Leukemia Flashcards

1
Q

Leukemias vs. Lymphomas: Overproduction of cells

A

Leukemias: Overproduction of various types of immature or mature cells in the bone marrow and/or peripheral blood. Lymphomas: Solid malignant tumors of the lymph nodes and related WBCs in bone tissue.

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2
Q

Leukemias vs. Lymphomas: Cell Types

A

Leukemias: Frequently involves WBCs of the myelogenous or lymphocytic cell types. Lymphomas: The distinctive cell type is the lymphocyte.

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3
Q

Leukemias vs. Lymphomas: Blood-brain barrier

A

Leukemias: Malignant cells easily trespass the blood-brain barrier. Lymphomas: Malignant cells are initially confined to lymph nodes, spleen, liver, and bone marrow, though they can spill into the circulating blood.

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4
Q

Leukemias vs. Lymphomas: Tumor location and spread

A

Leukemias: Malignant cells primarily in bone marrow and peripheral blood. Lymphomas: Solid tumors in lymph nodes and organs containing mononuclear phagocytic cells, may spill over into circulating blood.

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5
Q

Leukemia: Definition

A

Overproduction of immature or mature WBCs in the bone marrow or peripheral blood.

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6
Q

Leukemia: Disease course and WBC count

A

More blasts = shorter, fatal course; ↑ WBC with left shift.

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7
Q

Leukemia: M:E ratio

A

10:1.

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8
Q

Anemia type in acute leukemia

A

Normocytic, normochromic.

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9
Q

Acute Leukemias: Duration and cell forms

A

Short duration; numerous immature cells in bone marrow/peripheral blood; ↑ WBC count.

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10
Q

Chronic Leukemias: Duration and cell forms

A

Long duration; mostly mature cells in bone marrow/peripheral blood; WBC count varies (elevated or lower than normal).

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11
Q

FAB Classification of Leukemias

A

Based on morphology in Romanowsky-stained smear and cytologic/histochemical characteristics of cells.

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12
Q

Myeloperoxidase (MPO): Function

A

Used to differentiate AML blasts from ALL blasts.; found in primary granules of neutrophils, eosinophils, and monocytes

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13
Q

MPO Positive Cells

A

Neutrophilic granulocytes, Auer rods, leukemic blasts in FAB M1, M2, M3, eosinophils.

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14
Q

MPO Weakly Positive or Negative Cells

A

Monocytes.

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15
Q

MPO Negative Cells

A

Myeloblasts, basophils, lymphocytic and erythrocytic cell series.

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16
Q

Peroxidase Stain Reminders

A

May produce red-brown, dark brown, or black color; RBCs may turn brown due to pseudoperoxidase activity in hemoglobin.

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17
Q

Precautions for DAB Handling

A

Wear protective clothing, use mechanical pipetting aids, clean up spills instantly, wash hands after use, weigh benzidine in hood.

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18
Q

Peroxidase Enzyme Sensitivity

A

Sensitive to light; stain immediately or keep in dark. Older smears or those exposed to light should not be peroxidase negative.

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19
Q

Cyanide-resistant Peroxidase Stain

A

Detects eosinophilic leukemia; eosinophil peroxidase differs due to enzyme activity with sodium cyanide.

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20
Q

Sudan Black B (SBB): Function

A

Stains sterols, neutral fats, phospholipids in primary and secondary granules of neutrophils and lysosomal granules of monocytes.

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21
Q

SBB Positive Cells

A

Promyelocyte, myelocyte, metamyelocytes, bands, segmented neutrophils (strongly positive), leukemic blasts, Auer rods, eosinophils.

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22
Q

SBB Weakly Positive or Negative Cells

A

Myeloblasts, monocytic cells.

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23
Q

SBB Negative Cells

A

Lymphocytes and precursors, megakaryocytes, platelets, erythrocytes.

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24
Q

SBB Staining Reminders

A

Brownish-black granules in myelocytic precursors, few granules in monocytes, eosinophilic granules with central pallor.

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25
Q

SBB Staining Properties

A

Can be performed on specimens months old; reagents not carcinogenic.

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26
Q

SBB Disadvantages

A

Time-consuming (1-2 hours), possible false positives in lipid vacuole disorders, increased background in bone marrow specimens.

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27
Q

Lymphocytic Leukemias: Myeloperoxidase and Sudan Black B

A

Myeloperoxidase: negative, Sudan Black B: negative.

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28
Q

Most Common Childhood Leukemia

A

Acute Lymphocytic Leukemia (ALL).

