The myelodysplastic syndromes (MDS) are a group of diseases characterized by bone marrow failure and abnormalities in the appearance of blood cells. MDS results from mutations in bone marrow stem cells that impair differentiation and increase cell death. While some patients with MDS develop acute leukemia, most do not. MDS is diagnosed based on peripheral blood cytopenias and characteristic dysplastic changes seen in the bone marrow, including ring sideroblasts, hypogranular neutrophils, and micromegakaryocytes. Cytogenetic abnormalities are also important for diagnosis and prognosis. Morphologic evaluation remains key for diagnosis of MDS.

1. MYELODYSPLASTIC
SYNDROMES
Presented by
Marwa Ahmed Gamal Eldin

2. MYELODYSPLASTIC
SYNDROMES
The myelodysplastic syndromes (MDS) are
a group of diseases characterized by
increasing BM failure with quantitative
and qualitative (functional and
morphological) abnormalities of all three
myeloid cell lineages.

3. MDS
 In contrast to leukaemia, in which one specific
type of blood cell (the white cell) is produced
in excessively large numbers, the production
of any, and sometimes of all, types of blood
cells is affected.

4. MDS
 The myelodysplastic syndromes were formerly
referred to by many names including
preleukaemia.
 The term preleukaemia is no longer used
because it is very misleading.
 Although a minority of patients with MDS
develop acute leukaemia, most do not.
 When leukaemic transformation does occur, it
is to acute myeloid leukaemia (AML).

5. MDS
Two features:
1. Ineffective hemopoiesis; the combination of
a hyperactive marrow with low blood cell
counts is the hallmark of the disease.
2. Abnormality in the appearance of the bone
marrow and blood cells. These abnormalities
(e.g. white cells lacking normal granules) are
characteristic of the condition.

6. Pathophysiology of MDS
 MDS is thought to arise from mutations in the
multi-potent bone marrow stem cell.
 Differentiation of blood precursor cells is
impaired, and
 there is a significant increase in levels of cell
death apoptosis in bone marrow cells.
 If the overall percentage of bone marrow blasts
rises over a particular cutoff (20% for WHO
and 30% forFAB) then transformation to
leukemia (specifically acute myelogenous
leukemia or AML) is said to have occurred.

7. While recognition of leukemic transformation is
important, a significant proportion of the
morbidity and mortality attributable to MDS
results not from transformation to AML but
rather from the cytopenias seen in all MDS
patients.

8. Causes of myelodysplasia
 Primary myelodysplastic syndrome is of no known
cause but several risk factors are established.
 Therapy-related (secondary) myelodysplastic
syndrome occurs following treatment with either
chemotherapy (eg. Alkylating agents) or radiotherapy
for another neoplasm as Hodgkin's disease or ovarian
carcinoma.

9. Classification
 FAB classification of MDS
 WHO classification of MDS

10. FAB classification of MDS
Bone marrow
Peripheral blood
Blasts < 5%
Blasts < 1%
Refractory anemia
(RA)
Blasts < 5%
Ring sideroblasts >15% of total
erythrocytes
Blasts < 1%
Refractory anemia
with ringed
sideroblasts (RARS)
Blasts 5-20%
Blasts < 5%
RA with excess blasts
(RAEB)
Blasts 20-30% or Auer rods
present
Blasts > 5%
RAEB in
transformation
(RAEB-t)
As any of the above with
As any of the
above with
>1000/cmm
monocytes
Chronic
myelomonocytic
leukemia (CMML)

