This document describes myelodysplastic syndromes (MDS), a group of clonal hematopoietic stem cell disorders characterized by ineffective hematopoiesis leading to peripheral blood cytopenias. It discusses the history of MDS classification including the French-American-British (FAB) and World Health Organization (WHO) systems. Key features of the different MDS subtypes are outlined along with associated cytogenetic abnormalities, predisposing factors, theories of pathophysiology, clinical manifestations, and diagnostic evaluation.
2. Definition
MDSs are clonal disorders of the hematopoietic
stem cell characterized by ineffective
hematopoiesis leading to peripheral blood
cytopenias, reflecting defects in erythroid,
myeloid and megakaryocytic maturation and by
frequent evolution to AML.
3. Different terminology of MDS
Refractory anemia 1938 Rhoades and Barker
Preleukemic anemia 1949 Hamilton-Paterson
Preleukemia 1953 Block et al.
Refractory anemia with ringed sideroblasts 1956 Bjorkman
Refractory normoblastic anemia 1959 Dacie et al
Smoldering acute leukemia 1963 Rheingold et al
Chronic erythremic myelosis 1969 Dameshek
Preleukemic syndrome 1973 Saarni and Linman
Subacute myelomonocytic leukemia 1974 Sexauer et al
Chronic myelomonocytic leukemia 1974 Miescher and Farguet
Hypoplastic acute myelogenous leukemia 1975 Beard et al
Refractory anemia with excess myeloblasts 1976 Dreyfus
Hematopoietic dysplasia 1978 Linman and Bagby
Subacute myeloid leukemia 1979 Cohen et al
Dysmyelopoietic syndrome 1980 Streuli et al
Myelodysplastic syndromes 1982 Bennet et al
7. Theories of
Pathophysiology
involved
in MDS Development
Potential
Targets/Componen
ts Involved
Overall Result of Abnormality
Environmental/Aging
Aging Increased BM
apoptosis
Decreased hematopoietic stem cell
pool
Environmental Exposures Smoking
Radiation
Benzene
Viral Infections
Chemotherapy
Direct Toxicity to hematopoietic
stem cells.
Telomere Abnormalities Potential decreased
telomerase and
subsequent
telomere shortening
•Impaired ability to renew stem cell
pool.
•Genetic Instability
8. Genetic
Alterations
Cytogenetic
Abnormalities
Common Abnormalities:
• 5q- , 20q-
• Y- , Trisomy 8
• 7q-/Monosomy7, 17p Syndrome
• 11q23, 3q
• p53 mutations, Ras mutations
• Complex Cytogenetics
• Abnormalities: typically
unbalanced genetic loss
• Numerous theories of tumor
suppressor Loss
• Multi-Hit progression from low
risk MDS to AML
•Genetic Instability
Epigenetic
Modulation
•Hypermethylation
•Acetylation Alterations
Methylation and acetylation
abnormalities lead to silencing of
genes important in cell cycle,
differentiation, apoptosis,
angiogenesis
9. Altered Bone Marrow
Microenvironment
Altered Bone Marrow
Microenvironment
Cytokines
Upregulation of:
TNF- , IFN-gamma,
TGF-Beta, IL-1B, IL-6,
Il-11
•Alteration of growth, differentiation,
angiogenesis
•Immune modulation
Alterations in Apoptosis
via Signalling
•Increased TNF-
levels
•FAS: Increased
Apoptosis
•BCL-2 alterations
•Increased apoptosis and
proliferation in early stage MDS
leading to hypercellular marrow with
peripheral cytopenias
• Decreased apoptosis and
increased proliferation in later
stage MDS leading to progression
to AML
Increased Angiogenesis •Increased VEG-F
• Possible Increase:
gFGF and EGF
Angiogenin
Increased Microvessel Density
(MVD): role in pathogenesis not
clearly elucidated but associated
with progression to AML
10. Immune Dysregulation •T cell Expansion
•B cell alterations
•Increased T cells leading
to potential attack on
hematopoietic stem cells.
•Etiology: Possible chronic
antigenic stimulation
Abnormal
Differentiation
•Cell Cycle Maturation
arrest.
•Altered Proliferation.
•Transcription Factors
alterations
•Impaired maturation
•Cytopenias
• Progression to leukemia
11.
12.
