EXAM 3 review Flashcards
(121 cards)
1
Q
CGD
A
Cytochrome B dificiency + Granulomas accumulation
- Cytochrome B needed for respiratory burst
- H202 / hydrogen peroxide need to kill catalse positive organisms
- X linked recessive
2
Q
Chediak higashi
A
deficiency: defective fusion protein
accumulation: giant azurophilic granules
Autsomal recessive
3
Q
Gauchers disease
A
deficiency: Betaglucocerebrosidase
Accumulation: glucocerebroside
most common lipid storage disorder
Autosomal recessive
Gaucher cell
Type II: infantile, most severe
4
Q
Niemann Pick
A
deficiency: Sphingomyelinase
accumulation: sphingomyelim and cholesterol
foamy histocytes
2nd most common lipid storage disease
Autosomal recessive
5
Q
Tay Sachs
A
deficiency: Hexosaminidse A
Accumulation: lipids and gangliosides
Autosomal recessive
6
Q
Alder Reilly anomaly
A
Deficiency: Alpha L iduronidase
accumulation: mucopolysaccharides
- halo around the granule
- can be interpreted as toxic granulatio
7
Q
AML with t(8;21)(q22;q22)
A
RUNX1-RUNX1T1
8
Q
AML with inv(16)(p13q22) or t(16;16)(p13;q22)
A
CBFB-MYH11
9
Q
APL (acute prolymyelocytic leukemia) with t(15;17)(q22;q12)
A
PML-RARA
10
Q
AML with t(9;11)(p21;q23)
A
MLLT3-KNT2A
11
Q
AML with t(6;9)(p23;q43)
A
DEK-NUP214
12
Q
AML with inv(3)(q21q26) or t(3;3)(q21;q26)
A
GATA-2, MECOM
13
Q
AML with t(1;22)(p13;q13)
A
RBM15-MKL1
14
Q
B cell ALL with t(9;22)(q34;q11)
A
BCR-ABL1
15
Q
B cell ALL with t(v;11q23)
A
KMT2A rearranged
16
Q
B cell ALL with t(12;21)(p13;q22)
A
ETV6-RUNX1
17
Q
B cell ALL with hyperploidy
A
50-66 chromosomes
18
Q
B cell ALL with hypoploidy
A
<45 chromosomes
19
Q
B cell ALL with t(5;14)(q31;q32)
A
IL3-IGH
20
Q
B cell ALL with t(1;19)(q23;p13)
A
TCF3-PBX1
21
Q
M0 (AML NOS)
A
- myeloblast
- No maturation
- minimal differentation
- Cyto: negative
CD34,CD38, HLA-DR
22
Q
M1
A
- Myeloblast
- MPO(+), SBB(+), SE(+)
CD13, CD33, CD34, CD117
23
Q
MPO stain
Myeloperoxidase
A
- Stains myeloperoxidase in promary granules
- positive: Bluish-black granules
Can differentiate AML (+) from ALL (-)
24
Q
SBB - Sudan Black B Stain
A
- stains phospholipids
- positive: brownish-black granules
- present in granulocyte and monocyte lysosomal granules
AML(+); ALL (-)
25
SE - Specific esterase
- Stains specific esterase in primary granules
- positive: bright red granules
AML (+); ALL(-)
26
M2
- maturation
- myeloblast
- **Auer rods**
- MPO+, SBB+, SE+
CD11b,CD13,CD15,CD33,CD34
27
M4
- Myeloblasts + Monocytic
- MPO+, SBB+, SE+, NSE+
- Muramidase - antimicrobial enzyme in monocytic line. increased serum and urine muramidase
CD13, CD15, CD33, CD65
28
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) (-)
29
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
30
M5(A andB )
A - monoblast
B - Promonocytes
MPO+/-, SBB+/-, **NSE+, SE-**
Extramedullary disease
- **Cutaneous and gum infiltration -> gingival hypertrophy**
31
monoblast vs promonocyte
monoblast
- round nuclei, promonint nucleoli, delicate chromatin
- Basophilic cytoplasm
Promonocyte
- **Peaked crease**
32
M6
Erythroid Leukemia
BM
- >80 immature erythroid precursors
- >30% pronoromoblast
PAS+
CD235a ( glycophorin A)
33
PAS stain
Stains glycogen
- Positive = bright magenta
Used to differentiate
- **strongly + pure eryhtroid leukemia**
34
M7
Megakaryoblastic leukemia
- >20% blasts
- >50% megakaryoblasts
Electron microscopy platelet peroxidase positive
One or more **platelet** glycoproteins
- CD41
- CD42
- CD61
35
Acute Basophilic Leukemia
- basophilic lineage, but blast like morphology
MPO-,SBB-, NSE-, PASblock positivity
CD11b, CD33, CD34, CD124, **CD203c Basophil marker**
36
APMF
**CD34**
- BM - panmyeloif hyperplasia
- Reticulin fibrosis - collagen
- PB: pancytopenia
37
Myelodysplasia related changes
>2 lines with dysplasia
MDS, that goes beyond 20% blasts