11. WHO classification of MDS

12. Bone Marrow Findings
Blood Findings
Disease subtype
Erythroid dysplasia only-ie,
< 10% grans or megas dysplasia
< 5% blasts
< 15% ringed sideroblasts
Anemia
No or rare blasts
No Auer rods
< 1 x 109/L monocytes
Refractory anemia (RA)
15% ringed sideroblasts
< 5% blasts
Anemia
No blasts
No Auer rods
< 1 x 109/L monocytes
Refractory anemia with
ringed sideroblasts (RARS)
10% of cells in two or more
myeloid cell lines
< 5% blasts in marrow
No Auer rods
< 15% ringed sideroblasts
Cytopenias (bicytopenia or pancytopenia)
No or rare blasts
No Auer rods
< 1 x 109/L monocytes
Refractory cytopenia with
multilineage dysplasia (RCMD)
15% ringed sideroblasts
< 5% blasts
No Auer rods
Cytopenias (bicytopenia or pancytopenia)
No or rare blasts
No Auer rods
< 1 x 109/L monocytes
Refractory cytopenia with multilineage
dysplasia and ringed sideroblasts
(RCMD-RS)
Unilineage or multilineage dysplasia
5%–9% blasts
No Auer rods
Cytopenias
< 5% blasts
No Auer rods
< 1 x 109/L monocytes
Refractory anemia with excess blasts
– 1 (RAEB-1)
Unilineage or multilineage dysplasia
10%–19% blasts
Auer rods +/–
Cytopenias
5%–19% blasts
Auer rods +/–
< 1 x 109/L monocytes
Refractory anemia with excess blasts
– 2 (RAEB-2)
Unilineage gran or mega dysplasia
< 5% blasts
No Auer rods
Cytopenias
No or rare blasts
No Auer rods
Myelodysplastic syndrome,
unclassified (MDS-U)
Normal to increased megakaryocytes
with hypolobulated nuclei
< 5% blasts
No Auer rods
Isolated del (5q)
Anemia
< 5% blasts
Platelets normal or increased
MDS associated with isolated del (5q)

13. WHO classification of MDS
The major changes include:
 Lowering the threshold for defining acute myeloid leukemia (AML) .
 RCMD includes RA and RARS with 2 or 3 dysplastic cell lines.
 Subdividing RAEB into two categories depending on the number of blasts
in the blood and marrow.
 Removing chronic myelomonocytic leukemia (CMML) from the MDS
category into a new group of diseases; the MDS/MPD overlap diseases. .
 Addition of 5 q-syndrome that affects the elderly females and is
characterized by macrocytic anemia, thrombocytosis, erythroid dysplasia,
hypolobated micromegakaryocytic hyperplasia and the 5 q- chromosome
deletion (band q13 to q33). It is associated with good prognosis.

14. WHO classification of MDS
 Not all physicians concur with this
reclassification.
 This is because the underlying pathology of
the diseases is not well understood.
 It is difficult to classify things that are not well
understood.

15. Problems in classification of MDS
Still, other categories of MDS are not addressed
by this classification, such as hypocellular
MDS and MDS with fibrosis. These latter
entities remain problematic, and their
recognition as well as their place among the
other subcategories await further clarification.

16. Signs and symptoms of MDS
 The average age at diagnosis for MDS is about 65 years, but pediatric cases
have been reported.
 Some patients have a history of exposure to chemotherapy (especially
alkylating agents such as) or radiation (therapeutic or accidental), or both (e.g.,
at the time of stem cell transplantation for another disease).
 Males are slightly more frequently affected than females.
 About one-fifth of MDS patients have no signs or symptoms and are
diagnosed by chance as a result of a routine blood test.
 Those patients who do have symptoms present with clinical features due to
bone marrow failure.
 In about 80% of patients this is simple (transfusion-dependent ) anaemia.
 whilst about 20% present with infections or bleeding as the major clinical
problem.
 Because neutrophils, monocytes and platelets are often functionally impaired,
spontaneous infections in some cases, or bruising or bleeding in others, may
occur out of proportion to the severity of the cytopenia.

17. Laboratory diagnosis
 There are no definitive tests for MDS. It is a
diagnosis of exclusion and is made when a
patient has typical features of MDS with no
obvious underlying cause.
 Under the microscope, affected cells show
characteristic abnormalities both in the
circulating blood and in the bone marrow. This
is the defining feature of the disease.

