Acute Myeloid Leukemia with cytogenetic abnormality - PowerPoint PPT Presentation

View by Category
About This Presentation
Title:

Acute Myeloid Leukemia with cytogenetic abnormality

Description:

Acute Myeloid Leukemia with cytogenetic abnormality PARDIS NEMATOLLAHI,MD,ACP References 1-WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues,4th ... – PowerPoint PPT presentation

Number of Views:114
Avg rating:3.0/5.0
Slides: 68
Provided by: Pardi
Learn more at: http://edc.mui.ac.ir
Category:

less

Write a Comment
User Comments (0)
Transcript and Presenter's Notes

Title: Acute Myeloid Leukemia with cytogenetic abnormality


1
Acute Myeloid Leukemia with cytogenetic
abnormality
  • Pardis Nematollahi,md,acp

2
  • Acute myeloid leukemia (AML) is a heterogeneous
    group of diseases that represent clonal
    proliferations of immature, nonlymphoid, bone
    marrowderived cells that most often involve the
    bone marrow and peripheral blood and may present
    in extramedullary tissues

3
  • the FAB classification remained the primary
    system used by most pathologists and
    hematologists for many years. The terminology of
    the FAB classification continues to be used, but
    this system is now considered obsolete owing to
    its inability to accurately identify many
    prognostically significant disease types.

4
Acute Myeloid Leukemia Related Precursor
Neoplasms
  1. Acute myeloid leukemia with recurrent genetic
    abnormalities
  2. Acute myeloid leukemia with myelodysplastic-relate
    d changes
  3. Therapy-related myeloid neoplasms
  4. Acute myeloid leukemia,NOS
  5. Myeloid sarcoma
  6. Myeloid proliferation related to Down syndrome
  7. Blastic plasmacytoid dendritic cell neoplasms

5
Epidemiology
  • The incidence of AML is approximately 3.5 cases
    per 100,000 per year. The median age at diagnosis
    is 67 years, and there is a slight male
    predominance. The frequency of AML increases with
    age, with approximately 6 of cases occurring in
    children and adults younger than 20 years and
    more than 50 of cases occurring in patients 65
    years of age and older.

6
Etiology
  • The cause of many cases of AML is unknown,
    particularly those arising in children and young
    adults.
  • A subset of AML arises from a preexisting
    myelodysplastic syndrome (MDS) or is a secondary
    leukemia related to prior therapy for a
    nonleukemic disorder.
  • AML occurs more commonly in patients with some
    preexisting genetic disorders, including
    Fanconis anemia and Down syndrome.

7
Current Approach to Diagnosis of ALs Practice
of Multidisciplinary Correlations
  • Clinical history
  • Morphology (architecture and cytology)
  • Immunophenotyping
  • FC(Multiparameter flow cytometric methods),
    IHC, and cytochemistry
  • Cytogenetic/ FISH
  • Molecular genetic

8
Acute Myeloid Leukemia Related Precursor
Neoplasms
  1. Acute myeloid leukemia with recurrent genetic
    abnormalities
  2. Acute myeloid leukemia with myelodysplastic-relate
    d changes
  3. Therapy-related myeloid neoplasms
  4. Acute myeloid leukemia , NOS
  5. Myeloid sarcoma
  6. Myeloid proliferation related to Down syndrome
  7. Blastic plasmacytoid dendritic cell neoplasms

9
Acute myeloid leukemia with recurrent genetic
abnormalities
  • This group is characterized by recurrent genetic
    abnormalities of prognostic significance
  • The most common
  • t(8,21)
  • inv(16) or t(16,16)
  • t(15,17)
  • t(9,11)
  • t(6,9)
  • inv(3)
  • t(1,22)

Are considered as acute leukemia without regard
to blast cell count
10
  • Many of these diseases have characteristic
    morphological immunophenotypic features

11
Acute myeloid leukemia with t(8,21)
  • AML with t(821)(q22q22) has distinctive
    morphologic and immunophenotypic findings that
    correlate well with a specific cytogenetic
    abnormality
  • Generally show maturation in neutrophilic
    lineage
  • meeting the criteria for M2 AML in the FAB
    classification(Found in 10 of the prior acute
    myeloblastic leukemia with maturation (M2) of FAB
    classification)

12
Acute myeloid leukemia with t(8,21),cont
  • Morphology Cytochemistry
  • Large blasts with abundant basophilic cytoplasm ,
    often containing azurophilic granules(The blasts
    in the bone marrow have cytoplasmic hofs ,
    occasional Auer rods, and occasional large,
    salmon-colored granules)
  • Some blasts show very large granules(pseudo-chedia
    k-higashi )
  • Auer rods frequently found
  • Variable dysplasia is noted in myeloid series ,
    uncommon in other cell lines
  • Eosinophil precursors frequently increased but
    not abnormal
  • Basophils and/or mast cells sometimes increased
  • Monocytic series usually minimal or absent

