Acute Leukemia Flashcards

1
Q

Techniques in Identification of Acute Leukemia

A

▪ Morphologic and cytochemical stains
▪ Flow cytometry
▪ Genetic/molecular studies

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2
Q

French-American-British (FAB) Classifications of Acute Leukemia

A
  • Morphologic exam with cytochemical stain
  • Cytogenetic studies and T and B lymphocytes marker results
  • 30% blasts
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3
Q

WHO classification of Acute Leukemia

A
  • 20% blasts in BM
  • detect the presence/absence of genetic anomalies
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4
Q

Seen in patients with the blastic transformation of B and T cells

A

Acute Lymphoblastic Leukemia (ALL)

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5
Q

Most common leukemia in the
pediatric population (80%) vs. 20% of cases in adult

A

Acute Lymphoblastic Leukemia (ALL)

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6
Q

Treatment among adolescents and young adults is predominantly inspired by pediatric regimens with better survival rates

A

Acute Lymphoblastic Leukemia (ALL)

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7
Q

> 20% myeloid blasts

A

Acute Myelogenous Leukemia (AML)

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8
Q

Most common acute leukemia in adults

A

Acute Myelogenous Leukemia (AML)

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9
Q

most aggressive cancer with a variable prognosis depending upon the molecular subtypes

A

Acute Myelogenous/Myeloid Leukemia (AML)

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10
Q

Peak incidence of ALL in children

A

2 and 5 y/o

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11
Q

disease of childhood and adolescence, accounting for 25% of childhood cancers and up to 75% of childhood leukemia

A

ACUTE LYMPOBLASTIC LEUKEMIA (ALL)

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12
Q

T/F

In ALL, risk increases with age and most adult patients are older than 50 y/o

A

T

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13
Q

important prognostic indicator for survival of ALL

A

Subtype of ALL

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14
Q

WHO classification of ALL is synonymous with the? what are the classification?

A

FAB L1 and L2 classification

▪ Precursor B lymphoblastic leukemia/lymphoblastic lymphoma (precursor B-cell ALL) → neoplasm of lymphoblasts committed to the B-cell lineage
▪ Precursor T lymphoblastic leukemia/lymphoblastic lymphoma (precursor T-cell ALL) → neoplasm of lymphoblasts committed to the T-cell lineage

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15
Q

neoplasm of lymphoblasts committed to the B-cell lineage

A

Precursor B lymphoblastic leukemia/lymphoblastic lymphoma (precursor B-cell ALL)

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16
Q

neoplasm of lymphoblasts committed to the T-cell lineage

A

Precursor T lymphoblastic leukemia/lymphoblastic lymphoma (precursor T-cell ALL)

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17
Q

FAB Classification of ALL

A

L1 (children; homogenous)
L2 (older children and adults; heterogenous)
L3 (patients with leukemia secondary to Burkitt lymphoma)

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18
Q

size of blasts in L1

A

small

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19
Q

nuclear shape in L1

A

indistinct
regular with occasional cleft

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20
Q

nucleoli in L1

A

scant
rarely visible

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21
Q

cytoplasm in L1

A

invisible
moderately basophilic

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22
Q

One population of cells within the case

A

L1 (Homogenous)

