PRELIM LECTURE L4: MYELODYSPLASTIC SYNDROME

Question 1

MDS is a major clonal hematologic disorders characterized by

Answer 1

1) progressive cytopenias
2) defect in erythroid, myeloid, and/or megakaryocytic maturation

Question 2

T or F:
certain types of MDS can transform into AML

Answer 2

T

Question 3

median age of diagnosis of MDS

Answer 3

76 years old

Question 4

it was believed that the cell of origin of MDS is from what progenitor

Answer 4

myeloid progenitor

Question 5

percentage of px affected by MDS usually older than 65

Answer 5

10%

Question 6

percentage of px affected by MDS usually older than 90 and have CHIP

Answer 6

20%

Question 7

sources of genetic mutation of MDS

Answer 7

1) De Novo Mutation
2) Therapy Related MDS

Question 8

De Novo Mutation is aka

Answer 8

Primary MDS

Question 9

in therapy related MDS, how many years after the therapy is its median onset

Answer 9

4-7 years

Question 10

px who received what cytokines has increased risk for developing T-MDS

Answer 10

G-CSF
GM-CSF

(both for BM stimulation)

Question 11

T or F:
therapy related MDS is aggressive and may evolve quickly to AML

Answer 11

T

Question 12

T or F:
MDS can arise from germline mutation

Answer 12

T
(acknowledged by WHO in 2016)

Question 13

what inherited BM failure conditions can significantly increase the risk of developing MDS

Answer 13

1) Fanconi anemia
2) Diamond-Blackfan anemia
3) Schwachman-Diamond Syndrome

Question 14

3 highlight morphological abnormalities in MDS

Answer 14

1) dyserythropoiesis
2) dysmyelopoiesis
3) dysmegakaryopoiesis

Question 15

under dyserythropoiesis, what is the most common finding in PBS

Answer 15

oval macrocytes

Question 16

findings in PB and BM under dyserythropoiesis

Answer 16

1) oval macrocytes
2) hypochromic microcytes in the presence of adequate iron stores
3) dimorphic RBC
4) poikilocytosis
5) basophilic stippling
6) Howell-Jolly bodies
7) siderocytes
8) ring sideroblasts
9) BM erythrocytic hyperplasia/hypoplasia
10) RBC precursors with more than one nucleus
11) RBC precursors with abnormal nuclear shapes
12) RBC precursors with uneven cytoplasmic staining

Question 17

it is suspected if there is persistence of basophilia in the cytoplasm of otherwise white mature blood cell

Answer 17

dysmyelopoiesis

Question 18

persistence basophilia in cytoplasm of mature wbc can indicate:

Answer 18

nuclear cytoplasmic asynchrony

Question 19

nuclear cytoplasmic asynchrony findings include

Answer 19

hyposegmentation
hypersegmentation
nuclear rings

Question 20

abnormal granulation of neutrophils includes what findings

Answer 20

larger than normal granules
hypogranulation
absence of granules

Question 21

under dysmyelopoiesis, uneven staining includes what characteristics

Answer 21

dense ring of basophilia around the periphery w/ clear unstained are around the nucleus

OR

whole section of cytoplasm is unstained

Question 22

T or F:
promyelocyte or myelocyte devoid of primary granules indicate dysmyelopoiesis

Answer 22

T

Question 23

under dysmyelopoiesis, the BM may exhibit what findings

Answer 23

-granulocytic hypo/hyperplasia
-monocytic hyperplasia (common)

Question 24

what is considered the characteristic finding of BM biopsy specimen from MDS px

Answer 24

abnormal localization of immature precursor

Question 25

in some cases, myeloblast and promyelocyte tend to cluster in what area of marrow

Answer 25

cluster centrally

Question 26

according to box 33.2, morphologic evidences of dysmyelopoiesis are

Answer 26

1) persistent basophilic cytoplasm 2) abnormal granulation 3) abnormal nuclear shapes 4) uneven staining

Question 27

what are the common changes observed in dysmegakaryopoiesis

Answer 27

1) giant platelets 2) abnormal platelet aggregation (hypo or agranulation) 3) large fused granules in some platelets

Question 28

according to box 33.3, morphologic evidences of dysmegakaryopoiesis are

Answer 28

1) giant okatekets 2) platelets w/ abnormal granulation 3) circulating megakaryocytes 4) large mononuclear megakaryocytes 5) micromegakaryocytes or micromegakaryoblasts or both 6) abnormal nuclear shapes in megakaryocytes/megakaryoblasts

Question 29

essentials of differential diagnosis for MDS

Answer 29

thorough history and physical examination including questions about exposure to drugs and chemicals

Question 30

2 classifications of MDS

Answer 30

1) FAB classification 2) WHO classification

Question 31

how many classes of MDS are under FAB

Answer 31

5 classes

Question 32

the FAB categories are structured by what parameters

Answer 32

amount of dysplasia number of blasts in BM

Question 33

5 FAB classification

Answer 33

1) refractory anemia 2) refractory anemia with ring sideroblasts (RARS) 3) refractory anemia with excess blast (RAEB) 4) chronic myelomonocytic leukemia 5) refractory anemia with excess blast in transformation

Question 34

why does FAB classification did not view MDS in their totality

Answer 34

because it did not address: 1) T-MDS 2) hereditary form 3) childhood MDS

Question 35

what are the MAIN WHO classifications of MDS

Answer 35

1) MDS w/ single lineage dysplasia 2) MDS w/ ring sideroblasts 3) MDS w/ multilineage dysplasia 4) MDS w/ excess blasts 5) MDS with isolated del (5q) 6) MDS, unclassifiable 7) Childhood MDS

