Definition
A group of clonal stem cell diseases characterized by dysplastic and ineffective hematopoiesis
Diagnostic Criteria
Generally result in cytopenias Marrow is usually cellular
Displays dysplastic features (see below)Occasionally hypocellular , leading to special diagnostic problems
Occasionally increased fibrosis , leading to special diagnostic problems
Increased risk of blast transformation
Have been considered preleukemia by some
Occurs mainly in older patients
Select specific disorders below for details
Myelodysplastic Syndromes
Circulating Blasts
Marrow Blasts
Ring Sideroblasts
Dysplastic Lineages
Cytopenias
RCUD <1%
<5%
<15%
Any 1 lineage
1 or 2
RARS 0
<5%
≥15%
Only erythroid
1 or 2
RCMD <1%
<5%
Variable
2 or more lineages
1, 2 or 3
RAEB-1 <5%
5-9%
Variable
1 or more
1, 2 or 3
RAEB-2 5-19%
10-19% or Auer rods
Variable
1 or more
1, 2 or 3
del(5q) <1%
<5%
Variable
Frequently hypolobated small megakaryocytes
Usually 1 (anemia)
RCUD = refractory cytopenia (anemia, neutropenia or thrombocytopenia) with unilineage dysplasia; RARS = refractory anemia with ringed sideroblasts; RCMD = refractory cytopenia with multilineage dysplasia; RAEB = refractory anemia with excess blasts; del(5q) = 5q- syndrome
All MDS must not have absolute monocytosis
If chemotherapy or radiation therapy related, should be reported as "therapy-related myeloid neoplasm "
In children, consider provisional WHO entity "refractory cytopenia of childhood" for low blast count MDS
Myelodysplastic syndrome unclassifiable (MDS-U )
Must not meet criteria of any specific WHO category
Persistent cytopenia(s) with any of the following:
Unilineage marrow dysplasia with pancytopenia OR
<1% blasts in blood, <5% blasts in marrow and cytogenetic abnormalities but no lineage with ≥10% dysplastic forms OR
Findings of RCUD or RCMD but with 1% blasts in peripheral blood
(2-4% blasts would be classified as RAEB-1 )
Nonclonal causes must be excluded
Myelodysplasia is defined by morphologic features of abnormal cellular maturation in at least one bone marrow lineage
Not all features are applicable to all disorders
Dyserythropoeisis
Peripheral blood erythrocyte abnormalities
Normocytic, normochromic anemia
Macrocytosis
Dimorphic red blood cells (RBC)
Mixture of normal RBC and hypochromic microcytic RBC
Basophilic stippling
Poikilocytosis
Varying shapes, frequently macro-ovalocytes
Bone marrow erythroid lineage abnormalties
Erythroid hyperplasia or hypoplasia
Megaloblastoid / megaloblastic changes
Dyssynchronous maturation of nucleus and cytoplasm of erythroid precursors
Nucleus lags behind cytoplasm
Ring sideroblasts
≥5 iron granules encircling ≥1/3 of the nucleus
Usually either many or none
Cytoplasmic vacuoles
Also seen in copper deficiency
Nuclear changes
Multinuclearity
Nuclear budding, hyperlobulation and satellite nuclei
Internuclear bridging
Dysgranulopoiesis
Peripheral blood and/or bone marrow findings (easier seen in peripheral blood)
Hypogranularity
Pale cytoplasm almost indistinguishable from background on slide
Nuclear hypolobation or irregular hypersegmentation (>5 lobes)
Pseudo Pelger-Huet anomaly
Two equal size nuclear lobes connected by a thin strand of chromatin
Infrequent findings
Abnormal cytoplasmic granules (pseudo Chediak-Higashi granules)
Giant grey to red granules
Dohle bodies
Small blue cytoplasmic inclusions
Often found at periphery of cell
Auer rods
Rod-like structures formed by fusion of primary granules
May be found in blasts or maturing granulocytes
Dysmegakaryopoiesis
Peripheral blood platelet abnormalities
Giant
Larger than a red blood cell
Bizarre
Irregular shapes and protrusions
Hypogranularity
Compare to normal platelets with purple granules
Bone marrow megakaryocyte abnormalities
Micromegakaryocytes
Smaller than a promyelocyte
Nuclear hypolobation