13. FAB Classification of MDS
FAB Subtype Peripheral smear Bone Marrow
Refractory anemia
(RA)
Anaemia, blasts< 1%,
monocytes <1x109 /L
Blasts< 5%, ringed siderblasts
< 15% of erythroblasts
Refractory anemia
with Ringed
sideroblasts
(RARS)
Anaemia, blasts< 1%,
monocytes <1x109 /L
Blasts< 5%, ringed
siderblasts> than 15% of
erythroblasts
Refractory anemia
with excess blasts
(RAEB)
Anaemia, blasts>1%,
monocytes <1x109 /L OR
blasts <5%
Blasts 5%
BUT
Blasts 20%
14. FAB Subtype Peripheral smear Bone Marrow
Refractory anemia
with excess blasts in
transformation (RAEB-
T)
Anaemia, blasts 5%
OR present Auer rods
Blasts 20-29%
OR present Auer rods
CMML Monocytes>1x109 /L,
granulocytes often
increased, blasts
<5%.
Blasts upto 20%,
promonocytes often
increased.
15. Limitations of FAB classification
Prognostic differences between the refractory
anaemia (RA) with and without evident
myelodysplastic features in other lineages.
Same with RARS.
Prognostic differences between refractory
anaemia with excess of blasts (RAEB)
according to whether the bone marrow blast
percentage is 5-10% or 10-20%.
16. Limitations of FAB classification…..
Patients categorized as RAEB-T on the basis of
presence of Auer rods, but with BM blasts <20%
were found to have better prognosis than those
categorized as RAEB-T on basis of blast count in
PS and BM.
Furthermore with passage of years patients with
RAEB-T with more than 20% bone marrow blasts
were increasingly regarded and treated as acute
myeloid leukemia.
And this was also true of patients found to have
t(8;21) or inv(16) even when the bone marrow blast
count was less than 20%.
17. Limitations of FAB classification…..
In addition there was controversy as to whether
chronic myelomonocytic anaemia (CMML),
particularly when the white cell count was high,
was properly classified as MDS rather than as
myeloproliferative disorders (MPD).
Some cases were unclassifiable.
Ignores presence of cytogenetic abnormalities.
19. Subtype Blood Bone Marrow
Refractory
anaemia (RA,
RN, RT)/RCUD
Single or
bicytopenia, no
blasts
Unilineage dysplasia 10% of the
cells in one myeloid lineage, < 5%
blasts, <15% ringed sideroblasts
Refractory
anaemia with
ring sideroblasts
(RARS)
Anaemia, no blasts Erythroid dysplasia only, < 5%
blasts, 15% ringed sideroblasts
Refractory
cytopenia with
multilineage
dysplasia
(RCMD)
Cytopenia(s), no or
rare blasts (<1%), no
Auer rods, < 1 x
109/L monocytes
Dysplasia in 10% of cells in 2 or
more hematopoietic lineages, <15%
ring sideroblasts, < 5% blasts, no
Auer rods.
RCMD and
ringed
sideroblasts
(RCMD-RS)
Cytopenias
(bicytopenia or
pancytopenia), No or
rare blasts, No Auer
rods, < 1 x 109/L
monocytes
Dysplasia in 10% of cells in 2 or
more myeloid cell lines, < 5% blasts,
15% ringed sideroblasts, No Auer
rods
20. Subtype Blood Bone Marrow
Refractory anemia
with excess blasts-1
(RAEB-1)
Cytopenias,< 5%
blasts
No Auer rods, < 1 x
109/L monocytes
Unilineage or multilineage
dysplasia, no Auer rods,
5-9% blasts
Refractory anemia
with excess blasts-2
(RAEB-2)
Cytopenias, 5-19%
blasts, Auer rods ±, <
1 x 109/L monocytes
Unilineage or multilineage
dysplasia, Auer rods ±, 10-
19% blasts
MDS, unclassified
(MDS-U)
Cytopenia(s), No or
rare blasts (<1%), No
Auer rods
Unilineage dysplasia in
granulocytes or
Megakaryocytes, < 5%
blasts, No Auer rods
MDS associated with
isolated del(5q)
Anemia, < 1% blasts,
platelets normal or
increased
Normal to increased
megakaryocytes with
hypolobated nuclei, < 5%
blasts, No Auer rods Isolated
del(5q)
22. Myelodysplastic/Myeloprolifierative Neoplasms
(MDS/MPN) WHO Classification
Subtype Blood Bone Marrow
CMML-1 > 1 x 10/L monocytes, < 5%
blasts 9
Dysplasia in 1 hematopoietic
line, < 10% blasts
CMML-2 > 1 x 10 /L monocytes, 5%-
19% blasts or Auer rods
Dysplasia in 1 hematopoietic
line, 10%-19% blasts, or Auer
rods
Atypical chronic
myeloid leukemia
(CML), Bcr-Abl 1
negative
WBC 13 x 10 /L, neutrophil
precursors > 10%, < 20%
blasts
Hypercellular, < 20% blasts
Juvenile
myelomonocytic
leukemia (JMML)
> 1 x 10/L monocytes, <
20% blasts
> 1 x 10 /L monocytes, < 20%
blasts
MDS/MPN,
unclassifiable
('Overlap syndrome')
Dysplasia +
myeloproliferative features,
no prior MDS or MPN
Dysplasia + myeloproliferative
features
23. Changes made by WHO classification
The criteria for the diagnosis of AML was altered
(20% blasts).
