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AP/CP Board Review Hemepath > Acute Myelogenous Leukemias > Flashcards

Acute Myelogenous Leukemias Flashcards

1
Q

What are some general features

of AML?

A
  • most adult and infantile leukemias are myeloid
  • only 10% of leukemias in children are myeloid
  • median age is 65
  • AML usually presents with a very high WBC and abundant circulating blasts
  • sometimes will present with a soft tissue mass
    • chloroma, myeloid sarcoma
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2
Q

How is the diagnosis of

AML made?

A
  • 2 ways to arrive at the diagnosis:
    • blast >20%
    • < 20% blasts if there is a myeloid sarcoma or characteristic genetic abnormalities
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3
Q

How many cells must be counted

in order to determine blast percentage?

A
  • Bone marrow: 500 cells
  • Peripheral blood: 200 cells

Note: in APML, promyelocytes are included in the blast percentage while in Monocytic leukemia promonocytes are included

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4
Q

What is the classic immunophenotype seen

for AML by Flow cytometry?

A
  • CD34
  • CD13, CD33
  • HLA-DR
  • CD45

IMP: APL usually negative for HLA-DR and CD34

** negative for lymphoid markers but some may express CD7 and CD19

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5
Q

What is the gene that is coded

for in AML with t(8;21)(q22;q22)?

A
  • RUNX1 gene
    • encodes the alpha chain of core binding factor (CBFa)
  • represents 8-10% of de novo AML
  • affects young adults and is relatively chemosensitive
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6
Q

What is the morphology of the

blasts in AML with t(8;21)?

A
  • pronounced azurophilic granules
  • sometimes large pseudo-Chediak Higashi granules and Auer rods
  • Dysplastic mature granulocytes are present in the blood and bone marrow
    • display pseudo-Pelger-Huet nuclei with homogeneous pink cytoplasm
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7
Q

What marker, when positive by flow,

should make you consider AML with t(8;21)?

A
  • CD19
  • it’s expression should make you consider AML with t(8;21)
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8
Q

What immunomarker expression by

flow should suggest monoblasts?

A
  • expression of CD33 and CD11b
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9
Q

In AML with t(8;21) what is associated

with a poor prognosis ?

A
  • lack of or decreased expression of CD19
    • with retention of CD56 expression
    • this correlates with a KIT mutation
    • poor prognosis
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10
Q

What is the gene that is coded for

in AML inv (16)(p13q22) or

t(16;16)(p13;q22)?

A
  • it is a translocation resulting in the apposition of the MYH11 (myosin) and CBFB genes
  • affects younger adults
  • relatively chemosensitive
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11
Q

What is the morphology of the blasts in

AML with inv(16) or t(16;16)?

A
  • myelomonocytic differentiation
  • usually found in association with eosinophils
  • eosinophils usually have abnormal granules that look basophilic (eos-basos)
    • stain + with Naphthyl acetate esterase
    • this stain is negative in normal eosinophils
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12
Q

What is the immunophenotype of

AML with inv(16) or t(16;16)?

A
  • CD13, CD33
  • CD14, CD64
  • CD11b, HLA-DR, lysozyme
  • also can express CD2
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13
Q

What is the morphology and prognosis for

AML with inv(3) or t(3;3) ?

A
  • genes involved: GATA2-MECOM
  • can occur de novo or following MDS
  • morphology:
    • blasts seen in association with dysmorphic, small, hypolobated megakaryocytes
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14
Q

What is the clinical presentation of

AML t(15;17)(q22;q21)?

A
  • tendency to present in DIC and highly responsive to ATRA
  • bimodal distribution
    • late teen years and over age 60
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15
Q

What is the morphology of the blasts

for APL?

A
  • abnormal promyelocytes with kidney shaped or bilobed nuclei
  • cytoplasm varying from intensely granulated to agranular (microgranular variant)
    • microgranular variant can resemble acute monocytic leukemia
  • MPO reaction is quite strong in both variants
    • weak or negative in monoblasts
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16
Q

How do the hyper and hypogranular

variants present in peripheral blood?

A
  • Hypergranular variant
    • very few leukemic cells
  • Hypogranular variant
    • presents with a high blast count in blood
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17
Q

What is the immunohistochemical finding

for APL?

A
  • Positive:
    • CD33, CD13 (both strong)
    • CD15 (weak)
      • normal promyelocytes will be CD15 strong +
  • Negative:
    • HLADR and CD34
    • Note: these markers can be positive in the hypo/microgranular variant
      • also CD2
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18
Q

What are the translocation variants of

APL that are resistant to ATRA?

A
  • t(11;17)
  • t(5;17)
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19
Q

What are the three major RARa

breakpoints (for APL)?

