Lecture 10: Hodgkin's Lymphoma

Question 1

ToD: Lymphoma = Leukaemia

Answer 1

False

Question 2

What is lymphoma?

Answer 2

Cancer of WBC. Form solid tumours in lymphatics and reticuloendothelial system. Depending on the spread of the lymphoma, their WBC count may look normal.

Question 3

Which WBC does lymphoma specifically affect?

Answer 3

B-cell

Question 4

What cell are Reed-Sternberg cells derived from?

Answer 4

B-lymphocytes that don’t express an antibody

Question 5

What two CD receptors make it easier to identify Reed-Sternberg cells?

Answer 5

CD30 and C15 receptors

Question 6

Where do Reed-Sternberg cells originate from?

Answer 6

The germinal centres of lymphatic tissue

Question 7

Why is it the germinal centres that produce Reed-Sternberg cells? (2 marks)

Answer 7

Germinal centres are where all the proliferation of the cell and VDJ recombination occurs

Because germinal centres are found in the lymph node, lymph nodes are able to suppress apoptosis. This fact is made worse if there is malignancy in a lymph node.

Question 8

What are the histological features of a Reed-Sternberg cell? (2 points)

Answer 8

Large cells (50 microns)

Bi-lobed/ multinucleated cells

Question 9

What are the three clinical symptoms of Hodgkin’s Lymphoma?

Answer 9

Lymphadenopathy
Night sweats
Weight loss

Question 10

What is lymphadenopathy?

Answer 10

Swelling of the lymph nodes

Question 11

Why does weight loss occur because of HL?

Answer 11

Rapid proliferation causes the tumour to start sapping as many nutrients as possible, starving the rest of the body.

Question 12

What virus is associated with HL?

Answer 12

Epstein-Barr virus

Question 13

What percentage of HL patients are found with EBV DNA?

Answer 13

90%

Question 14

Describe why the EBV increases the chance of HL?

Answer 14

Can transform lymphocytes into a more cancerous version of itself.

If the EBV genes are inserted in the wrong place within the Host’s DNA then it can act as a huge disruptor during transcription and translation.

This can cause the cell to continue proliferating because the stop codon has stopped working.

Question 15

Which 3 EBV genes are associated with malignancy?

Answer 15

LMP1
LMP2a
EBNA1

Question 16

What are some non-specific tests for HL?

Answer 16

Full blood count
Serum lactate dehydrogenase
Liver function tests

Question 17

What are some specific tests for HL?

Answer 17

Lymph node biopsy
Immunohistochemistry

Question 18

Why can we use lactate dehydrogenase levels as a non-specific test?

Answer 18

The environment in the tumour becomes low in oxygen. To produce energy the lymphoma relies on glycolytic respiration.
Lactate dehydrogenase is released when tumour cells die.
The measurement within the blood can be used as an indicator that something is wrong.
By tiring out the mitochondria the tumour can stay alive longer

Question 19

How many types of HD are there?

Answer 19

5

Question 20

Which out of the 5 HD is a variant of classical HD?

Answer 20

Nodular lymphocyte predominant

Question 21

What cells characterise Nodular lymphocyte predominant HD?

Answer 21

Popcorn cells or lymphocyte predominant cell

Question 22

Name the 4 Classical Hodgkins lymphoma

Answer 22

Nodular sclerosis Hodgkins lymphoma
Lymphocyte rich classical Hodgkins lymphoma
Mixed cellularity Hodgkins lymphoma
Lymphocyte depletion Hodgkiins lymphoma

Question 23

What is the name of the common staging methodology for HD?

Answer 23

Ann Arbor system

Question 24

How many stages are in the Ann Arbor system?

Answer 24

4

Question 25

What does the B categorisation mean in the AA system?

Answer 25

Fever, night sweats and weight loss

Question 26

What does the S categorisation mean in the AA system?

Answer 26

Splenic involvement

Question 27

What does the E categorisation mean in the AA system?

Answer 27

Tissue other than lymphatics are involved

Question 28

What does the X categorisation mean in the AA system?

Answer 28

Large tumour (>10cm)

Question 29

What happens in Stage I of the AA system?

