Myeloproliferative Neoplasm

Question 1

Define myeloproliferative neoplasm

Answer 1

Clonal haemopoietic stem cell disorders which an increased production of one or more types of haemopoietic cells

Question 2

How is MDN different to leukaemia?

Answer 2

Results in overproduction of mature differentiated cells

Question 3

Describe the appearance of acute leukaemia microscopically

Answer 3

Monomorphic appearance with large cells and big nuclei - primitive cells

Question 4

Describe the appearance of MPN microscopically

Answer 4

Lots of nucleated cells - hypercellular, variety of cells at different stages of maturation

Question 5

Name the two subtypes of MPN

Answer 5

BCR ABL 1 positive

BCR ABL 1 negative

Question 6

What disease is BCR ABL 1 positive?

Answer 6

Chronic myeloid leukaemia - overproduction of granulocytes

Question 7

What diseases are BCR ABL 1 negative?

Answer 7

Polycythaemia vera
Essential thrombocytopenia
Primary myelofibrosis

Question 8

What blood results would suggest MPN?

Answer 8

High granulocyte count 
High red cell count/Hb
High platelets 
Eosinophilia/Basophilia 
Splenomegaly 
Thrombosis in unusual place

Question 9

What is chronic myeloid leukaemia?

Answer 9

Proliferation of myeloid cells

Question 10

Name the phases of chronic myeloid leukaemia

Answer 10

Chronic
Accelerated
Blast

Question 11

Describe the chronic phase of CML

Answer 11

Predominantly mature cells - intact maturation followed by a blast crisis similar to acute leukaemia with maturation defect

Question 12

Describe the accelerated phase of CML

Answer 12

Transition phase, high proportion of less mature cells

Question 13

State the clinical features of CML

Answer 13

Asymptomatic 
Splenomegaly (LUQ discomfort, early satiety) 
Hypermetabolic syndrome 
Gout 
Priapism - hyperleukocytosis

Question 14

Name the investigations done in CML

Answer 14

Blood count and film
Bone marrow sample
Philadelphia chromosome

Question 15

Describe the blood film in CML

Answer 15

Normal/reduced Hb, leukocytosis with neutrophilia

Myeloid precursors, eosinophilia, basophilia, thrombocytosis

Question 16

What will a bone marrow sample in CML look like?

Answer 16

Increased cellularity

Increased granulocytes

Question 17

What is the philadelphia chromosome?

Answer 17

Translocation chromosome

Results in fusion of ABL gene and BCR gene on chromosome 11 - tyrosine kinase which causes abnormal phosphorylation

Question 18

How is CML treated?

Answer 18

Tyrosine Kinase Inhibitor

Question 19

What are the common features of BCR ABL 1 negative MPNs?

Answer 19

Asymptomatic 
Increased cellular turnover - gout, fatigue, weight loss, sweats
Splenomegaly 
Marrow failure 
Thrombosis 
Erythromelagia

Question 20

What is erythromelagia?

Answer 20

Pain in hands and feet due to microvascular occlusion

Question 21

What is polycythaemia vera?

Answer 21

MPN characterised by high Hb and haematocrit accompanied by erythrocytosis

Question 22

Describe the difference between a true and pseudo polycythaemia

Answer 22

True - increase in proportion of red cells

Pseudo - normal red cells but reduced plasma volume causes increased Hct

Question 23

What causes secondary polycythaemia?

Answer 23

Hypoxia
Smoking
Tumours - erythropoietin secreting

Question 24

What causes pseudopolycythaemia?

Answer 24

Dehydration
Obesity
Diuretics

Question 25

State the features of polycythaemia vera

Answer 25

Headache Fatigue Itch - aquagenic puritis

Question 26

How is polycythaemia vera investigated?

Answer 26

FBC, blood film, look for secondary cause | JAK2 mutation - results in loss of auto-inhibition activation of erythropoiesis in the absence of ligand

Question 27

How is JAK2 mutation identified?

Answer 27

Genetic analysis of peripheral blood

Question 28

Describe the treatment of polycythaemia vera

Answer 28

Prevent thrombosis - venesect to haematocrit - aspirin Cytotoxic chemotherapy

Question 29

What is essential thrombocythaemia?

Answer 29

Over production of abnormal platelets

Question 30

Why can essential thrombocythaemia cause bleeding?

Answer 30

Acquired Von Willebrand disease - vWF absorbed onto the surface of abnormal platelets and reduces expression

Question 31

Name the clinical features of essential thrombocythaemia

Answer 31

Vaso-occlusive complications | Bleeding

Question 32

What diseases can present like essential thrombocythaemia?

Answer 32

CML | Reactive thrombocytosis

Question 33

How do you investigate essential thrombocythaemia?

Answer 33

Genetics - JAK2, CALR, MPL | Bone marrow - increased and abnormal megakaryocytes

Question 34

How is essential thrombocythaemia treated?

Answer 34

Anti-platelet aspirin Cytoreductive therapy to control proliferation - - hydroxycarbamide, IFN alpha

Question 35

State the characteristics of myelofibrosis

Answer 35

``` Marrow failure Bone marrow fibrosis Extramedullary hematopoiesis Leukoerythroblastic film Teardrop RBC ```

Question 36

What are the clinical features of myelofibrosis?

Answer 36

Marrow failure Splenomegaly Hypercatabolism

Question 37

How is myelofibrosis diagnosed?

Answer 37

Blood film Dry aspirate/trephine biopsy Genetics

Question 38

What classical RBC shape is seen on blood film?

Answer 38

Poikilocytes teardrop RBC in peripheral blood

Question 39

What is leukcoerythroblastic film?

Answer 39

Presence of neutrophil and red cell precursors in the peripheral blood

Question 40

What causes leukcoerythroblastic film?

Answer 40

Reactive - sepsis Marrow infiltration Myelofibrosis

Question 41

What will a trephine biopsy of myelofibrosis show?

Answer 41

Loss of fat spaces and dense network of reticulin fibres

Question 42

How is myelofibrosis treated?

Answer 42

Supportive - transfusion, antibiotics Allogenic stem cell transplant - potentially curable Splenectomy JAK 2 inhibitor