This document provides an overview of myelodysplastic syndrome (MDS). It discusses the history, classification, pathogenesis, diagnosis and management of MDS. MDS is a heterogeneous group of clonal stem cell neoplasms characterized by cytopenia, dysplasia and risk of progression to acute myeloid leukemia. The document reviews the World Health Organization classification of MDS subtypes based on dysplastic lineages, ring sideroblasts and blast percentage. It also discusses common cytogenetic abnormalities and molecular mutations in MDS. Diagnosis involves blood counts, bone marrow morphology, histology, immunophenotyping and genetic testing. Prognostic scoring systems guide treatment and management, which may include growth factors, immunosuppress

1. Myelodysplastic syndrome
Moderator : Dr Arathi.C.A
Presenter: Dr Santhi priya G
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Contents
• Introduction
• History
• Incidence
• Aetiology
• Classification
• Pathogenesis
• Cytogenetic abnormalities
in MDS
• Molecular basis of MDS
• Diagnosis
• Differential diagnosis
• Prognostic scoring
systems
• Management and
treatment
• Case discussion
• References

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Introduction
• The myelodysplastic syndromes (MDS) are a group of
clonal haematopoietic stem cell diseases
• Characterized by
– cytopenia,
– dysplasia in one or more of the major myeloid
lineages,
– ineffective haematopoiesis,
– recurrent genetic abnormalities and
– increased risk of developing acute myeloid leukaemia
(AML)

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History
• 1900 by Von Leube, leukanamie -a patient with severe
megaloblastic anaemia that progressed to acute leukaemia
• 1930s, the term ‘refractory anaemia- macrocytic anaemia
that was unresponsive to iron or other dietary haematinics
• 1980s, the term ‘myelodysplasia’, or ‘myelodysplastic
syndromes’ gained widespread acceptance and reflectsthe
heterogeneity of the disease

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Incidence
• Disease of elderly with median age of presentation being
65 years
• 3.5-4.5 per 1,00,000 in US
• Increases to >20 per 1,00,000 at >70 years
• India, median age of presentation being 45 years

6. Aetiology
HEREDITARY ACQUIRED
Constitutional genetic factors (Down’s
syndrome, Monosomy 7)
Senescence
Neurofibromatosis Radiation
Congenital neutropenia Mutagen/ Genotoxic
DNA repair defects ( Fanconi’sanemia,
ataxia telengiectasia etc.)
Alkylating agents, P 32, DNAtopoisomerase
II inhibitors
Mutagen detoxification(GST q1- null) Benzene, tobacco
Dyskeratosis congenita Aplastic anemia, PNH
Shwachman diamond syndrome Agricultural chemical solvents
Diamond Blackfan syndrome
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7. Pathogenesis
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8. Classification- FAB(1982)
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Classification- WHO(2016)
• MDS with single lineage dysplasia(MDS-SLD)
• MDS with multilineage dysplasia(MDS-MLD)
• MDS with ring sideroblasts(MDS-RS)
– MDS with single lineage dysplasia(MDS-RS-SLD)
– MDS with multilineage dysplasia(MDS-RS-MLD)
• MDS with isolated del(5q)

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Classification – WHO(2016) contd..
• MDS with excess blasts(MDS-EB)
– MDS with excess blasts-1(MDS-EB-1)
– MDS with excess blasts-2(MDS-EB-2)
• MDS, unclassifiable(MDS-U)
– MDS-U with 1% blood blasts
– MDS-U with single lineage dysplasia and
pancytopenia
– MDS-U based on defining cytogenetic abnormality
• Refractory cytopenia of chilhood

11. Cytogenetic abnormalities
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Molecular basis of MDS
Genes with mutations in MDS
SF3B1 DNMT3A
TET2 RUNX1
SRSF2 U2AF1
ASXL1 TP53
EZH2

13. Diagnosis
• Clinical features
• Blood counts
• Peripheral smear morphology
• Bone marrow morphology
• Bone marrow histology
• Immunophenotyping
• Cytogenetic abnormalities
• Molecular abnormalities
• Biochemical tests
₋ Conventionalkaryotyping
₋ MulticolourFISH
₋ Genesequencing
₋ SNParray
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Clinical features
• Anemia dominates the early course
• Gradual onset of fatigue and weakness, dyspnea, and
pallor
• One-half the patients are asymptomatic-incidentally on
routine blood counts
• 20% of patients have splenomegaly.

