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MLSCI330 Hematology > Leukocyte Disorders > Flashcards

Leukocyte Disorders Flashcards

1
Q

Cause of Pelger-Huet

A

mutation = decreased expression of β-lamin receptor

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2
Q

How to differentiate true vs Pseudo Pelger-Huet

A

Pelger-Huet = no clinical significance
Pseudo = disorders (MDS, AML, plasma cell myeloma, drugs) will have other affected characteristics

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3
Q

PBS of Pelger-Huet

A

Hypo-lobed neutrophils

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4
Q

Clinical significance of Pelger-Huet

A

Normal cell function

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5
Q

Cause of Alder-Reilly

A

Recessive allele = lacks enzymes to breakdown mucopolysaccharide for storage = mucopolysaccharide accumulation in cytoplasm

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6
Q

Clinical significance of Alder-Reilly

A
  • normal WBC function
    BUT = mental retardation, dwarfism, skeletal deformities, lifespan: 10-20 years
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7
Q

PBS of Alder-Reilly Anomaly

A
  • large pink granules in neutrophils
  • can be mistaken for toxicity but NO VACUOLES or NO DOHLE BODIES
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8
Q

Cause of Chediak Higashi

A

LYST gene mutation = abnormal Lysosomal Trafficking (transport of material to lysosomes)

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9
Q

Clinical Significance of Chediak Higashi

A
  • Defective de-granulation
  • Diminished delivery of enzymes to phagosomes
  • Abnormal chemotaxis
  • Short life expectancy
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10
Q

PBS of Chediak Higashi

A
  • “bubbly” granules = aggregation of primary + secondary granules
  • NEUTROPENIA, THROMBOCYTOPENIA
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11
Q

Cause of May-Hegglin Anomaly

A

MYH9 gene mutation (Myosin-heavy chain-9) = abnormal cytoskeletal proteins in PLATELETS

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12
Q

Clinical significance of May-Hegglin Anomaly

A
  • normal WBC function
  • possible bleeding tendencies due to thrombocytopenia
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13
Q

PBS of May-Hegglin Anomaly

A
  • Long BLUE inclusions in ALL GRANULOCYTES
  • THROMBOCYTOPENIA
  • GIANT PLTs
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14
Q

Cause of Chronic Granulomatous Disease

A

Mutation in gene responsible for producing NADPH oxidase complex = Neutrophils cannot produce super-oxides (anti-microbial)

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15
Q

Clinical significance of Chronic granulomatous disease

A
  • ABNORMAL NEUTROPHIL FUNCTION = cannot produce superoxides
  • recurrent INFECTIONS in lungs, tissues, skin, lymph nodes, liver
  • infection contained in macrophage-rich GRANULOMAS bc no superoxides for killing
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16
Q

Additional testing for Chronic Granulomatous Disease

A
  • Nitro-blue-tetrazolium reduction test
  • Flow cytometry
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17
Q

Cause of Infectious Mononucleosis

A

Infection of B-lymphocytes by EPSTEIN-BARR VIRUS

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18
Q

PBS of Infectious Mononucleosis

A
  • WBC increased
  • Reactive lymphocytes
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19
Q

Additional testing for Infectious Mononucleosis

A
  • Monospot POSITIVE
  • Immunological testing = EBV specific antigens
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20
Q

Which non-malignant disorder may develop an anti-i/ cold agglutinin syndrome ?

A

Infectious mononucleosis

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21
Q

Leukemia is a __ condition involving __ tissue.

A

Leukemia is a MALIGNANT condition involving HEMATOPOIETIC tissue.

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22
Q

Define oncogenes

A
  • Altered genes responsible for cell cycles/ proliferation/ regulation
  • Mutations that lead to cancer = abnormal cell processes + uncontrolled cell growth
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23
Q

Explain the body’s mechanism against oncogenes

A
  • tumor suppressor genes
  • promotes apoptosis of irregular cells
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24
Q

Leukemia can occur secondary to which conditions ?

A
  • Previous hematological disease (MPN, MDS, MM)
  • Genetic (Fanconi’s AA, Down syndrome)
  • Immunodeficiencies

MPN = Myeloproliferative neoplasms
MDS = Myelodysplastic syndrome
MM = Multiple Myeloma

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25
Q

Acute Leukemia characteristics

A
  • rapid onset
    >20% blasts
  • affects all ages
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26
Q

CBCD in Acute Leukemia

A
  • N/N anemia (RBC decreased)
  • WBC increased
  • THROMBOCYTOPENIA
  • NEUTROPENIA
    >20% blasts
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27
Q

Testing for Acute leukemia

A
  • PBS and BM morph
  • Immunophenotyping (Flow cytometry)
  • Special cytochemical stains
  • Enzyme markers
  • Cytogenetics
  • Molecular genetics
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28
Q

Differentiate myeloid vs lymphoid blasts

A

Myeloid:
- larger (more cytoplasm)
+/- auer rods
- azurophilic granules
- lacier chromatin

Lymphoid:
- smaller than myeloblasts
- scant cytoplasm
- less lacy chromatin
- rare granules

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29
Q

A positive Myeloperoxidase stain indicates __ BUT what does a negative result imply ?

