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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
What is the prognosis of AML with t(9;11)?
* usually a poor prognosis * BUT this AML has a better prognosis than other 11q23 aberrations
26
What is true about AML with t(9;22)?
* de novo AML with t(9;22) * p210 BCR-ABL translocation
27
What is classic about AML with t(1;22)?
* gene fusion: RBM15-MKL1 * often in infants without trisomy 21 * female predominance * megakaryoblastic differentiation * express CD41, CD61 and CD42b
28
What is true about AML with mutated NPM1?
* favorable prognosis * in the absence of FLT3-ITD * normal cytogenetics * "cup-shaped" nuclei in the blasts * often CD34 negative
29
What is the prognosis for AML with biallelic CEBPA mutation?
* favorable prognosis * must have absence of FLT3-ITD * normal cytogenetics * often in children and young adults
30
What is the prognosis of AML with mutated RUNX1?
* poor prognosis * not therapy related or MDS related AML
31
What is the morphology, age and prognosis for AML with t(8;21) ?
* abundant grey-blue cytoplasm * Auer rods * large granules (M2 like) * young adults affected * Favorable prognosis Molecular: * RUNX1/RUNX1T1 (AML1/ETO)
32
What is the immunophenotype of AML with t(8;21)?
* Positive * CD34 * HLA-DR * CD13 * CD33 * CD19 ( can also be negative sometimes)
33
What is the morphology, age, and prognosis for AML with inv(16) or t(16;16)?
* M4-like with increased eosinophils (abnormal) * eos-basos * seen in young adults * Favorable prognosis Molecular: * MYH11/CBFB
34
What is the immunophenotype for AML with inv(16) or t(16;16)?
* Positive * CD34 * HLA-DR * CD13 * CD33 * CD11b * CD14 * CD64
35
What is the morphology, age, and prognosis for AML with t(15;17)?
* promyelocytes * middle age individuals * Favorable prognosis Molecular: * PML/RARA
36
What is the immunophenotype of AML with t(15;17)?
* Positive: * CD13 * CD33 * CD15 and CD2 (can also be negative) * Negative: * CD34 * HLA-DR
37
What is the morphology, age and prognosis of AML with t(9;11)?
* M5-like morphology (monocytic) * children * Intermediate prognosis Molecular: * MLLT3/MLL
38
What is the immunophenotype of AML with t(9;11)?
* Negative: * CD34 * Positive * HLA-DR * CD13 and CD33 * CD56 (can also be negative) * CD14, CD64 * CD11b
39
What is the morphology, age, and prognosis of AML with t(6;9) ?
* any morphology, especially myelomonocytic (M4) with basophilia * seen in children and adults * poor prognosis Molecular: * DEK/NUP214
40
What is the immunophenotype of AML with t(6;9)?
* Positive: * CD34 * HLA-DR * CD13 * CD33 * Tdt
41
What is the morphology, age, and prognosis of AML with t(1;22)?
* megakaryocytic (M7-like) * infants * intermediate prognosis Molecular: * RBM15/MKL1
42
What is the immunophenotype of AML with t(1;22) ?
* Negative: * CD34 * HLA-DR * Positive: * CD13 * CD33 * CD41 * CD61
43
What is the morphology, age, and prognosis of AML with inv(3) or t(3;3)?
* M0, M1 or M7-like * thrombocytosis * giant, agranular platelets * adults * poor prognosis Molecular: * RPN1/EVI1
44
What is the morphology, age, and progonisis of therapy-related AML ?
* multilineage dysplasia * often increased eosinophils * usually occurs 5 years after therapy * poor prognosis Molecular: * Topoisomerase II associated: * 11q23 (MLL) or * 21q22 (RUNX1)
45
What is the immunophenotype of therapy-related AML?
* Positive: * CD34 * HLA-DR * CD13 * CD33 * CD56
46
What is the morphology, age, and prognosis of AML with MDS related changes?
* variable morphology, immunophenotype * elderly * slowly progressive, unresponsive to treatment Molecular: * MDS-like
47
What are the criteria for AML with MDS related changes?