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29
Q

FAB Classification: L1

A

70% of childhood ALL; markers: CALLA (CD10), TdT, CD19, CD20.

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30
Q

FAB Classification: L2

A

70% of adult ALL; markers: TdT.

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31
Q

FAB Classification: L3

A

Rare in children/adults; markers: sIg, CD19, CD20, CD22, CD24.

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32
Q

FAB Classification: Cell Size L1

A

Homogeneous population of small blasts.

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33
Q

FAB Classification: Cell Size L2

A

Heterogeneous population of large blasts.

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34
Q

FAB Classification: Cell Size L3

A

Homogeneous population of large blasts with nuclear and cytoplasmic vacuoles.

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35
Q

Nucleus L1

A

Uniformly round, small.

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36
Q

Nucleus L2

A

Irregular.

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37
Q

Nucleus L3

A

Round to oval.

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38
Q

Nucleolus L1

A

Single.

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39
Q

Nucleolus L2

A

Single to several.

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40
Q

Nucleolus L3

A

Two to five.

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41
Q

Chromatin L1

A

Slightly reticulated with perinucleolar clumping.

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42
Q

Chromatin L2

A

Fine.

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43
Q

Chromatin L3

A

Coarse with clear parachromatin.

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44
Q

Cytoplasm L1

A

Scant, blue.

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45
Q

Cytoplasm L2

A

Moderate, pale.

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46
Q

Cytoplasm L3

A

Moderate, blue, prominently vacuolated.

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47
Q

Cyto-chemistry L1

A

PAS+: Positive, Methyl Green Pyronin: Negative, ORO: Positive (sometimes).

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48
Q

Cyto-chemistry L2

A

PAS+: Positive, Methyl Green Pyronin: Negative, ORO: Positive (sometimes).

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49
Q

Cyto-chemistry L3

A

PAS: Negative, Methyl Green Pyronin: Positive, ORO: Positive.

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50
Q

Immunologic Markers: E Rosettes

A

T-ALL: Positive.

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51
Q

Immunologic Markers: Surface Ig

A

B-ALL: Positive.

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52
Q

Immunologic Markers: Serum Anti-ALL

A

Common ALL: Positive.

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53
Q

Most common type of leukemia in elderly, characterized by persistent lymphocytes

A

Chronic Lymphocytic Leukemia (CLL).

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54
Q

Chronic Lymphocytic Leukemia (CLL) cells present

A

Increased smudge cells, Rieder cells in peripheral blood smear.

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55
Q

Clinical Variations of CLL

A

Hairy-cell leukemia, Lymphosarcoma cell leukemia, Prolymphocytic leukemia.

56
Q

Acute lymphoblastic leukemia (ALL) Solid tumor counterpart

A

Lymphoma, poorly differentiated; lymphocytic.

57
Q

Chronic lymphocytic leukemia (CLL) Solid tumor counterpart

A

Lymphoma, well-differentiated; lymphocytic.

58
Q

Monocytic leukemia Solid tumor counterpart

A

Reticulum cell sarcoma.

59
Q

Acute myelogenous granulocytic leukemia Solid tumor counterpart

A

Chloroma.

60
Q

Plasma cell leukemia Solid tumor counterpart

A

Myeloma.

61
Q

Stem cell leukemia Solid tumor counterpart

A

Lymphoma, undifferentiated.

62
Q

Non-lymphocytic leukemias/myelogenous leukemias (granulocytes, monocytic progenitor) Initial stains: Myeloperoxidase and Sudan Black reaction

A

Positive.

63
Q

Acute Myelogenous Leukemia (AML) M0 - Myelocytic

A

AML, minimally differentiated/undifferentiated. MPO and SBB negative.

64
Q

Acute Myelogenous Leukemia (AML) M1 - Myelocytic

A

AML, without maturation. May demonstrate Auer rods.

65
Q

Acute Myelogenous Leukemia (AML) M2 - Myelocytic

A

AML, with maturation. Most common subtype of AML. May demonstrate Auer rods.

66
Q

Acute Myelogenous Leukemia (AML) M3 - Myelocytic

A

Acute Promyelocytic Leukemia (APL), associated with DIC and Faggot cells. Demonstrates Auer rods.

67
Q

Acute Myelogenous Leukemia (AML) M3V - APL, microgranular variant

A

Cells have characteristic ‘butterfly’, ‘bowtie’, ‘coin-on-coin’, or ‘apple core’ nuclei.

