are found in the blast gate or large lymphocyte area
- sometimes will be in the monocyte areas
- lymphocytes are activated T cell population
- CD3, CD8, CD38, and HLA-DR
- frequently see a loss of or dim expression of CD7
- CD5 can sometimes be lost
What is the importance of HLA-DR
expression in the lymphocytes associated with EBV infection?
- expression of HLA-DR helps indicate the reactive nature of the lymphocytes
- HLA-DR expression, with the exception of cutaneous T cell lymphomas, is not a feature in T cell LPDs
What are key features in post-splenectomy
lymphocytosis ?
- leukocytosis with thrombocytosis is common
- lymphocytosis is seen with a mild neutrophilia, monocytosis and eosiniphilia
- also will see Howell-jolly bodies -key
What are the flow cytometry findings of the
lymphocytosis associated with splenectomy?
- there may be a higher proportion of NK cells and gamma-delta T cells
What findings can be seen in neoplasia induced
lymphoid reactions?
- usually T and NK cells both increase
- Particularly these subsets
- CD3 and CD57+
- CD3 and HLADR+
- CD3 and CD16/56+
- CD4 and CD57+
- CD8 and CD57+
- CD8+ and CD28-
What is a flow cytometry features of
chronic T-cell activation ?
- Loss of CD28 in CD8+ T cells
- these activated T cells are capable of intense cytotoxic activity
- often see these T cells in patients with chronic immune stimulation
- neoplasia
- inflammatory disorders
- autoimmune disease
- GVHD
- Note:
- usually tumor responding T cells are CD8 positive
- except for CD4/CD57+ are seen in B cell neoplasms
What flow cytometric finding has been
associated in patients with CML or Ph+ B-ALL
on treatment with Dasatinib?
- Lymphocytosis due to LGL proliferations
- correlation with rapid early treatment response, but patients also report symptoms like fever and effusions
- Flow Immunophenotype
- CD2+, CD3+
- CD16+, CD56+ and CD57+
- IMP
- TCR clonality is also present
What is the flow cytometry immunophenotype
characteristic of T cell activation ?
- CD57, CD16, CD56
- HLA-DR
- CD25 and CD69
- with loss of CD28
What can be seen in autoimmunity ?
- lymphopenia
- IMP: most of the conditions are treated with lympocytotoxic medications
In general, medications are an important cause of lymphopenia
What are known lymphocytotoxic drugs?
- corticosteroids, methotrexate
- mercaptopurine and azathioprine
- alemtuzumab (anti-CD52)- severe lymphopenia
- fludaribine and cladribine
- purine analogue cytotoxic agents
- cause severe lymphopenia
What marker is upregulated on
neutrophils pretty early in response
to infection ?
- CD64
- well known to increase
- high sensitivity and specificity
- driven by inflammatory cytokines, endogenous GCSF and interferon gamma
- this marker appears to coincide with increased bactericidal and fungicidal activity
- Normally CD64 is not expressed by neutrophils
What immunophenotypic changes
can be seen with G-CSF therapy?
- induces a more primitive myeloid immunophenotype with increased expression in:
- CD34, HLA-DR, CD71, and CD14
- CD11b, CD16 and CD66 in granulocytes
- Decreased expression in:
- CD10, CD15, and CD16
- Note:
- expression of HLA-DR on lymphocytes is not affected
What phenotypic changes can be seen
in Monocytes in reactive conditions, including
GCSF therapy?
- expression of CD56
- CD16 and CD56 expression on monocytes is well known in potent APC which secrete TNFalpha
- CD16 and HLA-DR expression is a well-recognized response to HIV infection
Note: if there is more alterations of the monocytes and other marrow elements caution for a reactive condition should be given, it may be CMML or MDS
What marker is known to be expressed
on neuroblastoma metastatic to the bone marrow ?
- CD15
What is the T cell composition in
reactive pleural fluids ?
- CD8+ T cells with an activated immunophenotype
- HLA-DR+, CD57+, CD25+ and CD28-
In what situations can a lymphocytic
effusion be seen in the pleural cavity?
- connective tissue diseases
- tuberculosis
- sarcoidosis
- post-surgery
- lymphoma
- metastatic carcinoma
Note: proportions of CD4 and CD8 T cells should be similar to the peripheral blood
What is the definition of pleural fluid
eosinophilia ?
- >10% of the total nucleated cell count
- IL-5 attracts the cells
What features by flow of BAL fluid
can suggest the diagnosis of sarcoidosis ?
- increased amount of T cells
- generally BAL has 80% macrophages and 10% lymphocytes which are predominantly T cells
- in sarcoid 30-70% are T cells with an increased CD4:CD8 ratio 10:1 to 20:1
Note: in hypersensitivity pneumonitis the CD4:CD8 ratio is often reversed
Which carcinomas are least likely
to express EPCAM by flow cytometry?
- HCC
- Renal
- SCC