Question 36

what WHO classifications of MDS have subtypes

Answer 36

1) MDS with ring sideroblasts 2) MDS with excess blasts 3) Childhood MDS

Question 37

subtypes of MDS-RS

Answer 37

1) MDS-RS w/ single lineage dysplasia 2) MDS-RS w/ multilineage dysplasia

Question 38

subtypes of MDS-EB

Answer 38

MDS-EB-1 MDS-EB-2

Question 39

subtypes of Childhood MDS

Answer 39

refractory cytopenia of childhood (provisional)

Question 40

MDS-SLD is formerly known as

Answer 40

refractory cytopenia with unilineage dysplasia

Question 41

presenting symptoms of MDS-SLD

Answer 41

1) fatigue/shortness of breath 2) inc. infx due to neutropenia 3) petechia 4) bruising 5) bleeding due to thrombocytopenia

Question 42

MDS-MLD is formerly known as

Answer 42

refractory cytopenia with multiple lineage dysplasia

Question 43

characteristics of MDS-MLD

Answer 43

1) one or more cytopneia 2) dysplasia with multiple myeloid cell lines 3) <1% blast in PB 4) <5% blast in BM

Question 44

class of MDS where px have anemia and dyserythropoiesis

Answer 44

MDS-RS

Question 45

in MDS-RS, peripheral blood demonstrates what charcteristic

Answer 45

dimorphic

Question 46

what makes MDS-RS have dimorphic PB

Answer 46

mixed population hypochromic cells and normochromic cells

Question 47

percentage of MDS-RS w/ single lineage dysplasia

Answer 47

3-10%

Question 48

median age of MDS-RS w/ single lineage dysplasia

Answer 48

71 years old

Question 49

which subtype of MDS-RS has worse prognosis

Answer 49

MDS-RS with multilineage dysplasia

Question 50

common findings in this MDS class are trilineage cytopenia, significant dysmyelopoiesis, dysmegakaryopoiesis

Answer 50

MDS-EB

Question 51

percentage of blasts in BM and PB respectively in MDS-EB-1

Answer 51

5-9% blast in BM 2-4% blast in PB

Question 52

percentage of blasts in BM and PB respectively in MDS-EB-2

Answer 52

10-19% blast in BM 5-19% blast in PB

Question 53

MDS-EB subtype with auer rods regardless of blast count

Answer 53

MDS-EB-2

Question 54

which MDS-EB subtype has more aggressive course with a greater percentage of cases turning to AML

Answer 54

MDS-EB-2

Question 55

only WHO recognized MDS with defining cytogenetic abnormality

Answer 55

MDS with isolated del 5q

Question 56

MDS with isolated del 5q is aka

Answer 56

5q syndrome

Question 57

T or F: MDS with isolated del 5q predominantly affects men

Answer 57

F predominantly women

Question 58

at what median age does MDS with isolated del 5q occur

Answer 58

70 years old

Question 59

findings in px with MDS with isolated del 5q

Answer 59

1) anemia w/o other cytopenias or thrombocytosis 2) hypolobulated megakaryocyte 3) erythroid hypoplasia

Question 60

subtype of MDS that initially lack the specific changes necessary for classification into other MDS subtype

Answer 60

MDS Unclassifiable (MDS-U)

Question 61

T or F: MDS-U can develop and will be reclassified into its appropriate group

Answer 61

T

Question 62

diagnosis for MDS-U if px demonstrate what findings

Answer 62

1) 1% blast in PB 2) single lineage dysplasia 3) pancytopenia 4) MDS-defining cytogenetic abnormality

Question 63

T or F: De novo MDS in children are common

Answer 63

F it is rare

Question 64

in Childhood MDS, what inherited genes have increased frequency in mutating

Answer 64

1) RUNX1 2) SOS1 3) GATA2 4) ANKRD26

Question 65

MDS type that expresses Auer rods

Answer 65

MDS-EB-2

Question 66

percentage of erythroid precursors that are ring sideroblasts if there is SF3B1 mutation

Answer 66

<5%

Question 67

percentage of erythroid precursors that are ring sideroblasts if there is no SF3B1 mutation

Answer 67

15%

Question 68

MDS characterized by increased blasts

Answer 68

MDS-EB

Question 69

chromosome abnormalities are found in about how many percent of the cases of de novo MDS

Answer 69

50%

Question 70

chromosome abnormalities are found in about how many percent of the cases of T-MDS

Answer 70

90-95%

Question 71

what cytogenetic procedure can be used to cautiously predict response to treatment

Answer 71

karyotyping

Question 72

genetic variation that is found rarely in cases of de novo MDS

Answer 72

balance translocation

Question 73

percentage of px with MDS that have at least one mutation

Answer 73

90%

Question 74

median number of mutations per px

Answer 74

3

Question 75

how many genes harbor mutation in px with MDS

Answer 75

47 genes (many are not specific to MDS)

Question 76

how many groups of genes are affected by the mutation

Answer 76

5 groups

Question 77

3 different ways in which epigenetics may facilitate oncogenesis

Answer 77

1) Methylation of CpG islands 2) Histone Modification 3) Alteration of microRNA expression

Question 78

mutations in what two genes play an important role in altering CpG island methylation and histone methylation respectively

Answer 78

TET2 and ASXL1

Question 79

prognosis is limited only based on what characteristics

Answer 79

1) morphology 2) molecular 3) genetic 4) immunologic 5) clinical

Question 80

how many drugs are approved by US FDA that shows promise

Answer 80

three

Question 81

3 drugs approved by US FDA for MDS

Answer 81

1) Lenalidomide 2) Azacitidine 3) Decitabine

Question 81

T or F: MDS drugs can be used either alone or in combination with other therapies

Answer 81

T