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
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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
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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
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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.
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
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
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
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
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
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
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
39. 9/15/2020 SEMINAR-PESIMSR-MDS 39
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%)
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
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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
46. 9/15/2020 SEMINAR-PESIMSR-MDS 49
• 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.
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
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
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64. 9/15/2020 SEMINAR-PESIMSR-MDS 67
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