L26: Intro To Lymphomas & Myeloma

Question 1

Which cells are involved in lymphomas?

Answer 1

→mostly B lymphocytes
→ T lymphocytes
→natural killers

Question 2

What are the main functions of the lymph nodes?

Answer 2

→blood filtration/purification

→removal of excess fluids from tissues

→absorption and transport of lipids

→Immune system activation

Question 3

What are primary lymph organs?

Answer 3

→sites where stem cells can divide and become immunocompetent

Question 4

→What are secondary lymph organs?

Answer 4

→sites where most of the immune responses occur

Question 5

When lymphomas spread to the bone marrow, how are they detected?

Answer 5

→detectable in blood

Question 6

What are the traditional classifications of lymphomas?

Answer 6

→Non-Hodgkin’s

→Hodgkins

Question 7

What are the two types of Non-Hodgkin’s lymphomas?

Answer 7

→diffuse

→follicular

Question 8

What is the age of onset of HK and NHK lymphomas?

Answer 8

→HK= 75-79
→NHK= 80-84

Question 9

What are the warning signs of lymphomas?

Answer 9

→swelling of face and neck
→excessive sweating at night
→unexpected weight loss
→breathlessness
itchiness
→loss of appetite

Question 10

How are lymphomas diagnosed?

Answer 10

→lymph node biopsy
→immunophenotyping
→NGS
→FISH
→flow cytometry

Question 11

What are the PET stages of lymphomas?

Answer 11

→Stage 1= localized disease, single lymph node
→Stage 2= two or more lymph nodes on the same of the diaphragm
→Stage 3= two or more nodes above and below diaphragm
→Stage 4= widespread disease, multiple organs

Question 12

How do most lymphomas occur?

Answer 12

→when a B cell develops/acquires a mutation in its DNA

Question 13

What is Hodgkin lymphoma?

Answer 13

→Clonal B-cell malignancy

Question 14

What is the presentation of HK lymphomas?

Answer 14

→Presentation- non-painful enlarged lymph node(s)

Question 15

What are the risk factors of HK lymphomas?

Answer 15

→50% cases due to Epstein-Barr virus
→Family history
→HIV/AIDS

Question 16

How is HK lymphomas diagnosed?

Answer 16

→Excisional lymph node biopsy
→Reed-Sternberg cell present
→observed by light microscope

Question 17

What are the features of Reed-Sternberg cells?

Answer 17

→multinucleated

→condensed cytoplasm

Question 18

What is the treatment for HK lymphomas?

Answer 18

→Chemotherapy +/- radiotherapy

→Stem cell transplant

Question 19

What is the prognosis for HK lymphomas?

Answer 19

→5 year survival ~50-90% depending on age, stage and histology

Question 20

What are two high grade NHK lymphomas?

Answer 20

→diffuse large B cell

→Burkitt

Question 21

What is the main presentation of HK lymphomas?

Answer 21

→enlarged lymph node

Question 22

What is a cause of NHK lymphomas?

Answer 22

→Chromosome translocations detected using FISH

Question 23

What are the risk factors for NHK?

Answer 23

→virus infection

Question 24

What are viral risk factors for NHK?

Answer 24

→EBV (HHV4) in Burkitt’s lymphoma

→ Human T-cell leukaemia virus in adult T-cell lymphoma

→H.Pylori in gastric lymphoma

Question 25

What is the chromosome translocations in NHK?

Answer 25

→Ig heavy chain or light chain loci (chr14)

Question 26

How does Ig-BCL-2 fusion created?

Answer 26

→Ig gene has a powerful tissue specific enhancer in B-cells →translocation brings BCL-2 which is an apoptosis inhibitor under the influence of Ig enhancer

Question 27

Which chromosomes are involved in IG-BCL-2 fusion of follicular lymphoma?

Answer 27

→14 and 18

Question 28

Which chromosomes are involved in Ig-C-MYC fusion of Burkitt's lymphoma?