A

A positive Myeloperoxidase stain indicates MYELOblasts BUT a negative result cannot exclude myeloid lineage (too young to produce MPO)

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30
Q

Which cells produce Myeloperoxidase ?

A

Granulocytes and Monocytes (primary granules)

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31
Q

Sudan black stains which cells positive ?

A

Myeloid

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32
Q

Alpha-napthyl esterate stains which cells ? What is an interference ?

A
  • NSE pos = Monocytes > megakaryocytes
  • Sodium fluoride is an interference
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33
Q

PAS stains which cells ?

A

Lymphoblasts = BLOCK POSITIVE
Acute erythroleukemia (AEL), acute megakaryocytic leukemia (AMegL), acute lymphocytic leukemia (CLL) = POS

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34
Q

TdT (enzyme marker) is detected via __ in leukemic __ cells, but rarely in __.

A

TdT (enzyme marker) is detected via FLOW CYTOMETRY in leukemic LYMPHOID cells, but rarely in AML

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35
Q

Describe cytogenetics studies/ karyotpying

A
  • analysis of chromosomes in metaphase
  • detects NUMERIC and STRUCTURAL abnormalities
  • chemical stops mitosis and KCl separates chromosomes
  • fixative = methanol + acetic acid
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36
Q

Define lymphoma

A

Tumor mass (involving lymphocytes and lymph nodes) +/- hematopoietic involvement

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37
Q

ALL can be further classified based on the origin of the cell. What are they?

A

B cell or T cell

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38
Q

How to differentiate B cell vs T cell ALL ?

A

B cell: CD34, 10, 19, 20, 22, TdT+

T cell: CD1, 2, 3, 4, 5, 7, 8, TdT+

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39
Q

AML involves which cells ?

A

Granulocytes, monocytes, erythrocytes, and megakaryocytes

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40
Q

PBS/BM of APL

A

Acute promyelocytic leukemia:
- increased promyelocytes
- bundles of auer rods
- thrombocytopenia (associated with DIC)

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41
Q

APL stain results (MPO, SBB)

A

MPO pos
SBB pos

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42
Q

APL: Immunophenotyping

A

CD13, 33, 64, 117

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43
Q

PBS/ BM of AMML

A

Acute MyeloMonocytic Leukemia:
- normo/normo anemia (RBC decreased)
- increased monocytes in PBS
- NEUTROPENIA, THROMBOCYTOPENIA
- WBC increased (myeloblasts, monoblasts, precursors)

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44
Q

AMML stain results (MPO, SBB, NSE)

A

MPO pos
SBB pos
NSE pos

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45
Q

PBS/ BM of AMMonoL

A

Acute Monoblastic/ Monocytic Leukemia:
- 2 subtypes = predominant monoBLASTS OR monoCYTES
- auer rods in monocytic leukemia

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46
Q

AMMonoL stain results (NSE, MPO, SBB)

A

NSE pos
MPO/ SBB variable

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47
Q

PBS/ BM of Acute AEL

A

Acute Eryhthroid Leukemia:
- predominant nRBC in PBS/ BM
- 20% blasts
- dysplastic precursors

48
Q

AEL stain results (PAS, NSE)

A

PAS pos
NSE pos

49
Q

AEL: immunophenotyping

A

CD235

50
Q

PBS/ BM for AMegL

A
  • increased megakaryocytes, monocytes
  • megakaryoblastic fragments
  • large PLTs
51
Q

PBS/ BM of CML (chronic phase)

A
  • normo/normo anemia (decreased RBC)
  • increased WBCs, left shift (myeloid)
  • increased PLTs
  • nRBC
  • increased EOS and BASOS
  • blasts <2%
52
Q

PBS/ BM of CML as it progresses from chronic>accelerated>blast phase

A

Accelerated:
- anemia worsens (decreased RBC)
- WBC and PLTs increase
- BASOS increase
- blasts = 10-19%

Chronic:
- BLASTS >20%

53
Q

3 stages of CML

A

chronic > accelerated > blast

54
Q

LAP result for CML

A

negative; LAP enzyme is only detected in active neutrophils (leukemoid reaction)