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Blood counts(WHO-2016)
• Anemia: Hb<10g/dl
• Leucopenia: absolute neutrophil count <1.8x109/L
• Thrombocytopenia: platelet count<100x109/l
• Monocytes<1x109/L

16. PB and BM Morphology
Or Doughnut
‘Pince- nez’nuclei
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:Pawn –ball

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BM histology
• Hypercellular marrows
• 10% hypocellular marrow
• Dysplasia
• Abnormal localization of immature precursors (ALIP)
• Reticulin fibrosis

19. ALIP
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20. Morphological features of subtypes of MDS(WHO)
Entity name No of
dyspl
astic
linea
ges
No
of
cyto
peni
as
Ring
sideroblasts
as % of
marrow
erythroid
elements
BM and
PB blasts
Cytogenetics
MDS-SLD 1 1-2 < 15 %/<5% BM 5%,
PB<1%, no
Auer rods
Any, unless fullfills all
criteria for MDS with
isolated del (5q)
MDS-MLD 2-3 1-3 <15%/<5% BM 5%,
PB<1%, no
Auer rods
Any, unless fullfills all
criteria for MDS with
isolated del (5q)
MDS-RS
MDS-RS-SLD 1 1-2 ≥15%/≥5%
BM 5%,
PB<1%, no
Auer rods
Any, unless fullfills all
criteria for MDS with
isolated del (5q)
MDS-RS-MLD 2-3 1-3 ≥15%/≥5% BM 5%,
PB<1%, no
Auer rods
Any, unless fullfills all
criteria for MDS with
isolated del (5q)
MDS with isolated 1-3 1-2 None or any BM 5%, del(5q) alone or with 1
del(5q) PB<1%, no additional abnormality,
9/15/2020 SEMINAR-PESIMSR
Auer rods
-MDS
except loss of chromosome
7 or del (7q) 20

21. MDS-SLD
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22. MDS-SLD
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23. MDS-SLD
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24. MDS-SLD
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25. Morphological features of subtypes of MDS(WHO)
Entity name No of
dyspl
astic
linea
ges
No
of
cyto
peni
as
Ring
sideroblasts
as % of
marrow
erythroid
elements
BM and
PB blasts
Cytogenetics
MDS-SLD 1 1-2 < 15 %/<5% BM 5%,
PB<1%, no
Auer rods
Any, unless fullfills all
criteria for MDS with
isolated del (5q)
MDS-MLD 2-3 1-3 <15%/<5% BM 5%,
PB<1%, no
Auer rods
Any, unless fullfills all
criteria for MDS with
isolated del (5q)
MDS-RS
MDS-RS-SLD 1 1-2 ≥15%/≥5%
BM 5%,
PB<1%, no
Auer rods
Any, unless fullfills all
criteria for MDS with
isolated del (5q)
MDS-RS-MLD 2-3 1-3 ≥15%/≥5% BM 5%,
PB<1%, no
Auer rods
Any, unless fullfills all
criteria for MDS with
isolated del (5q)
MDS with isolated 1-3 1-2 None or any BM 5%, del(5q) alone or with 1
del(5q) PB<1%, no additional abnormality,
9/15/2020 SEMINAR-PESIMSR
Auer rods
-MDS
except loss of chromosome
7 or del (7q) 25

26. MDS-RS-SLD
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27. Morphological features of subtypes of MDS(WHO)
Entity name No of
dyspl
astic
linea
ges
No
of
cyto
peni
as
Ring
sideroblasts
as % of
marrow
erythroid
elements
BM and
PB blasts
Cytogenetics
MDS-SLD 1 1-2 < 15 %/<5% BM 5%,
PB<1%, no
Auer rods
Any, unless fullfills all
criteria for MDS with
isolated del (5q)
MDS-MLD 2-3 1-3 <15%/<5% BM 5%,
PB<1%, no
Auer rods
Any, unless fullfills all
criteria for MDS with
isolated del (5q)
MDS-RS
MDS-RS-SLD 1 1-2 ≥15%/≥5%
BM 5%,
PB<1%, no
Auer rods
Any, unless fullfills all
criteria for MDS with
isolated del (5q)
MDS-RS-MLD 2-3 1-3 ≥15%/≥5% BM 5%,
PB<1%, no
Auer rods
Any, unless fullfills all
criteria for MDS with
isolated del (5q)
MDS with isolated 1-3 1-2 None or any BM 5%, del(5q) alone or with 1
del(5q) PB<1%, no additional abnormality,
9/15/2020 SEMINAR-PESIMSR
Auer rods
-MDS
except loss of chromosome
7 or del (7q) 27