* 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
What are the clinical, IHC and prognisis for AML with MDS related changes?
* 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
What are some of the drugs that can lead to therapy related AML?
* Topoisomerase II inhibitors * Alkylating agents * Ionizing radiation Note: the response to treatment is poor
50
What is the latency period for the different drugs / treatments that can cause AML?
* 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
How many categories of AML, NOS are there?
* 7 categories- all do NOT have cytogenetic abnormalities * M0 * M1 * M2 * M4 * M5 * M6 * M7 * M3 was APL
52
What is the morphology and prognosis for AML, NOS M0 ?
* undifferentiated blasts * \< 3% positvie for SBB or MPO or NSE * agranular cytoplasm * blasts usually \> 30% * often seen in infants and adults * poor prognosis
53
What is the immunohistochemical profile for AML, NOS M0 ?
* 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
What is the morphology and prognisis for AML, NOS M1 ?
* \> 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
What are the immunohistochemical findings for AML, NOS M1 ?
* Positive * CD34 * HLA-DR * CD13 * CD33 * CD117
56
What is the morphology and prognosis of AML, NOS M2 ?
* 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
What is the immunohistochemical profile of AML, NOS M2 ?
* Positive: * CD34 --\> may not be expressed * HLA-DR * CD13 * CD33 * CD117 * CD15
58
What is the morphology and prognosis for AML, NOS M4 ?
* acute myelomonocytic leukemia * monocytic cells \> 20% (amongst non-erythroid cells) * granulocytic cells \>20 % * Frequently responds to therapy!
59
What is the immunohistochemical profile for AML, NOS M4 ?
* Positive * CD34 -/+ * HLA-DR * CD13 * CD33 * CD117 * CD14 * CD11b, CD64 * CD4
60
What is the morphology and prognosis of AML, NOS M5 ?
* \> 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
What is the immunohistochemical profile for AML, NOS M5 ?
* IMP: usually CD34 negative * Positive: * HLA-DR * Monocytic markers * CD4, CD14, CD64, CD11b, lysozyme * Myeloid markers * CD13, CD33, CD117
62
What is the morphology and prognosis for AML, NOS M6 (erythroleukemia) ?
* \> 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
What are the immunohistochemical findings for AML, NOS M6 ?
* Positive: * CD34 -/+ * HLA-DR * CD13 * CD33 * CD117 * CD235 (glycophorin) * Note: CD7 can be dim positive sometimes
64
What is the morphology and prognosis for AML, NOS M7 ?
* 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
What is the immunohistochemical profile for AML, NOS M7 ?
* CD34 and HLA-DR -/+ * Postivie * CD13 * CD33 * CD117 * CD41 * CD61
66
What is Acute panmyelosis with myelofibrosis?
* acute neoplastic proliferation of panmyeloid elements, in conjunction with marrow fibrosis
67
What disorders is acute panmyelosis with myelofibrosis associated with?
* end stage MPN, AML with MDS related changes * M7 AML must be excluded
68
What is the clinical presentation of acute leukemia in Down Syndrome?
* 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
What is Transient abnormal myelopoiesis (TAM) ?
* 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
What somatic gene mutation can be seen in blasts in both TAM and Down Syndrome associated AML ?
* GATA-1 gene somatic mutation Note: * both Down syndrome associated AML and TAM, the blast type is megakaryoblastic or mixed megakaryoblastic-erythroblastic
71
What mutations are seen in myeloid neoplasms without a pre-existing disorder or organ dysfunction?
* CEBPA and DDX41 mutations
72
What mutations are seen in myeloid neoplasms with pre-existing platelet disorders?
* RUNX1 * ANKRD26 * ETV6 mutations
73
What mutations are seen in myeloid neoplasms with other organ dysfunction?
* GATA2 * associated with bone marrow failure syndromes * telomere biology disorders * neurofibromatosis * Noonan syndrome * Down syndrome
74
When should a genetic predisposition syndrome be suspected in someone who presents with a myeloid neoplasm ?
* 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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