38
Neutrophilc myelodsyplasia related changes
- hypogranulation
- hyposegmentatio
- pseudo pelger-huet
- bizarre segmentation
39
Erythrocytic - myelodsyplasia related changes
Howel jolly bodies
Multi nucleated,
megaloblastic,
vacuoles
40
Thrombocytic myelodsyplasia related changes
micormegakaryocytes with decreased lobulation
41
Therapy related AML
- Cytotoxic
- radiation treeatment
Alkylating agents/radiation (5-6 years post exposure)
Topoisomerase II inhibitors (2-3 years post exposure)
42
AML - downs syndrome
**Transient abnormal myelopoiesis**
- 10% of children with downs
- temporary AML presentation
**Myeloid Leukemia assiciated with Downs Syndrome**
- M7 - acute megakaryoblastic leukemia
43
Myeloid sarcoma - AML
outside red bone marrow
MPO+, SE+, NSE+
44
Germline predisposition AML
Fanconi's anemia
- development of myelodysplastic syndrome with excess blasts
45
Ambigious lineage AML
- doesnt match anything
- or mixture
46
MDS definition
heterogenous group of clonal hematological malignancies characterized by
- PB cytopenias
- Transform into acute leukemia
- Dysplastic features
47
In MDS there is an
abnormal increase in intramedullarry apoptosis in BM
- imbalance of cytokines
48
PB dyserythropoiesis
- internuclear bridging
- anistocytosis with macrocytosis
- howell jolly body
- basophilic stippling
- teardrop cell
49
BM dyserythropoiesis
- Asynchronous development
- Nuclear budding
- internuclear bridging
50
Dysgranulocytopoiesis
PB
- Hyposegmentation
- Bilobulation (Pseudo-Pelger huet)
BM
- Hyposegmentation (pseudo - pelger - huet )
- hypogranulation/agranulation
51
Dysmegakaryocytopoiesis
PB
- giant platelet
BM
- megakaryocytes with detached nuclei
- hypogranulation
52
MDS --> AML
Blasts increase
Leukopenia - changes to leukocytosis
53
MDS affects + genetics
elderly, 70
LOSS of genetic material
- chromosome deletions
54
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
55
Draw table for MDS
:)
56
CML affected cell
granulocyte
57
CNL affected cell
neutrophils
58
CEL affected cell
eosinophil
59
PV cell
pancytosis
60
ET affected cell
megakaryocytes/PLT
61
PMF affected cell
Fibrosis
62
CML gene
BCR-ABL1+
63
CML definition
increase in granulocytes in PB and marked granulocytic hyperplasia in BM
LOW LAP score
64
1st human disease traced to a chrom. abnormality:
**Philadelphia chromosome**
**CML**
- 90-95% of patients with CML
65
Philadelphia chromosome
(9;22)
66
BCR-ABL gene produces
p210 tyrosine kinase
67
CML clinical features
symptoms
malaise/fatugie
- anemia
Abdomen fullness
loss of apetite
- splemomegaly
Night sweats
Weight loss
Bone tenderness/aching
68
3 CML phases
Chronic
Accelerated
Blast phase
69
CML chronic phase
- usualy diagnosed in this phase
- disease remains stable for several years
- responsive to chemo
70
CML accelerated phase
- 3-5 years after onset (untreated)
- worsening symptoms
-
71
blast phase CML
conversion of CML to aggressive form of acute leukemia that is difficult to treat
72
CML lab findings
WBC count >100,000 microL - leukocytosis
Decreased Hgb and Hct
- anemia (normochromic, normocytic)
- thrombocytosis
73
First indicator of CML
basophilia
>2% in chronic phase
74
Myelocyte bulge
chronic phase
CML
more myelocytes than metamyelocytes
75
PB smear CML
chronic phase
- giant platelets
- nRBCs
- Anisocytosis
- Basophilic stippling
- polychromasia
76
CML- chronic phase BM
Marked granulocytic hyperplasia
Increased
- megakaryocytes
- basophilic
- eosinophilic
- neutrophils
77
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
78
CML blast phase findings
BM
- **Blasts more than or equal to 20% and in clusters**
PB
**blasts>20%**
79
CML cytogenetics
t(9;22)(q34;q11)(BCR-ALB1+)
80
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
81
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
