EXAM 3 review Flashcards
CGD
Cytochrome B dificiency + Granulomas accumulation
- Cytochrome B needed for respiratory burst
- H202 / hydrogen peroxide need to kill catalse positive organisms
- X linked recessive
Chediak higashi
deficiency: defective fusion protein
accumulation: giant azurophilic granules
Autsomal recessive
Gauchers disease
deficiency: Betaglucocerebrosidase
Accumulation: glucocerebroside
most common lipid storage disorder
Autosomal recessive
Gaucher cell
Type II: infantile, most severe
Niemann Pick
deficiency: Sphingomyelinase
accumulation: sphingomyelim and cholesterol
foamy histocytes
2nd most common lipid storage disease
Autosomal recessive
Tay Sachs
deficiency: Hexosaminidse A
Accumulation: lipids and gangliosides
Autosomal recessive
Alder Reilly anomaly
Deficiency: Alpha L iduronidase
accumulation: mucopolysaccharides
- halo around the granule
- can be interpreted as toxic granulatio
AML with t(8;21)(q22;q22)
RUNX1-RUNX1T1
AML with inv(16)(p13q22) or t(16;16)(p13;q22)
CBFB-MYH11
APL (acute prolymyelocytic leukemia) with t(15;17)(q22;q12)
PML-RARA
AML with t(9;11)(p21;q23)
MLLT3-KNT2A
AML with t(6;9)(p23;q43)
DEK-NUP214
AML with inv(3)(q21q26) or t(3;3)(q21;q26)
GATA-2, MECOM
AML with t(1;22)(p13;q13)
RBM15-MKL1
B cell ALL with t(9;22)(q34;q11)
BCR-ABL1
B cell ALL with t(v;11q23)
KMT2A rearranged
B cell ALL with t(12;21)(p13;q22)
ETV6-RUNX1
B cell ALL with hyperploidy
50-66 chromosomes
B cell ALL with hypoploidy
<45 chromosomes
B cell ALL with t(5;14)(q31;q32)
IL3-IGH
B cell ALL with t(1;19)(q23;p13)
TCF3-PBX1
M0 (AML NOS)
- myeloblast
- No maturation
- minimal differentation
- Cyto: negative
CD34,CD38, HLA-DR
M1
- Myeloblast
- MPO(+), SBB(+), SE(+)
CD13, CD33, CD34, CD117
MPO stain
Myeloperoxidase
- Stains myeloperoxidase in promary granules
- positive: Bluish-black granules
Can differentiate AML (+) from ALL (-)
SBB - Sudan Black B Stain
- stains phospholipids
- positive: brownish-black granules
- present in granulocyte and monocyte lysosomal granules
AML(+); ALL (-)
SE - Specific esterase
- Stains specific esterase in primary granules
- positive: bright red granules
AML (+); ALL(-)
M2
- maturation
- myeloblast
- Auer rods
- MPO+, SBB+, SE+
CD11b,CD13,CD15,CD33,CD34
M4
- Myeloblasts + Monocytic
- MPO+, SBB+, SE+, NSE+
- Muramidase - antimicrobial enzyme in monocytic line. increased serum and urine muramidase
CD13, CD15, CD33, CD65
NSE Stain - Non specifc esterase in monocytic cell
- positive = Brick Red Stain
- Both = stains strongly positive in monocytic cell line
- acetate = positive in megakaryocyte and light in T lymphocytes
AML - Monocytic (+)
AML - Granulocytic (AML with minimal differentation) (-)
combined esterase
Stains both specific and nonspecific.
Specific: blue
Nonspecific: red/brown
- positive, or both -> myelomonocytic leukemia
- positive, for non specific only -> acute monocytic leukemia
M5(A andB )
A - monoblast
B - Promonocytes
MPO+/-, SBB+/-, NSE+, SE-
Extramedullary disease
- Cutaneous and gum infiltration -> gingival hypertrophy
monoblast vs promonocyte
monoblast
- round nuclei, promonint nucleoli, delicate chromatin
- Basophilic cytoplasm
Promonocyte
- Peaked crease
M6
Erythroid Leukemia
BM
- >80 immature erythroid precursors
- >30% pronoromoblast
PAS+
CD235a ( glycophorin A)
PAS stain
Stains glycogen
- Positive = bright magenta
Used to differentiate
- strongly + pure eryhtroid leukemia
M7
Megakaryoblastic leukemia
- >20% blasts
- >50% megakaryoblasts
Electron microscopy platelet peroxidase positive
One or more platelet glycoproteins
- CD41
- CD42
- CD61
Acute Basophilic Leukemia
- basophilic lineage, but blast like morphology
MPO-,SBB-, NSE-, PASblock positivity
CD11b, CD33, CD34, CD124, CD203c Basophil marker
APMF
CD34
- BM - panmyeloif hyperplasia
- Reticulin fibrosis - collagen
- PB: pancytopenia
Myelodysplasia related changes
> 2 lines with dysplasia
MDS, that goes beyond 20% blasts
Neutrophilc myelodsyplasia related changes
- hypogranulation
- hyposegmentatio
- pseudo pelger-huet
- bizarre segmentation
Erythrocytic - myelodsyplasia related changes
Howel jolly bodies
Multi nucleated,
megaloblastic,
vacuoles
Thrombocytic myelodsyplasia related changes
micormegakaryocytes with decreased lobulation
Therapy related AML
- Cytotoxic
- radiation treeatment
Alkylating agents/radiation (5-6 years post exposure)
Topoisomerase II inhibitors (2-3 years post exposure)
AML - downs syndrome
Transient abnormal myelopoiesis
