Week- concepts of malignancy in haematology Flashcards

1
Q

What is the only cell that comes from both myeloid and lymphoid lineage?

A

Dendritic cells.

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2
Q

How can you identify more mature cells in the blood (methods)?

A

Can look at morphology- e.g. structure of the nucleus, things in the cytoplasm etc. Cell surface antigens e.g. glycophorin A- for red cells Enzyme expression-e.g. myeloperoxidase inhibitors= neutrophils

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3
Q

Which colour granules do eosinophils have?

A

Red granules

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4
Q

Which colour granules do neutrophils have?

A

Blue granules.

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5
Q

What do neutrophils look line under a microscope?

A

Multisegmented nucleus

Blue granules

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6
Q

What do eosinophils look like under the microscope?

A

Red granules.

Bilobed nucleus.

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7
Q

How can we identify normal stem cells/progenitor cells?

A

Cell surface antigens (immunophenotyping)

Cell culture assays and animal models (not routinely used)

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8
Q

What occurs in malignant haemopoeisis?

A

Usually characeterised by increased number of abnormal and dysfunctional cells and loss of normal activity.

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9
Q

What are the ways in which their can be increased numbers of abnormal and dysfunctional cells?

A

Increased proliferation

Lack of differentiation

Lack of maturation

Lack of apoptosis.

NOTE- dont need all of these characteristics to be considered malignant.

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10
Q

There are two scenarios in which malignancies can occur. Can you describe these in terms of myeloid leukaemias?

A

On the left-

There is proliferation of abnormal progenitors with a block in maturation (meanign you have lots of immature cells)

e.g. acute myeloid leukaemia.

On the right-

Proliferation of abnormal progenitors with no block in maturation (meaning you have lots of normal looking mature cells)

e.g. chronic myeloid leukaemias

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11
Q

This is what normal bone marrow looks like, how will someone with acute leukaemias marrow differ? (think of the cells present in acute myeloid leukaemia)

A

There will be lots of immature (therefore large) and not differentiated cells.

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12
Q

This is what normal bone marrow looks like, how will someone with chronic leukaemias marrow differ? (think of the cells present in acute myeloid leukaemia)

A

There will be lots of cells present like in acute ones, however also there will be mature cells (e.g. neutrophils as seen in this slide).

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13
Q

What causes haematological malignancies?

A

Genetics

Somatic mutations in regulatory genes (driver genes- mutations in genes that control growth).

Recurrent cytogenetic abnormalities (e.g. deletions, chromosonal translocations). They are not causative however do contribute.

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14
Q

What is meant by the term clones?

A

A population of cells derived from a single parent cell.

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15
Q

How is normal haemopoeisis described in terms of ‘clones’?

A

Polyclonal- coming from several cells.

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16
Q

How is malignant haemopoesis described in terms of clones?

A

Monoclonal- derived from one cell.

NOTE- means that in malignancy, you tend to just see proliferation of one cell type whereas in normal haemopoesis you see lots of cell types.

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17
Q

What is meant by a driver mutation?

A

A mutation in a gene that provides a selective growth advantage.

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18
Q

What is meant by passenger mutations?

A

These are mutations that do not confer a selective growth advantage. However they will be present in cancers.

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19
Q

NOTE-

Acquiring cancer-

As you grow up you acquire passenger mutations. These do not affect cell growth and therefore do not cause cancer (as cancer is uncontrolled cell growth). However as soon as you acquire a driver mutation (these affect cell growth) it becomes problematic. You can get uncontrolled proliferation, lack of apoptosis, lack of maturation or differentiaion due to these.

A
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20
Q

NOTE-

Acute lymphoblastic leukaemia- they looked at a child of age 10 who had this disease, and then looked back at her Guthrie card to see if the mutation was present at birth. They found that it was, therefore the initial ‘hit’ was present at birth, however more mutations were acquired throughout life making the child acquire the cancer.

NOTE- driver mutations are present frequently BUT only some go on to confer cancer.

A
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21
Q

How can haematological malignancies be categorised?

A

Based on cell lineage

Based on developmental stage

Based on anatomical site involved.

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22
Q

If the malignancy is based on cell lineage, what can the cells be?

A

Either myeloid or lymphoid.

NOTE- lymphoid means lymphocytes so B cells, T cells, NK cells, dendritic cells

Myeloid means it could be RBCs, granulocytes or dendritic cells.

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23
Q

If the cell involved is primitive, what can it be called? Use the example of a lymphocytic malignancy?

A

Lymphoblastic (blast means immature)

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24
Q

If the cell involved is mature, what can it be called? Use the example of a lymphocytic malignancy?

A

Lymphocytic

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25
Q

If the blood is involved, what is the term used?

A

Leukaemia.

26
Q

If the lymph nodes are involved, what is the term used?

A

Lymphoma.

27
Q

What is a myeloma?

A

A plasma cell malignancy in the bone marrow.

28
Q

NOTE-

Chronic lymphocytic leukaemia- involves both the blood and the lymph nodes. This is because it affects mature lymphocytes e.g. T cells and B cells, which reside in the blood and lymph nodes.

A
29
Q

How do acute leukaemias and high grade lymphomas differ from chronic leukaemias and low grade lymphomas?

A

They are histologically and usually clinically more aggressive.