28. MDS-MLD
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30. Morphological features of subtypes of MDS(WHO)
Entity name No of
dyspl
astic
linea
ges
No
of
cyto
peni
as
Ring
sideroblasts
as % of
marrow
erythroid
elements
BM and
PB blasts
Cytogenetics
MDS-SLD 1 1-2 < 15 %/<5% BM 5%,
PB<1%, no
Auer rods
Any, unless fullfills all
criteria for MDS with
isolated del (5q)
MDS-MLD 2-3 1-3 <15%/<5% BM 5%,
PB<1%, no
Auer rods
Any, unless fullfills all
criteria for MDS with
isolated del (5q)
MDS-RS
MDS-RS-SLD 1 1-2 ≥15%/≥5%
BM 5%,
PB<1%, no
Auer rods
Any, unless fullfills all
criteria for MDS with
isolated del (5q)
MDS-RS-MLD 2-3 1-3 ≥15%/≥5% BM 5%,
PB<1%, no
Auer rods
Any, unless fullfills all
criteria for MDS with
isolated del (5q)
MDS with isolated 1-3 1-2 None or any BM 5%, del(5q) alone or with 1
del(5q) PB<1%, no additional abnormality,
9/15/2020 SEMINAR-PESIMSR
Auer rods
-MDS
except loss of chromosome
7 or del (7q) 30

31. Morphological features of subtypes of MDS(WHO)
Entity name No of
dyspl
astic
linea
ges
No
of
cyto
peni
as
Ring
sideroblasts
as % of
marrow
erythroid
elements
BM and
PB blasts
Cytogenetics
MDS-SLD 1 1-2 < 15 %/<5% BM 5%,
PB<1%, no
Auer rods
Any, unless fullfills all
criteria for MDS with
isolated del (5q)
MDS-MLD 2-3 1-3 <15%/<5% BM 5%,
PB<1%, no
Auer rods
Any, unless fullfills all
criteria for MDS with
isolated del (5q)
MDS-RS
MDS-RS-SLD 1 1-2 ≥15%/≥5%
BM 5%,
PB<1%, no
Auer rods
Any, unless fullfills all
criteria for MDS with
isolated del (5q)
MDS-RS-MLD 2-3 1-3 ≥15%/≥5% BM 5%,
PB<1%, no
Auer rods
Any, unless fullfills all
criteria for MDS with
isolated del (5q)
MDS with isolated 1-3 1-2 None or any BM 5%, del(5q) alone or with 1
del(5q) PB<1%, no additional abnormality,
9/15/2020 SEMINAR-PESIMSR
Auer rods
-MDS
except loss of chromosome
7 or del (7q) 31

32. MDS with isolated del(5q)
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33. Morphological features of subtypes of MDS(WHO)
Entity name No of
dyspl
astic
linea
ges
No
of
cyto
peni
as
Ring
sideroblasts
as % of
marrow
erythroid
elements
BM and PB blasts Cytoge
netics
MDS-EB
MDS-EB-1 1-3 1-3 None or any
BM 5-9% or PB 2-4%,BM<10%
and PB<5%, no Auer rods
Any
MDS-EB-2 1-3 1-3 None or any BM 10-19% or PB 5-19 % or
Auer rods, BM and PB <20%
Any
MDS-U
With 1%
blood blasts
1-3 1-3 None or any
BM-5%,PB=1%, no Auer rods Any
With SLD and
pancytopenia
1 3 None or any BM-5%,PB<1%, no Auer rods Any
Based on
defining
cytogenetic
9/a1b5/n20o2r0mality
0 1-3 <15%
SEMINAR-PESIMS
BM-5%,PB<1%, no Auer rods
R-MDS
MDS-
defining
abnorm
alit3y3