55
Q

Chronic Leukemia is classified based on __ and __

A

Chronic Leukemia is classified based on AFFECTED CELL LINE and GENETIC ABNORMALITIES

56
Q

3 categories of Chronic Leukemia

A
  1. Mature B-cell Neoplasms (CLL, hairy cell, MM, Hodgkins)
  2. Myeloproliferative neoplasms (CML, PV, primary myelofibrosis, ET)
  3. Myelodysplastic syndromes (MDS)
57
Q

T or F: CLL does not terminate into an acute leukemia

A

TRUE; CLL does NOT terminate into an acute leukemia.
- patients often die due to other complications/ infections

58
Q

Which cells do CLL affect ?

A

B-cells/ plasma cells

59
Q

Pathophysiology of CLL

A
  • B-lymphs cannot progress into plasma cells = hypogammaglobulinemia = more susceptible to infections
  • abnormal immunoglobulins lead to autoimmunity (AIHA or Thrombocytopenic Purpura)
60
Q

Hairy cell leukemia is a subtype of __.

A

Hairy cell leukemia is a subtype of CLL

61
Q

Additional testing for Hairy cell leukemia

A

TRAP pos
Immunophenotyping = CD20, increased side scatter; co-expression of CD103 & CD22

TRAP = tartrate resistant acid phosphatase stain

62
Q

Immunophenotyping results for Hairy cell leukemia

A
  • Increased C20
  • Co-expression of CD103 AND CD11c
63
Q

Plasma cell neoplasms are a subtype of __.

A

Plasma cell neoplasms are a subtype of MATURE B-CELL NEOPLASMS

64
Q

What is secreted by plasma cell neoplasms ?

A
  • Immunoglobulins/ paraproteins
  • aka M-proteins
65
Q

List 3 conditions under Plasma cell neoplasms

A
  1. Monoclonal gammopathy of undetermined significance
  2. Plasma cell myeloma (Multiple myeloma)
  3. Waldenström macroglobulinemia
66
Q

% of plasma cells in Monoclonal gammopathy of undetermined significance

A

<10%

67
Q

How to differentiate Waldenstrom’s macroglobulinemia vs Plasma cell myeloma

A

Waldenstrom’s mactoglobulinemia:
- serum electrophoresis = IgM
- asymptomatic

Plasma cell myeloma:
- serum electrophoresis = IgG or IgA
- CRAB symptoms (increased Ca2+)

CRAB = calcium elevations, renal damage, anemia, bone lesions

68
Q

2 classifications of lymphomas

A
  1. Hodgkin’s lymphomas
  2. Non-hodgkin’s lymphoma
69
Q

Testing for Hodgkin’s lymphomas

A

Reed-sternberg cells in lymph node biopsies (rarely in PBS)

70
Q

What do Reed-sternberg cells resemble ?

A

“Owl-eyes”

71
Q

Differentiate Hodgkin’s vs Non-Hodgkin’s lymphomas

A

Hodgkin’s:
- commonly in YOUNGER adults
- affects UPPER lymph nodes (neck, chest, armpit)
- Reed-sternberg cells (“owl-eyes”)

Non-Hodgkin’s:
- in all ages
- any lymph node
- no RS cells

72
Q

What are Myeloproliferative neoplasms ?

A
  • clonal disorders affecting MYELOID lineage
  • commonly in older adults
  • genetic stem-cell mutation = uncontrolled cell proliferation
73
Q

Cell differentiation and metabolism is influenced by the activity of __.

A

Cell differentiation and metabolism is influenced by the activity of TYROSINE ACTIVITY.

74
Q

What does uncontrolled tyrosine kinase activity lead to ?

A
  • increased CELL PROLIFERATION/ CELL CYCLES
  • inability to perform apoptosis when they should
75
Q

Cause of CML

A
  • mutation between chromosome 9 and 22 = BCR-ABL fusion gene
  • forms Philadelphia chromosome
  • BCR-ABL protein increases tyrosine kinase activity in granulocytes
76
Q

Treatment for CML

A
  • tyrosine kinase inhibitors
  • interferon-alpha = suppresses Philadelphia chromosome
  • transplants (BM/ stem cell)
  • immunotherapy to destroy abnormal cells
77
Q

Cause of PV

A

Polycythemia Vera:
- radiation/ toxin exposure = point mutation in JAK2 gene
- valine amino acid replaced by PHENYLALANINE = JAK2 V617F mutation

78
Q

Pathophysiology of PV

A
  • JAK2 V617F mutation = JAK2 kinase continuously triggers EPO receptors WITHOUT EPO
  • increased proliferation of RBCs INDEPENDENT OF EPO
  • patients develop anemia, BM fibrosis, and splenomegaly
79
Q