30
Q

What are the features of histological aggression?

A

Large cells with high nuclear: cytoplasmic ratio (nucleus occupies a large proportion of the cell), prominent nucleoli (shows high RNA turnover), rapid proliferation.

31
Q

What are the features of clinical aggression?

A

Rapid progression of symptoms.

32
Q

Using the terms we’ve discussed, describe what acute myeloid leukamia is?

A

Agressive cancer involving cells of myeloid lineage. Also involves the blood/bone marrow.

33
Q

Using the terms we’ve discussed, describe what acute lymphoblastic leukamia is?

A

Aggressive cancer affective primitive cells of the lymphoid lineage. Also involves the blood and lymph nodes.

34
Q

Using the terms we’ve discussed, describe what chronic myeloid leukamia is?

A

Mature cells of myeloid lineage, less aggressive cancer. Involving blood and bone marrow.

35
Q

Using the terms we’ve discussed, describe what chronic lymphocytic leukamia is?

A

Less aggressive cancer involing mature lymphoid cells. Affecting both blood and bone marrow.

36
Q

Describe acute leukaemia?

A

Rapidly progressing defect of the bone marrow/blood with maturation defects.

Defined as excess of blasts (>20%) within the peripheral blood or bone marrow.

Decrease/loss of normal haemopoetic reserve (this means due to the block in maturation, the normal red cells, platelets and neutrophils do not appear)

37
Q

What are the two types of acute leukaemia?

A

Acute myeloid leukaemia (AML)

Acute lymphoblastic leukaemia (ALL)

38
Q

What is acute lymphoblastic leukaemia?

How common is it?

A

Malignancy of the primitive lymphoid cells that is aggressive, affecting the blood and bone marrow.
This is the most common childhood cancer.

39
Q

How does acute lymphoblastic leukaemia clinically present?

A

Generally presents with symptoms due to marrow failure e.g. anaemia, infections, bleeding.

Bone pain

Tends to involve areas outwith the bone marrow e.g. CNS and testis.

40
Q

Who commonly gets acute myeloid leukaemia?

A

Tends to be the elderly (>60s)

41
Q

How does acute myeloid leukaemia present?

A

Tends to present similarly to ALL- with marrow failure. Therefore infections, anaemia, bleeding. Bone pain

Certain subtypes present quite characteristically- e.g. disseminated intravascular coagulation or gum infiltrations.

42
Q

Acute myeloid leukaemia can either be ‘de novo’ or secondary to other things. What is it commonly secondary too?

A

Pre-existing haematological disease.

43
Q

How would you investigate acute leukaemias?

A

Start simple with an FBC and blood film.

Then do a coagulation screen- because some are associated with coagulation deficits.

Bone marrow aspirate- look at the morphology of the cells

Then use immunophenotyping to distinguish between myeloid and lymphoid lineage.

44
Q

What will a blood film in acute leukaemia show?

A

Lots of immature cells. Loss of normal components of bone marrow.

Auer rod- associated with acute myeloid leukaemias.

45
Q

Which test gives you a definative diagnosis in acute leukaemias?

A

Immunophenotyping- allows you to distinguish between the two types because of the presence of proteins.

46
Q

Why is cytogenetics important in acute leukaemias?

A

It can give you an indication on prognosis.

47
Q

Generally, how would you treat acute leukaemias?

A

Chemotherapy

48
Q

How would you treat acute myeloid leukaemia?

A

Intensive chemotherapy treatment. Usually consisting of 2-4 cycles. Prolonged hospitalisation.

49
Q

How would you treat acute lymphoblastic leukaemia?

A

Can last up to 2-3 years. You use different phases of treatment with varying intensity. Targeted treatments are used in certain subsets.

50
Q

What sort of line is chemotherapy delivered through?

A

Hickman line- goes straight into the left jugular vein.

51
Q

When doing chemotherapy, you suppress the bone marrow. What are some problems that are associated with this?

A

Anaemia

Neutropenia

Infections- gram negative are the ones to be worried about.

Thrombocytopenia- bleeding, purpura, petechiae.

52
Q

If someone with neutropenia has a fever, what is the immediate management?

A

Give brisk broad spectrum antibiotics mainly targeting gram negative bacteria.

53
Q

Why are gram negative bacteria so dangerous in someone with neutropenia?

A

Can cause fulimant life threatining sepsis in patients with neutropenia.

54
Q

What are some side effects associated with chemotherapy treatment?

A

Nausea and vomiting

Hair loss

Liver and renal dysfunction

Tumour lysis syndrome (occurs during 1st course of treatment)

Infection- likely to be fungal if prolonged fever unresponsive to antibiotics.

Late effects- e.g. loss of fertility, cardiomyopathy.

55
Q

NOTE- is treatment worth the effort?

Many patients will go into remission. However often patients relapse. Some patients also die of treatment associated toxicity.

A
56
Q

Childhood ALL cure rates?

A

85-90%

57
Q

Adult ALL cure rates?

A

30-40%

58
Q

Adult AML (~60) cure rates?

A

40-50%

59
Q

Adult AML >60 cure rates?

A

10%.

60
Q

Are there any other options for treating leukaemias other than chemotherapy?

A

Targeted treatments e.g. molecular treatments

Allogeneic stem cell transplantation.