Myelodysplastic Syndrome

Question 1

MDS definition

Answer 1

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

Question 2

T or F. recurrent cytogenetic abnormalities are present in 40-50% of MDS patients

Answer 2

T, majority comes from acquired somatic gene mutations

Question 3

MDS WHO Classification

Answer 3

• # of cytopenies
• # of myeloid lineades showing dysplasia
• presence of ringed sideroblasts
• blast % in PB and BM
• isolated del (5q), a recurrent cytogenetic abnormality

Question 4

T or F. MDS in children is very common

Answer 4

F! rare; unique characteristics and diagnostic criteria that differ from those of MDS in adults

Question 5

majority of MDS patients present with this

Answer 5

symptoms related to cytopenia - most commonly anemia with 1/3 patients dependent in RBC transfusion

Question 6

besides anemia, clinical presentation of MDS

Answer 6

• presentation secondary to neutropenia, or thrombocytopenia less common
• infrequently = organomegaly

Question 7

some dysplastic features, such as these are strongly associated with MDS

Answer 7

micromegakaryocytes

Question 8

assessing dysplasia in BM

Answer 8

200 erythroid precursors, 200 neuts and precursors and 30 megs asessed

Question 9

Dysgranulopoiesis

Answer 9

• pseudo-Pelger Huet
• apo or hypogranulation of cytoplasm
• clumped chromatin
• macrocytosis
• N:C asynchrony

Question 10

Dyserythropoiesis

Answer 10

• nuclear bridging
• cytoplasmic granulation
• multiple nuclei
• nuclear lobulation
• macrocytic/megaloblastic chnges

Question 11

Dysmegakaryopoiesis

Answer 11

• separated single nuclei
• micromegakarycyte
• small binucleated megakaryocyte
• round, non-lobulated megakaryocyte

Question 12

T or F. PAS is positive in dyserythropoiesis

Answer 12

T!

Question 13

other diagnoses for dyserythropoiesis other than MDS

Answer 13

• congenital dyserythropoietic anemia (isolated dyserythro…)
• parvovirus B19 = erythroblastopenia with giant pronormoblasts
• MMF ( erythroblastopenia)

Question 14

this may result in transient marked dysplasia of all myeloid lineages

Answer 14

chemotherapeutics

Question 15

G-SF (granulocyte colony stimulating factor) therapy causes…

Answer 15

left shift, marked hypergranularity, and nuclear hyposegmentation

Question 16

what are micromegakaryocytes?

Answer 16

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

Question 17

normal megs

Answer 17

• uninuclear

- with lobated nuclei

Question 18

MDS with SLD

Answer 18

• unexplained cytopenia
• > /= to 10% dysplastic cells in one lineage
• majority = refractory anemia or bicytopenia
• Del(20q)
• gain of chromosome 8
• chromosome 5&7 abnormalities

Question 19

MDS with RS

Answer 19

• must exclude 2ry cause of ringed sideroblasts
• typically anemia
• SF3B1 mutation

Question 20

erythroid precursors w abnormal accumulation of iron within mitochondria, including some iron deposited as mitochondrial ferritin

Answer 20

ringed sideroblasts

Question 21

MDS-RS morphology

Answer 21

• 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

Question 22

iron-stained aspirate of MDS-RS

Answer 22

15% or greater

UNLESS SF3B1 is confirmed, then 5%

Question 23

MDS-RS trephine

Answer 23

normocellular to markedly hypercellular, marked erythroid proliferation
- megs normal

Question 24

MDS-MLD cytogenetics

Answer 24

• trisomy 8, monosomy 7, del(7q), monosomy 5, del(5q)

Question 25

MDS-MLD molecular

Answer 25

• STAG2
• ASXL1
• SRSF2
• RUNX1
• CBL
• TP53
• TET2

Question 26

MDS-MLD peripheral blood findings

Answer 26

• anisopoikilocytosis with macrocytosis

- neuts may show nuclear clumping + hyposegmentation or lack of lobulation

Question 27

MDS-MLD BM findings

Answer 27

• 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

Question 28

MDS-EB

Answer 28

• MDS-EB-1 = 5-9% blasts in BM and 2-4% in PB

- MDS-EB-2 = 10-19% in BM, 5-19% in PB

Question 29

T or F. The presence of auer rods = MDS-EB-1

Answer 29

F! MDS-EB-2 irrespective of blast percentage

Question 30

blasts tend to form aggregates in this MDS

Answer 30

MDS-EB (CD34 is helpful)

Question 31

MDS-DEL(5Q)

Answer 31

may occur in isolation or with one other cytogenetic abnormality except monosomy 7 or del(7q)

Question 32

etiology of MDS-DEL(5Q)

Answer 32

the presumed loss of tumour suppressor genes in the minimally deleted region (5q33.1)

Question 33

MDS-DEL(5Q) PB findings

Answer 33

macrocytosis with or without thrombocytosis

if pancytopenia = MDS, unclassifiable

Question 34

MDS-DEL(5Q) BM findings

Answer 34

• hypercellular or normocellular
• erythroid HYPOplasia
• dyserythro… less pronounced

Question 35

tool used to detect del(5q)

Answer 35

FISH analysis

Question 36

TP53 mutation

Answer 36

present in a significant subset of MDS-DEL(5Q); associated with increased AML transformation, inferior therapeutic response and shorter survival