PBS/ BM of PV

A

PBS:
- INCREASED RBCs
- normo/ normo
- increased PLTs and WBCS

BM:
- normal M:E
- fibrotic over time
- decreased EPO and iron stores

80
Q

Testing for PV

A

Molecular genetics: JAK2 V617F mutation

81
Q

How to differentiate PV, secondary PV, and relative PV

A

PV: increased RBCs, WBCs and PLTs with decreased EPO
Secondary PV: increased RBCs AND EPO, but normal WBC and PLTs
Relative: increased RELATIVE RBCs (less plasma volume = more concentrated), BUT normal EPO, WBCs and PLTs

NOTE: all will have HIGH HEMATOCRIT and HEMOGLOBIN

82
Q

Cause of Primary Myelofibrosis

A
  • Various genetic mutations including JAK2 V617F
  • overproduction of HSC = increased proliferation of myeloid lines
83
Q

Which cell lines are affected in Primary Myelofibrosis ?

A

over-production of hematopoietic cells and stimulation of fibroblasts

84
Q

PBS/ BM of Initial phase in Primary Myelofibrosis

A

PBS:
- increased WBCs and PLTs
- normo/ normo anemia (decreased RBCs)

BM:
- hypercellular; increased M:E

85
Q

Which Myeloproliferative neoplasm may progress into hypo/ micro over time ?

A

Polycythemia Vera

86
Q

PBS/ BM of Fibrotic phase in Primary Myelofibrosis

A

PBS:
- normo/ normo anemia (decreased RBCs)
- DECREASED WBCs and PLTs (large/ giant)
- LEUKO ERYTHRO BLASTIC = myeloprecursors + nRBC + blasts
- poikilocytosis (ELLIPTO + TEARS)

BM:
- dry tap
- DECREASED WBCs and PLTs

87
Q

Additional testing for Primary Myelofibrosis

A
  • Trephine biopsy due to dry tap
  • Molecular genetics = multiple mutations
88
Q

Which cells are affected in Essential Thrombocythemia ?

A

MEGAKARYOCYTES and PLATELETS

89
Q

Cause of ET

A

Essential Thrombocythemia:
- multiple mutations including JAK2, MPL, CALR = abnormal platelets (function + morph)

90
Q

PBS/ BM of Essential thrombocythemia

A

PBS:
- INCREASED and ABNORMAL PLATELETS (>600)
- normo/ normo anemia (decreased RBCs)
- megakaryocyte fragments

BM:
- INCREASED and ABNORMAL MEGAKARYOCYTES
- decreased iron stores

91
Q

Additional testing for ET

A

Essential Thrombocythemia:
- Molecular genetics = multiple mutations including JAK2, MPL, CAR

92
Q

MDS can progress into __.

A

MDS can progress into AML.

93
Q

Abnormal findings of granulocytes in MDS

A

PBS:
- decreased WBCs (being destroyed in BM)
- hypogranulated neuts
- hypo/hypergranulated neuts

BM:
- karryohexis (mitotic figures)
- <20% blasts

94
Q

Abnormal findings of erythoids in MDS

A

PBS:
- normo/normo OR dimorphic anemia (decreased RBCs)
- POIKILOCYTOSIS (BASOPHILIC STIPPLING, OVAL MACROCYTES, tears, schistocytes, howell jolly bodies, acanthocytes, spherocytes, elliptocytes)
- nRBCs

95
Q

Abnormal findings of megakaryocytes in MDS

A

PBS:
- GIANT PLTs
- PLT clumps
- hypogranular PLTs
- megakaryocytic fragments

BM: <20% blasts
- hypercellular; increased M:E

96
Q

PBS/ BM in Mature B-cell neoplasm (CLL)

A

PBS:
- increased SMALL LYMPHS/ smudge cells; neutropenia
- normo/ normo anemia (decreased RBCs)

BM:
- increased small lymphs; >30%
- decreased granulocytes, erythrocytes

97
Q

PBS/ BM of Hairy cell leukemia

A

PBS:
- increased hairy cells (SMALL LYMPHS)
- normo/ normo anemia (decreased RBCs)
- decreased PLTs (due to fibrosis)

BM:
- dry tap due to fibrosis
- decreased PLTs

98
Q

PBS/ BM of Plasma cell myeloma/ multiple myeloma

A

PBS:
- normo/ normo anemia (decreased RBCs)
- DECREASED WBCs (neutropenia), PLTs, retics
- plasma cells
- rouleaux