RAEB-T------ RAEB-II category.
Problem relating to the classification of CMML/a
CML was resolved by creation of MDS/MPD
category to which both were assigned together with
other cases with features overlapping between
MDS/MPD.
24. Changes made by WHO classification…..
Poor prognostic significance of multilineage
dysplasia in RA and RARS is recognized and new
categories of refractory cytopenia with
multilineage dysplasia and refractory cytopenia
with multilineage dysplasia and ringed
sideroblasts are recognized.
The poor prognostic significance of more than
10% bone marrow blasts, in comparison with 5-
10% bone marrow blasts is recognized and
RAEB is therefore separated into RAEB-I and
RAEB-II.
25. Changes made by WHO
classification…..
The good prognostic significance of MDS with no
increase in blast cells and with an isolated
deletion of long arm of chromosome 5 is
recognized and assigned to a specific category.
It is recognized that there are some cases that
cannot be readily classified and category for such
cases is provided.
All cases of MDS/MPD in infants and children are
assigned to a single category- designated
juvenile myelomonocytic leukemia.
26. Drawback of WHO classification
They incorporate very little cytogenetic and
molecular genetic information.
Only the 5q- syndrome is defined.
27. Clinical manifestations
The symptoms experienced by patients with MDS
are related to the type and severity of the
peripheral blood cytopenias.
Symptoms-
o Fatigue,
o decreased exercise tolerance,
o bleeding,
o easy bruisability, or recurrent bacterial infections.
28. Physical examination
• Pallor
• Peripheral oedema
• Evidence of heart failure (severe anaemia).
• Petechiae on the lower extremities or on the buccal mucosa
(if severe thrombocytopenia is present).
• Splenomegaly may be present, especially in patients with
chronic myelomonocytic leukemia (CMML).
29. Laboratory tests
Decrease of one peripheral blood count or multiple
cytopenias.
Anaemia- Microcytic/normocytic/macrocytic.
Reticulocytopenic (corrected reticulocyte count <1%).
Leukopenia due to a decrease in the absolute neutrophil
count
Leukoerythroblastic picture.
An absolute monocytosis (monocytes >1000/μL) is present
in CMML.
Thrombocytopenia may be present but
Thrombocytosis ( refractory anaemia (RA) and an isolated
5q− abnormality, or in some cases of RARS).
30. Bone marrow
Essential to diagnose MDS.
The BM trephine biopsy provides better assessment
of marrow cellularity and is required to evaluate the
existence of fibrosis. Abnormal distribution of cells is
detectable.
The bone marrow biopsy usually is hypercellular for
the age of the patient.
However, approx 15% of patients have a
hypocellular marrow (cellularity <25%).
31. Bone marrow..…
Granulocytic precurosrs may be clustered centrally
rather than showing their normal paratrabecular
distribution.
This phenomenon has been designated as
abnormal localization of immature precurors (ALIP).
ALIPs are diagnostically important if they are
detected in since their presence confirms MDS
rather than a secondary anaemia.
Use of antiglycophorin antibody highlights the
presence of clusters of immature erythroid cells and
helps to distinguish from ALIPs.
