White blood cell cases App Flashcards
Normal Leukocytes
- Neutrophils (60-70%)
- Lymphocytes (20-30%)
- Monocytes (5-10%)
- Eosinophils (3-5%)
- Basophils (less than 1%)
Neutrophilia
- Neutrophils > 7000/μL
- Acute stress, inflammation, infection (especially
bacterial), medications (steroids), pregnancy - Mobilization from marginal and marrow storage pools
- Leukemoid reaction
Lymphocytosis
- Lymphocytes > 5000/μL (adults)
- Infectious process (especially viral), clonal disorders
- Reactive, “atypical” lymphocytes
Monocytosis
- Monocytes > 800/μL
- Chronic inflammation or infection (tuberculosis),
clonal disorders
Eosinophilia
- Eosinophils > 350/μL
- Parasitic infections, allergic reactions, asthma,
neoplasia, collagen vascular diseases - Hypereosinophilic syndrome (> 1500/μL)
Basophilia
- Hypersensitivity reactions, endocrine disorders, clonal chronic myeloproliferative disorders (CML)
Leukopenia
- Neutrophils < 1500/μL
- Increased risk for infection
- Decreased/ineffective production, increased
consumption/destruction - Agranulocytosis
Lymphopenia
- Lymphocytes < 1500/μL
- Usually decreased CD4+ T cells
- Decreased production, increased destruction (HIV, steroids), increased loss
Morphologic Abnormalities in Leukocytes
In cases of reactive neutrophilia, granulocytes may demonstrate cytoplasmic changes, including toxic granulation, Döhle bodies, and vacuolization. These are non-specific changes, usually related to an underlying infectious or inflammatory process. Alder-Reilly anomaly refers to marked toxic granulation seen not only in neutrophils, but also in other types of leukocytes, in association with mucopolysaccharidoses. The “toxic granulation” in these cases represents accumulation of mucopolysaccharide material within the cells. May-Hegglin anomaly is an autosomal dominant inherited disorder characterized by the presence of large needle-like Döhle bodies in neutrophils (without evidence of any underlying infection) and giant platelets. In Chediak-Higashi syndrome, abnormally large, fused lysosomal granules can be observed in all types of leukocytes.
Neutrophils may demonstrate abnormalities in the segmentation of their nuclei. Pelger-Huët anomaly refers to hyposegmentation (two lobes or less) of neutrophils and may be inherited as an autosomal dominant trait or acquired (pseudo Pelger-Huët anomaly) in association with a bone marrow stem cell disorder (myelodysplasia). Hypersegmentation (more than five lobes) of neutrophils is characteristic of megaloblastic anemia but can also be seen in patients receiving chemotherapy (hydroxyurea).
Functional Leukocyte Disorders
- Chronic granulomatous disease
- X-linked, deficiency of NADPH oxidase (respiratory
burst) - Myeloperoxidase deficiency
- Inherited/acquired, hypochlorous acid generation,
Candidal infections - Chediak-Higashi syndrome
- Autosomal recessive, abnormal fused lysosomes,
platelet dysfunction, albinism
Leukemias
- Acute
– Maturation arrest, increase in blasts (20%) - Myeloid vs. lymphoid, Auer rods
- Chronic
- Maturing/mature cells (few blasts)
- Myeloid vs. lymphoid
- Ancillary studies (flow cytometry, cytogenetics,
molecular diagnostics)
Stem cells (blasts) CD markers
CD34+, TDT+ (lymphoid), CD10 (lymphoid)
All leukocytes CD markers
CD45+
Granulocytes CD markers
CD13+, CD15+, CD33+, CD117+, MPO+
Monocytes CD markers
CD14+, CD64+, CD4+
T lymphocytes CD markers
CD3+, CD2+, CD5+
Helper T cells CD markers
CD3+, CD4+
Cytotoxic/suppresor T cells
CD3+, CD8+
B lymphocytes CD markers
CD19+, CD20+, CD22+, CD10+ (subset), Surface Ig+
NK cells CD markers
CD16+, CD56+
Thrombocytes (platelets) CD markers
CD61+, CD41+, CD42+
Erythrocytes CD markers
Glycophorin C, CD71+
Cell types and CD markers diagram
Cytogenetics in AML
Cytogenetics in ALL
UTI -> could lead to sepsis and septic shock
UTIs usually come from gram negative or top of the list
leukocytosis, bandenia expected
but the picture doesnt show many white cells -> in severe infections you might see leukopenia as the white blood cells move into the tissues and out of the blood
left shift, neutrophils have bands and segmentation and vacuolization and granularity with some doule bodies -> shows differentiation
eosinophils present -> red stained cytoplasm
neutrophil changes implcate toxic effects in the body and these point you more towards reactive changes vs proactive changes in cancer
no clear leukocytosis
lymphocytes present
to see activation of cells in the blood, check to see whether their nucl ei are dense or open, shows euchromatin or heterochromatin showing level of expression
polyclonal process -> all leukocytes look different as they should, there is a spectrum of how they react
if they did look the same, it would be a monoclonal process pointing to cancer
in this case, it would probably be something like infectious mono because of the activated lymphocytes and infectous etiology
leukocytosis
is it reactive or clonal leukocytosis? could be clonal
acute leukemia because of the lymphoblastic proliferation. high nuclear: cytoplasm ratio, somewhat dispersed chromatin.