13
Acute myeloid leukemia with t(821)A, Blasts
show a variable number of granules, suggesting
cell maturation. One blast contains thin Auer
rods. B, Perinuclear hofs (green arrows) and
large pink granules (black arrows) are
characteristic features of this type of AML.
14
Chediak-Higashilike granules
15
On this high-power view, blasts are seen with
some maturing myeloid elements as demonstrated by
the appearance of granules. There is, however, a
maturation arrest as PMNs and bands are not
present
16
Centrosomes are evidence of myeloid
differentiation
17
Acute myeloid leukemia with t(8,21),cont
  • Immunophenotyping
  • Characteristic immunophenotype high intensity
    expression of CD34,HLA-DR,MPO,CD13,weak CD33
  • Sometimes population of blasts showing maturation
    asynchrony(co expression of CD34,CD15)
  • Frequently express lymphoid markers
    CD19,PAX5,cCD79a
  • Some cases weak TdT expression
  • Sometimes CD56 expression

18
Acute myeloid leukemia with t(8,21),cont
  • Prognosis and predictive factors
  • Good response to chemotherapy
  • High complete remission rate and long term
    disease-free survival
  • CD56 with adverse prognosis

19
The differential diagnosis
  • 1-APL
  • 2- mixed phenotype acute leukemia
  • 3-MDS
  • 4- Regenerative changes that include the effects
    of growth factors

20
Acute myeloid leukemia with t(16,16) or inv(16)
  • Definition
  • Is an AML that usually shows monocytic and
    granulocytic differentiation
  • Characteristically with abnormal eosinophil
    component in the BM, meeting the criteria for AML
    M4EO in the FAB classification

21
Acute myeloid leukemia with t(16,16) or
inv(16),cont
  • Morphorphology and Cytochemistry
  • In addition to usual morphological features of
    acute myelomonocytic leukemia,variable number of
    eosinophilia at all stages of maturation
  • The eosinophilic granules are often larger than
    those normally present in immature
    eosinophils,purple violet in color,some obscure
    the cell morphology,mature eos show nuclear
    hyposegmentation
  • Auer rods may observed in myeloblast
  • At least 3 of blasts show MPO reactivity
  • PB such as acute myelomonocytic leukemia ,
    abnormal and increased eos

22
Acute myeloid leukemia with inv(16) A and B,
Both cases show blasts with monocytoid nuclear
features and abundant cytoplasm. One leukemia (A)
exhibits numerous eosinophil precursors, some of
which have the characteristic large basophilic
granules. The other (B) shows only one abnormal
eosinophil.
23
AML with inv(16) The dysplastic eosinophil
precursors are shown at a higher magnification.
Note both eosinophilic and basophilic granules
are present in the cytoplasm of these cells.
24
Acute Myeloid Leukemia with inv 16 Acute
myelomonocytic leukemia with abnormal eosinophils
(arrow).
25
Acute Myeloid Leukemia with inv( 16 ) The arrow
marks an abnormal immature eosinophil found in
the bone marrow of a patient with an acute
myeloid leukemia with inv (16)
26
Acute myeloid leukemia with t(16,16) or
inv(16),cont
  • Immunophenotype
  • Complex immunophenotype with multiple blast
    population
  • 1-Immature blasts with CD34 and CD117
  • 2-blasts differentiating towards
    granulocytes(CD13,CD15,CD56,MPO)
  • 3-blasts differentiating towards
    monocytes(CD14,CD4,CD64,CD11b,CD11c)
  • 4-Maturation asynchrony
  • 5-Aberrant expression of CD2

27
The differential diagnosis
  • 1-myelomonocytic types of AML, NOS
  • 2-Reactive monocytic proliferations
  • 3-CMML

28
Acute myeloid leukemia with t(16,16) or
inv(16),cont
  • Prognosis and predictive factors
  • Longer complete remission
  • Older patients have decreased survival

29
Acute promyelocytic leukemia with t(15,17)
  • Definition
  • APL is an AML in which abnormal promyelocytes
    predominate
  • Both hypergranular or typical and microgranular
    or hypogranular types exist
  • Epidemiology
  • 5-8 of all AML
  • Can occur in any age , dominantly adults in mid
    life

30
Acute promyelocytic leukemia with t(15,17),cont
  • Clinical features
  • Frequently associated with DIC
  • In microgranular APL,the leukocyte count is very
    high