32. Bone marrow ..…
Abnormal megakaryocytes are readily assessed.
Megakaryocytes may be clustered or found in
paratrabecular position.
Apoptosis is increased.
Nonspecific abnormalities- increased
macrophages, prominent mast cells, lymphoid
follicles and plasma cell aggregates.
34. Cytochemical reactions
Most important and essential- Perl’s stain for iron.
SBB and MPO- Ensure that all cases with Auer
rods are recognized and classified as RAEB-T
(FAB) or RAEB-2 (WHO).
In CMML- NSE is necessary to identify monocyte
component in bone marrow.
PAS- Erythroblasts
38. Megakaryocyte
PS Bone marrow
Giant platelets Micromegakaryocytes
Hypogranular or agranular Hypogranulation
platelets Multiple small nuclei
39.
40.
41.
42.
43.
44.
45.
46.
47.
48.
49.
50. Refractory anaemia, RCUD, RN, RT (WHO)
10-20% of MDS.
Older adults, median age- 65-70years.
PS-
Anaemia, marked anisocytosis, poikilocytosis.
Normochromic, normocytic/macrocytic,
occasional hypochromia.
Blasts are uncommon, less than 1%.
51. Refractory anaemia (WHO)…….
Unilineage dysplasia must be present in 10% of cells
of one myeloid lineage.
Bone marrow is usually hypercellular but can be
normocellular or hypocellular.
Ring sideroblasts are less than 15% of erythroblasts
and blasts are less than 5%.
Low or intermediate IPSS scores.
Progression to AML in 2%.
52. Refractory anaemia with ring sideroblasts
(WHO)
3-11% cases of MDS.
PS-
Anaemia, normocytic normochromic, often
macrocytic, microcytic hypochromic, giving
dimorphic picture.
Pappenheimer bodies may be present.
Platelet counts increased, but not more than
450x109/L
53. Refractory anaemia with ring sideroblasts
(WHO)………
Bone marrow shows erythroid hyperplasia.
Myeloblasts are <5% of BM nucleated cells.
15% or more of red cell precursors are ring
sideroblasts.
Iron laden macrophages may be prominent.
Very low rate of evolution to AML.
54.
55. Refractory cytopenia with
multilineage dysplasia (WHO)
Comprises about 30% of cases of MDS.
Mostly elderly patients.
PS-
Cytopenias (Hb<10g/dl, absolute neutrophil count
<1.8x 109 /L and platelet count <100x 109 /L)
<1% blasts,
Auer rods not present and
monocytes are less than 1x 109 /L.
56. Refractory cytopenia with
multilineage dysplasia…..
Bone marrow-
Hypercellular
Dysplasia in 10% of the cells in at least two myeloid
lineages (neutrophils and/or erythroid precursors
and/or megakaryocytes).
<5% blasts, no Auer rods.
>15% ring sideroblasts.
Intermediate scores according to IPSS.
Frequency of leukemic transformation at the end of
two years in approximately 10%.
57. Refractory anaemia with excess of
blasts-1
Comprises around 40% of cases (RAEB-1 &
RAEB-2).
PS-
Cytopenia.
Anisopoikilocytosis, large/giant/hypogranular
platelets, abnormal cytoplasmic granularity and
nuclear segmentation of neutrophils, Auer rods
absent.
<5% blasts.
Monocyte count 1X109 /L
58. Refractory anaemia with excess of
blasts-1…..
Bone marrow-
Dysplasia in at least 10% of cells of one or more myeloid
lineages.
Hypercellular, unilineage/multilineage dysplasia, 5-9%
blasts and no Auer rods.
Abnormalities in three myeloid cell lines (trilineage
dysplasia).
Biopsy- both erythropoiesis and megakaryopiesis
dislocated towards paratrabecular areas that are
predominantly occupied by granulopoietic cells.
Median survival is around 18 months.
59. Refractory anaemia with excess of
blasts-2
It is categorized as RAEB-2 if bone marrow blasts
are 10-19%, if the peripheral blood blasts are 5-
19% (regardless of bone marrow blast count) or if
Auer rods are present.
Dysplasia in at least 10% of cells of one or more
myeloid lineages.
More than a third patient suffered transformation
to AML.
Median survival poor than RAEB-1.
60. MDS associated with isolated 5q
deletion syndrome
This is MDS associated with isolated 5q- .