68
Q

2nd most common subtype of AML. May demonstrate Auer rods.

A

Acute Myelomonocytic Leukemia (AMML) M4 - Myelocytic Monocytic

69
Q

AMML with increased marrow eosinophils.

A

Acute Myelomonocytic Leukemia (AMML) M4E

70
Q

Schilling Leukemia.

A

Acute Monocytic Leukemia (AMOL) M5 - Monocytic

71
Q

AML poorly differentiated. Seen in children; >80% monoblasts in BM.

A

Acute Monocytic Leukemia (AMOL) M5A

72
Q

Well differentiated. Seen in middle-aged adults; <80% monoblasts in BM.

A

Acute Monocytic Leukemia (AMOL) M5B

73
Q

Di Guglielmo’s Syndrome. Demonstrates Auer rods.

A

Acute Erythroleukemia M6 - Erythrocytic Myelocytic

74
Q

AML M6 reaction with PAS. Strongly positive (L1, L2, M6).

A

Acute Erythroleukemia M6

75
Q

Di Guglielmo’s Syndrome anemia type: macrocytic, normochromic.

A

Anemia Type: Di Guglielmo’s Syndrome

76
Q

Acute Megakaryocytic Leukemia requires immunocytochem staining for accurate diagnosis.

A

M7 - Megakaryocytic, Factor VIII stains positive.

77
Q

Acute basophilic leukemia.

A

AML 8 - Acute Basophilic Leukemia.

78
Q

M1, M2, M3 leukemia positive cytochemical stains.

A

Positive for MPO, SBB, Naphthol AS-D, Chloroacetate (SE).

79
Q

M4 (AMML) leukemia positive cytochemical stains.

A

Positive for MPO, SBB, Naphthol AS-D, Chloroacetate (SE), α-Naphthyl Butyrate Esterase (NSE), α-Naphthyl Acetate Esterase (NSE).

80
Q

M5 (AMoL) leukemia cytochemical stains.

A

Positive or negative for SBB, positive for α-Naphthyl Butyrate Esterase (NSE), α-Naphthyl Acetate Esterase (NSE).

81
Q

M6 leukemia cytochemical stains.

A

Positive or negative for MPO, SBB, Naphthol AS-D, Chloroacetate (SE).

82
Q

M7 leukemia cytochemical stains.

A

Localized positivity for α-Naphthyl Acetate Esterase (NSE) and positive for Factor VIII stain.

83
Q

Myelocytic leukemia positive cytochemical stains.

A

Positive for MPO, SBB, SE, Naphthol AS-D.

84
Q

Monocytic leukemia positive cytochemical stains.

A

Positive for NSE, Butyrate Esterase.

85
Q

ICC Classification AML subtypes with ≥10% blasts

A

Includes t(15;17)/PML::RARA, t(8;21)/RUNX1::RUNX1T1, inv(16)/CBFB::MYH11, t(9;11)/MLLT3::KMT2A, t(6;9)/DEK::NUP214, t(3;3)/GATA2::MECOM, mutated NPM1.

86
Q

ICC Classification AML subtypes with ≥20% blasts

A

t(9;22)/BCR::ABL1, myelodysplasia-related gene mutations, myelodysplasia-related cytogenetic abnormalities.

87
Q

WHO 2022 Classification usually represents

A

No blast threshold for classification.

88
Q

WHO 2022 Classification AML subtypes with ≥20% blasts

A

BCR::ABL1 fusion, CEBPA mutation, myelodysplasia-related, defined by differentiation.

89
Q

Chronic Myelogenous Leukemia (CML) AKA,

A

Chronic granulocytic leukemia

90
Q

Chromosome Associated with CML,

A

Philadelphia Chromosome (Ph1)

91
Q

First description of Philadelphia Chromosome,

A

Peter C. Nowell, 1960

92
Q

Cause of Philadelphia Chromosome,

A

Reciprocal translocation between chromosomes 9 and 22

93
Q

Result of translocation in CML,

A

Formation of BCR-ABL1 fusion gene

94
Q

Three clinical phases of CML,

A

Chronic phase, Accelerated phase, Blast crisis

95
Q

Percentage of CML patients with Philadelphia Chromosome,

A

0.9

96
Q

Significance of Philadelphia Chromosome in CML,

A

Indicates good prognosis

97
Q

Chromosomes involved in CML translocation,

A

Chromosome 9 and 22

98
Q

Parts of chromosomes involved in translocation,

A

Long arms of chromosomes 9 and 22

99
Q

Must be differentiated from Chronic Myelogenous Leukemia (CML) because it may cause confusion,

