Basics of malignant haematology

Question 1

What happens in haematological malignancy?

Answer 1

In haematological malignancy, there is a combination of increased numbers of abnormal and dysfunctional cells,

These dysfunctions are a loss of normal activity such as haemopoiesis and immune function

Question 2

What are the main mechanisms of malignant haematology?

Answer 2

• Increased proliferation
• Lack of differentiation/maturation
• Lack of apoptosis

Question 3

What is meant by acute haematological malignancy?

Answer 3

Acute malignancy involves the proliferation of abnormal progenitors with a block in differentiation or maturation

This leads to build up of abnormal progenitors within the bone marrow

Question 4

What is meant by chronic haematological malignancy?

Answer 4

Chronic malignancy involves the proliferation of abnormal progenitors, but no differentiation/maturation block

This leads to release of abnormal mature cells instead of build up in the marrow, which can crowd out normal blood cells

Question 5

Which class (Acute or chronic) presents most commonly with pancytopenia?

Answer 5

Acute

Question 6

How do haematological malignancies occur?

Answer 6

They follow the double hit hypothesis, so there is usually a genetic hit, followed by a another environmental or epigenetic hit

Question 7

What are some pieces of evidence for the double hit hypothesis in haematological malignancy?

Answer 7

• Identical twins, one of which developed cancer at 5 years old while the other never did (Shows not just genetic mutations to blame)
• Haematological malignancies can be traced back to heel prick blood samples (Guthrie cards) taken at birth, so must be a genetic aspect, but not fully
• 10% of those over 60 will have mutations that have been classified as causes of malignancy, but will not have the condition, supporting the claim of a multiple hit theory

Question 8

What are driver mutations?

Answer 8

Driver mutations are mutations that provide a selective growth advantage and therefore promote cancer development

Question 9

What are passenger mutations?

Answer 9

Passenger mutations do not provide a growth advantage

Question 10

What is a clone?

Answer 10

A clone is a population of cells that are derived from a single cell

Question 11

How can driver mutations cause malignancy?

Answer 11

A selective pressure can cause division of the cells containing driver mutations over those without

These cells will then pass on the driver mutation to the clones

Clones can diversify, but contain a similar genetic backbone, so will be monoclonal (Normal is polyclonal)

Question 12

What are the 5 main ways in which haematological malignancies can be classified?

Answer 12

• Anatomical site
• Lineage
• Compartment of haemopoietic tree
• Histology
• Pathophysiology

Question 13

What are the 2 main anatomical sites in malignant haematology?

Answer 13

1. Blood and bone marrow
2. Lymph nodes and other tissue

Question 14

What is a cancer of the blood and bone marrow called?

Answer 14

Leukaemia

Question 15

What is a cancer of the lymph nodes and other tissue sites known as?

Answer 15

Lymphoma

Question 16

What are the 2 main blood cell lineages?

Answer 16

Lymphoid lineage
Myeloid lineage

Question 17

What are the 2 main compartments of the haematopoietic tree?

Answer 17

Primitive compartment - Progenitors and stem cells

Less-primitive compartment - Blasts and mature cells

Question 18

What is the name given to a cancer of the primitive compartment?

Answer 18

Blastic

Question 19

What is the name given to a cancer affecting the less-primitive compartment?

Answer 19

Cystic

Question 20

What is meant by high or low grade?

Answer 20

This refers to the cancers activity and how dysplastic the cells are

Question 21

What are some histological features of aggression in cancer?

Answer 21

• Large cells with high nuclear-cytoplasmic ratio
• Prominent nucleoli
• Rapid proliferation

Question 22

What is a clinical sign of aggression of a cancer?

Answer 22

Rapid progression of symptoms

Question 23

What are some of the more aggressive haematological cancers?

Answer 23

Acute leukaemias
High-grade lymphomas

Question 24

What would tumour marker MPO (Myeloperoxidase) show the presence of?

Answer 24

Myeloid cells

Question 25

What would tumour markers CD19 and CD20 show the presence of?

Answer 25

B-lymphocytes

Question 26

What would tumour marker CD3 show the presence of?

Answer 26

T-lymphocytes

Question 27

What would tumour markers CD34 and tdt show the presence of?

Answer 27

Primitive compartment cells