Etiology- loss of tumour suppressor gene in the
deleted region.
In the FAB classification patients with 5q-
anomaly fell into RA, RARS or RAEB categories.
Patients are mainly women, usually middle aged
or elderly.
PS- Cytopenias, 1% blasts,
61. MDS associated with isolated 5q deletion
syndrome…..
Bone marrow-
Hypercellular/normocellular.
Erythroid hyperplasia.
Megakaryocytes are increased in number and are
normal to decreased in size with hypolobated
nuclei.
<5% blasts.
The rate of leukemic transformation is 3%.
62.
63. MDS unclassifiable
It is a subtype of MDS which initially lacks findings
appropriate for classification into any other MDS
category.
Diagnostic criteria-
1. Pancytopenia in a patient who would otherwise fit
the criteria for RCUD OR
2. PS blasts <1% on two occasions in a patient who
would otherwise meet the criteria for RCUD and
RCMD OR
64. MDS- U
4. Unequivocal dysplasia in not present in10% of the
cells in any lineages but a clonal cytogenetic
abnormality giving presumptive evidence of MDS
is present AND
5. PS blasts are not greater than 1%.
6. Bone marrow blasts <5%.
65. Childhood MDS
Uncommon in children, accounts for less than 5% of
all haematopoietic neoplasms in patients less than
14 years of age.
Refractory cytopenia of childhood (RCC) is a
myelodysplastic syndrome characterized by
persistent cytopenia with <5% blasts in the bone
marrow and <2% blasts in the peripheral blood.
Monosomy 7 is the most common cytogenetic
abnormality (significantly higher probability of
progression).
66. RCC…..
Dysplastic changes in at least 10% of cells of at
least two myeloid lineages.
Erythroid island with at least 20 cells maturation
arrest with excess proerythroblasts, increased
mitosis in erythroid cells.
The detection of micromegakaryocytes is a strong
indicator of RCC.
About 75% of children with RCC show
considerable hypocellularity of the bone marrow.
67. Disorders which may present with
morphological features indistinguishable from
refractory cytopenia of childhood
Infections (CMV, Herpes, parvovirus B19, Leishmaniasis).
Vitamin def (B12, Folate, Vit E).
Metabolic disorders (mevalonate kinase def).
Rheumatic ds.
Autoimmune lymphoproliferative disorder (FAS def).
Inherited BM failure disorders (Facnconi anaemia,
dyskeratosis congenita, Shwachmann-Diamond syndrome).
PNH.
Acquired aplastic anaemia during haematological recovery.
68. Other categories or features of MDSs
Hypocellular MDS-
FAB group initially described MDS having a
hypercellular or normocellular bone marrow.
Subsequently it became apparent that some
cases, approximately 15% in all had a hypocellular
bone marrow.
Their prognosis does not differ from MDS in
general.
D/Ds- Hypocellular AML and aplastic anaemia.
69.
70. MDS with myelofibrosis
Some patients with MDS have considerable
reticulin deposition.
It is important to distinguish these cases from M7
AML with myelofibrosis.
M7 AML has more than 20% blasts whereas MDS
with myelofibrosis has fewer.
They have high incidence of complex
chromosomal abnormalities and poor prognosis.
71. Therapy related MDS
Distinctive haematological and cytogenetic
features.
Eosinophilia and basophilia are more common.
Marked trilineage dysplasia, hypocellularity and
reticular fibrosis are common.
Cytogenetic abnormalities are more often present
than in de novo MDS.
Very poor prognosis.
72. Chronic Myelomonocytic Leukemia (CMML)
Clonal haematopoietic malignancy that is
characterized by features of both MPD and MDS.
Absence of Philadelphia and BCR/ABL fusion gene.
Persistent Monocytosis >1x109/L in PS.
No rearrangement of PDGFRA/PDGFRB.
<20% blasts (PS & BM), including myeloblasts,
monoblasts and promonocytes
Dysplasia in 1 or more BM lineages or clonal
cytogenetic abnormality or monocytosis persisting for
atleast 3 months.
73. CMML…..
• CMML-1 blasts+promonocytes<5% PS and
<10% BM
• CMML-2 blasts+promonocytes 5-19% PS
and 10-19% BM or Auer rods+.