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23
Q

chromatin pattern of L1

A

Homogeneous

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24
Q

size of blasts in L2

A

Large, heterogenous

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25
nuclear shape in L2
CLEFFS/indented, prominent
26
nucleoli in L2
large, abundant (1 or more)
27
cytoplasm in L2
moderately clefted varies in color
28
size of blasts in L3
large; homogenous size
29
nuclear shape in L3
round/oval
30
nucleoli in L3
1-3 prominent, basophilic
31
cytoplasm of L3
prominent, vacuoles deeply basophilic
32
L3 is aka
Burkitt Lymphoma type
33
CLINICAL SIGNS AND SYMPTOMS OF ALL that varies from days to weeks
▪ Pain in the extremities (legs) - tissue infiltration of leukemic cells ▪ Lymphadenopathy and hepatomegaly - 75% ▪ Leukemic meningitis and cranial nerve palsies - nerve infiltration by leukemic blasts
34
Total leukocyte count of ALL in 60-70% pt.
50-100 × 10^9/L
35
Total leukocyte count of ALL in <15% pt.
> 100 × 10^9/L extreme leukocytosis
36
Total leukocyte count of ALL in 25% pt.
leukocytopenia
37
Peripheral Blood Smear of ALL
Predominance of Blast cell Close to 100% lymphoblasts, lymphocytes & smudge cells
38
most reliable indicators of a cell’s origin for ALL
Immunophenotyping Genetic analysis
39
characterize Lymphoid progenitors (B and T)
CD34 Terminal deoxynucleotidyl transferase (TdT) Human leukocyte antigen-DR subregion (HLA-DR)
40
characterized by specific B cell antigens that are expressed at different stages of B cell development
B-ALL
41
ALL subtypes
Early (pro/pre-pre) B-ALL Intermediate (common) B-ALL Pre-B-ALL T-ALL
42
Immunophenotype of Early (pro/pre-pre) B-ALL
CD34 CD19 cytoplasmic CD22 TdT
43
Immunophenotype of Intermediate (common) B-ALL
CD34 CD19 cytoplasmic CD22 TdT CD10*
44
Immunophenotype of Pre-B-ALL
CD34 CD19 cytoplasmic CD22 TdT (variable)* cytoplasmic u*
45
Immunophenotype of T-ALL
CD2 CD3 CD4 CD5 CD7 CD8 TdT
46
seen in the majority of B and T cell ALL, which produce changes that affect normal B and T cell development and underlie the pathogenesis of these neoplasms
Cytogenetic abnormalities
47
alters the Notch receptor signaling pathway (responsible for normal T cell development)
T-ALL- gain of NOTCH1 gene
48
has the worst prognosis among ALLs
B-lymphoblastic leukemia/lymphoma with t(9;22)(q34;q11.2); BCR-ABL1 mutation (Philadelphia chromosome–positive ALL)
49
Nonspecific, decreased production of normal BM elements
ACUTE MYELOID LEUKEMIA (AML)
50
CLINICAL SIGNS AND SYMPTOMS OF AML
▪ Pallor, fatigue, fever, bruising, and bleeding ▪ Anemia ▪ Thrombocytopenia ▪ Neutropenia ▪ Splenomegaly ▪ DIC and other bleeding abnormalities ▪ malignant cell infiltration in gums and mucosal site
51
AML WBC count
5 -30 x 10^9/L
52
present in the PBS in AML
Myeloblasts
53
Common abnormalities in lab test with AML
Hyperuricemia – caused by increased cellular turnover Hyperphosphatemia – due to cell lysis Hypocalcemia – latter two are involved in progressive destruction Hypokalemia – also common at presentation
54
Caused by the breakdown products of dying cancer cells? which causes?
Tumor lysis syndrome acute uric acid nephropathy renal failure
55
FAB Classification of AML
M0 (Myeloid) M1 (Myeloid) M2 (Myeloid) M3 (Promyelocytic) M4 (Myelomonocytic) M5 (Monocytic) M6 (Erythroleukemia) M7 (Megakaryocytic)
56
Undifferentiated blasts, AML— not otherwise categorized
M0 (Myeloid)
57
Blasts and promyelocytes predominate without further maturation of myeloid cells. What is the WHO synonym?
M1 (Myeloid) WHO: Acute Myeloid Leukemia WITHOUT Maturation
58
Myeloid cells demonstrate maturation beyond the blast and promyelocyte stage. What is the WHO synonym?
M2 (Myeloid) WHO: Acute Myeloid Leukemia WITH Maturation
59
Promyelocytes predominate in the bone marrow. What is the WHO synonym?
M3 (Promyelocytic) WHO: Acute Promyelocytic Leukemia
60
Both myeloid and monocytic cells are present to the extent of at least 20% of the total leukocytes What is the WHO synonym?
M4 (Myelomonocytic) WHO: Acute Myelomonocytic Leukemia
61
M4 is aka
Naegeli type Monocytic Leukemia
62
Most cells are monocytic with 2 subtypes (a and b) What is the WHO synonym?
M5 (Monocytic) WHO: Acute Monoblastic Leukemia (FAB M5a) Acute Monocytic Leukemia (FAB M5b)
63
characterized by large blasts in bone marrow and peripheral blood; common in young adults
FAB M5a
64
differentiated type by monoblasts, promonocytes, and monocytes; common during middle age
FAB M5b
65
Refered to as Schilling’s type
