MDS

Question 1

Give a background of myelodysplasia

Answer 1

MDS is a group of clonal stem cell disorders which is characterised by cytopenia, dysplasia, ineffective haematopoiesis, recurrent genetic abnormalities and an increased risk of developing acute myeloid malignancies.
This leads to ineffective haematopoiesis due to increased apoptosis meaning that cells die inside the bone marrow space before entering the blood stream which results in cytopenias.

Question 2

What are the thresholds for cytopenia?

Answer 2

Hb<10g/dl
Neutropenias <1.8
Platelets of <100

Question 3

What are some cytogenetic abnormalities seen with MDS?

Answer 3

loss of chromosome 7
loss of chromosome Ycy
del 5q
isochromosome 17q
loss of chromosome 13
del 11q
del 12q

Question 4

Describe some morphological findings on the blood film of an MDS patients

Answer 4

Dysplasia in one or more myeloid lineages - erythroid, myeloid or granulocytic, >10% of all nucleated cells on the film, dysplasis usually accompanied by increase in blast percentage

Question 5

What are the subtypes of MDS?

Answer 5

Number of cytopenias
Number of myeloid lineages Manifesting dysplasia
Presence of ring-sideroblasts
Blast percentage in the blood and bone marrow

Question 6

What is the epidemiology of MDS?

Answer 6

It is a rare disease an incidence of about 3-4 per 100,000 population per year
Median age at diagnosis is 75
Classified under myeloid malignancies
Survival extremeley variable, ranges over 5 years to less than 6 months after diagnosis
Incidence rises with age - can progress to AML (30%)

Question 7

What is the aetiology of MDS?

Answer 7

Environmental exposure to benzene, chemicals, solvents, insecticides, pesticides and cigarette smoking
Treatment related
Family history of haematological neoplasm
Increased associated with inherited haematological disorders - fanconi anaemia, dyskeratosis congenita, down’s syndrome

Question 8

What is the clinical presentation of MDS?

Answer 8

Symptoms related to cytopenias:
Anaemia
Increased infection
Thrombocytopenia

Question 9

Describe some characteristic findings on the blood film of an MDS patient showing erythroid dysplasia

Answer 9

There is internucleur bridging, multinuclearity, nuclear alterations - budding, karyorrhexis, megaloblastoid changes

Ringed siderobasts - iron laden mitochondria as a perinuclear ring, vascuolisation, PAS positivity

Question 10

Describe some characteristic findings on the blood film of an MDS patient showing myeloid dysplasia

Answer 10

Pseudo Pelger-Huet anomaly - Nuclear hyposegmentation of while cells
or there is nuclear hypersegmentation!

Cytoplasmic gypogranularity - pseudo chediak-Higashi granules are giant autophagosomes

Presence of auer rods

Question 11

Describe some characteristic findings on the blood film of an MDS patient showing Megakaryocyte dysplasia

Answer 11

Megakaryocytes can be monolobated as opposed to multilobated

Megakaryocytes with separated nuclei

Question 12

Which cytogenetic abnormality is the most frequent? What is its prognosis?

Answer 12

del 5q
This is characterised by hypolobated/monolobated megakaryocytes, refractory macrocytic anaemia and normal/elevated platelet count

del Y- is also favourable
Favourable clinical course

Question 13

Which mutation is seen with ring sideroblasts?

Answer 13

SF3B1 - associated with presence of ring sideroblasts and this encodes for a protein required for maturation of 40S ribosomal subunits