Myelodysplastic Syndrome Flashcards
MDS definition
group of clonal hematopoetic stem cell diseases characterized by:
cytopenia,
dysplasia in one or more of the major myeloid lineages,
ineffective hematopoiesis,
recurrent genetic abnormalities and
increase risk of developing AML
T or F. recurrent cytogenetic abnormalities are present in 40-50% of MDS patients
T, majority comes from acquired somatic gene mutations
MDS WHO Classification
- # of cytopenies
- # of myeloid lineades showing dysplasia
- presence of ringed sideroblasts
- blast % in PB and BM
- isolated del (5q), a recurrent cytogenetic abnormality
T or F. MDS in children is very common
F! rare; unique characteristics and diagnostic criteria that differ from those of MDS in adults
majority of MDS patients present with this
symptoms related to cytopenia - most commonly anemia with 1/3 patients dependent in RBC transfusion
besides anemia, clinical presentation of MDS
- presentation secondary to neutropenia, or thrombocytopenia less common
- infrequently = organomegaly
some dysplastic features, such as these are strongly associated with MDS
micromegakaryocytes
assessing dysplasia in BM
200 erythroid precursors, 200 neuts and precursors and 30 megs asessed
Dysgranulopoiesis
- pseudo-Pelger Huet
- apo or hypogranulation of cytoplasm
- clumped chromatin
- macrocytosis
- N:C asynchrony
Dyserythropoiesis
- nuclear bridging
- cytoplasmic granulation
- multiple nuclei
- nuclear lobulation
- macrocytic/megaloblastic chnges
Dysmegakaryopoiesis
- separated single nuclei
- micromegakarycyte
- small binucleated megakaryocyte
- round, non-lobulated megakaryocyte
T or F. PAS is positive in dyserythropoiesis
T!
other diagnoses for dyserythropoiesis other than MDS
- congenital dyserythropoietic anemia (isolated dyserythro…)
- parvovirus B19 = erythroblastopenia with giant pronormoblasts
- MMF ( erythroblastopenia)
this may result in transient marked dysplasia of all myeloid lineages
chemotherapeutics
G-SF (granulocyte colony stimulating factor) therapy causes…
left shift, marked hypergranularity, and nuclear hyposegmentation
what are micromegakaryocytes?
megs that are approximately the size of a promyelocyte or smaller, with a non-lobated or bi-lobated nucleus
- the most reliable and reproducible dysplastic feature of the megakaryocytic lineage
normal megs
- uninuclear
- with lobated nuclei
MDS with SLD
- unexplained cytopenia
- > /= to 10% dysplastic cells in one lineage
- majority = refractory anemia or bicytopenia
- Del(20q)
- gain of chromosome 8
- chromosome 5&7 abnormalities
MDS with RS
- must exclude 2ry cause of ringed sideroblasts
- typically anemia
- SF3B1 mutation
erythroid precursors w abnormal accumulation of iron within mitochondria, including some iron deposited as mitochondrial ferritin
ringed sideroblasts
MDS-RS morphology
- ringed sideroblasts
- PB = normochromic, macrocytic/normocytic anemia
- may see dimorphic red cells
- BM = increase in erythroid dysplasia (megaloblastoid features and nuclear segmentation)
- hemosiderin-laden macs are often abundant
iron-stained aspirate of MDS-RS
15% or greater
UNLESS SF3B1 is confirmed, then 5%
MDS-RS trephine
normocellular to markedly hypercellular, marked erythroid proliferation
- megs normal
MDS-MLD cytogenetics
- trisomy 8, monosomy 7, del(7q), monosomy 5, del(5q)
MDS-MLD molecular
- STAG2
- ASXL1
- SRSF2
- RUNX1
- CBL
- TP53
- TET2
MDS-MLD peripheral blood findings
- anisopoikilocytosis with macrocytosis
- neuts may show nuclear clumping + hyposegmentation or lack of lobulation
MDS-MLD BM findings
- normo- or hypercellular
- erythroid precursors increased
> vacuoles, marked nuclear irregularity, internuclear chromatin bridging, multilobulated, nuclear budding, multinucleating and megaloblastic nuclei - may or may not be BM fibrosis
MDS-EB
- MDS-EB-1 = 5-9% blasts in BM and 2-4% in PB
- MDS-EB-2 = 10-19% in BM, 5-19% in PB
T or F. The presence of auer rods = MDS-EB-1
F! MDS-EB-2 irrespective of blast percentage
blasts tend to form aggregates in this MDS
MDS-EB (CD34 is helpful)
MDS-DEL(5Q)
may occur in isolation or with one other cytogenetic abnormality except monosomy 7 or del(7q)
etiology of MDS-DEL(5Q)
the presumed loss of tumour suppressor genes in the minimally deleted region (5q33.1)
MDS-DEL(5Q) PB findings
macrocytosis with or without thrombocytosis
if pancytopenia = MDS, unclassifiable
MDS-DEL(5Q) BM findings
- hypercellular or normocellular
- erythroid HYPOplasia
- dyserythro… less pronounced
tool used to detect del(5q)
FISH analysis
TP53 mutation
present in a significant subset of MDS-DEL(5Q); associated with increased AML transformation, inferior therapeutic response and shorter survival