18. Peripheral blood
 Pancytopenia is a frequent finding.
 Red cells
Anemia-macrocytic or dimorphic
-hypochromic
Normoblasts may be present.
The reticulocyte count is low.
 Granulocytes
Often reduced in number.
Hypogranularity.
Nuclear hyposegmentation (pseudo-Pelger-Huet anomaly (single or bilobed
nucleus).
 Platelets
Thrombocytopenia.
Large platelets.
Micromegakaryocytes.
 When a patient is found to have cells on the blood film suggestive of MDS
a full clinical history will be taken to rule out other causes and a bone
marrow sample will be obtained.

19. Bone marrow
 The most important findings in the BM are the dysplastic changes and, in some
cases, increased myeloblasts.
 In the majority of cases the bone marrow will be more active than normal
(hyperplastic) and this feature, combined with the characteristic dysplasia in
appearance of the cells and the low blood cell numbers will make the diagnosis
straightforward. These dysplastic changes are the defining features of the
disease.
 Cells that are difficult to identify as either agranular myelocytes, monocytes or
promonocytes are frequent.
 In about 10% the BM is hypocellular and may resemble aplastic anemia.
 Myelofibrosis is occasionally present, particularly with therapy-related MDS.
 Iron stores are often increased.

20. MDS
 Dysplasia can affect all three lineages seen in the bone marrow.
 The best way to diagnose dysplasia is by morphology and special
stains used on the bone marrow aspirate and peripheral blood
smear.
 Dysplasia in the myeloid series is defined by:
 Erythroid series
 Binucleated erythroid percursors and karyorrhexis
 N-C asychrony and megaloblastoid chromatin.
 Erythroid nuclear budding
 Erythroid nuclear strings or internuclear bridging (also seen in congenital
dyserythropoietic anemias)
 PAS-positive erythroblasts. (globular in vacuoles or diffuse cytoplasmic
staining within erythroid precursors in the bone marrow aspirate). Note:
One can see PAS vacuolar positivity in L1 and L2 blasts.
 Ringed sideroblasts seen on Prussian blue iron stain (10 or more iron
granules encircling 1/3 or more of the nucleus and >15% ringed
sideroblasts when counted amongst red cell precursors).

21. MDS DYSERYTHROPOIESIS
Multinucleate polychromatic

22. MDS DYSERYTHROPOIESIS
Ring sideroblasts

23. MDS DYSERYTHROPOIESIS
Perl’s stain showing iron overload in macrophages of a
bone marrow fragment, i.e., increased iron stores.

24. MDS DYSERYTHROPOIESIS
Macrocytosis, biphenotypic population

26. MDS
 Granulocytic series dysplasia
 Hypersegmented neutrophils (also seen in Vit
B12/Folate deficiency)
 Hyposegmented neutrophils (Pseudo-Pelger Huet)
 Hypogranular neutrophils or pseudo Chediak
Higashi large granules
 Dimorphic granules (basophilic and eosinophilic
granules) within eosinophils
 MPO – deficient neutrophils.

27. MDS DYSGRANULOPOIESIS

Monocytoid cells and an agranular neutrophil.

28. MDS DYSGRANULOPOIESIS

White cells showing pseudo-Pelger cells, agranular
myelocytes and neutrophils.

29. MDS DYSGRANULOPOIESIS
Hypogranulation, nuclear-cytoplasmic asynchrony

30. MDS DYSGRANULOPOIESIS
Pseudo-Pelerg-Huet anomaly

31. MDS DYSGRANULOPOIESIS
Hypersegmented , hypogranulation

32. MDS DYSGRANULOPOIESIS
Aberrant granulation

34. MDS
 Megakaryocytic series dysplasia (can be the most
subjective)
 Hyposegmented nuclear features in megakaryocytes
(hypolobation or monolobation)
 Hypersegmented (osteoclastic appearing)
megakaryocytes
 Micromegakaryocytes.
 Hypogranulation.