A
  • bcr1 - located within intron 6
  • bcr2- (exon 6)
  • bcr3- (intron 3)
    • bcr 3 may have microgranular features
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20
Q

What is Differentiation Syndrome

in APL?

A
  • called Retinoic acid syndrome
  • potentially life threatening complication of treatment with ATRA
  • Present with:
    • fever, weight gain, anasarca
    • effusions, hypotension, renal failure
  • Risk correlates with initial WBC > 5 x 10^9
  • Dexamethasone treatment can prevent or ameliorate it
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21
Q

What is AML with t(6;9) associated with?

A
  • genes: DEK-NUP214
  • there is basophilia and multilineage dysplasia
  • often in younger adults and children
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22
Q

What age group is AML t(9;11)(p22;q23)

usually seen in and what genes are involved?

A
  • common in children
  • AML with KMT2A (MLL) gene anomalies
  • FISH is significantly more sensitive for detection
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23
Q

What is the immunohistochemical profile

for AML with t(9;11)?

A
  • monoblastic FAB M4-M5
  • CD4, CD14, CD64
  • CD11b and lysozyme

IMP:

  • CD34 usually negative
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24
Q

What gene fusion is common in

infants with AML containing the MLL gene?

A
  • t(4;11)
  • produces MLL/AF4 gene fusion
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25
Q

What is the prognosis of AML with

t(9;11)?

A
  • usually a poor prognosis
  • BUT this AML has a better prognosis than other 11q23 aberrations
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26
Q

What is true about AML with t(9;22)?

A
  • de novo AML with t(9;22)
  • p210 BCR-ABL translocation
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27
Q

What is classic about AML

with t(1;22)?

A
  • gene fusion: RBM15-MKL1
  • often in infants without trisomy 21
  • female predominance
  • megakaryoblastic differentiation
    • express CD41, CD61 and CD42b
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28
Q

What is true about AML with

mutated NPM1?

A
  • favorable prognosis
    • in the absence of FLT3-ITD
    • normal cytogenetics
  • “cup-shaped” nuclei in the blasts
  • often CD34 negative
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29
Q

What is the prognosis for AML with

biallelic CEBPA mutation?

A
  • favorable prognosis
    • must have absence of FLT3-ITD
    • normal cytogenetics
  • often in children and young adults
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30
Q

What is the prognosis of AML

with mutated RUNX1?

A
  • poor prognosis
  • not therapy related or MDS related AML
31
Q

What is the morphology, age and prognosis

for AML with t(8;21) ?

A
  • abundant grey-blue cytoplasm
    • Auer rods
    • large granules (M2 like)
  • young adults affected
  • Favorable prognosis

Molecular:

  • RUNX1/RUNX1T1 (AML1/ETO)
32
Q

What is the immunophenotype of

AML with t(8;21)?

A
  • Positive
    • CD34
    • HLA-DR
    • CD13
    • CD33
    • CD19 ( can also be negative sometimes)
33
Q

What is the morphology, age, and prognosis

for AML with inv(16) or t(16;16)?

A
  • M4-like with increased eosinophils (abnormal)
    • eos-basos
  • seen in young adults
  • Favorable prognosis

Molecular:

  • MYH11/CBFB
34
Q

What is the immunophenotype for

AML with inv(16) or t(16;16)?

A
  • Positive
    • CD34
    • HLA-DR
    • CD13
    • CD33
    • CD11b
    • CD14
    • CD64
35
Q

What is the morphology, age, and prognosis

for AML with t(15;17)?

A
  • promyelocytes
  • middle age individuals
  • Favorable prognosis

Molecular:

  • PML/RARA
36
Q

What is the immunophenotype of

AML with t(15;17)?

A
  • Positive:
    • CD13
    • CD33
    • CD15 and CD2 (can also be negative)
  • Negative:
    • CD34
    • HLA-DR
37
Q

What is the morphology, age and prognosis

of AML with t(9;11)?

A
  • M5-like morphology (monocytic)
  • children
  • Intermediate prognosis

Molecular:

  • MLLT3/MLL
38
Q

What is the immunophenotype of

AML with t(9;11)?

A
  • Negative:
    • CD34
  • Positive
    • HLA-DR
    • CD13 and CD33
    • CD56 (can also be negative)
    • CD14, CD64
    • CD11b
39
Q

What is the morphology, age, and prognosis of

AML with t(6;9) ?

A
  • any morphology, especially myelomonocytic (M4) with basophilia
  • seen in children and adults
  • poor prognosis

Molecular:

  • DEK/NUP214
40
Q

What is the immunophenotype of

AML with t(6;9)?