- 10% of children with downs
- temporary AML presentation
Myeloid Leukemia assiciated with Downs Syndrome
- M7 - acute megakaryoblastic leukemia
Myeloid sarcoma - AML
outside red bone marrow
MPO+, SE+, NSE+
Germline predisposition AML
Fanconi’s anemia
- development of myelodysplastic syndrome with excess blasts
Ambigious lineage AML
- doesnt match anything
- or mixture
MDS definition
heterogenous group of clonal hematological malignancies characterized by
- PB cytopenias
- Transform into acute leukemia
- Dysplastic features
In MDS there is an
abnormal increase in intramedullarry apoptosis in BM
- imbalance of cytokines
PB dyserythropoiesis
- internuclear bridging
- anistocytosis with macrocytosis
- howell jolly body
- basophilic stippling
- teardrop cell
BM dyserythropoiesis
- Asynchronous development
- Nuclear budding
- internuclear bridging
Dysgranulocytopoiesis
PB
- Hyposegmentation
- Bilobulation (Pseudo-Pelger huet)
BM
- Hyposegmentation (pseudo - pelger - huet )
- hypogranulation/agranulation
Dysmegakaryocytopoiesis
PB
- giant platelet
BM
- megakaryocytes with detached nuclei
- hypogranulation
MDS –> AML
Blasts increase
Leukopenia - changes to leukocytosis
MDS affects + genetics
elderly, 70
LOSS of genetic material
- chromosome deletions
Myeloproliferative neoplasm definition
Mature Myeloid proliferation
Group of disorders that are considered clonal malignancies of the hematopoietic stem cell
adults >40 years old
- BM hyperplasia and spelonmegaly or hepatosplenomegaly
Draw table for MDS
:)
CML affected cell
granulocyte
CNL affected cell
neutrophils
CEL affected cell
eosinophil
PV cell
pancytosis
ET affected cell
megakaryocytes/PLT
PMF affected cell
Fibrosis
CML gene
BCR-ABL1+
CML definition
increase in granulocytes in PB and marked granulocytic hyperplasia in BM
LOW LAP score
1st human disease traced to a chrom. abnormality:
Philadelphia chromosome
CML
- 90-95% of patients with CML
Philadelphia chromosome
(9;22)
BCR-ABL gene produces
p210 tyrosine kinase
CML clinical features
symptoms
malaise/fatugie
- anemia
Abdomen fullness
loss of apetite
- splemomegaly
Night sweats
Weight loss
Bone tenderness/aching
3 CML phases
Chronic
Accelerated
Blast phase
CML chronic phase
- usualy diagnosed in this phase
- disease remains stable for several years
- responsive to chemo
CML accelerated phase
- 3-5 years after onset (untreated)
- ## worsening symptoms
blast phase CML
conversion of CML to aggressive form of acute leukemia that is difficult to treat
CML lab findings
WBC count >100,000 microL - leukocytosis
Decreased Hgb and Hct
- anemia (normochromic, normocytic)
- thrombocytosis
First indicator of CML
basophilia
>2% in chronic phase
Myelocyte bulge
chronic phase
CML
more myelocytes than metamyelocytes
PB smear CML
chronic phase
- giant platelets
- nRBCs
- Anisocytosis
- Basophilic stippling
- polychromasia
CML- chronic phase BM
Marked granulocytic hyperplasia
Increased
- megakaryocytes
- basophilic
- eosinophilic
- neutrophils
CML accelerated phase BM and PB
BM
- increasing blasts 5-19%
- megakaryocyte clusters
- fibrosis
PB
- increasing blasts and promyelocytes
- basophils >20%
- thrombocytopenia
worsening splenomegaly, bone pain and anemia
CML blast phase findings
BM
- Blasts more than or equal to 20% and in clusters
PB
blasts>20%
CML cytogenetics
t(9;22)(q34;q11)(BCR-ALB1+)
FISH
PT-PCR
CML
fluorescence in situ hybridization
PT-PCR, reverse transcriptase polymerase chain reaction
- extremely sensitive
- used to detect residual disease or recurrence after treatment
LAP stains
leukocyte alkaline phosphatase activity in granules
- present in normal neutrophilic granules
- decreased/absent in malignantion neutrophilic granules
returns to normal or increased
- remission of disease with therapy
- infect
toxic vacuoles
Leukemoid RXN: increased
CML: absent
Toxic granulation
Leukemoid RXN: increased
CML: absent
Dohle bodies
Leukemoid RXN: increased
CML: absent
Eosinophilia
Leukemoid RXN: normal
CML: increased
Basophilia
Leukemoid RXN: normal
CML: increased
Myelocyte bulge
Leukemoid RXN: absent
CML: present
LAP score
Leukemoid vs CML
Leukemoid RXN: high
CML: low
Ph chromosome
Leukemoid RXN: negative
CML: positive
CML treatment
only proven cure: allogenic bone marrow transplant
CNL major criteria
WBC count >25,000 microL
and
>80% band or segmented neutrophils
BM CNL
granulocytic proliferation
CNL mutation
CSF3R
CNL important
how does CNL differ from CML?