35. MDS DYSMEGAKARYOPOIESIS
Hypogranular platelets

36. MDS DYSMEGAKARYOPOIESIS
Circulating micromegakaryocyte

37. MDS DYSMEGAKARYOPOIESIS
Abnormal megakaryocyte

38. MDS DYSMEGAKARYOPOIESIS
Mononuclear megakaryocyte

39. MDS
Atypical localization of immature precursors (ALIPs)
 It refers to the distribution of developing granulocytes on BM
trephine biopsy sections.
 Normally, the most immature granulocytic precursors are located
in groups along the BM trabeculae or adjacent to blood vessels.
As they mature, they extend towards more central areas between
bone trabeculae.
 In an MDS, the most mature granulocytic precursors may be
found in clusters remote from the usual paratrabecular location.
 This morphology can be difficult to recognize from treated
leukemia and recovering immature normal marrow elements.

40. MDS
 Despite active investigations, morphology
remains the cornerstone for diagnosis.

41. Morphologic problems
One of the most difficult diagnostic challenges in MDS is that morphologic
dysplasia is not specific for MDS but can be seen in other conditions,
including:
 megaloblastic anemia.
 congenital dyserythropoietic anemia.
 sideroblastic anemia.
 exposure to toxins such as arsenic and alcohol.
 after cytotoxic and growth-factor therapy.
 HIV or parvovirus B19 infections.
 Modest dyserythropoiesis is also not uncommon when there is brisk erythroid
hyperplasia or regeneration, i.e., "stress erythropoiesis.
These are known to give a pseudomyelodysplastic picture in one of the cell lines,
however, all three cell lines are never morphologically dysplastic in these
entities with the exception of chloramphenicol, arsenic toxicity and other
poisons.

42. MDS
 Myelodysplasia is a diagnosis of exclusion and must be made
after proper determination of iron stores, vitamin deficiencies,
and nutrient deficiencies.
 Causes of secondary dysplasia must be considered and excluded
by appropriate clinical and laboratory studies prior to rendering a
diagnosis of MDS.
 Furthermore, a small number of dysplastic erythroid,
granulocytic or megakaryocytic cells can be seen in marrow
specimens from normal individuals. Hence, the guideline that
10% of the cells in a lineage should be dysplastic to consider the
lineage as dysplastic and as evidence for MDS is a reasonable
rule.

43. Cytogenetics of MDS
 No cytogenetic abnormality is specific for MDS. However, some
unique cytogenetic/morphologic correlations exist, the most
common of which is the "5q- syndrome," described in the
classification section.
 Cytogenetic studies play a major role in confirmation of
diagnosis and prediction of clinical outcome in MDS.
 Clonal chromosomal abnormalities are detected in 40%–70% of
cases of de novo MDS, and 95% of cases of therapy-related
MDS (t-MDS).
 In t-MDS, deletion of part or all of chromosomes 5 and/or 7 or
trisomy 8 can be detected.

44. Cytogenetics of MDS
 Deletion 5q
 Monosomy 7
 Trisomy 8
 Loss of Y chromosome
 Deletion 20q
 3q rearrangements
 Various abnormalities of chromosome 11
 Various abnormalities of chromosome 17p
 Other complex chromosomal defects

45. International Prognostic Scoring System
1. Presence of the following
abnormalities:
Good = normal or –Y only, 5q- only
or 20q- only
Intermediate = Complex (3+
abnormalities), or abnormal
chromosome 7
Poor = All other abnormalities
2. Count 1 each for:
Hemoglobin level below 10g/dl,
Absolute neutrophil count (ANC)
below 1.8 x 109/l
Platelet count below 100 x 109/l
IPSS Score
Value
Indicators
0
5% or less
Blasts
0.5
5 to 10%
1.5
11 to 20%
2.0
21 to 30%
0
Good
Cytogenetics
0.5
Intermediate
1.0
Poor
0
0/1
Blood cytopaenias
0.5
2/3

46. International Prognostic Scoring System
The individual scores for bone marrow blast percentage,
karyotype and cytopaenias are added together to give
the IPSS score. The scores for the risk groups are as
follows:
0
Low
0.5-1.0
INT-1
1.5-2.0
INT-2
>2.5
High