• CMML needs to be distinguished from aCML with
which it shares some features. It has been
recommended that cases in which more than
15% of circulating white cells are granulocyte
precursors should be categorized as aCML and
cases with fewer as CMML.
74.
75.
76. Atypical chronic myeloid leukaemia
aCML is a rare Ph-negative, BCR-ABL1 negative
condition.
Higher median age and worse prognosis than
CGL.
C/F- Anaemia and spleenomegaly.
78. Leucocytosis with dysplastic neutrophils and precursors; precursors (promyelocytes
to metamyelocytes) at least 10% of leucocytes, basophils usually less than 2%
Fewer than 10% monocytes in the blood
Fewer than 20% blasts in blood and bone marrow
Hypercellular bone marrow with dysplasia at least in granulocyte lineage
No Ph chromosome, BCR-ABL1 fusion gene or rearrangement of PDGFRA or
PDGFRB
Diagnosis of atypical chronic myeloid lekemia
79.
80.
81. Juvenile myelomonocytic leukemia (JMML)
It is a Ph-negative condition which occurs mainly in
children less than 5 years of age.
Encompasses previously designated juvenile chronic
myeloid leukaemia, the infantile monosomy 7
syndrome and other MDS/MPD of childhood.
There is an increased incidence in children with
neurofibromatosis and in Down’s syndrome.
Clinical features often include anaemia, hepatomegaly,
splenomegaly, lymphadenopathy and rash.
83. Monocytes >1X109/L
Fewer than 20% blast cells (plus promonocytes) in the blood
and bone marrow
No Ph chromosome or BCR-ABL1 fusion gene
Two or more of the following criteria:
•Hb F increased for age.
•Immature granulocytes in PS.
•WBC>10X109/L
•Clonal chromosomal abnormality (monosomy 7 not excluded).
•Myeloid progenitors hypersensitive to GM-CSF in vitro
Diagnosis of juvenile myelomonocytic lekemia
87. Meets criteria for one of the
categories of MDS
Prominent myeloproliferative
features.
No preceding history of MDS or MPN and cannot be
assigned to a more specific category of MDS/MPN
No BCR-ABL1 or rearrangement of PDGFRA, PDGFRB or FGFR1.
No isolated del (5q), t(3;3) or inv(3)
Diagnosis of myelodysplastic/myeloproliferative
neoplasm, unclassifiable
And
88.
89.
90. Evolution of MDS
Patients with MDS may die of marrow failure as a
direct consequence of MDS or may die following
transformation to acute leukemia.
Myelodysplastic syndromes may evolve into other
MDS.
Change is usually into a worse prognostic
category and very rarely into favorable.
Thus RA and RARS may evolve into either
CMML.
91. Evolution of MDS…..
Variation in number of monocytes can alter
classification, mainly between CMML and RAEB and
rarely ring sideroblasts disappear so that RARS
converts to RA.
When acute leukemia supervenes it may develop
within a brief period or there may be stepwise
evolution over weeks and months.
Acute leukemia that occurs in MDS is always AML,
but rare cases of ALL and bilineage/biphenotypic
leukemia have been reported.
93. Has there been exposure to cytotoxic drugs or
radiation
No
Are there 5-19% blast cells in the blood or 10-19%
blast cells in the bone marrow or Auer rods
Are there no more than 5% blasts cells in the
blood and 5-9% in the bone marrow
No
No
Is there an isloated 5q-
No
Is there multilineage dysplasia
No
RA or RARS
Yes
Therapy related MDS
Yes
RAEB-II
Yes
RAEB-I
Yes
5q- syndrome
Yes
RCMD
94. References
1. Barabara Bain. The WHO classification of Myelodysplastic
syndromes. Exp Oncol 2004, 26 (3):166-69.
2. Barbara Bain, David Clark and Bridget Wilkins. Bone marrow
pathology, 4th edition, 2008.
3. Who classification of tumours of haematopoietic and
lymphoid tissue. 4th edition, 2008.
4. Ha Thanh Nishino, MD; Chung-Che Chang. Myelodysplastic
Syndromes. Clinicopathologic Features, Pathobiology, and
Molecular Pathogenesis. Arch Pathol Lab Med—Vol 129,
October 2005.
5. Raphael Itzykson, Lionel Ades, and Pierre Fenaux. Biology
and Prognostic Factors of Myelodysplastic Syndrome.