A
  • Positive:
    • CD34
    • HLA-DR
    • CD13
    • CD33
    • Tdt
41
Q

What is the morphology, age, and prognosis

of AML with t(1;22)?

A
  • megakaryocytic (M7-like)
  • infants
  • intermediate prognosis

Molecular:

  • RBM15/MKL1
42
Q

What is the immunophenotype of

AML with t(1;22) ?

A
  • Negative:
    • CD34
    • HLA-DR
  • Positive:
    • CD13
    • CD33
    • CD41
    • CD61
43
Q

What is the morphology, age, and prognosis of

AML with inv(3) or t(3;3)?

A
  • M0, M1 or M7-like
    • thrombocytosis
    • giant, agranular platelets
  • adults
  • poor prognosis

Molecular:

  • RPN1/EVI1
44
Q

What is the morphology, age, and progonisis of

therapy-related AML ?

A
  • multilineage dysplasia
    • often increased eosinophils
  • usually occurs 5 years after therapy
  • poor prognosis

Molecular:

  • Topoisomerase II associated:
    • 11q23 (MLL) or
    • 21q22 (RUNX1)
45
Q

What is the immunophenotype of

therapy-related AML?

A
  • Positive:
    • CD34
    • HLA-DR
    • CD13
    • CD33
    • CD56
46
Q

What is the morphology, age, and prognosis of

AML with MDS related changes?

A
  • variable morphology, immunophenotype
  • elderly
  • slowly progressive, unresponsive to treatment

Molecular:

  • MDS-like
47
Q

What are the criteria for AML

with MDS related changes?

A
  • at least 20% blasts
  • and one of the following:
    • history of MDS
    • MDS related cytogenetic abnormality
    • multilineage dysplasia ( >50% of 2 cell lines)
  • Absence of the following:
    • prior cytotoxic therapy
    • any of the known recurrent genetic abnormalities of AML
48
Q

What are the clinical, IHC and prognisis

for AML with MDS related changes?

A
  • affects mainly the elderly
    • follows a period of antecedent MDS
    • or can arise de novo
  • Positive IHC
    • CD34, CD13, CD33
  • Prognosis
    • relatively poor
    • leukemias are slowly progressive and do not respond to chemotherapy
49
Q

What are some of the drugs that can

lead to therapy related AML?

A
  • Topoisomerase II inhibitors
  • Alkylating agents
  • Ionizing radiation

Note: the response to treatment is poor

50
Q

What is the latency period for the different

drugs / treatments that can cause AML?

A
  • Topoisomerase II inhibitors
    • 1-5 years
    • may have KMT2A (MLL) gene rearrangements
  • Alkylating agents and radiation
    • 5-10 years

IMP: the incidence IS DOSE dependent

51
Q

How many categories of AML, NOS

are there?

A
  • 7 categories- all do NOT have cytogenetic abnormalities
    • M0
    • M1
    • M2
    • M4
    • M5
    • M6
    • M7
  • M3 was APL
52
Q

What is the morphology and prognosis

for AML, NOS M0 ?

A
  • undifferentiated blasts
    • < 3% positvie for SBB or MPO or NSE
    • agranular cytoplasm
    • blasts usually > 30%
  • often seen in infants and adults
  • poor prognosis
53
Q

What is the immunohistochemical profile

for AML, NOS M0 ?

A
  • blasts usually express myeloid markers
  • Positive:
    • CD34
    • HLA-DR
    • CD13
    • CD33
    • CD117

Note: myeloid antigens indicating greater degree of maturation are negative: CD14, CD15, CD11b

54
Q

What is the morphology and prognisis for

AML, NOS M1 ?

A
  • > 3% of blasts are positive for SBB or MPO or CAE (chloroacetate esterase)
    • still considered without maturation
    • > 90% show no maturation
  • prognosis is poor
55
Q

What are the immunohistochemical findings

for AML, NOS M1 ?

A
  • Positive
    • CD34
    • HLA-DR
    • CD13
    • CD33
    • CD117
56
Q

What is the morphology and prognosis of

AML, NOS M2 ?

A
  • with maturation –> must have maturation in >10% blasts
    • undifferentiated myeloblasts <89%
  • Monocytic differentiation is present in < 20% of nonerythroid cells (know)
    • or else M4/M5 must be considered
    • abundant grey-blue cytoplasm, Auer rods and large granules
    • eos and basos may be increased
  • Frequently responds to therapy
57
Q

What is the immunohistochemical profile

of AML, NOS M2 ?

A
  • Positive:
    • CD34 –> may not be expressed
    • HLA-DR
    • CD13
    • CD33
    • CD117
    • CD15
58
Q

What is the morphology and prognosis for

AML, NOS M4 ?