M5 (Monocytic)
66
aka M6 (Erythroleukemia)
Erythemic Myelosis Di Guglielmo syndrome
67
Abnormal proliferation of both erythroid and granulocytic precursors; may include abnormal megakaryocytic and monocytic proliferations What is the WHO synonym?
M6 (Erythroleukemia) WHO: Acute Erythroid Leukemia
68
Large and small megakaryoblasts with a high nuclear cytoplasmic ratio; Pale; agranular cytoplasm What is the WHO synonym?
M7 (Megakaryocytic) WHO: Acute Megakaryoblastic Leukemia
69
WHO Classification of AML
ACUTE MYELOID LEUKEMIA WITH CERTAIN GENETIC ABNORMALITIES ACUTE MYELOID LEUKEMIA, NOT OTHERWISE SPECIFIED ACUTE LEUKEMIAS OF AMBIGUOUS LINEAGE
70
WHO Classification: ACUTE MYELOID LEUKEMIA WITH CERTAIN GENETIC ABNORMALITIES
AML with t(8;21) AML with inv(16) or t(16;16) AML with t(9;11) APL with t(15;17)
71
WHO Classification: ACUTE MYELOID LEUKEMIA, NOT OTHERWISE SPECIFIED
AML with minimal differentiation AML without maturation AML with maturation Acute myelomonocytic leukemia Acute monoblastic/monocytic leukemia Acute erythroid leukemia Acute megakaryoblastic/megakaryocytuc leukemia Acute basophilic leukemia
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WHO Classification: ACUTE LEUKEMIAS OF AMBIGUOUS LINEAGE
Acute undifferentiated leukemia Mixed phenotype acute leukemia with t(9;22) Mixed phenotype acute leukemia with t(v;11q23) Mixed phenotype acute leukemia, B lymphocytes-myeloid cells Mixed phenotype acute leukemia, T-myeloid
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CYTOCHEMICAL STAINS
MYELOPEROXIDASE SUDAN BLACK B CHLOROACETATE ESTERASE (NAPTHOL AS-D) - SPECIFIC ESTERASE NON-SPECIFIC ESTERASE PERIODIC ACID SCHIFF (PAS) ACID PHOSPHATASE STAIN TERMINAL DEOXYRIBONUCLEOTIDYL TRANSFERASE (TdT) TOLUIDINE BLUE / METACHROMATIC STAIN
74
stain used to differentiate AML (+) to ALL (-)
MYELOPEROXIDASE SUDAN BLACK B
75
stain must be FRESH because enzymes are unstable
MYELOPEROXIDASE
76
MYELOPEROXIDASE is a marker for
Auer Rods (due to primary granules)
77
(+) result in MPO
black precipitate or reddish brown (Phi bodies) --> AML
78
Stains lipids & phospholipids
SUDAN BLACK B
79
Stain prepared as Air dry and Fresh can be both used
SUDAN BLACK B
80
(+) result of SUDAN BLACK B
black --> AML
81
Stains granulocytic lineage
CHLOROACETATE ESTERASE (NAPTHOL AS-D/SPECIFIC ESTERASE
82
stain that differentiate granulocytic leukemia (+) from monocytic leukemia (-)? what is the positive result?
CHLOROACETATE ESTERASE (NAPTHOL AS-D) (+): red granules
83
Stains monocytic lineage including megakaryocytes and macrophage
NON-SPECIFIC ESTERASE
84
Stains used to differentiate monocytic leukemia from granulocytic leukemia
CHLOROACETATE ESTERASE (NAPTHOL AS-D) NON-SPECIFIC ESTERASE
85
To differentiate monocytic leukemia from granulocytic leukemia in NSE, these are used:
✓ α-naphthyl acetate esterase ✓ Sodium Fluoride – added to inhibit monocytic series ✓ α-naphthyl butyrate esterase
86
stains monocyte, plasma cell, and megakaryocyte as (+) red brown
α-naphthyl acetate esterase
87
stains monocytic series with (+) dark red precipitate
α-naphthyl butyrate esterase
88
Stains most carbohydrates in all red cells except PRONORMOBLAST
PERIODIC ACID SCHIFF (PAS)
89
PERIODIC ACID SCHIFF (PAS) is useful for
AML M6 or Erythroleukemia
90
(+) result of PAS? what are the stained cells?
magenta or purple Basophils, lymphocytic series, plasma cells, erythrocytic cell series
91
Stains ACP found in lysosomes in myelocytic lineage and lymphocytic lineage
ACID PHOSPHATASE STAIN
92
used in ACID PHOSPHATASE STAIN to stain purple to red granules
heparin
93
used to identify Hairy Cell Leukemia which is resistant to L-tartrate (TRAP) in ACP stain
Tartaric acid
94
(+) result of ACP stain
purple to red granules
95
Can stain ALL due to polymerase immunoperoxidase
TERMINAL DEOXYRIBONUCLEOTIDYL TRANSFERASE (TdT)
96
differentiate ALL (+) to AML (-)
TERMINAL DEOXYRIBONUCLEOTIDYL TRANSFERASE (TdT)
97
Stains acid mucopolysaccharide of mast cells and basophils
TOLUIDINE BLUE / METACHROMATIC STAIN
98
Compare AML (M1,M2, M3) from AMML (M4) using stains
BOTH +: MPO, SBB, SE BOTH -: Factor VIII AML (M1,M2, M3) NEGATIVE: NSE AMML (M4) POSITIVE: NSE
99
result of stain in AML (M5)
MPO, SE, Factor VIII: - NSE: + SBB: -/+
100
result of stain in M6 (erythroleukemia)
MPO, SBB, SE: + myelo, - normo NSE, Factor VIII: -
101
result of stain in M7 (megakaryocytic)
MPO, SBB, SE, alpha-naphthyl butyrate esterase: - alpha-naphthyl acetate esterase: + localized factor VIII: +