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Hematopathology WHO MPN, Mastocytosis, MPN/MDS, & MDS > General Overview of MDS > Flashcards

General Overview of MDS Flashcards

1
Q

Definition of MDS ?

A
  • clonal hematopoietic stem cell disease characterized by:
    • cytopenias
      • in at least one lineage
    • dysplasia in one or more of the major myeloid lineages
    • ineffective hematopoiesis
    • recurrent genetic abnormalities
    • increased risk of developing AML
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2
Q

What are the recommended thresholds

for cytopenias in MDS ?

A
  • hemoglobin <10 g/dL
  • platelet count <100 X10^9/L
  • absolute neutrophil count <1.8 x19^9/L
  • however, can have higher numbers on CBC as long as there is definitive morphologic or cytogenetic findings present
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3
Q

Which specific MDS categories

can have associated thrombocytosis?

A
  • platelets >450 x 10^9/L
  • MDS with del 5q
  • MDS with inv(3) or t(3;3)
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4
Q

What percentage of MDS cases

have recurrent cytogenetic abnormalities ?

A
  • 40-50%

IMP: acquired somatic mutations are seen in the vast majority of MDS cases at diagnosis

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5
Q

What is the general epidemiology

of MDS ?

A
  • generally seen in older adults (median age: 70)
    • MDS affecting children is rare and has it’s own diagnostic criteria
  • male predominance
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6
Q

What are the microscopic findings

in MDS ?

A
  • classification depends on:
    • number of dysplastic lineages
    • blasts in PB and BM
    • and presence of RS

Note: the lineages with cytopenias are NOT necessarily the ones that contain dysplasia.

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7
Q

What has been observed regarding greater

% of blasts in the PB vs. BM ?

A
  • in cases with more % blasts in PB (~13% of all MDS) compared to the BM
    • those cases tend to act more aggressively
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8
Q

What is a general rule in making the diagnosis

of MDS ?

A
  • cannot make the diagnosis without a detailed medication and drug history
  • no case of MDS should be re-classified in a patient on growth factor therapy, including erythropoietin
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9
Q

What are things that can cause a clinical

and morphologic picture of MDS ?

A
  • drugs
  • infections
  • autoimmune disorders
  • metabolic deficiencies
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10
Q

What are the criteria for call a lineage dysplastic ?

A
  • generally >10% of the precursor cells for erythroid and myeloid lineages
  • >10% of megakaryocytes and must evaluate at least 30 megas
    • some advocate for a threshold of 30-40% for dysplasia in megas

IMP: for cases with single lineage dysplasia, erythroids are usually the lineage that is dysplastic

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11
Q

What drug can cause ring sideroblast

formation ?

A
  • Isoniazole
  • it does this in the absence of vitamin B6 supplementation
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12
Q

Which medications can lead to

marked neutrophil hyposegmentation ?

A
  • cotrimoxazole (antibiotic)
  • immunosuppresants
    • tacrolimus
    • mycophenolate mofetil
      • also can lead to erythroblastopenia
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13
Q

Which medical conditions can

clinically mimic MDS ?

A
  • hypothyroidism
  • infections
  • autoimmune diseases
  • PNH
  • bone marrow lymphomatous involvement
    • particularly LGL and Hairy cell leukemia
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14
Q

What is a feature on bone marrow biopsy

core of aggressive MDS ?

A
  • Abnormal localization of immature precursors
    • aggregates (3-5 cells) or clusters (>5 cells)
    • they are usually localized in the center of the bone and away from bony trabeculae
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15
Q

What are some features that help differentiate

hypoplastic MDS from aplastic anemia ?

A
  • dysplasia (most often in the megakaryocytes)
  • increased blasts identified by CD34 stain
  • abnormal karyotype
    • most often trisomy 8
      • although this can occasionally be seen in aplastic anemias

IMP: MDS-associated somatic mutations have been reported in as many as 1/3 of aplastic anemia patients

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16
Q

What must be excluded when considering

a diagnosis of hypoplastic MDS ?

A
  • must exclude marrow injury due to a toxin, infection or autimmune disorder
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17
Q

What marrow finding, independent of the blast count,

indicates an aggressive clinical course in MDS?

A
  • significant degrees of myelofibrosis (grade 2-3)
  • seen in ~10-15% of MDS cases
  • not a significant subtype but these patients tend to do worse
    • blast counts may not be accurate due to significant fibrosis and hemodilute aspirates
  • unlike PMF, MDS with fibrosis is NOT associated with splenomegaly, leukoerythroblastosis or intrasinusoidal hematopoiesis
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18
Q

What are the immunophenotypic changes in

the myeloids in MDS ?

A
  • abnormal or asynchronous maturation patterns
    • asynchrony of CD15 and CD16 in granulocytes
    • altered expression of CD13 in relation to CD11b or CD16
    • aberrant expression of CD7 or CD56 on:
      • progenitors
      • granulocytes
      • monocytes

Note: also will have decreased hematogones in MDS

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19
Q

What are the immunophenotypic findings

of erythroids in MDS ?

A
  • increased coefficient of variation
  • decreased intensity of CD71 or CD36 expression
20
Q

What is loss of 17p associated with ?