34. MDS-EB-1
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35. Morphological features of subtypes of MDS(WHO)
Entity name No of
dyspl
astic
linea
ges
No
of
cyto
peni
as
Ring
sideroblasts
as % of
marrow
erythroid
elements
BM and PB blasts Cytoge
netics
MDS-EB
MDS-EB-1 1-3 1-3 None or any
BM 5-9% or PB 2-4%,BM<10%
and PB<5%, no Auer rods
Any
MDS-EB-2 1-3 1-3 None or any BM 10-19% or PB 5-19 % or
Auer rods, BM and PB <20%
Any
MDS-U
With 1%
blood blasts
1-3 1-3 None or any
BM-5%,PB=1%, no Auer rods Any
With SLD and
pancytopenia
1 3 None or any BM-5%,PB<1%, no Auer rods Any
Based on
defining
cytogenetic
9/a1b5/n20o2r0mality
0 1-3 <15%
SEMINAR-PESIMS
BM-5%,PB<1%, no Auer rods
R-MDS
MDS-
defining
abnorm
alit3y5

36. MDS-EB-2
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38. Morphological features of subtypes of MDS(WHO)
Entity name No of
dyspl
astic
linea
ges
No
of
cyto
peni
as
Ring
sideroblasts
as % of
marrow
erythroid
elements
BM and PB blasts Cytoge
netics
MDS-EB
MDS-EB-1 1-3 1-3 None or any
BM 5-9% or PB 2-4%,BM<10%
and PB<5%, no Auer rods
Any
MDS-EB-2 1-3 1-3 None or any BM 10-19% or PB 5-19 % or
Auer rods, BM and PB <20%
Any
MDS-U
With 1%
blood blasts
1-3 1-3 None or any
BM-5%,PB=1%, no Auer rods Any
With SLD and
pancytopenia
1 3 None or any BM-5%,PB<1%, no Auer rods Any
Based on
defining
cytogenetic
9/a1b5/n20o2r0mality
0 1-3 <15%
SEMINAR-PESIMS
BM-5%,PB<1%, no Auer rods
R-MDS
MDS-
defining
abnorm
alit3y8

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Childhood MDS
• Aggressive clinical course
• More often associated with preexisting marrow failure or
congenital abnormalities
• Monosomy 7 is most common cytogenetic abnormality
for primary MDS
• Bone marrow transplantation is the treatment

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Minimal diagnostic criteria for MDS in children
• At least two of the following:
– Sustained unexplained cytopenia (neutropenia,
thrombocytopenia or anemia)
– At least bilineage morphologic myelodysplasia
– Acquired clonal cytogenetic abnormality in
hematopoietic cells
– Increased blasts (> 5%)

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Types of childhood MDS
• Refractory cytopenia of childhood
• Conventional MDS in children
– MDS-EB
– t- MDS
– MDS-RS

42. Bone marrow findings in refractory cytopenia of
childhood(WHO-2016)
Bone marrow biopsy Bone marrow aspirate cytology
Erythropoiesis Patchy distribition
Left shift
Increased
Nuclear lobulation
Multinuclearity
Megaloblastoid changes
Granulopoiesis Marked decrease
Left shift
Pseudo – pelger- huet anomaly
Agranulation of cytoplasm
Hypogranulation of cytoplasm
Nuclear- cytoplasmic maturation
defects
Megakaryopoiesis Marked decrease
Dysplastic changes
Micromegakaryocytes
Micromegakaryocytes
Multiple separated nuclei
Small round nuclei
Lymphocytes May be increased focally or
dispersed
May be increased
CD9
3/
1
45
/
+2
0
2
c0
ells No increase SEMINAR-PESIMSR-MDS 43

43. Hypocellular MDS(h-MDS)
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• Differential diagnosis of this group includes
– Toxic myelopathy
– Autoimmune disorders
– HypoplasticAML

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Secondary / therapy related MDS(s- MDS and t-
MDS)
• Stromal changes like increased reticulin (grade 2-3)
• Stromal edema
• Gelatinous marrow transformation are observed
• Necrosis of bone and marrows
• Plasma cells
• Reactive lymphoid nodules
• Granulomas

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• Therapy related MDS (t-MDS) is of 2 types
– MDS occurring after many years of alkylating drug
intake and are associated with -7/ del 7q and /or -5/del
5q abnormalities
– MDS resulting after > 2 yrs of use of topoisomerase II
inhibitor drugs like epipodophyllotoxins e. g.
etoposide and teniposide.