Prominent in 5q- syndrome
A single lobe is typically seen in a small megakaryocyte
Multinucleation
Distinct nuclei without a connecting strand of chromatin
Cytoplasmic hypogranularity
Dita Gratzinger MD PhD
Original posting: 10/23/11
Supplemental studies
Cytogenetic studies should be performed in all cases of myelodysplasia or suspected myelodysplasia
FISH for MDS associated abnormalities is not indicated for screening but is helpful if <20 metaphases were examined on karyotyping
In the setting of persistent cytopenia in the absence of definitive morphologic features of MDS:
The following abnormalities are considered presumptive evidence of MDS
Deletions
-5, del(5q)
-7, del(7q)
del(9q)
del(11q)
del(12p)
t(12p)
-13, del(13q)
i(17q), t(17p)
idic(X)(q13)
Translocations
t(1;3)(p36.3;q21.2)
t(2;11)(p21;q23)
t(3;21)(q26.2;q22.1)
inv(3)(q21q26.2) and t(6;9)(p23;q24)
Most frequently present as AML and need to be closely monitored for overt transformation
t(11;16)(q23;p13.3)
The following are commonly found in MDS but are not by themselves considered definitional for MDS
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Clinical
International Prognostic Scoring System (IPSS)
Points are assigned based on abnormal findings
Points:
0
0.5
1
1.5
2
BM blast %
<5
5-10
-
11-20
21-30
Cytogenetic Group
Good
Intermediate
Poor
Number of cytopenic lineages
0-1
2-3
Cytogenetic groups
Good: Normal, -Y, del(5q), del(20q)
Intermediate: All others
Poor: Complex, chromosome 7 abnormalities
Cytopenias
Hemoglobin <10 mg/dl
Absolute neutrophil count <1.8 x 103 /μL
Platelets <100 x 103 /μL
Risk groups are determined based on points assigned as above
Risk Group
Points
Median Survival
Evolution to Acute Leukemia
Low
0
5.7 years
9.4 years
Intermediate-1
0.5-1.0
3.5 years
3.3 years
Intermediate-2
1.5-2.0
1.2 years
1.1 years
High
>2.5
0.4 years
0.2 years
Treatment based on risk group assigned and ability to tolerate therapy including
Supportive care
Immunosuppressive agents
Bone marrow transplantation
Intensive cytotoxic treatment
Demethylating agents
Farnesyl transferase inhibitors
Blood 89:2079, 1997
Classification / Lists
WHO 2008 Classification of Myeloid Neoplasms
Myelodysplastic/Myeloproliferative Neoplasms (MDS/MPN)
Bibliography
Swerdlow SH, Campo E, Harris NL, Jaffe ES, Pileri SA, Stein H, Thiele J, Vardiman JW eds. WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues, World Health Organization Classification of Tumours 2008
Hofmann WK, Koeffler HP. Myelodysplastic syndrome. Annu Rev Med. 2005;56:1-16.
Parker JE, Mufti GJ, Rasool F, Mijovic A, Devereux S, Pagliuca A. The role of apoptosis, proliferation, and the Bcl-2-related proteins in the myelodysplastic syndromes and acute myeloid leukemia secondary to MDS. Blood. 2000 Dec 1;96(12):3932-8.
Oriani A, Annaloro C, Soligo D, Pozzoli E, Cortelezzi A, Lambertenghi Deliliers G. Bone marrow histology and CD34 immunostaining in the prognostic evaluation of primary myelodysplastic syndromes. Br J Haematol. 1996 Feb;92(2):360-4.
Greenberg P, Cox C, LeBeau MM, Fenaux P, Morel P, Sanz G, Sanz M, Vallespi T, Hamblin T, Oscier D, Ohyashiki K, Toyama K, Aul C, Mufti G, Bennett J. International scoring system for evaluating prognosis in myelodysplastic syndromes. Blood. 1997 Mar 15;89(6):2079-88. Erratum in: Blood 1998 Feb 1;91(3):1100.
Verburgh E, Achten R, Maes B, Hagemeijer A, Boogaerts M, De Wolf-Peeters C, Verhoef G. Additional prognostic value of bone marrow histology in patients subclassified according to the International Prognostic Scoring System for myelodysplastic syndromes. J Clin Oncol. 2003 Jan 15;21(2):273-82.
Germing U, Gattermann N, Aivado M, Hildebrandt B, Aul C. Two types of acquired idiopathic sideroblastic anaemia (AISA): a time-tested distinction. Br J Haematol. 2000 Mar;108(4):724-8.