A

LEUKEMOID REACTION (LR)

100
Q

LEUKEMOID REACTION (LR) is characterized by,

A

Excessive leukocytic response in peripheral blood

101
Q

WBC count in LEUKEMOID REACTION (LR),

A

Greater than 50 X 10⁹ /L (with neutrophilia and marked left shift)

102
Q

Marked left shift in LEUKEMOID REACTION (LR),

A

Presence of immature neutrophilic forms

103
Q

Most frequent WBC increase in LEUKEMOID REACTION (LR),

A

Neutrophils

104
Q

Generally used to distinguish LR from CML,

A

LEUKOCYTE (NEUTROPHIL) ALKALINE PHOSPHATASE (LAP/NAP) TEST

105
Q

Principle of LAP/NAP Test,

A

↑ LAP activity observed in neutrophils that have undergone normal growth

106
Q

KAPLOW’S METHOD Principle,

A

Hydrolysis of sodium alpha naphthyl phosphate by alkaline phosphatase produces a colored precipitate with a diazotised amine

107
Q

Fixative used in KAPLOW’S METHOD,

A

Methanol and formalin

108
Q

Buffer used in KAPLOW’S METHOD,

A

Propanediole

109
Q

Substrate in KAPLOW’S METHOD,

A

Sodium alpha naphthyl phosphate

110
Q

Initial stain used in KAPLOW’S METHOD,

A

Brentamine fast game salt

111
Q

Counterstain used in KAPLOW’S METHOD,

A

Aqueous Mayer’s hematoxylin

112
Q

Procedure for LAP Test (Kaplow’s Method),

A

Immerse dry blood smear in fixative for 30 seconds, then dry

113
Q

Working substrate for LAP test,

A

Made up of buffer, substrate, and initial stain

114
Q

After applying working substrate in KAPLOW’s LAP,

A

Allow to stand for at least 10 minutes

115
Q

Counterstaining time for KAPLOW’s LAP,

A

10 to 15 minutes

116
Q

After counterstaining in KAPLOW, where is it mounted,

A

Glycerol

117
Q

Examination of KAPLOW’s LAP under the microscope,

A

Look for reddish-brown to black precipitate in neutrophil cytoplasm

118
Q

Scoring of neutrophils in LAP test,

A

Count 100 segmented neutrophils and bands, score based on precipitate

119
Q

Score for no precipitate,

A

0

120
Q

Score for slightly diffused precipitate,

A

1+

121
Q

Score for moderately diffused precipitate,

A

2+

122
Q

Score for heavily diffused precipitate,

A

3+

123
Q

Score for very heavily diffused precipitate,

A

4+

124
Q

Normal LAP score range,

A

15 to 100

125
Q

Interpretation of normal LAP score,

A

Leukomoid reaction

126
Q

Interpretation of decreased LAP score,

A

CML

127
Q

Examples of cases with INCREASED KAPLOW’S (LAP) SCORE,

A

Third trimester pregnancy, PCV, Infections, Intoxication

128
Q

Examples of cases with DECREASED KAPLOW’S (LAP) SCORE,

A

CML, Paroxysmal nocturnal hemoglobinuria, Sideroblastic anemia, Myelodysplastic syndrome

129
Q

Leukocyte types in CML vs. LEUKEMOID REACTION,

A

CML: Blasts/promyelocytes, LEUKEMOID REACTION: Myelocytes

130
Q

Toxic granulation in CML vs. LEUKEMOID REACTION,

A

CML: Absent, LEUKEMOID REACTION: Present

131
Q

Eosinophils/Basophils in CML vs. LEUKEMOID REACTION,

A

CML: Decreased (↓), LEUKEMOID REACTION: Increased (↑)

132
Q

LAP score in CML vs. LEUKEMOID REACTION,

A

CML: Decreased (↓), LEUKEMOID REACTION: Increased (↑)

133
Q

Philadelphia chromosome in CML vs. LEUKEMOID REACTION,

A

CML: Usually present, LEUKEMOID REACTION: Absent

134
Q

Splenomegaly in CML vs. LEUKEMOID REACTION,

A

CML: Usually prominent, LEUKEMOID REACTION: Mild (if present)

135
Q

Platelet count in CML vs. LEUKEMOID REACTION,

A

CML: >600 or <50 X 10⁹/L, LEUKEMOID REACTION: Normal