47. MDS
Although a bone marrow biopsy specimen is not always necessary to
establish a diagnosis of MDS, it offers valuable diagnostic and
prognostic information:
 Dysplasia, particularly of megakaryocytes, can be appreciated in well-prepared
biopsies.
 Evidence of disruption of the normal marrow architecture, such as abnormal
localization of immature precursors (ALIP), lends further support for the
diagnosis of MDS.
 An underappreciated role of the biopsy is that it may provide evidence for
another disease that can mimic MDS clinically, such as lymphoma or
metastatic tumor.
 In cases of MDS that are hypocellular or associated with fibrosis, the biopsy is
essential for diagnosis.

48. Myelodysplastic/
Myeloproliferative
Diseases

49. MDS/MPD
 The myelodysplastic/myeloproliferative
diseases (MDS/MPD) are clonal myeloid
disorders that possess both dysplastic and
proliferative features but are not properly
classified as either myelodysplastic syndromes
(MDS) or chronic myeloproliferative disorders
(CMPD).

50. MDS/MPD
This category is composed of 3 major myeloid
disorders:
 Chronic myelomonocytic leukemia (CMML).
 Juvenile myelomonocytic leukemia (JMML).
 Atypical chronic myeloid leukemia (aCML).
Myeloid disease that shows features of both MDS and
CMPD but does not meet the criteria for any of the 3
major MDS/MPD entities is designated as
myelodysplastic/myeloproliferative disease,
unclassifiable (MDS/MPD-U).

51. MDS/MPD
 Patients with MDS/MPD do not have a
Philadelphia chromosome or BCR/ABL fusion
gene.
 In general, the treatment of these diseases is
tailored to the manifestations, myeloproliferative
or myelodysplastic, that predominate in the
individual patient.

52. Chronic Myelomonocytic Leukemia
Chronic myelomonocytic leukemia (CMML) was
classified as a myelodysplastic syndrome (MDS)
under the French-American-British scheme. The
World Health Organization classification
removed CMML from MDS, placing it in the
new category MDS/MPD.

53. CMML
CMML is characterized by the following:
 Persistent monocytosis >1 x 109/L in the peripheral blood.
 No Philadelphia chromosome or BCR/ABL fusion gene.
 <20% blasts in the blood or bone marrow.
 Dysplasia involving one or more myeloid lineages or, if
myelodysplasia is absent or minimal, either an acquired clonal
cytogenetic bone marrow abnormality or at least 3 months of
persistent peripheral blood monocytosis, if all other causes are
ruled out.

54. CMML
Clinical features of CMML include the following:
 The median age at diagnosis of CMML is 65 to 75.
 Fever, fatigue, night sweats, and weight loss.
 Infection.
 Bleeding caused by thrombocytopenia.
 Hepatomegaly (in some patients).
 Splenomegaly (in some patients).
 In patients with normal or slightly decreased white blood cell
count, clinical features may be identical to MDS.
 In patients with elevated white blood cell count, features are
more like chronic myeloproliferative disorders (CMPD),
including more frequent splenomegaly and hepatomegaly.

55. CMML
Morphologically, the disease is characterized by:
1. Persistent peripheral blood monocytosis (always >1 x 109/L)
that may exceed 80 x 109/L with monocytes typically
accounting for >10% of the white blood cells.
2. Fewer than 20% blasts are seen in the blood or bone marrow.
3. Neutrophilia occurs in nearly 50% of patients with neutrophil
precursors (e.g., promyelocytes and myelocytes) accounting for
>10% of the white blood cells.
4. Mild normocytic anemia is common.
5. Moderate thrombocytopenia is often present.

56. CMML
Bone marrow findings include the following:
 Hypercellularity (75% of cases).
 Blast count <20%.
 Granulocytic proliferation (with dysgranulopoiesis).
 Monocytic proliferation, dyserythropoiesis (e.g.,
megaloblastic changes, abnormal nuclear contours,
ringed sideroblasts, etc.).
 Micromegakaryocytes and/or megakaryocytes with
abnormally lobated nuclei (as many as 80% of the
cases).
 Fibrosis (30% of the cases).

