Myelodysplastic Syndromes

((MDS
By
Ahmed Hassan El- Sebaie
Assisstant Lecturer of Clinical Pathology
Faculty of Medicine - Mansoura University
 :-Definition
It is a group of acquired clonal stem cell disorder
characterized by ;
- Dysplasia of one or more hemopiotic cell line

with characteristic morphological abnormalities.

- Ineffective hematopiosis due to increased
apoptosis causing cytopenia.
 :-Causes
1. Primary : (idiopathic)
2. Secondary :
 Radiotherapy

 Alkylating agent (as procabazine )

 Chemicals ( as benzene , pesticide or smoking )

 Following autologus transplantation

 Genetic predisposition : as Down’s

syndrome – Fanconi’s anemia

:-Pathogenesis
 Somatic mutation of stem cell result in
formation of functionally and structurally
defective blood cells with short survival.
 Increased blood cell proliferation with
enhanced apoptosis leading to peripheral
cytopenia.
 The defective clone has the growth
advantage over the normal hemopiotic cells
:- Clinical features
 Age : usually between 60 and 75 years old. Few
patient under 50 y, MDS are rare in children
 Sex : common in male than female
 Fatigue , weakness, dyspnea due to anemia.
 Fever, infection due to neutropenia
 Easy bruising, petechie and bleeding tendency due to
thrompocytopenia
 Organomegaly, HSM and lymphadenopathy
:- Laboratory diagnosis
1. CBC: Pancytopenia or isolated cytopenia.
2. P.B morphology;
- RBCs : macrocytic anemia ( in 80% of cases(
Abnormal morphology as oval macrocytes,
anisopoikilocytosis, fragmented RBCs,
basophilic stripling, howell jolly bodies and
elliptocytosis.
- WBCs : Neutropenia (in 60% of cases )
Abnormal morphology of neutrophils as
hypogranulation of cytoplasm ,
hyposegmentation of nucleus ( acquired
Pelger-Huet anomaly ).
Paramyloid Cells : mononuclear cells with
abnormal morphology
Vriable number of blast cells.
Anisopoikilocytosis of red cells , hypogranulated
neutrophilic band
hypolobated neutrophil with marked hypogranulation
Platelets :
Thrombocytopenia ( in 25 – 50
% of cases)giant platelets with
hypogranulation
 Reticulocyte : decreased due

to in effective erythropiosis
3. Bone marrow aspiration:
-Trilineage dysplasia, Hypercellular ( in 90% of cases )
and Hypocellular with fibrosis (in 10% of cases ).
- Erythroid series show dyserythropiotic changes as ;
 Erythroid hyperplasia with megaloplastic features.

 Nuclear fragmentation (Karyorrhexis).

 Nuclear budding or lobulation

 Multinucleated erythroblast.

 Giant erythroblast.

 Internuclear bridging.

 Increased sidrotic granules and increased sidroblasts

ring sideroblast
Nuclear budding of erythroblast
Multinucleated erythroblast
- Myeloid series show ;
 granulocyte hyperplasia with hypogranular

neutrophils and abnormal lobulation of

nucleus ( round segmented or bilobed
[ Pseudo Pelger-Huet anomaly] )
 Increase the number of monocyte and

promonocyte.
 Variable number of blast ( up to 29%).

 Paramyloid cells present

Pseudo Pelger-Huet neutrophil
Blast cell and monolobed neutrophil
- Megakaryocyte :
 micromegakaryocyte

 Non lobed or bilobed

megakaryocyte.
 Hypogranular megakaryocyte.
4. Bone marrow biopsy:
 BM is hypercellular or normocellular in

majority and hypocellular in MDS secondary

to cytotoxic chemotherapy.
 In [MDS] myeloid precursors are seen in

intertrabcular space due to autocrine

production of vascular endothelial growth
factors.
N.B: normally precursors are seen close to bony
trabeculae and around blood vessels.
5. Cytogenetics :
 Genetic abnormalities are numerical rather than structural

 Present in 50% of 1ry MDS and in 80% of 2ry MDS.

 Types ;

- del 5q / monosomy 5 ( commonest ).

- del 7q / monosomy 7.
- Trisomy 8.
- t( 11q23 )
- del 17p
- del 20q
These abnormalities are detected by [FISH] technique.
 6. Genetic studies:
Mutation of oncogenes and tumor suppressor
genes as ; RAS mutation, P53 gene, CSF-1R
gene and AML-1 gene.

