Specific MDS Categories Flashcards
What is the definition of MDS
with single lineage dysplasia ?
- single lineage dysplasia (>10% of dysplastic cells)
- usually cytopenia (anemia) or bicytopenia
- can have neutropenia with thrombocytopenia
Note: the lineage with dysplasia and which cytopenias are present should be identified in the report
How should cases with unknown SF3B1 mutation status and
5-14% RS be classified and single lineage dysplasia ?
- MDS with single lineage dysplasia
In what situation would a patient be observed
for 6 months prior to rendering a diagnosis
of MDS-SLD ?
- if there is SLD and cytopenias but NO clonal abnormality
IMP: all non-clonal causes must first be excluded prior to rendering this diagnosis.
Which supplement has been implicated
with severe cytopenias and dysplastic changes ?
- Zinc supplementation
What essentially excludes the diagnosis
of MDS-SLD?
- presence of peripheral blood blasts
- occasionally rare blasts may be seen (<1%)
- If
- 1% blasts on peripheral blood on 2 successive occasions
- <5% blasts in the bone marrow
- this should be diagnosed as MDS-U due to the more aggressive clinical course
What entities should be investigated for
persistent neutropenia or thrombocytopenia ?
- these are significantly less common than anemia in the general population
- exclude:
- Familial occurrence
- comorbid conditions like immune disorders, T-LGL leukemia
- viral infection
- medications
What is the epidemiology of
MDS-SLD ?
- accounts for up to 20% of cases
- generally older adults with no sex predilection
- generally present with symptoms of the cytopenia they have
Review microscopic section pg. 108-109.
What cytogenetic abnormalities
have been more frequently described in
MDS-SLD ?
- del 20q
- gain of chromosome 8
- abnormalities in chromosome 5 and 7
What 2 genes tend to be
mutated in MDS-SLD ?
- most commonly mutated (but not specific)
- TET2
- ASXL1
IMP: SF3B1 mutation is rare
What is the prognosis of patients
with MDS-SLD ?
- median survival is ~66 months
- rate of progression to AML at 5 years - 10%
What is the definition of MDS-RS ?
- cytopenias, morphologic dysplasia and RS >15%
- or SF3B1 mutation and >5% RS
- BM blasts < 5%, PB blasts <1%, NO Auer rods
- Two Categories
- MDS-RS SLD:
- anemia and erythroid dysplasia
- MDS-RS MLD:
- any cytopenias and dysplasia in 2-3 lineages
- MDS-RS SLD:
What is the epidemiology of
MDS-RS ?
- MDS-RS SLD: 11% of MDS cases
- MDS-RS MLD: 13% of MDS cases
- older age group with similar frequency in M:F
Note: the liver and spleen may show evidence of iron overload
What is a ring sideroblast?
- erythroid precursor with abnormal accumulation of iron in the mitochondria
- some iron deposited as mitochondrial ferritin
Read microscopic findings pg. 109-110.
What are other causes of
ring sideroblasts ?
- alcohol
- toxins ( lead and benzene)
- drugs (isonizid)
- copper deficiency (which may be induced by zinc toxicity)
- congenital sideroblastic anemia
- tends to present at a much younger age
- patients have a microcytic anemia
Read genetic profile of MDS-RS p. 110.
What are the prognostic and predictive factors
for MDS-RS ?
- SLD: 1-2% of cases progress to AML
- OS: 69-108 months
- MLD: 8% progress to AML
- OS 28 months
IMP: in SF3B1 mutants MDS-RS cases, RUNX1 mutation associated with shorter survival.
What is the definition of MDS-MLD ?
- one or more cytopenias and dysplastic changes in 2 or more myeloid lineages
- BM blasts: <5%
- PB blasts: <1%
- No auer rods
- monocytes are < 1x10^9/L
What is the definition of
a micromegakaryocyte?
- they are the size of a promyelocyte or smaller
- non-lobated or bilobated nucleus
For classification purposes in MDS,
how should the % of blasts be determined ?
- based on microscopic differential on the aspirate smear
- should not be done based on the flow cytometry %
What is the prognosis for
patients with MDS-MLD?
- have similar mutation profiles to those with excess blasts and AML by whole genome sequencing.