57. CMML
CMML with eosinophilia
 A subtype of CMML associated with severe
tissue damage secondary to eosinophil
degranulation.
 All criteria for CMML are present, and the
eosinophil count in the peripheral blood is >1.5
x 109.

58. CMML
Although clonal cytogenetic abnormalities are found in 20% to 40% of
patients with CMML, none is specific.
Prognostic factors associated with shorter survival include the following:
 Low hemoglobin level.
 Low platelet count; high white blood cell, monocyte, and lymphocyte counts.
 Presence of circulating immature myeloid cells.
 High percentage of marrow blasts.
 Low percentage of marrow erythroid cells.
 Abnormal cytogenetics.
 High levels of serum LDH and ß2-microglobulin.
 Progression to acute leukemia occurs in approximately 15% to 20% of cases.

59. Juvenile Myelomonocytic Leukemia
JMML (also known as juvenile chronic myelomonocytic leukemia) is a rare
hematopoietic malignancy of childhood accounting for about 2% of all
childhood leukemias.
A definitive diagnosis requires the following:
Major criteria (all 3 required)
 No Philadelphia chromosome or BCR/ABL fusion gene.
 Peripheral blood monocytosis >1 x 109/L.
 <20% blasts (including promonocytes) in the blood and bone marrow.
Minor criteria (2 or more required)
 Fetal Hemoglobin (Hb F) increased for age.
 Immature granulocytes in the peripheral blood.
 White blood cell count >10 x 109/L.
 Clonal chromosomal abnormality (e.g., monosomy 7).

60. JMML
Clinical features:
 Constitutional symptoms (e.g., malaise, pallor, and
fever) or evidence of an infection.
 Symptoms of bronchitis or tonsillitis (in approximately
50% of cases).
 Bleeding diathesis.
 Maculopapular skin rashes (in 40%-50% of cases).
 Lymphadenopathy (in approximately 75% of cases).
 Hepatosplenomegaly (in most cases).

61. JMML
The clinical and laboratory features of JMML can
closely mimic a variety of infectious diseases,
including those caused by:
 Epstein-Barr virus.
 cytomegalovirus.
 human herpesvirus 6.
 histoplasma.
 mycobacteria.
 toxoplasma.

62. JMML
Morphologically, the peripheral blood picture in this disease
shows:
 leukocytosis, anemia, and frequently, thrombocytopenia.
 The median reported white blood cell count varies from 25 x
109/L to 35 x 109/L.
 The leukocytosis is comprised of neutrophils, promyelocytes,
myelocytes, and monocytes.
 Blasts, including promonocytes, usually account for <5% of the
white blood cells and always for <20%.
 Nucleated red blood cells are seen frequently.
 Thrombocytopenia is typical and may be severe.

63. JMML
Bone marrow findings include the following:
 Hypercellularity with granulocytic proliferation.
 Hypercellularity with erythroid precursors (in
some patients).
 Monocytes comprising 5% to 10% of marrow
cells (30% or more in some patients).
 Minimal dysplasia.
 Reduced numbers of megakaryocytes.

64. JMML
Prognosis
 Prognosis is related to age at the time of diagnosis. The
prognosis is better in children younger than 1 year at
the time of diagnosis. Children older than 2 years at the
time of diagnosis have a much worse prognosis.
 A low platelet count and a high Hb F level have been
associated with a worse prognosis.
 Approximately 10% to 20% of cases may evolve to
acute leukemia.

65. Atypical Chronic Myelogenous
Leukemia
aCML is characterized pathologically by the following:
 Peripheral blood leukocytosis with increased numbers of mature and
immature neutrophils.
 Prominent dysgranulopoiesis.
 No Philadelphia chromosome or BCR/ABL fusion gene.
 Neutrophil precursors (e.g., promyelocytes, myelocytes, and metamyelocytes)
>10% of white blood cells.
 Minimal absolute basophilia with basophils <2% of white blood cells.
 Absolute monocytosis with monocytes typically <10% of white blood cells.
 Hypercellular bone marrow with granulocytic proliferation and granulocytic
dysplasia.
 <20% blasts in the blood or bone marrow.
 Thrombocytopenia.

