Myelodysplastic Syndrome and Myeloproliferative Neoplasms Flashcards
Myelodysplastic syndrome (MDS) refers to a group of clonal hematopoietic stem cell disorders characterized by: (2)
Ineffective hematopoiesis
Increased risk of transformation to acute myeloid leukemia (AML)
What do clones in MDS do?
replace the marrow to a varying extent, and result in ineffective production of blood cells in one or more of the myeloid lineages (granulocytic, erythroid, and/or platelet)
Two clinical scenarios of MDS:
Primary/idiopathic
Secondary/Therapy-related (t-MDS)
Primary / idiopathic MDS
Usually in person over 50 years old with insidious onset. Median age of dx is 70. Incidence is 3-5/100,000
Secondary / Therapy related MDS
Occurs as part of a spectrum of t-AML… usually occurs 2-8 years after use of alkylating agents or exposure to fields of active marrow to IR… usually contains whole or partial deletions of chromosome 5/7
At what age does primary / idiopathic MDS usually present?
incidence?
> 50
median 70
3-5/100,000
Secondary / therapy related MDS
occurs how many years post therapy?
usually deletions in which 2 chromosomes?
2-8 years post use of alkylating agents
chromosomes 5and/or7
When is the diagnosis of MDS usually considered?
when there has been at lease one persistent (several months) peripheral cytopenia…
if there is only one cytopenia, it is usually anemia, but rarely persistent isolated neutropenia or persistent isolated thrombocytopenia can be due to MDS.
Persistent cytopenias of two or more lineages in an elderly person is suspicious for MDS
The diagnosis of MDS can be made by evaluating the marrow. Evaluation of the marrow should show (2)
morphologic evidence of dysplastic changes in at least 10% of the cells in one or more lineages
clonal cytogenetic findings typical of MDS.
Morphologic evidence of dysplastic changes in at least 10% of the cells in one or more lineages (dyshematopoiesis) … These findings can be as follows (3Ds)
- Dyserythropoeisis
- Dysgranulopoiesis
- Dysmegakaryopoiesis
What is it called when you see RBC precursors with nuclear budding, irregularly shaped nuclei, lack of coordination between nuclear and cytoplasmic maturation, and INCREASED RING SIDEROBLASTS?
Dyserythropoiesis
Dyserythropoesis most characteristic feature?
Nuclear irregularities
Prominent ring sideroblasts
Megalablastoid chromatin patterns in RBC precursors
What is it called when you see nuclear hypolobation of mature neutrophils, including neutrophils with bilobed nuclei - called pseudo-Pelger-Huet cells, also cytoplasmic hypogranularity of neutrophils?
Dysgranulopoiesis
Dysgranulopoiesis most characteristic finding?
pseudo Pelger Huet cells (dysplastic neutrophils with two nuclear lobes)
poor cytoplasmic granulation
What is it called when you see megakaryocytes with hypolobated or non-lobated nuclei, often hyperchromatic nuclei, megakaryoctyes often of small size?
dysmegakaryopoiesis
Dyserythropoeisis
Dysgranulopoiesis
Dysmegakaryopoiesis
These are all examples of _____________ which aids in the diagnosis of MDS
dyshematopoiesis
What clonal cytogenetic findings are typical of MDS (3)
- complex karyotypes with whole or partial deletion of chromosome 5 and or 7
- note deletion 5q is an isolated cytogenetic finding; seen with a specific type of MDS
- Trisomy 8; many others
In the absence of clonal cytogenetic evidence of MDS, care should be taked in establishing a diagnosis of MDS. Potential non-neoplastic causes of secondary myelodysplasia should be excluded first. These include (4)
- Certain drugs (many chemotherapeutic)
- Deficiencies in B12, folic acid, essential elements
- Viral infection
- Toxin exposure, especially heavy metals such as arsenic
MDS can be either low or high grade
What characterizes low grade
What characterizes high grade?
LOW: Myeloblasts account for less than 5% of marrow cells, and less than 2% of peripheral
HIGH: Myeloblasts account for 5%-19% of marrow cells, and/or 2%-19% or more of peripheral
Low grade MDS with dysplasia in only one lineage
Mostly cases of refractory anemia, rarely may be refractory neutropenia or refractory thrombocytopenia
Relatively good prognosis
- >5years
- only 2% to AML by 5 years
Refractory Cytopenia with Unilineage Dysplasia (RCUD)
Low grade MDS with dysplasia in 2 or more lineages
Worse prognosis than RCUD
- Median survival 2.5 years
- 10 percent of cases transform to AML by 2 years
Refractory Cytopenia with multilineage dysplasia (RCMD)
High grade MDS 5-9% blasts in marrow, and/or 2-4% blasts in blood Relatively dismal prognosis - median survival of 16 months - 25% will transform to AML
Refractory anemia with excess blasts-1 (RAEB-1)
High grade MDS 10-19% blasts in marrow, and/or 5-19% blasts in blood Very dismal prognosis - median survival of 9 months - 33% will transform to AML
Refractory anemia with excess blasts-2 (RAEB-2)
In the setting of a persistent cytopenia, the diagnosis of MDS can be established using one or more modalities (3)
- morphological evidence
- increased myeloblasts but less than 20%
- clonal cytogenetic abnormality