petechial hemmorhages are usually an issue with platelets
clonal: look more alike than different
Images:
- bottom normal, top patient, in r4 in our patient, a lot of cells that have low cd45 and low side scatter, there are lymphoblasts, can check with cd34
tdt, myeloperoxidase tests to see if myeloblasts or lymphoblasts
- cd34 positive indicates blast cell, maybe not lymphoblasts as cd10 is an ALL indicator, cd19 marks b cells - not positive, + for cd 15,13,33 which mark myeloid cells, myeloperoxidase positive, tdt negative -? acute myeloid leukemia
we want 61% ceullarity for a 39 year old and this image has ~100% cellularity in bone marrow
homogeneous environment when bone marrow should be heterogeneous
cytogenetics: karyotype 8:21 reciprocal translocation -> good prognosis
larger chromosome usually comes first in karyotype making translocations easier to differentiate
15:17 location, APML, acute promyeloid leukemia, most patients have DIC as promyeloid cells turnover and release granules but all-trans retin oid acid (treatment) causes cell maturation of the cells so you can kill them wihtout DIC as a consequence
AML:
clonal large promyelocytes with large granules and auer rods
pericentric inversion of chromosome 16 - favorable prognosis
leukocytosis
is this acute leukemia? no because there are signs of maturation signifying a chronic condition
seems like there are a lot of cells in different stages of maturation with a lot of granules inside them -> myeloid cells
there is effective hematopoeisis here showing different stages of maturation
around 20% of these cells are blasts as they should be
bone marrow shows hypercellularity with different stages of maturation and heterogeneity -> not stuck at blast stage
CML - 9:22 translocation -> philadelphia chromosom -> creates a novel fusion protein that has tyrosine kinase activity
abl on 9, BCR on 22, creates bcr abl fusion protein
can detect this by FISH or PCR
leukocytosis
a lot of white cells are not intact, normal mature lymphocytes, in this condition, we have very delicate cells -> smudge cells since they smudge on a smear
chronic leukemia as they dont look like blasts (progenitors) -> adding albumin ot the blood stabilizes the cell membrane and you wont see these smudges on smear prep
is it CLL or is it reactive?
bone marrow looks hypercellular and homogenous
flow cytometry - r1 has a lot of cells -> too many lymphoid cells
CD19->kappa, lambda -> mature b cells because expressing ig light chains
normally you see kappa and lambda in a 2:1 ratio, but here we have clonality indicating light chain restriction
Cd34, cd10 negative -> not lymphoblasts
Cd19 positive - b cells
Cd20, Cd5, Cd23 -> cd20 cd5 coexpression -> abberant expression of a marker -> also cd23 positive
abberantly expresses cd23 and cd5 along with cd20 so this is chronic lymphocytic leukemia (small lymphocytic lymphoma if in lymph nodes)
CLL cytogenetics: 13q deletions, rb gene is missing as it is on 13q
trisomy 12 in some cases of CLL
normal to slightly elevated wbc count
lymphoid cells have abundant cytoplasm with projections -> looks hairy -> b cell derived hair cell leukemia, not usually LN involvement
bone marrow is very cellular and homogenous -> abundant cytoplasm -> look like fried eggs
tremendous increase in reticulin fibers in bone marrow
tartrate resistant acid phosphatase activity - trap stain positive
cd19 positive and lambda light chain restricted, cd23 cd5 negative, flow -r1 = increase lymphoctyes