American Society of Clinical Oncology 2011.
6. E.D. Warlick and B.D. Smith. Myelodysplastic Syndromes:
Review of Pathophysiology and Current Novel Treatment
Approaches. Current Cancer Drug Targets 2007, 7:541-558
Notes de l'éditeur
Dysfunction of enzymes required for detoxification, DNA mismatch repair, or differentiation
Degree of elevation of blast count
Although the FAB group classified MDS as CMML, atypical chronic myeloid leukemia, a condition characterized by equal if not more dysplasia, was characterized as a type of chronic myeloid leukemia.
BM trephine biopsy section, RAEB-T, showing increased numbers of blasts forming a small cluster (centre) (an abnormal localization ofimmature precursors or ALIP).
PB film, MDS, showing anisocytosis, poikilocytosis and two pseudo-Pelger–Huëtneutrophils, one of which is also hypogranular.
Refractory cytopenia with multilineage dysplasia (RCMD). Bone marrow aspirate (Wright–Giemsa stain – 100x). Erythroid precursors with nuclear irregularity and myeloid precursors with hypogranulation and hyposegmentation
Leishman Stain (×100 magnification). Showing dyserythropoiesis. B) May–Grunwald Giemsa Stain (×100 magnification). Arrow showing binucleate erythroblast. C) Leishman Stain (×200 magnification). Showing multinucleate erythroblast and erythroid dysplasia
REFRACTORY CYTOPENIA WITH MULTILINEAGE DYSPLASIA: dysplastic erythroid precursor with multi-nucleation and nuclear fragments (arrow) and dysplastic myeloid precursor with both eosinophilic and basophilic granulation (arrowhead)
Bone marrow biopsy shows uniformly small and monolobatedmegakaryocytes (arrows).
BM aspirate, RA, showing a binucleatemicromegakaryocyte which is budding platelets
Dysplasia in myeloid precursors can be manifested by dysplastic granulation with granules of eosinophilic type and basophilic type (arrow)
Abnormal nuclear lobation such as seen in this myelocyte with two nuclei (long arrow), abnormal distribution of granules causing granular polarity (arrowhead), and mixed eosinophilic and basophilic granulation (top arrow)
Neutrophils with ring-like nuclei (ringed-neutrophil, arrow), A megaloblastoiderythroid precursor is also seen (arrowhead)
BM aspirate, RARS, showing numerous ring sideroblasts, several of which can be seen to have defectively haemoglobinized cytoplasm.Perls’ stain .940
Megakaryocytes- Megakaryocytes- Normal/increased and cytologically abnormal. They have non-lobed or bilobed nuclei but are mainly more than 30-40um in diameter.Thus they differ from the mononuclear and binuclear micromegakaryocytes associated with other forms of MDS.
Myelodysplastic syndrome with isolated del (5q). A, B) Bone marrow aspirate (40x and 100x). Hypolobatedmegakaryocyte seen. C, D) Bone marrow biopsy – (10x and 40x – H&E stain). Hypercellular bone marrow with myeloid proliferation associated with hypolobated or nonlobatedmegakaryocytes
BM trephine biopsy section from a patient with hypoplastic MDS (RAEB) showing: (a) a disorganized marrow of low cellularity;
BM trephine biopsy section in CMML, showing neutrophilic and monocytic hyperplasia, a hypolobulatedmegakaryocyte and a megakaryocyte in mitosis.Paraffin-embedded, H&
PB, aCML (Ph-negative), showing a myelocyte, a bizarre macropolycyte, an abnormal monocyte, an unidentifiable cell and a lymphocyte.
BM aspirate, aCML showing granulocytic and monocytic hyperplasia
PB, JMML, showing a monocyte, a basophil, dysplastic neutrophils, neutrophil precursors and thrombocytopenia
BM aspirate, JMML, showing granulocyte precursors and a dysplastic binucleatedmicromegakaryoc
Good indicates normal, 2Y,del(5q); poor, complex ($3 abnormalities), chromosome 7 anomalies; and intermediate, other abnormalities.‡ Neutropenia indicates neutrophil level less than 1800/mL; anemia, hemoglobin level less than 10 g/dL (,6.21 mmol/L); and thrombocytopenia,platelet level less than 100 000/mL.