31
Acute promyelocytic leukemia with t(15,17),cont
  • Morphology and Cytochemistry
  • Nuclear size and shape
  • Cytoplasmic granules,Faggot cells are
    characteristic
  • MPO reaction
  • Cases of microgranular APL are characterized by
    distinct morphological features such as paucity
    or absence of granules, and predominantly bilobed
    nuclear shape
  • Cases of microgranular may misdiagnosed as acute
    monocytic leukemia
  • 1-small number of typical promyelocytes and
    faggot cells
  • 2-marked elevated leukocyte count
  • 3-strong MPO reaction

32
Acute promyelocytic leukemia (FAB M3), bone
marrow aspirate. The blasts are relatively
monomorphous and show heavily granulated
cytoplasm without Auer rods (compare with acute
myeloid leukemia with maturation). Karyotyping
showed t(1517).
33
Faggot" cell in acute promyelocytic leukemia A
"faggot" cell present on the peripheral smear
from a patient with acute promyelocytic leukemia
is shown. The cytoplasm contains multiple Auer
rods, singly and in bundles.
34
Flaming promyelocyte . Abnormal promyelocyte
with disintegrating cytoplasm which, in turn,
liberates Auer rods and granules into the
surrounding marrow. These "flaming" promyelocytes
are one of the characteristic cells found in APL.
35
Acute promyelocytic leukemia (FAB M3), bone
marrow aspirate. Numerous blasts are present,
showing folded and lobated nuclei and abundant
cytoplasm containing Auer rods and granules.
Karyotyping showed t(1517).
36
APL Some abnormal promyelocytes have a distinct
folding pattern to the nucleus as shown by the
cell marked with the arrow.
37
AML-M3, Hypogranular Variant At higher
magnification of the cells shown on the previous
slide, the nuclear convolutions are more
apparent. Azurophilic granules are present in the
cell on the left. A peinuclear hof can not be
seen in any of the hypogranular promyelocytes.
38
Acute promyelocytic leukemia (FAB M3), bone
marrow aspirate. The blasts are very large, with
lobated nuclei, fine dust-like cytoplasmic
granules, and numerous Auer rods. Karyotyping
showed t(1517).
39
Acute promyelocytic leukemia (FAB M3), bone
marrow clot. The marrow is replaced by a diffuse
infiltrate of blasts with abundant, heavily
granulated cytoplasm.
40
Acute promyelocytic leukemia with t(15,17),cont
  • Immunophenotyping
  • Absence of HLA-DR and CD34(microgranular may
    express dim HLA-DR and commonly dim CD34
  • Bright expression of CD33
  • Heterogenous expression of CD13
  • Many cases CD117
  • Commonly CD64
  • Microgranular shows CD34 CD2 expression

41
Differential diagnosis
  • Hypergranular variant
  • Agranulocytosis and
    maturation arrest at promyelocyte
  • Regenerative hyperplasia
  • AML without maturation with
    negativity for CD34 and HLA-DR(next slide)
  • Microgranular variant
  • AML with monocytic
    differentiation

42
HLA-DR and CD34 negative AML without
maturation,shows fish mouth deformity or cup like
nuclear inclusion
43
Arrow marks "thumbprinting" which is
characteristic of myeloid blasts.
44
Acute promyelocytic leukemia with t(15,17),cont
  • Prognosis predictive factors
  • APL has a particular sensitivity to ATRA which
    acts as a differentiating agent
  • Prognosis in APL treated optimally with ATRA is
    more favourable than for any other AML
    cytogenetic subtype

45
Acute myeloid leukemia with t(9,11),MLL
  • Is usually associated with monocytic
    differentiation
  • May occur in any age ,but is more common in
    children
  • May presented with DIC or extramedullary myeloid
    sarcoma

46
Acute myeloid leukemia with t(9,11),MLL,cont
  • Morphology cytochemistry
  • There is a strong association with acute
    monocytic and acute myelomonocytic leukemia
  • Monoblasts and promonocytes show strong
    positivity for non specific esterase
  • Monoblasts are negative for MPO
  • Promonocytes may show weak reactivity with MPO

47
Acute myeloid leukemia with t(911) The
morphologic appearance is variable. A, This case
shows abundant basophilic cytoplasm, suggestive
of monocytic differentiation. B, This case shows
blasts with a more myeloblastic appearance,
including some cells with granules. Although
myelomonocytic or monocytic features are most
common, there are no specific morphologic
features of this translocation.
48
Acute myeloid leukemia with t(9,11),MLL,cont
  • Immunophenotype
  • Cases of AML with MLL in children
  • Strong CD33, CD4 , HLA-DR
  • Low CD 13 , CD 14 ,CD34
  • Cases of AML with MLL in adults
  • Express some markers of monocytic differentiation
    CD4 , CD14 , CD64 ,CD11b ,CD11c
  • Variable expression of immature markers,CD34 ,
    CD117

