MDS & Myeloproliferative Neoplasms (complete) Flashcards
What are the 2 main features that characterize myelodysplastic syndrome (MDS)?
Marrow is replaced by a malignant clone derived from a stem/progenitor cell, causing…
1) Ineffective hematopoiesis
2) Increased risk of transformation to acute myeloid leukemia
What are the 2 clinical scenarios of MDS? Describe them
1) Primary/idiopathic
2) Secondary/therapy related
Describe primary/idiopathic MDS
- usually in >50yo, median = 70yo
- 3-5 cases per 100K persons a year
- Incidence higher in elderly persons
Describe secondary/therapy-related MDS
- Part of therapy-related AML spectrum
- usually diagnosed 2-8 years after DNA-alkyl agents/ionizing radiation
- Usually contains complex karyotype w/ whole/partial deletions of chromosomes 5 and/or 7
What are the 3 different ways to make a diagnosis of MDS?
1) Morphologic evidence of dysplasia
2) Increased myeloblasts, but less that 20% of blood/BM cells
3) Presence of a clonal cytogenetic abnormality
Describe morphologic evidence of dysplasia in diagnosing MDS
- > 10% of cells in one lineage appear dysplastic (dyshematopoiesis)
Three types of dyshematopoiesis:
1) Dyserythropoiesis
2) Dysgranulopoiesis
3) Dysmegakaryopoiesis
This would be a GREAT time to go back and look at cells representing the above — GO LOOK AT THEM NOW
Describe the presence of clonal cytogenetic abnormalities when diagnosing MDS
- Complex karyotype w/ whole/partial deletions of chromosomes 5 and/or 7
- Isolated deletion 5q
- Trisomy 8
What are the 4 possible causes of secondary myelodysplasia that might mimic MDS?
If they don’t have elevated myeloblasts or cytogenetic abnormalities, THINK:
1) Vitamin deficiency (B12, folate)
2) Toxin exposure (eg heavy metals)
3) Exposures to certain drugs
4) Viral infections
Contrast low grade MDS and high grade MDS with regards to diagnostic criteria and prognosis
Low: Myeloblasts are NOT increased in frequency (account for <20% (account for 5-19% of BM, 3-19% of blood cells)
What are the 2 reasons for frequent occurrence of splenomegaly and hepatomegaly in patients with MPNs?
1) Sequestration of excess blood cells
2) Extramedullary hematopoiesis
What are the 3 possible negative end points for MPNs?
1) Transformation to acute leukemia (usually AML, also ALL)
2) Development of myelodysplasia w/ ineffective hematopoiesis (transform to MDS)
3) Excessive BM fibrosis w/ BM failure
What are the 4 MPNs?
1) Chronic myelogenous leukemia (CML)
2) Polycythemia vera (PV)
3) Primary myelofibrosis (PMF)
4) Essential thrombocythemia (ET)
Describe chronic myelogenous leukemia (CML) and discuss blood cells counts, marrow findings, and usual cytogenetic/molecular abnormalities
BCC:
- Neutrophilic leukocytosis
- ^ basophils, platelets
MF: hypercellular BM w/ granulocytic hyperplasia (not just 1 cell type like AML) — also abnormal megakaryocytes
CA: BCR-ABL1 gene fusion
Describe polycythemia vera (PV) and discuss blood cells counts, marrow findings, and usual cytogenetic/molecular abnormalities
BCC:
- ^ RBC mass (erythrocytosis)
- ^ neutrophils, platelets
MF: Trilineage hyperplasia — clusters of bizarre megakaryocytes
CA: All cases contain JAK2 mutation — usually a V617F point mutation
Describe primary myelofibrosis (PMF) and discuss blood cells counts, marrow findings, and usual cytogenetic/molecular abnormalities
BCC: Increased platelets and neutrophils in blood
MF: Granulocytic and megakaryocytic hyperplasia
CA: Cases lacking JAK2 mutations often have mutations of MPL or CALR
