Haematological Malignancy

Question 1

How common are haematological cancers?

Answer 1

10% of all human cancers

Question 2

What gender do haematological cancers generally tend to affect most?

Answer 2

Men

Question 3

What leukaemia is most common in young children?

Answer 3

ALL - peaks 2-4y

Question 4

What leukaemia is most common in adults?

Answer 4

AML

Question 5

What is Hodgkin lymphoma associated with?

Answer 5

EBV (especially in older patients)

Question 6

Describe the incidence of Hodgkin lymphoma

Answer 6

Peak in 18-35yos and peak in 70s

Question 7

Describe the pathogenesis of haematological malignancy

Answer 7

Multistep process:
Genetic mutation to long lived cell that conveys survival advantage –> produces malignant clones –> malignant clones dominate the tissue (e.g. bone marrow/lymph nodes)

Question 8

If the malignant clones start dominating the tissue what can occur?

Answer 8

Bone marrow failure (anaemia, thrombocytopenic bleeding, infection due to neutropenia)

Question 9

If a mutation occurs in the hemopoietic stem cell causing leukaemia what is the cell called?

Answer 9

Leukaemia stem cell

Question 10

What are the two most important properties of the hemopoietic stem cell?

Answer 10

Multipotential - can go down myeloid/lymphoid lineage

Self-renewing - one daughter cell will differentiate another will replace the hemopoietic stem cell

Question 11

What cells are granulocytes?

Answer 11

Eosinophils, neutrophils, basophils, mast cells

Question 12

What cells are included in the myeloid lineage?

Answer 12

Granulocytes, monocytes, platelets, erythrocytes

Question 13

What cells are included in the lymphoid lineage?

Answer 13

B cells

T cells

Question 14

In ALL, where does the mutation occur and what cells will accumulate?

Answer 14

Occurs in hemopoietic stem cell or early lymphoid progenitor leading to accumulation of lymphoblasts

Lymphoblasts retain their ability to proliferate rapidly but do not differentiate

Rapidly accumulation of these cells –> bone marrow failure (acute presentation)

Question 15

In AML, where does the mutation occur and what cells will accumulate?

Answer 15

Hemopoietic stem cells or early myeloid progenitor cells

Proliferation occurs, differentiation blocked –> accumulation of early myeloid cells in bone marrow –> bone marrow failure & acute presentation

Question 16

Where do lymphomas most commonly occur?

Answer 16

Mutations of lymphocytes in the germinal centre of the lymph nodes (as this is where there is the most genetic pressure)

Question 17

Differentiate between lymphoma and leukaemia

Answer 17

Leukaemia - mostly in blood and bone marrow

Lymphoma - in lymph tissue mostly

Question 18

What is the most common leukaemia?

Answer 18

Chronic lymphocytic leukaemia

Question 19

How is CLL different when it presents in the lymph nodes?

Answer 19

If presents with swollen lymph nodes, biopsy of lymph nodes will show exact same morphology as if it was in the bone marrow
BUT it is known as small cell lymphocytic lymphoma instead

Question 20

What are the features of Burkitt lymphoma?

Answer 20

Rapidly growing, very aggressive and tends to present with a lump

Question 21

What are the acute leukaemias?

Answer 21

Acute lymphoblastic leukaemia

Acute myeloid leukaemia

Question 22

What are the chronic leukaemias?

Answer 22

Chronic myeloid leukaemia

Chronic lymphocytic leukaemia

Question 23

What are the malignant lymphomas?

Answer 23

Non-Hodgkin lymphoma

Hodgkin lymphoma

Question 24

What are the main differences between the acute and chronic leukaemias?

Answer 24

Acute: leukaemic cells do not differentiate; chronic: able to differentiate (not fully)

Acute: bone marrow failure, chronic: proliferation without bone marrow failure

Acute: acute presentation, rapidly fatal if untreated, chronic: survival for a few years

Question 25

What is the triad of bone marrow failure?

Answer 25

``` Anaemia Thrombocytopenic bleeding (purpura/mucosal membrane bleeding) Infection (due to neutropenia, predominantly fungal and bacterial infections) ```

Question 26

What is the appearance of the bone marrow in acute leukaemia?

Answer 26

Absolutely packed with blasts

Question 27

What is key about the petechiae seen in bone marrow failure?

Answer 27

Non-blanching

Question 28

Aside from petechiae what other abnormal bleeding may you see in bone marrow failure?

Answer 28

Mucosal bleeding | Subscleral bleeding

Question 29

What infections might you see in bone marrow failure?

Answer 29

``` Staph aureus (e.g. tunnel infections, cellulitis), pseudomonas Aspergillosus ```

Question 30

Describe the structure of a lymph node

Answer 30

Paracortex surrounding outside Cortex is outer area, with inner medulla In medulla there are B cell follicles composed of a marginal zone, mantle zone and germinal centre

Question 31

Where are B cells found in the lymph nodes?

Answer 31

Follicles

Question 32

Where are T cells found in the lymph nodes?

Answer 32

Paracortex

Question 33

Where are plasma cells found in the lymph nodes?

Answer 33

Medulla

Question 34

What occurs in the germinal centre?

Answer 34

B cells undergoing expansion and selection

Question 35

Where do B cells mature?

Answer 35

In the germinal centre of lymph nodes where they are forced to rearrange their genetic material to change into a plasma cell against a specific antigen

Question 36

Where do T cells mature?

Answer 36

Thymus

Question 37

What is the name of the process of genetic rearrangement that occurs in the germinal centre of lymph nodes?

Answer 37

Somatic hypermutation

Question 38

What are the different presentations of lymphomas?

Answer 38

Nodal disease (lymphadenopathy) occurs in HL 90% and NHL 60% of the time Extranodal disease, e.g. in CNS Systemic (B) symptoms

Question 39

What are the systemic B symptoms?

Answer 39

Fever, drenching night sweats, >10% loss of body wt, pruritus, fatigue Indicative of a poorer prognosis

Question 40

What is important to remember when trying to palpate and check lymph nodes?

Answer 40

Not all lymph nodes can be felt, e.g. mediastinal lymph nodes

Question 41

What is the reason for localised and painful lymph nodes?

Answer 41

Bacterial infection

Question 42

What are reasons for localised and painless lymph nodes?

Answer 42

Rare infections (TB, scratch fever) Metastatic cancer - HARD Lymphoma - RUBBERY Reactive

Question 43

What are reasons for generalised and painful lymph nodes?

Answer 43

Viral infections (EBV, CMV, hep, HIV)

Question 44

What are reasons for generalised and painless lymph nodes?

Answer 44

``` Lymphoma Leukaemia Connective tissue diseases Sarcoidosis Reactive Drugs, e.g. phenytoin ```

Question 45

What are the clinical features of multiple myeloma?

Answer 45

Lytic lesions and bone pain (cytokines --> osteoclast induction) Anaemia (of chronic dx) Recurrent infections (neutropenia) Renal failure (deposition of light chains) Amyloidosis (light chain accumulation in tissues) Bleeding tendency Hyperviscosity syndrome