82
toxic vacuoles
Leukemoid RXN: increased
CML: absent
83
Toxic granulation
Leukemoid RXN: increased
CML: absent
84
Dohle bodies
Leukemoid RXN: increased
CML: absent
85
Eosinophilia
Leukemoid RXN: normal
CML: increased
86
Basophilia
Leukemoid RXN: normal
CML: increased
87
Myelocyte bulge
Leukemoid RXN: absent
CML: present
88
LAP score
Leukemoid vs CML
Leukemoid RXN: high
CML: low
89
Ph chromosome
Leukemoid RXN: negative
CML: positive
90
CML treatment
only proven cure: allogenic bone marrow transplant
91
CNL major criteria
WBC count >25,000 microL
and
>80% band or segmented neutrophils
92
BM CNL
granulocytic proliferation
93
CNL mutation
CSF3R
94
CNL important
how does CNL differ from CML?
**Basophilia and Eosinophilia NOT present**
**No philadelphia chromosome**
**LAP increased**
95
CEL basics
clonal expansion of eosinophil precursor
96
CEL major criteria
PB eosinophils >1,500ul
normal (0-500)
**NO philadelphia chromosome**
97
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
98
PV clincal feature
chronic disease with insidious onset
(asymptomatic/routine doctor visit)
- thrmobosis/bleeding
- splenomegaly/hepatomegaly
- **hypervscosity**
- **hypertension**
- gout
99
PV lab findings
pancytosis
- increased RBC count, Hgb, Hct
- Increased PLT
- Increased granulocytosis
100
PV BM
hyperceullarity with pancytosis
101
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
102
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
103
relative polycythemia
increased RBC due to decreased plasma volume
- dehydration/burns
aka tertiary polycythemia
increased cells:
relative - RBC only
PV - multiple cell lines
104
PV treatment
Therapeutic phlebotomy
1 unit weekly, decrease Hct
men <45%
women <40%
105
ET definition
chronic myeloproliferative disorder characterized by
- **marked thrombocytosis**
- **abnormal platelet function**
- **increased risk of thrmobsis and hemorrhage**
106
ET clinical features
chronic disrase with insidious onset (asymptomatic/routine doctor visit)
possible symptoms
- thrombosis /hemorrhage - most common
107
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
108
ET BM
increase in megakaryocytic cells
- larger than usual
- clusters
- hyperlobulated
109
ET lab findings
abnormal platelet aggregation
can also have
- decreased platelet adhesion
- storage pool defects
- prolonged bleeding times
Cytogenetics:
- JAK2 (50-60% cases)
110
Reactive thrombocytosis
increased platelet count due to something else
- acute hemorrhage
- postsplenectomy
- chronic infection
- drug induced
- trauma
111
Reactive thrombocytosis vs. ET
**PLT count >1,000,000/uL**
- RT - infrequent
- ET - frequent
**BM megakaryocyte clusters**
- RT - not present
- ET - commong
112
disease often based on exclusion
ET
113
PMF basics
Primary myelofibrosis
fibrosis - excessive formation of fibrous (connective) tissue
114
PrePMF
BM is hypercellular
increased granulocytic and megakaryocytic proliferation mimics ET and PV
115
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
116
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
117
PMF lab findings
Decreased RBC, Hgb, Hct
WBC and PLT variable
smear
- Teardrop cell
- megakaryocyte fragments and large PLT
118
fibrotic stage of PMF - BM
- fibrosis
- often results in **dry tap**
- due to increased fibrosis. andlow cellularity
119
PMF coagulation
increased fibrin degradation products (D-dimer)
extramedullary hematopoiesis in liver can cause dysfunction
- liver = coagulation factor producer
120
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
121
PMF treatment
asymptomatic
- no treatment/monitor
Symptomatic: cytotoxic therapies/and or radiation
Splenectomy
- risk of operative thrombovytosis
**allogenic stem cell transplant**
- only curative treatment
