This document provides an overview of myelodysplastic syndrome (MDS). It discusses the introduction, history, classification, pathogenesis, diagnosis and management of MDS. Some key points: - MDS is a group of clonal stem cell diseases characterized by cytopenia, dysplasia, ineffective hematopoiesis, genetic abnormalities and risk of AML. - The 2016 WHO classification categorizes MDS based on dysplastic lineages, cytopenias, ring sideroblast percentage, blast percentage and cytogenetics. Subtypes include MDS with single lineage dysplasia, multilineage dysplasia, ring sideroblasts, isolated del 5q, excess blasts and unclassifiable.

1. Myelodysplastic syndrome
Moderator : Dr Arathi.C.A
Presenter: Dr Santhi priya G
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2. 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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3. 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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4. 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 reflects the
heterogeneity of the disease
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5. 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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6. Aetiology
HEREDITARY ACQUIRED
Constitutional genetic factors (Down’s
syndrome, Monosomy 7)
Senescence
Neurofibromatosis Radiation
Congenital neutropenia Mutagen/ Genotoxic
DNA repair defects ( Fanconi’s anemia,
ataxia telengiectasia etc.)
Alkylating agents, P 32, DNA topoisomerase
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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9. 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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10. 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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11. Cytogenetic abnormalities
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12. Molecular basis of MDS
Genes with mutations in MDS
SF3B1 DNMT3A
TET2 RUNX1
SRSF2 U2AF1
ASXL1 TP53
EZH2
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13. Diagnosis
• Clinical features
• Blood counts
• Peripheral smear morphology
• Bone marrow morphology
• Bone marrow histology
• Immunophenotyping
• Cytogenetic abnormalities
• Molecular abnormalities
• Biochemical tests
₋ Conventional karyotyping
₋ Multicolour FISH
₋ Gene sequencing
₋ SNP array
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14. 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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15. Blood counts(WHO-2016)
• Anemia: Hb<10g/dl
• Leucopenia: absolute neutrophil count <1.8x109/L
• Thrombocytopenia: platelet count<100x109/l
• Monocytes<1x109/L
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16. PB and BM Morphology
‘Pince- nez’ nuclei
Or Doughnut
:Pawn –ball
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17. 9/15/2020 SEMINAR-PESIMSR-MDS 17

18. BM histology
• Hypercellular marrows
• 10% hypocellular marrow
• Dysplasia
• Abnormal localization of immature precursors (ALIP)
• Reticulin fibrosis
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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
del(5q)
1-3 1-2 None or any BM 5%,
PB<1%, no
Auer rods
del(5q) alone or with 1
additional abnormality,
except loss of chromosome
7 or del (7q)9/15/2020 SEMINAR-PESIMSR-MDS 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
del(5q)
1-3 1-2 None or any BM 5%,
PB<1%, no
Auer rods
del(5q) alone or with 1
additional abnormality,
except loss of chromosome
7 or del (7q)9/15/2020 SEMINAR-PESIMSR-MDS 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
del(5q)
1-3 1-2 None or any BM 5%,
PB<1%, no
Auer rods
del(5q) alone or with 1
additional abnormality,
except loss of chromosome
7 or del (7q)9/15/2020 SEMINAR-PESIMSR-MDS 27

28. MDS-MLD
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29. 9/15/2020 SEMINAR-PESIMSR-MDS 29

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
del(5q)
1-3 1-2 None or any BM 5%,
PB<1%, no
Auer rods
del(5q) alone or with 1
additional abnormality,
except loss of chromosome
7 or del (7q)9/15/2020 SEMINAR-PESIMSR-MDS 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
del(5q)
1-3 1-2 None or any BM 5%,
PB<1%, no
Auer rods
del(5q) alone or with 1
additional abnormality,
except loss of chromosome
7 or del (7q)9/15/2020 SEMINAR-PESIMSR-MDS 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
abnormality
0 1-3 <15% BM-5%,PB<1%, no Auer rods MDS-
defining
abnorm
ality9/15/2020 SEMINAR-PESIMSR-MDS 33

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
abnormality
0 1-3 <15% BM-5%,PB<1%, no Auer rods MDS-
defining
abnorm
ality9/15/2020 SEMINAR-PESIMSR-MDS 35

36. MDS-EB-2
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37. 9/15/2020 SEMINAR-PESIMSR-MDS 37

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
abnormality
0 1-3 <15% BM-5%,PB<1%, no Auer rods MDS-
defining
abnorm
ality9/15/2020 SEMINAR-PESIMSR-MDS 38

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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40. 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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41. Types of childhood MDS
• Refractory cytopenia of childhood
• Conventional MDS in children
– MDS-EB
– t- MDS
– MDS-RS
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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
CD 34+ cells No increase9/15/2020 SEMINAR-PESIMSR-MDS 43

43. Hypocellular MDS(h-MDS)
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44. • Differential diagnosis of this group includes
– Toxic myelopathy
– Autoimmune disorders
– Hypoplastic AML
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45. 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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46. • 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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47. MDS-Eo
• This rare form of MDS demonstrates clonal eosinophilia
showing hyposegmented and dysplastic eosinophils
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48. MDS with marrow fibrosis (MDS-f)
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49. 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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50. 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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51. Prognostic scoring systems and risk stratification
• International prognostic scoring system
• WHO prognostic scoring system
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52. International prognostic scoring system
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53. 9/15/2020 SEMINAR-PESIMSR-MDS 56

54. WHO prognostic scoring system
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56. Management and treatment
• Supportive care
• Haematopoietic growth factors
• Immunosuppresion
• Chelation therapy
• Intensive chemotherapy
• Allogeneic stemcell transplantation
• Hypomethylating drugs
• Lenalidomide
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57. 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
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58. Peripheral smear
• The neutrophilic cells show marked hyposegmentation
and hypogranulation.
• Red blood cell (RBC) morphology includes anisocytosis
and poikilocytosis, teardrop cells, ovalocytes, and
schistocytes.
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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
forms with nuclear separation and single nucleated forms.9/15/2020 SEMINAR-PESIMSR-MDS 62

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

61. • ?Subtype of MDS
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62. • karyotype showed multiple complex
abnormalities.
• what is the prognosis?
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63. WHO prognostic scoring system
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64. 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 and Myelodysplasia.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
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65. • Thank you!!
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