Answer 29

Involvement of single lymph node region or single extralymphatic site (Ig)

Question 30

What happens in Stage II of the AA system?

Answer 30

Involvement of two or more lymph node regions on same side of diaphragm; may include localised extra lymphatic involvement on same side of diaphragm (IIg)

Question 31

What happens in Stage III of the AA system?

Answer 31

Involvement of lymph node regions on both sides of the diaphragm; may include spleen (IIIs) or localised extranodal disease (IIIg)

Question 32

What happens in Stage IV of the AA system?

Answer 32

Diffuse extra lymphatic disease (e.g. in liver, bone marrow, lung, skin)

Question 33

What percentage of HL cases, is the spleen involved?

Answer 33

30%

Question 34

ToD: Spleen involvement differs based on the type of HL

Answer 34

True

Question 35

What percentage of HL cases, is the skin involved?

Answer 35

<1% of cases

Question 36

What percentage of HL cases, is the skin indirectly involved?

Answer 36

30%

Question 37

What symptoms are seen on skin when the skin is indirectly involved?

Answer 37

Itching, hives, rash.

Question 38

What is paraneoplastic syndrome?

Answer 38

Caused by chemokine synthesis by tumour or the host immune response directed against the tumour

Question 39

What causes indirect skin conditions seen in HL patients?

Answer 39

Paraneoplastic syndrome

Question 40

What atypical symptoms does paraneoplastic syndrome cause?

Answer 40

Endocrine Haematological Skin Neuronal

Question 41

What is the name of the point system that is used in the prognosis of HL?

Answer 41

International Prognostic Factors Project

Question 42

How many points are symptoms allocated if we are looking at stage 1 and 2 of the disease?

Answer 42

1

Question 43

What are the 5 prognostic features used for stage 1 and 2 of the disease?

Answer 43

Bulky tumour ESR >50mm/hr (Erythrocyte Sedimentation Rate) >3 sites of involvement B symptoms Extranodal disease

Question 44

What are the 6 prognostic features used for advanced Hodgkins disease?

Answer 44

Serum albumin <4 g/dl Haemoglobin <105 g/l Male Age >45 years old Leucocytosis > 15 x10^9 cells/l Lymphopenia <0.6 x 10^6 cells/l

Question 45

What treatment is given during the early stage of Hodgkins disease?

Answer 45

ABVD therapy Surgery to remove tumour

Question 46

What does ABVD stand for in the context of 'ABVD therapy'?

Answer 46

Adriamycin, bleomycin, vinblastine and dacarbazine

Question 47

What is used to treat advanced Hodgkin's disease?

Answer 47

BEACOPP or G-CSF

Question 48

What does BEACOPP stand for in the context of treatment?

Answer 48

Bleomycin, etoposide, adriamycin, cyclophosphamide, vincristine, procarbazine and prednisone

Question 49

What does Adriamycin do?

Answer 49

Inhibits topoisomerase II (intercalating poison)

Question 50

What does Bleomycin do?

Answer 50

Induces dsDNA breaks

Question 51

What does Vinblastine do?

Answer 51

Disrupts microtubule formation

Question 52

What does Dacarbazine do?

Answer 52

Alkylating agent

Question 53

What are the remission rates following ABVD?

Answer 53

70-90%

Question 54

When are drugs during ABVD therapy infused?

Answer 54

Via IV on days 1 and 15

Question 55

How many cycles of ABVD are usually prescribed?

Answer 55

6

Question 56

What stage of HL are patients treated with BEACOPP instead of ABVD?

Answer 56

Stage 2 and above

Question 57

What does Etoposide do?

Answer 57

Topoisomerase II non-intercalating poison

Question 58

What does Cyclophosphamide do?

Answer 58

Alkylating agent

Question 59

What does Procarbazine do?

Answer 59

Alkylating agent

Question 60

What is Prednisone?

Answer 60

Steroid

Question 61

What is the remission induction rate of BEACOPP?

Answer 61

80%

Question 62

What are three other supportive therapies?

Answer 62

Prophylactic antimicrobials Blood products Antiemetic drugs

Question 63

What is recommended for refractive lymphoma?

Answer 63

Brentuximab vedotin Nivolumab and Pembrolizumab