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MDS-Eo
• This rare form of MDS demonstrates clonal eosinophilia
showing hyposegmented and dysplastic eosinophils

48. MDS with marrow fibrosis (MDS-f)
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Familial MDS(myeloid neoplasms with
germline predisposition)
• Families with > 2 cases of MDS/acute leukemia/
unexplained cytopenias/cases with organ manifestations
fitting into the category of hereditary myeloid malignancy
syndrome (HMMS) should be screened for familial MDS.

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Differential diagnosis for MDS
• Vit B12 and folic acid deficiency
• Exposure to arsenic and other heavy metals
• Congenital dyserythropoietic anemias
• PNH
• HIV
• G-CSF therapy
• Parvo virus B 19 therapy

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Prognostic scoring systems and risk stratification
• International prognostic scoring system
• WHO prognostic scoring system

52. International prognostic scoring system
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54. WHO prognostic scoring system
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Management and treatment
• Supportive care
• Haematopoietic growth factors
• Immunosuppresion
• Chelation therapy
• Intensive chemotherapy
• Allogeneic stemcell transplantation
• Hypomethylating drugs
• Lenalidomide

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Case
65-year-old male, complaints of fatigue, malaise, anorexia
• RBC 1.60x1012/L
• Hb 5.8 g/dL (58 g/L)
• Hct 0.17 L/L (17%)
• WBC 10.5 x109/L
• Platelets 39x109/L
• Reticulocyte Count
0.8%
• WBC Differential
– 44% segmented
neutrophils
– 7% band neutrophils
– 6% lymphocytes
– 28% eosinophils
– 1% metamyelocytes
– 1% myelocytes
– 9% promyelocytes
– 4% blasts

58. 9/15/2020 SEMINAR-PESIMSR-MDS 61
Peripheral smear
• The neutrophilic cells show marked hyposegmentation
and hypogranulation.
• Red blood cell (RBC) morphology includes anisocytosis
and poikilocytosis, teardrop cells, ovalocytes, and
schistocytes.

59. Bone marrow
• Cellularity of about 75%
• Myeloid hyperplasia with
• 9% blasts
• 26% promyelocytes
• 18% myelocytes
• 6% metamyelocytes
• 4% bands
• 37% eosinophils
• M:E was 12:1
• The myelocytes were hypogranular, and some had two nuclei and
blasts
• The erythroid precursors showed megaloblastoid changes.
• Megakaryocytes were adequate in number but showed abnormal
9/15/2f0o20rmswith nuclear separaS
E
tiM
oI
N
nA
R
a-
nP
E
dS
I
M
siS
nR
-
gM
lD
eSnucleated forms. 62

60. 9/15/2020 SEMINAR-PESIMSR-MDS 63

61. 9/15/2020 SEMINAR-PESIMSR-MDS 64
• ?Subtype of MDS

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• karyotype showed multiple complex
abnormalities.
• what is the prognosis?

63. WHO prognostic scoring system
9/15/2020 SEMINAR-PESIMSR-MDS 66

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References
• Raj K, Mufti G J. The myelodysplastic syndromes.In
Hoffbrand A V,Higgs D R, Keeling D M, Mehta A B:
Postgraduates haematology. 7th ed.Wiley Blackwell: 2016.
P.438-73
• Young N S. Myelodysplasia.In Bone Marrow Failure
Syndromes Including Aplastic Anemia andMyelodysplasia.In
Kasper et al. Harrison’s principles of internal medicine. 19th
ed. McGraw-Hill Edu: 2015. P. 669-72
• World Health Organization Classification of Tumours . Steven
H. Swerdlow .Elias Campo.Nancy Lee Harris .Elaine S. Jaffe
.Stefano A. Pileri .Harald Stein .Jorgen Thiele.International
Agency for Research on Cancer. 4th edition. Lyon, 2017
• Tejinder Singh. Atlas and text of hematology. 4th edition.
Volume 2. pg315-345. 2018

65. 9/15/2020 SEMINAR-PESIMSR-MDS 68
• Thank you!!