General Overview of MDS Flashcards
(45 cards)
Definition of MDS ?
- clonal hematopoietic stem cell disease characterized by:
- cytopenias
- in at least one lineage
- dysplasia in one or more of the major myeloid lineages
- ineffective hematopoiesis
- recurrent genetic abnormalities
- increased risk of developing AML
- cytopenias
What are the recommended thresholds
for cytopenias in MDS ?
- hemoglobin <10 g/dL
- platelet count <100 X10^9/L
- absolute neutrophil count <1.8 x19^9/L
- however, can have higher numbers on CBC as long as there is definitive morphologic or cytogenetic findings present
Which specific MDS categories
can have associated thrombocytosis?
- platelets >450 x 10^9/L
- MDS with del 5q
- MDS with inv(3) or t(3;3)
What percentage of MDS cases
have recurrent cytogenetic abnormalities ?
- 40-50%
IMP: acquired somatic mutations are seen in the vast majority of MDS cases at diagnosis
What is the general epidemiology
of MDS ?
- generally seen in older adults (median age: 70)
- MDS affecting children is rare and has it’s own diagnostic criteria
- male predominance
What are the microscopic findings
in MDS ?
- classification depends on:
- number of dysplastic lineages
- blasts in PB and BM
- and presence of RS
Note: the lineages with cytopenias are NOT necessarily the ones that contain dysplasia.
What has been observed regarding greater
% of blasts in the PB vs. BM ?
- in cases with more % blasts in PB (~13% of all MDS) compared to the BM
- those cases tend to act more aggressively
What is a general rule in making the diagnosis
of MDS ?
- cannot make the diagnosis without a detailed medication and drug history
- no case of MDS should be re-classified in a patient on growth factor therapy, including erythropoietin
What are things that can cause a clinical
and morphologic picture of MDS ?
- drugs
- infections
- autoimmune disorders
- metabolic deficiencies
What are the criteria for call a lineage dysplastic ?
- generally >10% of the precursor cells for erythroid and myeloid lineages
- >10% of megakaryocytes and must evaluate at least 30 megas
- some advocate for a threshold of 30-40% for dysplasia in megas
IMP: for cases with single lineage dysplasia, erythroids are usually the lineage that is dysplastic
What drug can cause ring sideroblast
formation ?
- Isoniazole
- it does this in the absence of vitamin B6 supplementation
Which medications can lead to
marked neutrophil hyposegmentation ?
- cotrimoxazole (antibiotic)
- immunosuppresants
- tacrolimus
- mycophenolate mofetil
- also can lead to erythroblastopenia
Which medical conditions can
clinically mimic MDS ?
- hypothyroidism
- infections
- autoimmune diseases
- PNH
- bone marrow lymphomatous involvement
- particularly LGL and Hairy cell leukemia
What is a feature on bone marrow biopsy
core of aggressive MDS ?
- Abnormal localization of immature precursors
- aggregates (3-5 cells) or clusters (>5 cells)
- they are usually localized in the center of the bone and away from bony trabeculae
What are some features that help differentiate
hypoplastic MDS from aplastic anemia ?
- dysplasia (most often in the megakaryocytes)
- increased blasts identified by CD34 stain
- abnormal karyotype
- most often trisomy 8
- although this can occasionally be seen in aplastic anemias
- most often trisomy 8
IMP: MDS-associated somatic mutations have been reported in as many as 1/3 of aplastic anemia patients
What must be excluded when considering
a diagnosis of hypoplastic MDS ?
- must exclude marrow injury due to a toxin, infection or autimmune disorder
What marrow finding, independent of the blast count,
indicates an aggressive clinical course in MDS?
- significant degrees of myelofibrosis (grade 2-3)
- seen in ~10-15% of MDS cases
- not a significant subtype but these patients tend to do worse
- blast counts may not be accurate due to significant fibrosis and hemodilute aspirates
- unlike PMF, MDS with fibrosis is NOT associated with splenomegaly, leukoerythroblastosis or intrasinusoidal hematopoiesis
What are the immunophenotypic changes in
the myeloids in MDS ?
- abnormal or asynchronous maturation patterns
- asynchrony of CD15 and CD16 in granulocytes
- altered expression of CD13 in relation to CD11b or CD16
- aberrant expression of CD7 or CD56 on:
- progenitors
- granulocytes
- monocytes
Note: also will have decreased hematogones in MDS
What are the immunophenotypic findings
of erythroids in MDS ?
- increased coefficient of variation
- decreased intensity of CD71 or CD36 expression
What is loss of 17p associated with ?
- MDS or AML with pseudo-Pelger Huet anomaly
- vacuolated, small neutrophils
- TP53 mutation
- unfavorable clinical course
- most common in therapy related MDS
What is usually seen in a complex
karyotype and what is the prognosis ?
- by definition >3 abnormalities
- usually have abnormalities in:
- chromosome 5 and or 7
- del 5q or t5q or loss of chromosome 7 or del 7q
- chromosome 5 and or 7
- generally associated with a poor clinical course
What are the morphologic
correlates for del 20q ?
- dysmegakaryopoiesis
- thrombocytopenia
What are the morphologic
correlates in inv(3) or t(3;3) ?
- abnormal megakaryocytes
- thrombocytosis
What clonal cytogenetic abnormalities
when present alone do NOT suffice for
a diagnosis of MDS ?
- loss of Y chromosome
- gain of chromosome 8
- del 20q
Note:
- these can be seen in other conditions. If no morphologic defining critieria then these do not count.
