Chapter 3: Myelodysplastic Syndrome (MDS)

Subtypes:

· Refractory anemia (RA)

· Refractory anemia with ringed sideroblasts (RARS)

· Refractory cytopenia with multilineage dysplasia (RCMD)

· Refractory anemia with excess blasts (RAEB)

· Myelodysplastic syndrome, unclassifiable

· Myelodysplastic syndrome a/w isolated del (5q) chromosome abnormality (5q- syndrome)

General:

· Dysplasia

· Ineffective haematopoiesis

· Blasts <20% in blood and BM

Clinical Features:

· Related to:

o Anemia, most frequently

o Neutropenia, thrombocytopenia

o Organomegaly is infrequently observed

Etiology:

· Primary MDS: virus, benzene, cigarette smoking, Fanconi’s anemia

· Therapy related: alkylating agents

Morphology:

· Dyserythropoiesis

· Dysgranulopoiesis

· Megakaryocytic dysplasia

· BM: hypercellular (sometimes normo- or hypocellular)

Differential:

· Non-clonal disorders with dysplastic changes:

o Congenital dyserythropoietic anemia

o Parvovirus B19

o G-CSF: hypergranularity, Dohle bodies, blasts can be 10% or more

o PNH

Prognosis:

· Poor with more blasts

· Karyotype:

o Normal, -Y,-5q, -20q → good

o 3 or more chromosome abnormalities, chromosome 7 → poor

· Poor with cytopenia: Hgb<10; Neutrophils <1500; Plt < 100 K

Refractory Anemia (RA)

General:

· 5-10% of MDS

· Unequivocal dyserythropoiesis

· Exclude: drug, toxin, viral, immunologic, congenital disease, vitamin deficiency
(B12/folate)

· Blasts:

o Blood: <1%

o BM: <5%

· Etiology: unknown

· Sites: blood and BM

· Genetics: abnormal in 25% of cases, usually -20q, +8, abnormal 5, 7

· Prognosis:

o Median survival 66 months

o Rate of progression to AML ~6%

Refractory Anemia with Ringed Sideroblasts (RARS)

General:

· Epidemiology: 10-12% of MDS

· Findings in RA plus 15% or more of erythroid precursors being ringed sideroblasts (RS)

· RS: erythroid precursor in which 1/3 or more of the nucleus is encircled by 10 or more siderotic granules

· Blasts in BM <5%

· BM morphology:

o Erythroid hyperplasia

o Dysplasia, restricted to erythroid lineage

§ Nuclear lobation

§ Megaloblastoid features

o Abundant hemosiderin-laden macrophages

· Rule out: antituberculosis medication, alcoholism, sideroblastic anemia

· Sites: blood, BM, liver and spleen

· Clinical features: moderate anemia, progressive iron overload

· Etiology: unknown

· Genetics: <10% of cases clonal (if developed during the course of the disease→reevaluate and appropriately reclassify patient)

· Prognosis:

o median survival 6y

o 1-2% of cases → leukemia

Refractory cytopenia with multilineage dysplasia (RCMD)

· Morphology

o Dysplastic changes in ³10% of the cells in 2 or more myeloid cell lines

o Neutrophils may show hypogranulation and/or hyposegmentation

o Erythroids may show

§ Cytoplasmic vacuoles

§ Marked nuclear irregularity including

· Multilobation

· Multinucleation

· Megaloblastoid nuclei

o Megakaryocytes may show

§ Hypolobation

§ Small size

o Blasts <5%

· Prognosis

o 11% progress to acute leukemia

o Overall median survival 33 months

Refractory anemia with excess blasts (RAEB)

· PB Morphology:

· Uni- or multilineage abnormalities

§ RBC: anisopoikilocytosis with macrocytes

§ Neutrophils: hypogranulation and nuclear hyposegmentation

§ Atypical platelets

§ 0-19% blasts

· BM Morphology:

o Usually hypercellular (hypocellular in 10-15%)

o Abnormal localization of immature precursors (ALIP): cluster of 5-8 cells (blasts and promyelocytes), 3 or more/section → recheck smear and BM, note in report.

o Dysgranulopoiesis, dyserythropoiesis, dysmegakaryopoiesis

o 5-19% blasts (myeloid phenotype CD13/ CD33/ CD117)

o RAEB-1, Blasts, <5 % (blood) or 5-9% (BM)

o RAEB-2, Blasts, 5-19 % (blood) or 10-19% BM

· Epidemiology:

o >50 years old

o ~40% of pts with MDS

· Prognosis:

o RAEB-1→25% progress to AML

o RAEB-2→33% progress to AML

o Remainder→BM failure

o Median survival

§ RAEB-1 ~18 months

§ RAEB-2 ~10 months

Myelodysplastic syndrome, unclassifiable (MDS, U)

· General:

o Myelodysplastic syndrome which lacks findings appropriate for classification as RA, RARS, RCMD, RAEB

· Morphology

o No specific findings

o Dysplasia restricted to neutrophils or megakaryocytes (may be marked)

5q- Syndrome

· A myelodysplastic syndrome a/w an isolated del (5q)

· <5% blasts in PB and BM

· Epidemiology

o Middle age to older women (predominantly but not exclusively)

· PB Morphology

o Marked macrocytic anemia

o Slight leukopenia

o Platelet count normal or elevated

o <5% blasts

· BM Morphology

o Normocellular or hypercellular

o Megakaryocytes normal or increased in number, many hypolobated

o Variable degree of erythroid dysplasia

o <5% blasts

o Scattered aggregates of small lymphocytes

· Genetics

o Del (5q), between bands q31 and q33

o Break points and size of deletion are variable

o No other cytogenetic abnormalities, by definition

· Prognosis and predictive factors

o Long survival

o Karyotypic evolution is uncommon

o Additional cytogenetic abnormalities a/w evolution to AML or MDS of higher grade

o Significance of isolated del (5q) and >5% blasts is not clear