BM:
- plasma/ flame/ mott cells
- ostolytic lesions
- hypercellular

99
Q

PBS/ BM of Waldenstrom’s macroglobinemia

A

PBS:
- normo/ normo anemia (decreased RBCs)
- DECREASED WBCs (neutropenia), PLTs, retics
- rouleaux

BM:
- plasma cytoid lymphs (resemble plasma cells WITHOUT halos)

100
Q

Common test results for Plasma cell neoplasms (Plasma cell myeloma and Waldenstrom’s macroglobulinemia)

A

ESR increased
PT and PTT prolonged
Bence jones proteins in urine

101
Q

Additional testing for CML

A

LAP stain = neg
Cytogenetics = Philadelphia chromosome (chromosome 9 to 22 translation)
Molecular genetics = BCR-ABL fusion gene

102
Q

What causes the spherocytes seen in CLL ?

A

AIHA secondary to CLL; autoAb coat RBCs and are spliced by macrophages in the spleen

103
Q

Why may a leukomoid reaction be mistaken with CML ?

A

Leukomoid reaction:
- increased NEUTROPHILS due to infections, hemorrhage, hemolysis

CML:
- ALL MYELOIDS INCREASED

104
Q

How to differentiate Leukemoid reaction from CML

A

Leukomoid reaction:
- LAP stain POS
- NEUTROPHILS increased

CML:
- LAP stain neg
- ALL MYELOIDS INCREASED
- Molecular genetics = BCR-ABL fusion gene
- Cytogenetics = Philadelphia chromosome (9 to 22 translation)

105
Q

Immunophenotyping for AML

A

CD13, 33, 64, 17

106
Q

Why may platelet satellite be observed in blood samples of healthy individuals ?

A
  • EDTA chelates calcium
  • this exposes Ag on RBCs
  • autoAb binds to GP2 B3A Fc receptors
  • platelets satellite around RBCs
107
Q

Which statement is correct with respect to toxic granulation?

a.
It appears in lymphocytes in response to inflammation

b.
It is associated with chronic myelogenous leukemia

c.
It is usually seen along with a ‘left shift’

d.
It is similar to inclusions seen in Chediak-Higashi

A

c.
It is usually seen along with a ‘left shift’

108
Q

Which of the following statements about left shift is FALSE?

a.
Bands and myeloids are present in the peripheral blood.

b.
It can be caused by a malignant or non-malignant process

c.
It often accompanies a high WBC count

d.
It affects the lymphocytic cell line

A

d.
It affects the lymphocytic cell line

109
Q

An absolute lymphocytosis with reactive lymphocytes suggests which of the following conditions?

a.
Bacterial infection

b.
Viral infection

c.
Parasitic infection

d.
Acute leukemia

A

b.
Viral infection

110
Q

Which of the following is NOT a cause of eosinophilia?

a.
Myeloproliferative neoplasms

b.
Helminth infection

c.
Malarial infection

d.
Bacterial infections

A

d.
Bacterial infections

111
Q

The following peripheral blood abnormalities are diagnostic clues in MDS EXCEPT:

a.
Oval macrocytes

b.
Target cells

c.
Agranular neutrophils

d.
Elliptocytes

A

b.
Target cells

112
Q

What are the abnormal inclusions in Chédiak-Higashi anomaly composed of?

a.
Ribosomal material that looks like dohle-like bodies

b.
Excess lipids that cannot be broken down

c.
fused granules that inhibit bactericidal functions

d.
Excess mucopolysaccharides that disrupt cell function

A

c.
fused granules that inhibit bactericidal functions

113
Q

The heterophile antibody can be found in

a.
Infectious mononucleosis

b.
Acute lymphocytic leukemia

c.
Leukemoid reaction

d.
Bacterial pneumonia

A

a.
Infectious mononucleosis

114
Q

Which of the following statements is true regarding infectious mono?

a.
Patient will have relative and absolute lymphocytosis

b.
The bone marrow will show a decreased M:E ratio

c.
The WBC differential will show a left shift

d.
B-lymphocytes will demonstrate characteristic reactive morphology

A

a.
Patient will have relative and absolute lymphocytosis

115
Q

Which of the following is a feature of secondary polycythemia?

a.
Increased oxygen saturation

b.
Decreased plasma volume

c.
Increased erythropoietin

d.
Normal hematocrit

A

c.
Increased erythropoietin

116
Q

Which of the following cytoplasmic inclusion is composed of RNA?

a.
May-Hegglin inclusions

b.
Alder-Reilly inclusions

c.
Heinz bodies

d.
Dohle bodies

A

d.
Dohle bodies

MLSCI330 Hematology (10 decks)

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