49
Acute myeloid leukemia with t(9,11),MLL,cont
  • Prognosis and predictive factors
  • Has intermediate survival

50
Acute myeloid leukemia with t(69)
  • Is an AML with or without monocytic features
  • is often associated with basophilia and
    multilineage dysplasia

51
Acute myeloid leukemia with t(69),cont
  • Morphology and cytochemistry
  • May shows morphologic and cytochemical features
    of any type of FAB subtype of AML other than APL
    and acute megakaryoblastic leukemia
  • Marrow and PB basophilia
  • Most cases show granulocytic and erythroid
    dysplasia and less common megakaryocytic
    dysplasia
  • Ring sideroblast may be seen

52
Acute myeloid leukemia with t(69) Blast cells
exhibit variable morphology but are often
associated with admixed basophils (arrows). A,
Blasts with monocytic features. B, Myeloblasts
without maturation and dysplastic erythroid
precursors.
53
Acute myeloid leukemia with t(69),cont
  • Immunophenotype
  • Blasts consistently express MPO,CD13,CD33,CD38,HLA
    -DR
  • Most cases express CD117 , CD34 ,
  • Half are TdT positive

54
Differential diagnosis
  • 1-AML with myelodysplastic related changes
  • 2-Blast transformation of CML

55
Acute myeloid leukemia with t(69),cont
  • Prognosis and predictive factors
  • Poor prognosis
  • Elevated WBC
  • Increased BM blast

Shorter overall survival
56
Acute myeloid leukemia with inv(3)
  • May present de novo or from prior MDS
  • Normal or elevated plt count
  • BM atypical hypermegakaryosis
  • Multilineage dysplasia

Morphological findings
57
Acute myeloid leukemia with inv(3),cont
  • Clinical features
  • Anemia and normal to elevated plt count
  • May have HSM
  • LAP is uncommon

58
Acute myeloid leukemia with inv(3),cont
  • Morphology and cytochemistry
  • May show any type of FAB classification of AML
    other than APL
  • Blood findings normal to elevated plt count
  • Giant and
    hypogranular plt
  • bare megakaryocyte
    nuclei
  • Hypogranular PMN
    with pseudo pelger huet anomaly
  • BM findings Atypical hypermegakaryosis
  • Dyserythropoietic
    and dysgranulopoiesis are common
  • Marrow eos , bas
    mast cells may increased

59
Acute myeloid leukemia with inv(3)(q21q26.2)
. A, Increased blasts with mono- and bilobed
megakaryocytes are typical of this disorder. B,
Distinctive hypolobated megakaryocytes are
apparent on the biopsy specimen.
60
Acute myeloid leukemia with inv(3),cont
  • Immunophenotyping
  • Blast cells express CD13 , CD33 , HLA-DR , CD34 ,
    CD38
  • Some aberrantly express CD7
  • Some express CD41 , CD61

61
Acute myeloid leukemia with inv(3),cont
  • Prognosis and predictive factors
  • Is an aggressive disease

62
Acute myeloid leukemia(megakaryoblastic) with
t(122)
  • Is an AML showing maturation in the megakaryocyte
    lineage
  • Is uncommon(lt1 of all AML)
  • Most commonly occurs in infants without Down
    syndrome
  • FgtM

63
Acute myeloid leukemia(megakaryoblastic) with
t(122),cont
  • Morphology cytochemistry
  • Similar to acute megakaryoblastic leukemia , NOS
  • Small and large megakaryoblast(cytoplasm is
    basophilic , often agranular,may show bleb or
    pseudopod)
  • Micromegakaryocytes are common
  • Reticulin and collagen fibrosis
  • Blasts are negative for MPO

64
Acute myeloid leukemia (megakaryoblastic) with
t(122). A, Hemodilute aspirate shows rare blasts
with basophilic cytoplasm and blebbing. B, Core
biopsy shows blasts and atypical megakaryocytes.
65
Acute myeloid leukemia(megakaryoblastic) with
t(122),cont
  • Immunophenotyping
  • CD41 , CD61
  • Myeloid associated markers may be positive,CD13 ,
    CD33
  • Often negativeCD34 , CD45 , HLA-DR
  • Negative MPO , TdT
  • Prognosis and predictive factors
  • Poor

66
References
  • 1-WHO Classification of Tumours of Haematopoietic
    and Lymphoid Tissues,4th Edition,2008
  • 2-Pathology of Bone marrow and Blood cells,Diane
    C.Farhi,2nd Edition,2009
  • 3-Flowcytometry in evaluation of hematopoietic
    neoplasms,Sindhu Cherian,2012
  • 4-Hematopathology,Elaine S. Jaffe ,2011
  • 5-Henry,s Cinical Diagnosis and Management by
    Laboratory Methods,22nd Edition 2011

67
(No Transcript)
About PowerShow.com