A
  • MDS or AML with pseudo-Pelger Huet anomaly
    • vacuolated, small neutrophils
  • TP53 mutation
  • unfavorable clinical course
  • most common in therapy related MDS
21
Q

What is usually seen in a complex

karyotype and what is the prognosis ?

A
  • by definition >3 abnormalities
  • usually have abnormalities in:
    • chromosome 5 and or 7
      • del 5q or t5q or loss of chromosome 7 or del 7q
  • generally associated with a poor clinical course
22
Q

What are the morphologic

correlates for del 20q ?

A
  • dysmegakaryopoiesis
  • thrombocytopenia
23
Q

What are the morphologic

correlates in inv(3) or t(3;3) ?

A
  • abnormal megakaryocytes
  • thrombocytosis
24
Q

What clonal cytogenetic abnormalities

when present alone do NOT suffice for

a diagnosis of MDS ?

A
  • loss of Y chromosome
  • gain of chromosome 8
  • del 20q

Note:

  • these can be seen in other conditions. If no morphologic defining critieria then these do not count.
25
Q

What unbalanced chromosomal abnormalities in the setting

of unexplained cytopenias but no

definitive dysplasia are enough to call MDS-U ?

A
  • loss of chromosome 7 or del 7q
  • del 5q or t5q
  • isochromsomes 17q or t(17p)
  • loss of chromsomes 13 or del 13q
  • del 11q
  • del 12p or t(12p)
  • del 9q
  • idic(x)(q13)
26
Q

What balanced chromosomal aberrations in the setting of cytopenias

but no morphologic dysplasia

are enough to diagnose MDS-U ?

A
  • t(11;16)
  • t(3;21)
  • t(1;3)
  • t(2;11)
  • inv(3) or t(3;3)
  • t(6;9)

Note: cytogenetic abnormalities are present in ~50% of MDS cases. 80-90% of cases have somatic mutations in recurring genes.

27
Q

Which mutations when present are

associated with severe granulocytic dysplasia ?

A
  • ASXL1
  • RUNX1
  • TP53
  • SRSF2
28
Q

Why are somatic mutations alone

NOT enough to diagnose MDS ?

A
  • these mutations can occur in healthy individuals without evidence of MDS
    • even in the setting of cytopenia
29
Q

Which is the only somatic mutation

that has it’s own MDS diagnostic category ?

A
  • SF3B1
  • only one infuencing MDS subtype
30
Q

What are the low-risk MDS

groups ?

A
  • MDS with single lineage dysplasia
  • MDS with ring sideroblasts and single lineage dysplasia
  • MDS with isolated del 5q
31
Q

What is the intermediate risk group

for MDS ?

A
  • MDS with multi-lineage dysplasia
  • MDS with ring sideroblasts and multi-lineage dysplasia
32
Q

What is the high risk MDS group?

A
  • MDS with excess blasts
33
Q

What two mutations tend to affect

MDS response to hypomethylating agents?

A
  • TET2
  • DNMT3A
34
Q

How does TP53 mutation affect treatment

in MDS del 5q ?

A
  • MDS del 5q is usually sensitive to Lenalidomide
  • with TP53 mutation it becomes insensitive

Note: TP53 is a poor prognostic indicator and shows more aggressive disease

35
Q

Which mutations when present show conflicting

data or a neutral impact on prognosis in MDS ?

A
  • TET2 (DNA methylation)
  • ZRSR2 (RNA splicing)
  • IDH1/IDH2 (DNA methylation)
36
Q

What gene confers a good prognosis

in MDS?

A
  • SF3B1 (RNA splicing)
37
Q

What are the transcription factors

genes that confer an adverse prognosis in MDS ?

A
  • BCOR
  • NRAS
  • RUNX1
38
Q

What are the RNA splicing genes that

confer an adverse prognosis in MDS?

A
  • SRSF2
  • U2AF1
39
Q

What are the histone modifying genes that

confer an adverse prognosis in MDS ?

A
  • ASXL1
  • EZH2
40
Q

What are the other gene categories/genes

that confer an adverse prognosis in MDS ?

A
  • DNMT3A (DNA methylator)
  • TP53 (tumor suppressor)
  • STAG2 (cohesin complex)
  • CBL (signalling)
41
Q

What defining cytogenetic abnormalities

are considered to have very good prognosis ?

A
  • loss of Y chromosom
  • del 11q
42
Q

What defining cytogenetic abnormalities

have a good prognosis ?

A
  • Normal karyotype
  • del 5q
  • del 12p
  • del 20q
  • double, including del 5q
43
Q

What defining cytogenetic abnormalities have

an intermediate prognosis in MDS ?

A
  • del 7q
  • gain of chromosome 8
  • gain of chromosom 9
  • isochromosome 17q
  • single or double abnormalities not specified in other groups
  • two or more independent non-complex clones
44
Q

What defining cytogenetic abnormlities are

considered a poor prognostic factor ?

A
  • loss of chromosome 7
  • inv(3), t(3q), or del(3q)
  • double including loss of chromosome 7 or del 7q
  • complex karyotype
45
Q

What is generally a very poor

prognostic group cytogenetically ?

A
  • > 3 abnormalities
    • complex karyotype

Hematopathology WHO MPN, Mastocytosis, MPN/MDS, & MDS (17 decks)

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