- prognosis relates to karyotype and other mutations as well as blast % and dysplasia
- evolve to AML 15-28% at 2 and 5 years respectively
- median overall survival is 36 months
What is the definition of MDS-EB ?
in general:
- 5-19% blasts in BM
- 2-19% blasts in PB
- overall must be < 20% blasts
- Have EB-1 and EB-2
- EB-1
- 5-9% blasts in BM
- 2-4% blasts in PB
- No Auer rods
- EB-2
- Auer rods or
- 10-19% blasts in BM
- 5-19% blasts PB
- EB-1
What is the epidemiology of
MDS-EB ?
- accounts for ~40% of all MDS
- >50 year old patient
- etiology is unknown but exposures have been implicated:
- environmental toxins
- pesticides
- petroleum derivatives
- heave metals
- cigarette smoke
Review the microscopic findings
for MDS-EB on pg. 113-114.
The presence of what genetic findings
is associated with a poor prognosis
in MDS-EB ?
- high-risk (complex karyotype)
- mutations in :
- TP53
- RUNX1
- ASXL1
What entity can MDS-EB with myelofibrosis
overlap with clinically and morphologically ?
- Acute panmyelosis and fibrosis
- abruspt onset of fever and bone pain
- along with higher blast counts
Expression of what immunophenotypic
marker has been associated with
worse prognosis in MDS-EB ?
- CD7
How often do FLT3 and NPM1 occur
in MDS-EB?
- These are rare in MDS-EB but common in AML
- IF they are present these patients progress more quickly to AML
What is the prognosis of
MDS-EB ?
- tend to have progressive bone marrow failure with increased cytopenias
- 25-33% progress to AML (EB-1 and EB-2 respectively
- median survival: 16 months and 9 months respectively
What is the definition of
MDS with isolated del 5q ?
- anemia (with or without other cytopenias)
- may have thrombocytosis
- cytogenetics:
- del 5q
- may have another abnormality except for monosomy 7 or del 7q
- PB blasts <1%
- BM blasts <5%
- Auer rods are absent
What is the epidemiology and etiology
of MDS with del 5q ?
- occurs more often in women, median age 65
- etiology is a presumed loss of tumor suppressor genes or genes in the minimally deleted region of 5q33.1
Note: haploinsufficiency of additional genes on 5q (APC [another WNT pathway regulator] and EGR1) may also contribute to disease pathogenesis.
What are the clinical features of MDS del 5q ?
- often a severe, macrocytic anemia
- thrombocytosis is present in 1/3-1/2 of cases
- note: thrombocytopenia is uncommon
- pancytoepenia is rare
- IMP: if there is a del 5q but the patient has pancytopenia it is essential to classify this as MDS-U because the clinical behavior is uncertain.
What are the key microscopic findings of MDS del 5q ?
- erythroid hypoplasia is usually seen
- dysplasia in erythroid is less pronounced
- megakaryocytes
- increased to normal in number
- normal to slightly decreased in size
- non-lobated to hypolobated nuclei
- significant granulocytic dysplasia is not seen
- Ring sideroblasts can be present and do not exclude the diagnosis if all other features are identified
What is the cell of origin
in MDS del 5q ?
- hematopoietic stem cell
- FISH for del 5q shows the abnormality in differentiating erythroid, myeloid and megakaryocytic cells
- generally not seen in mature lymphoid cells
What are the genetics of MDS del 5q ?
- defining abnormality: interstitial deletion of chromosome 5
- size of the deletion and the breakpoints vary
- bands q31-q33 are invariably deleted
- another abnormality may be present with the exception of monosomy 7 or del 7q
- Note:
- a small subset of patients also show concomitant JAK2 V617F and MPL mutations
What are the prognostic and predictive factors
of MDS del5q ?
- 66-145 months with transformation to AML occurring in <10% of cases
- good prognosis
- significant granulocytic dypslasia has been associated with additional cytogenetic abnormalities and an inferior outcome
What is the available treatment for
MDS del 5q ?
- Lenalidomide (thalidomide analogue)
- promotes ubiquitin mediated degradation
What mutation should be evaluated for in MDS del 5q
and why is it important ?
- TP53 mutation
- present in a significant subset of cases and is associated with an increased risk of leukemic transformation
- predicts inferior response to lenalidomide
- predicts shorter survival
- recommended that TP53 be evaluated in every case of del 5q
What is the definition of MDS-U ?
- category of MDS that initially lack appropriate findings for classification into any other MDS category.
Read p. 116