A
  • acute myelomonocytic leukemia
    • monocytic cells > 20% (amongst non-erythroid cells)
    • granulocytic cells >20 %
  • Frequently responds to therapy!
59
Q

What is the immunohistochemical profile for

AML, NOS M4 ?

A
  • Positive
    • CD34 -/+
    • HLA-DR
    • CD13
    • CD33
    • CD117
    • CD14
    • CD11b, CD64
    • CD4
60
Q

What is the morphology and prognosis of

AML, NOS M5 ?

A
  • > 80% show monocytic differentiation
    • Acute monocytic/monoblastic leukemia
    • Non-erythroid cells
    • monoblasts, promonocytes, and monocytes
  • Manifests with bleeding disorders and soft tissue infiltration
    • Gingival enlargement, CNS infiltrate
  • Poor prognosis
  • t(8;16)
    • associated with hemophagocytosis
61
Q

What is the immunohistochemical profile

for AML, NOS M5 ?

A
  • IMP: usually CD34 negative
  • Positive:
    • HLA-DR
    • Monocytic markers
      • CD4, CD14, CD64, CD11b, lysozyme
    • Myeloid markers
      • CD13, CD33, CD117
62
Q

What is the morphology and prognosis for

AML, NOS M6 (erythroleukemia) ?

A
  • > 20% show erythroid differentiation
    • undifferentiated/proerythroblastic
    • erythroid cytoplasm may contain vacuoles and display PAS positivity (like ALL blasts)
  • respond poorly to treatment, poor prognosis

Note:

  • also called diGuglielmo Syndrome
63
Q

What are the immunohistochemical findings

for AML, NOS M6 ?

A
  • Positive:
    • CD34 -/+
    • HLA-DR
    • CD13
    • CD33
    • CD117
    • CD235 (glycophorin)
  • Note: CD7 can be dim positive sometimes
64
Q

What is the morphology and prognosis for

AML, NOS M7 ?

A
  • megakaryoblastic, blasts with blebbing
    • > 50% of blasts should show megakaryotic differentiation
  • Associated with:
    • Mediastinal germ cell tumors
    • i(12p)

Note: AMLs and transient myeloproliferative disorders associated with Down’s Syndrome often are M7 type

65
Q

What is the immunohistochemical profile for

AML, NOS M7 ?

A
  • CD34 and HLA-DR -/+
  • Postivie
    • CD13
    • CD33
    • CD117
    • CD41
    • CD61
66
Q

What is Acute panmyelosis

with myelofibrosis?

A
  • acute neoplastic proliferation of panmyeloid elements, in conjunction with marrow fibrosis
67
Q

What disorders is acute panmyelosis with

myelofibrosis associated with?

A
  • end stage MPN, AML with MDS related changes
  • M7 AML must be excluded
68
Q

What is the clinical presentation of

acute leukemia in Down Syndrome?

A
  • shows increased chemosensitivity
    • especially with Methotrexate
    • relatively favorable prognosis
    • Megakaryoblastic differentiation
  • Down syndrome associated AML arises at an early age (1-5 years)
    • in 1-2 % of children
69
Q

What is Transient abnormal myelopoiesis (TAM) ?

A
  • can cause hydrops
  • arises in the first week of life, presenting with a very high WBC and hepatosplenomegaly
  • complete clinicopathological resolution without therapy

IMP: ~30% of children with TAM can develop true Down Syndrome associated AML during childhood

70
Q

What somatic gene mutation can be seen in blasts in

both TAM and Down Syndrome associated AML ?

A
  • GATA-1 gene somatic mutation

Note:

  • both Down syndrome associated AML and TAM, the blast type is megakaryoblastic or mixed megakaryoblastic-erythroblastic
71
Q

What mutations are seen in myeloid neoplasms

without a pre-existing disorder or organ dysfunction?

A
  • CEBPA and DDX41 mutations
72
Q

What mutations are seen in myeloid neoplasms

with pre-existing platelet disorders?

A
  • RUNX1
  • ANKRD26
  • ETV6 mutations
73
Q

What mutations are seen in myeloid neoplasms

with other organ dysfunction?

A
  • GATA2
    • associated with bone marrow failure syndromes
    • telomere biology disorders
    • neurofibromatosis
    • Noonan syndrome
    • Down syndrome
74
Q

When should a genetic predisposition syndrome

be suspected in someone who presents with

a myeloid neoplasm ?

A
  • personal history of multiple cancers
  • thrombocytopenia or bleeding propensity
  • preceding MDS/AML
  • Family history
  • other features of bone marrow failure syndromes

AP/CP Board Review Hemepath (12 decks)

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