Answer 28

→t(8;14)(q24;q32)

Question 29

What does the Epstein Barr virus due to B-cells in those immunosuppressed?

Answer 29

→directly transforms B-lymphocytes in culture. →Due to viral oncogene LMP-1 →high grade lymphoma.

Question 30

What are the features of low grade NHK?

Answer 30

→Normal tissue architecture partially preserved -normal cell of origin recognisable →Divide slowly →May be present for many months before diagnosis →Behave in an indolent fashion

Question 31

What are the features of high grade NHK?

Answer 31

→Loss of normal tissue architecture -normal cell of origin hard to determine →Divide rapidly →Present for a matter of weeks before diagnosis →May be life-threatening

Question 32

What are the diagnostic techniques for NHK?

Answer 32

→Immunophenotyping →Cytogenetics –FISH →Light chain restriction →PCR-For clonal Ig gene rearrangement

Question 33

What is NHK diagnosis similar to?

Answer 33

→chronic myeloid leukaemia

Question 34

What are the treatments for NHK?

Answer 34

→Chemotherapy Radiotherapy Stem cell transplant Monoclonal Ab therapy

Question 35

Example of MAb for NHK

Answer 35

→Rituximab (anti-CD20)

Question 36

What is normally found on surface of lymphoma cells?

Answer 36

→CD20 | →Antibodies mark the CD20 and then is killed by releasing cytotoxin

Question 37

What is the survival rate in nHK?

Answer 37

→70%

Question 38

What is myeloma?

Answer 38

→Tumour of the bone marrow that involves plasma cells

Question 39

What are the initial symptoms of myeloma?

Answer 39

→Absence of initial symptoms

Question 40

What are the later symptoms of myeloma?

Answer 40

→bone pain, →bleeding, →frequent infections, →anaemia

Question 41

What do abnormal plasma cells produce?

Answer 41

→paraprotein

Question 42

What are paraproteins?

Answer 42

→monoclonal immunoglobulin or light chain

Question 43

How are Bence-Jones proteins detected?

Answer 43

→blood or urine | →homogeneous gel migration

Question 44

Why is there hypercalcaemia observed in myelomas?

Answer 44

→Myeloma cells produce cytokines (esp. IL-6) → bone marrow stromal cells to release the cytokine RANKL → osteoclasts activation →Calcium released

Question 45

What are the three features of myelomas that give rise to clinical features?

Answer 45

→Suppression of normal bone marrow, blood cell and immune cell function 2. Bone resorption and release of calcium 3. Pathological effects of the paraprotein –(single monoclonal Ig in the serum- high levels – malignancy)

Question 46

Why is there hyper viscosity syndrome in myeloma?

Answer 46

→paraprotein precipitates in kidney →renal failure →Deposited as amyloid in many tissues

Question 47

What are the diagnostic techniques of multiple myeloma?

Answer 47

→Serum electrophoresis for paraprotein →Urine electrophoresis →Bone marrow biopsy for increased levels of plasma cells →Erythrocyte sedimentation rate (ESR)-

Question 48

Why is ESR performed for myeloma?

Answer 48

→high due to stacking of the RBC- forms Rouleaux's due to increased paraprotein →Flow cytometry and cytogenetics to detect cause →Radiological investigation of skeleton for lytic lesions

Question 49

What are the treatments for MM?

Answer 49

→Radiotherapy →chemotherapy combinations →targeted therapies →immunotherapy (CAR-T), →allogeneic hematopoietic stem cell transplantation (ASCT) in young patients.

Question 50

What is the survival rate for MM?

Answer 50

→35%

Question 51

Which type of cancers are stem cells and bone marrow transplants mainly used for?

Answer 51

→AML

Question 52

What are the two types of stem cell transplants?

Answer 52

→allogenic | →autologous

Question 53

What is CART cell therapy?

Answer 53

→treatment of haematological cancers | →T cells produce chimeric antigen receptors on their surface