Basophilia and Eosinophilia NOT present
No philadelphia chromosome
LAP increased
CEL basics
clonal expansion of eosinophil precursor
CEL major criteria
PB eosinophils >1,500ul
normal (0-500)
NO philadelphia chromosome
PV definition
chronic abnormality of the hematopoietic stem cell characterized by uncontrolled proliferation of
- erythroid cells
- granulocytic cells (neutrophils)
- megakaryocytic cells (PLT)
thoery: JAK2 V617F mutation
PV clincal feature
chronic disease with insidious onset
(asymptomatic/routine doctor visit)
- thrmobosis/bleeding
- splenomegaly/hepatomegaly
- hypervscosity
- hypertension
- gout
PV lab findings
pancytosis
- increased RBC count, Hgb, Hct
- Increased PLT
- Increased granulocytosis
PV BM
hyperceullarity with pancytosis
PV lab findings coag
Normal PT/APTT, but
- adjust anticoagulant for high Hct
- High Hct = less plasma
- failure to adjust anticoagulant (sodium citrate) = falsely increased PT/APTT
Secondary Polycythemia
increased RBC due to response to other factors
- Hypoxia
- EPO producing tumor
Increased cells
- secondary RBC only; PV - multiple cell lines
- EPO
- secondary increased; PV - decreased
relative polycythemia
increased RBC due to decreased plasma volume
- dehydration/burns
aka tertiary polycythemia
increased cells:
relative - RBC only
PV - multiple cell lines
PV treatment
Therapeutic phlebotomy
1 unit weekly, decrease Hct
men <45%
women <40%
ET definition
chronic myeloproliferative disorder characterized by
- marked thrombocytosis
- abnormal platelet function
- increased risk of thrmobsis and hemorrhage
ET clinical features
chronic disrase with insidious onset (asymptomatic/routine doctor visit)
possible symptoms
- thrombosis /hemorrhage - most common
ET lab findings
increased PLT count >450,000 uL
can be as high as 1 million/uL
Normocytic + normochromic RBCs
- can develop IDA from GI/mucosal bleeds
splenic atrophy
- howell jolly
- target cells
- acanthocytes
ET BM
increase in megakaryocytic cells
- larger than usual
- clusters
- hyperlobulated
ET lab findings
abnormal platelet aggregation
can also have
- decreased platelet adhesion
- storage pool defects
- prolonged bleeding times
Cytogenetics:
- JAK2 (50-60% cases)
Reactive thrombocytosis
increased platelet count due to something else
- acute hemorrhage
- postsplenectomy
- chronic infection
- drug induced
- trauma
Reactive thrombocytosis vs. ET
PLT count >1,000,000/uL
- RT - infrequent
- ET - frequent
BM megakaryocyte clusters
- RT - not present
- ET - commong
disease often based on exclusion
ET
PMF basics
Primary myelofibrosis
fibrosis - excessive formation of fibrous (connective) tissue
PrePMF
BM is hypercellular
increased granulocytic and megakaryocytic proliferation mimics ET and PV
Overt PMF
FIbrotic stage
-“classic triad”
- BM fibrosis
-
PB leukoerythrooblastosis and Teardrop cell
1. immature myeloid cells and nRBCs -
Myeloid metaplasia (abnormal change in myeloid tissue)
1. extramedullary hematopoiesis due to BM fibrosis
PMF clinical features
- insidious onset - symptom free for years
- diagnosis made at a routine doctor visiti
symp:
- fever
- anorexia/weight loss
- night sweats
- bone pain
- anemia symptoms
PMF lab findings
Decreased RBC, Hgb, Hct
WBC and PLT variable
smear
- Teardrop cell
- megakaryocyte fragments and large PLT
fibrotic stage of PMF - BM
- fibrosis
- often results in dry tap
- due to increased fibrosis. andlow cellularity
PMF coagulation
increased fibrin degradation products (D-dimer)
extramedullary hematopoiesis in liver can cause dysfunction
- liver = coagulation factor producer
CML vs PMF
CML
- marked leukocytosis
- RBC morphology - normal
- Ph chrom
- LAP decreased
PMF
- WBC count: <30x10^3 /uL
- RBC morphology - teardrop cell
- Ph chrom. absent
- LAP normal/increased
PMF treatment
asymptomatic
- no treatment/monitor
Symptomatic: cytotoxic therapies/and or radiation
Splenectomy
- risk of operative thrombovytosis
allogenic stem cell transplant
- only curative treatment