Malignancy

Question 1

Which haematological malignancies are of bone marrow origin?

Answer 1

Acute leukaemia
Chronic lymphocytic leukaemia
Myeloproliferation
Myelodysplasia

Question 2

What happens in malignant haemopoiesis?

Answer 2

Malignant haemopoiesis is largely characterised by increased numbers of dysfunctional cells with loss of the normal haemopoietic reserve

Question 3

What is myeloma?

Answer 3

Plasma cell malignancy accumulating in the bone marrow

Question 4

What is acute leukaemia?

Answer 4

No or very little differentiation in mutated haemopoietic stem cells, resulting in immature or undifferentiated blasts in the bone marrow that have a huge proliferative capacity, causing them to eventually spill over into the blood
This overwhelms the other cells of the bone marrow and causes loss of haemopoietic reserve

Question 5

How can acute leukaemia be defined clinically?

Answer 5

20% or more blasts in either the peripheral blood or bone marrow

Question 6

What is the most common childhood cancer?

Answer 6

Acute lymphoblastic leukaemia

Question 7

What is acute lymphoblastic leukaemia (ALL)?

Answer 7

A malignant disease of lymphocytes, characterised by poorly differentiated cells or ‘blasts’ causing lots of proliferation of these mutated cells

Question 8

How might ALL present?

Answer 8

Marrow failure: anaemia, infections, bleeding
Bone pain
High WCC and involvement of extra-medullary areas e.g. CNS, lymph nodes sometimes causing venous obstruction

Question 9

In which age group does acute myeloid leukaemia (AML) present?

Answer 9

Elderly - >60

Question 10

How might AML present?

Answer 10

Marrow failure: anaemia, infections, bleeding
DIC
Gum infiltration

Question 11

What investigations should be done for acute leukaemia?

Answer 11

Blood film
Coagulation screen
Bone marrow aspirate

Question 12

What is looked for in bone marrow aspirate in acute leukaemia?

Answer 12

Morphology
Immunophenotype (looking for lineage specific proteins on the cell surface)
Cytogenetics

Question 13

What marker is present on the most common acute lymphoblastic leukaemia blast cells?

Answer 13

CD10

Question 14

How can acute lymphoblastic anaemia present?

Answer 14

Blast infiltration of other organs:

• lymphadenopathy
• hepatosplenomegaly
• CNS
• testes

Question 15

What markers tend to be present in adult ALL?

Answer 15

None - very primitive cell malignancy

Question 16

What haematological conditions might AML be associated with?

Answer 16

CML
Myeloproliferative disorders
Myelodysplastic disorders
Might be associated with chemotherapy for solid tumours

Question 17

How might AML present?

Answer 17

Bone marrow failure
Gum infiltration
Bleeding tendencies

Question 18

What can be seen on blood film with acute myeloblastic leukaemia in 30% of cases?

Answer 18

Auer rods

Question 19

What malignancy are auer rods associated with?

Answer 19

AML

Question 20

What type of CLL is most common (T or B cell)?

Answer 20

B cell (95%)

Question 21

What gender is more susceptible to CLL?

Answer 21

Men - diagnosed twice as much

Question 22

What age group tends to present with CLL?

Answer 22

> 60

Question 23

How does CLL cause lymphadenopathy and splenomegaly?

Answer 23

Small, mutated lymphocytes proliferate in the bone marrow and eventually some spill over into blood
This results in lymphocytosis, and migrate and seed in lymph nodes and in the liver and spleen

Question 24

How is the lymphadenopathy described in CLL?

Answer 24

‘Widespread’ and ‘rubbery’

Question 25

What immune disorders is CLL associated with??

Answer 25

Autoimmune - becuase of B cell dysregulation: AI haemolytic disease and thrombocytopenia Reduced immunity due to abnormal lymphocytes, causing repeated LRTI

Question 26

What will be seen on blood film in CLL?

Answer 26

Lymphocytosis Smear cells Marrow lymphocytic infiltration

Question 27

What are smear cells?

Answer 27

Abnormal lymphocytes that have been disrupted by the smearing process

Question 28

How is early disease CLL treated?

Answer 28

Watchful waiting - very indolent course

Question 29

What can happen in 5% of CLL?