7. Immunephenotyping:
 Dysregulation in expression of CD 34 CD 36

and CD 71 which are normally expressed in

Bone marrow cells.
 Over expression od CD 16 and CD 117 on blast

cells.
8. Other investigations:-
 Ferrokinitics to diagnose ineffective
erythropiosis.
 Hb F : increased in JMML.

 Hb H : increased in acquired Hb H disease.

 Granulocytic function

 Platelet function
 :-Classifications
( I ( FAB classification ;
1. Refractory anemia (RA)
2. RA with ringed sidroblast (RARS).
3. RA with excess blast (RAEB).
4. RA with excess blast in transformation
(RAEB-t).
5. Chronic myelomonocytic leukemia
(CMML)
 ( II ) WHO classification :-
Disease Blood finding
Refractory cytopenia with unilineage Unicytopenia or bicytopeniaNo Unilineage dysplasia: > 10% of
dysplasia (RCUD(:[Refractory anemia or rare blasts (<1%(
(RA(; Refractory neutropenia (RN(;
Refractory thrombocytopenia (RT(]
Refractory anemia with ring sideroblasts Anemia
(RARS( No blasts
Refractory cytopenia with multilineage Cytopenia(s(
dysplasia (RCMD( No or rare blasts (<1%(
No Auer rods
< 1 X 10’ /L monocytes
Refractory anemia with excess Cytopenia(s(
blasts-1 (RAEB-1( < 5% blasts
No Auer rods
< 1 X 10’ /L monocytes
Refractory anemia with excess Cytopenia(s(
5 – 19 % blasts
blasts-2 (RAEB-2(
Auer rods ±
< 1 X 10’ /L monocytes
Myelodysplastic syndrome – unclassified Cytopenias
(MDS-U(
< 1% blasts
MDS associated with isolated del(5q( Anemia
Usually normal or
increased platelet count
No or rare blasts (<1%(
From www.bloodjournal.org at SWETS SUBSCRIPTION SERVICES on May 31, 2009
Bone marrow finding
the cells in one myeloid lineage
< 5 % blasts
< 15 %of erythroid precursors are
ring sideroblasts
≥15 % of erythroid precursors are
ring sideroblasts
Erythroid dysplasia only
< 5 % blasts
Dysplasia in ≥ 10% of the cells in ≥ 2 myeloid lineage (neutrophil and/or erythroid
precursors and/or Megakaryocytes(
< 5 % blasts in marrow
No Auer rods
+ 15 % ring sideroblasts
Unilineage or multilineage dysplasia
5 – 9 % blasts
No Auer rods
Unilineage or multilineage dysplasia
10 – 19 % blasts
Auer rods ±
Unequivocal dysplasia in <10% of cells in one or more myeloid lineages when
accompanied by a cytogenetic abnormality considered as presumptive evidence for a
diagnosis of MDS.
< 5 % blasts
Normal to increased megakaryocytes with hypolobated nuclei < 5 %
blasts Isolated del(5q( cytogenetic abnormality No Auer rods
:-Prognosis
(I)Adverse prognostic factors including;
1. Clinically : - Therapy related MDS
2. Peripheral blood :
- Sever cytopenia
- Increased LDH , B2 microglobulin
3. Bone Marrow morphology:
- Increased blast cells
- Trilineage dysplasia
4. Chromosomal abnormalities :
- Monosomy 5 , 7.
- Del 3q, 5q, 7q, 17p.
- Abnormality of ch 11q23
5. genetics :
- P53 and RAS genes mutation
- over expression of WT1
- P15 hypermethylation
- Telomere shortening
6. Immunephenotype : CD 7 + Blast cells
(II) Scoring system ;
Score value 0.0 0.5 1.0 1.5 2.0
Blast cells <5 5 - 10 ---- 11 - 20 21 - 30

Karyotype Good Intermediate Poor ---- ----

Cytopenia 0 /1 2/3 ---- ---- ----

N.B:
• Cytopenia : Hb < 10 gm/dl - neutrophil < 1.5 X 109 / L
- Plt < 100 X 109 / L
• Kryotype : Good ; Normal, del 5q or loss of Y
Poor ; Complex ( > 3 abnormalities( or del 7q
:-D.D
 Megaloblastic anemia due to B12 and Folic a
deficiency.
 Heavy metal intoxication.
 Acute alcoholic intoxication
 Viral infection
 Chronic infection
 Congenital dyserythropiotic anemia
 AML (M2, M4, M6)