PRELIM LECTURE L4: MYELODYSPLASTIC SYNDROME Flashcards
Ma'am Mitchao notes-based
MDS is a major clonal hematologic disorders characterized by
1) progressive cytopenias
2) defect in erythroid, myeloid, and/or megakaryocytic maturation
T or F:
certain types of MDS can transform into AML
T
median age of diagnosis of MDS
76 years old
it was believed that the cell of origin of MDS is from what progenitor
myeloid progenitor
percentage of px affected by MDS usually older than 65
10%
percentage of px affected by MDS usually older than 90 and have CHIP
20%
sources of genetic mutation of MDS
1) De Novo Mutation
2) Therapy Related MDS
De Novo Mutation is aka
Primary MDS
in therapy related MDS, how many years after the therapy is its median onset
4-7 years
px who received what cytokines has increased risk for developing T-MDS
G-CSF
GM-CSF
(both for BM stimulation)
T or F:
therapy related MDS is aggressive and may evolve quickly to AML
T
T or F:
MDS can arise from germline mutation
T
(acknowledged by WHO in 2016)
what inherited BM failure conditions can significantly increase the risk of developing MDS
1) Fanconi anemia
2) Diamond-Blackfan anemia
3) Schwachman-Diamond Syndrome
3 highlight morphological abnormalities in MDS
1) dyserythropoiesis
2) dysmyelopoiesis
3) dysmegakaryopoiesis
under dyserythropoiesis, what is the most common finding in PBS
oval macrocytes
findings in PB and BM under dyserythropoiesis
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
it is suspected if there is persistence of basophilia in the cytoplasm of otherwise white mature blood cell
dysmyelopoiesis
persistence basophilia in cytoplasm of mature wbc can indicate:
nuclear cytoplasmic asynchrony
nuclear cytoplasmic asynchrony findings include
hyposegmentation
hypersegmentation
nuclear rings
abnormal granulation of neutrophils includes what findings
larger than normal granules
hypogranulation
absence of granules
under dysmyelopoiesis, uneven staining includes what characteristics
dense ring of basophilia around the periphery w/ clear unstained are around the nucleus
OR
whole section of cytoplasm is unstained
T or F:
promyelocyte or myelocyte devoid of primary granules indicate dysmyelopoiesis
T
under dysmyelopoiesis, the BM may exhibit what findings
-granulocytic hypo/hyperplasia
-monocytic hyperplasia (common)
what is considered the characteristic finding of BM biopsy specimen from MDS px
abnormal localization of immature precursor
in some cases, myeloblast and promyelocyte tend to cluster in what area of marrow
cluster centrally
according to box 33.2, morphologic evidences of dysmyelopoiesis are
1) persistent basophilic cytoplasm
2) abnormal granulation
3) abnormal nuclear shapes
4) uneven staining
what are the common changes observed in dysmegakaryopoiesis
1) giant platelets
2) abnormal platelet aggregation (hypo or agranulation)
3) large fused granules in some platelets
according to box 33.3, morphologic evidences of dysmegakaryopoiesis are
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
essentials of differential diagnosis for MDS
thorough history and physical examination including questions about exposure to drugs and chemicals
2 classifications of MDS
1) FAB classification
2) WHO classification
how many classes of MDS are under FAB
5 classes
the FAB categories are structured by what parameters
amount of dysplasia
number of blasts in BM
5 FAB classification
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
why does FAB classification did not view MDS in their totality
because it did not address:
1) T-MDS
2) hereditary form
3) childhood MDS
what are the MAIN WHO classifications of MDS
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
what WHO classifications of MDS have subtypes
1) MDS with ring sideroblasts
2) MDS with excess blasts
3) Childhood MDS
subtypes of MDS-RS
1) MDS-RS w/ single lineage dysplasia
2) MDS-RS w/ multilineage dysplasia
subtypes of MDS-EB
MDS-EB-1