66. aCML
Clinical features:
 Anemia.
 Thrombocytopenia.
 Splenomegaly (in 75% of cases).

67. aCML
Morphologically
 The white blood cell count in the peripheral blood is variable.
Median values range from 35 x 109/L to 96 x 109/L, and some
patients may have white blood cell counts >300 x 109/L.
 Blasts in the peripheral blood typically account for <5% of the
white blood cells. I
 Immature neutrophils usually total 10% to 20% or more.
 The percentage of monocytes is rarely >10%.
 Minimal basophilia may be present.
 Nuclear abnormalities, such as acquired Pelger-Huët anomaly,
may be seen in the neutrophils.
 Moderate anemia (often showing changes indicative of
dyserythropoiesis) and thrombocytopenia are common.

68. aCML
Bone marrow findings:
 Granulocytic hypercellularity.
 Blast count <20%.
 Dysgranulopoiesis
 Megakaryocytic dysplasia.
 Erythroid precursors >30% of marrow cells
with dyserythropoiesis present (in some cases).

69. aCML
 Thrombocytopenia and marked anemia are poor
prognostic factors.
 Atypical CML evolves to acute leukemia in
approximately 25% to 40% of patients.
 In the remainder, fatal complications include
resistant leukocytosis, anemia,
thrombocytopenia, hepatosplenomegaly,
cerebral bleeding associated with
thrombocytopenia, and infection.

70. Myelodysplastic/Myeloproliferative
Disease, Unclassifiable
 Myelodysplastic/Myeloproliferative Disease,
Unclassifiable (MDS/MPD-U) (also known as
mixed myeloproliferative/myelodysplastic
syndrome, unclassifiable and overlap syndrome,
unclassifiable) shows features of both
myeloproliferative disease and myelodysplastic
disease but does not meet the criteria for any of
the other MDS/MPD entities.

71. Myelodysplastic/Myeloproliferative
Disease, Unclassifiable
Diagnostic criteria for MDS/MPD-U can be either:
 The combination of all 4 sets of criteria :
 Clinical, laboratory, and morphologic features of myelodysplastic
syndrome with <20% blasts in the blood and bone marrow.
 Prominent myeloproliferative features, e.g. platelet count >600 x 109/L
associated with megakaryocytic proliferation, or white blood cell count
>13.0 x 109/L with or without splenomegaly.
 No history of an underlying chronic myeloproliferative disorder (CMPD),
MDS, or recent cytotoxic or growth factor therapy that could cause the
myelodysplastic or myeloproliferative features.
 No Philadelphia chromosome or BCR/ABL fusion gene, del(5q),
t(3;3)(q21;q26), or inv(3)(q21q26).
 Mixed myeloproliferative and myelodysplastic features that
cannot be assigned to any other category of MDS, CMPD, or
MDS/MPD.

72. MDS/MPD-U
Clinical characteristics:
 Features of both MDS and CMPD.
 Hepatomegaly.
 Splenomegaly.

73. MDS/MPD-U
Laboratory features:
 Anemia and dimorphic erythrocytes on the peripheral blood smear.
 Thrombocytosis (platelet count >600 x 109/L) or leukocytosis (white blood
cell count >13 x 109/L) are present.
 Neutrophils may exhibit dysplastic features.
 Giant or hypogranular platelets may be present.
 Blasts make up <20% of the white blood cells and of the nucleated cells of
the bone marrow.
 The bone marrow is hypercellular and may exhibit proliferation in any or all
of the myeloid lineages. Dysplastic features are present in at least one cell line.
 No cytogenetic or molecular findings are available that are specific for
MDS/MPD-U. Because of its rare occurrence, the prognosis and predictive
factors are unknown.

74. THANK YOU