Answer 29

Can transform into a high grade B cell lymphoma that is resistant to treatment

Question 30

Which region of the lymph node are B cells found in?

Answer 30

Cortex

Question 31

Which region of the lymph node are T cells found in?

Answer 31

Paracortex

Question 32

What occurs in the medulla?

Answer 32

The cords and sinuses come together to form the efferent lymphatic system where the lymph exits This is also where arteries and veins come in

Question 33

Where does afferent lymph come into the lymph node?

Answer 33

Through the capsule, and exits via medulla

Question 34

What are the germinal centres of the lymph nodes?

Answer 34

Areas where white cells are exposed to and primed with antigens

Question 35

What are the causes of lymph node enlargement?

Answer 35

Infection Inflammation (HIV/lupus) Malignancy

Question 36

What is the most common cause of follicular hyperplasia?

Answer 36

Prominent B cell activation | Most commonly HIV

Question 37

What can the causes of chronic inflammation of the lymph nodes be divided into?

Answer 37

Follicular hyperplasia (B cell activation) Paracortical (T cell) Granular (TB)

Question 38

What broad category accounts for 80% of all lymphoma?

Answer 38

Non-hodgkins lymphoma

Question 39

Which is more common: B cell or T cell lymphoma?

Answer 39

B cell

Question 40

Why are high grade lymphoma more curable?

Answer 40

Chemotherapy targets mutated cells during cell cycle - high grade proliferates lots

Question 41

What is Burkitt's lymphoma associated with?

Answer 41

EBV

Question 42

What are the high grade lymphomas?

Answer 42

Burkitt's lymphoma Diffuse large B-cell lymphoma Mantle cell lymphoma

Question 43

What are the low grade lymphomas?

Answer 43

Small lymphocytic lymphoma Follicular Marginal zone

Question 44

Where does diffuse large B cell lymphoma come from?

Answer 44

Mutation in the centroblast

Question 45

What are the symptoms of lymphoma?

Answer 45

Fever Night sweats Painful lymphadenopathy Infiltration in CNS, skin or GI tract

Question 46

How is high grade lymphoma treated?

Answer 46

Intensive chemotherapy

Question 47

How is low grade lymphoma treated?

Answer 47

Watch and wait except in gastric NHL (proton pump inhibitors and antibiotics)

Question 48

What are the two broad types of Hodgkins lymphoma?

Answer 48

Classical | Nodular lymphocytic

Question 49

What is the characteristic cell of Hodgkins lymphoma?

Answer 49

Reed-sternberg cell

Question 50

What symptom is classical for Hodgkins lymphoma?

Answer 50

Alcohol induced pain

Question 51

What is myeloma a malignancy of?

Answer 51

Plasma cells

Question 52

What is the pathology in myeloma?

Answer 52

Monoclonal plasma cells produce monoclonal antibody, termed paraproteins

Question 53

What age group does myeloma present in?

Answer 53

>60

Question 54

What causes Bence-Jones proteins in the urine?

Answer 54

Excess light chain protein production causes them to leak into the urine as BJ proteins

Question 55

How can the presence of paraproteins be detected?

Answer 55

Serum electrophoresis

Question 56

How can an abnormal paraprotein band be identified once detected on electrophoresis?

Answer 56

Serum immunofixation

Question 57

What are the most important sites that abnormal plasma cells are in?

Answer 57

Bone marrow: skull, rib and vertebrae

Question 58

How does myeloma present?

Answer 58

Bone pain Hypercalcaemia Renal failure Bone marrow infiltration - anaemia, neutropenia

Question 59

Why does bone pain occur in myeloma?

Answer 59

Inflammation caused by abnormal plasma cells activates osteoclasts, causing lytic bone lesions

Question 60

What fractures are typically associated with myeloma?

Answer 60

Vertebral crush fractures

Question 61

What are the symptoms of hypercalcaemia?

Answer 61

``` Stones Bones Abdominal groans Psychiatric moans Thirst Dehydration Renal impairment ```

Question 62

What is the treatment for multiple myeloma?

Answer 62

``` Increase fluid intake Bisphosphonates Local radiotherapy (bone lesions) EPO + transfusions Prednisolone Bone marrow transplant Chemotherapy ```

Question 63

What translocation can predispose to leukaemia?

Answer 63

Philadelphia chromosome predisposes to CML | t(9;22)