MDS-EB-2
subtypes of Childhood MDS
refractory cytopenia of childhood (provisional)
MDS-SLD is formerly known as
refractory cytopenia with unilineage dysplasia
presenting symptoms of MDS-SLD
1) fatigue/shortness of breath
2) inc. infx due to neutropenia
3) petechia
4) bruising
5) bleeding due to thrombocytopenia
MDS-MLD is formerly known as
refractory cytopenia with multiple lineage dysplasia
characteristics of MDS-MLD
1) one or more cytopneia
2) dysplasia with multiple myeloid cell lines
3) <1% blast in PB
4) <5% blast in BM
class of MDS where px have anemia and dyserythropoiesis
MDS-RS
in MDS-RS, peripheral blood demonstrates what charcteristic
dimorphic
what makes MDS-RS have dimorphic PB
mixed population hypochromic cells and normochromic cells
percentage of MDS-RS w/ single lineage dysplasia
3-10%
median age of MDS-RS w/ single lineage dysplasia
71 years old
which subtype of MDS-RS has worse prognosis
MDS-RS with multilineage dysplasia
common findings in this MDS class are trilineage cytopenia, significant dysmyelopoiesis, dysmegakaryopoiesis
MDS-EB
percentage of blasts in BM and PB respectively in MDS-EB-1
5-9% blast in BM
2-4% blast in PB
percentage of blasts in BM and PB respectively in MDS-EB-2
10-19% blast in BM
5-19% blast in PB
MDS-EB subtype with auer rods regardless of blast count
MDS-EB-2
which MDS-EB subtype has more aggressive course with a greater percentage of cases turning to AML
MDS-EB-2
only WHO recognized MDS with defining cytogenetic abnormality
MDS with isolated del 5q
MDS with isolated del 5q is aka
5q syndrome
T or F:
MDS with isolated del 5q predominantly affects men
F
predominantly women
at what median age does MDS with isolated del 5q occur
70 years old
findings in px with MDS with isolated del 5q
1) anemia w/o other cytopenias or thrombocytosis
2) hypolobulated megakaryocyte
3) erythroid hypoplasia
subtype of MDS that initially lack the specific changes necessary for classification into other MDS subtype
MDS Unclassifiable (MDS-U)
T or F:
MDS-U can develop and will be reclassified into its appropriate group
T
diagnosis for MDS-U if px demonstrate what findings
1) 1% blast in PB
2) single lineage dysplasia
3) pancytopenia
4) MDS-defining cytogenetic abnormality
T or F:
De novo MDS in children are common
F
it is rare
in Childhood MDS, what inherited genes have increased frequency in mutating
1) RUNX1
2) SOS1
3) GATA2
4) ANKRD26
MDS type that expresses Auer rods
MDS-EB-2
percentage of erythroid precursors that are ring sideroblasts if there is SF3B1 mutation
<5%
percentage of erythroid precursors that are ring sideroblasts if there is no SF3B1 mutation
15%
MDS characterized by increased blasts
MDS-EB
chromosome abnormalities are found in about how many percent of the cases of de novo MDS
50%
chromosome abnormalities are found in about how many percent of the cases of T-MDS
90-95%
what cytogenetic procedure can be used to cautiously predict response to treatment
karyotyping
genetic variation that is found rarely in cases of de novo MDS
balance translocation
percentage of px with MDS that have at least one mutation
90%
median number of mutations per px
3
how many genes harbor mutation in px with MDS
47 genes
(many are not specific to MDS)
how many groups of genes are affected by the mutation
5 groups
3 different ways in which epigenetics may facilitate oncogenesis
1) Methylation of CpG islands
2) Histone Modification
3) Alteration of microRNA expression
mutations in what two genes play an important role in altering CpG island methylation and histone methylation respectively
TET2 and ASXL1
prognosis is limited only based on what characteristics
1) morphology
2) molecular
3) genetic
4) immunologic
5) clinical
how many drugs are approved by US FDA that shows promise
three
3 drugs approved by US FDA for MDS
1) Lenalidomide
2) Azacitidine
3) Decitabine
T or F:
MDS drugs can be used either alone or in combination with other therapies
T
