Introduction To Lymphoma And Myeloma

Question 1

1. What is lymphoma?

Answer 1

cancer of the mature white blood cells (lymphocytes) that mostly affect B lymphocytes but also T lymphocytes.

Question 2

2. What is lymphoma caused by?

Answer 2

Specific gene mutations and chromosomal translocations

Question 3

3. What is the function of the lymphatic system?

Answer 3

• blood filtration/purification
• removal of excess fluids from tissues
• absorption and transport of lipids
• Immune system activation

Question 4

4. What is the difference between primary and secondary lymph organs?

Answer 4

o Primary lymph organs are sites where stem cells can divide and become immunocompetent.
o Secondary lymph organs are sites where most of the immune responses occur.

Question 5

5. Explain the process of how lymphoma can affect so many lymph organs?

Answer 5

1. Lymphoma affect lymphocytes in different maturation sites causing uncontrolled division.
2. This increases organ size: lymph nodes (adenopathy) and other lymph organs (splenomegaly).
3. This spreads to other tissues through lymphatic system and might infiltrate in bone marrow (detectable in blood) and/or other organs.

Question 6

6. Explain the traditional classification of Lymphoma?

Answer 6

Lymphoma can be separated into Hodgkin’s and Non-Hodgkin’s. Non-Hodgkin can further be separated into diffuse and follicular

Question 7

7. What % of lymphoma cases are Hodgkin and what % are non-Hodgkin?

Answer 7

Hodgkin = 17%

Non-Hodgkin = 83%

Question 8

8. Of all cancer cases , what % and how many cases between 2014-2016 have there been for Hodgkin and Non-Hodgkin Lymphoma?

Answer 8

Hodgkin’s:

• 1% of all cases
• 2000 new cases

Non-Hodgkin’s

• 4% of all cases
• 13,800 new cases

Question 9

9. What is the peak rate age range for Hodgkin and Non-Hodgkin?

Answer 9

Hodgkin:
-Peak rate in 75-79 year olds

Non-Hodgkin:
-Peak rate in 80-84 year olds

Question 10

10. What %increase has there been in incidence rates for Hodgkin and Non-Hodgkin?

Answer 10

Hodgkin:
-+36% in incidence rates

Non-Hodgkin:
-+39% change in incidence rates

Question 11

11. What are the main symptoms of lymphoma?

Answer 11

• Fever
• Swelling of neck,face
• Lumps in neck,armpit,groin
• Excessive Sweating at night
• Itchiness
• Breathlessness
• Unexpected Weight loss
• Appetite Loss
• Feeling of weakness

Question 12

12. In what ways can we diagnose lymphoma?

Answer 12

•	Flow cytometry
•	FISH
•	NGS
•	Biopsy needle- immunophenotyping. 
o	PET staging: Step I to Step IV.

Question 13

13. Explain what you see in from stages I through to IV?

Answer 13

Stage I:
-localised disease; single lymph node region or single organ

Stage II:
-Two or more lymph node regions on the same side of the diaphragm

Stage III:
-Two or more lymph node regions above and below the diaphragm

Stage IV:
Widespread disease; multiple organs , with or without lymph node involvement

Question 14

14. What is the Aetiology of lymphoma?

Answer 14

-A multifactorial disorder -> interrupts the immune system -> exposure to infection->Infections transform cells -> cell cycle dysregulation,
apoptosis inhibition,
genomic instability and increased metastasis = higher angiogenesis and the formation of lymphoma cells for tumour formation.

When a B cell develops/acquires a mutation in it’s DNA.

Question 15

15. What is lymphoma classfication according to WHO (2016)?

Answer 15

oMature B-cell neoplasms
oMature T-cell and NK neoplasms
oHodgkin lymphoma

Question 16

16. In both Hodgkin and Non-Hodgkin Lymphoma, what is the PRESENTATION?

Answer 16

Hodgkin:
o Clonal B-cell malignancy which is presented by non-painful enlarged lymph node(s).

Non-Hodgkin:
enlarged lymph node(s) (some grow slowly and other grow fast).

Question 17

17. In both Hodgkin and Non-Hodgkin Lymphoma, what is the RISK FACTORS?

Answer 17

Hodgkin:
classic form of Epstein-Barr virus (EBV),
family history, HIV/AIDS

Non-Hodgkin:
• Virus infections e.g. EBV (HHV4) in Burkitt’s lymphoma
• Human T-cell leukaemia virus in adult T-cell lymphoma

Question 18

18. What is the diagnosis for Hodgkin Lymphoma?

Answer 18

Excisional lymph node biopsy where a whole lymph node is removed.
•Shows Reed-Sternberg cells: giant abnormal cells with more than 1 nucleus.

Question 19

19. What is the treatment for Hodgkin Lymphoma?

Answer 19

Chemotherapy +/- radiotherapy and stem cell transplant.

Question 20

20. What is the outcome of treatment for Hodgkin lymphoma?

Answer 20

o Prognosis 5 year survival.

• 50-90% depending on age, stage and histology, especially good results in young adults (97%).

Question 21

21. What is the cause for Non-Hodgkin Lymphoma?

Answer 21

•Chromosome translocations involving the Ig heavy chain or light chain loci on chr14.

Question 22

22. Which cell types express high numbers of Ig genes?

Answer 22

B Cells

Question 23

23. What do all Ig gene contain

Answer 23

A powerful tissue specific enhancer- its normal role is activating the promoter of the rearranged v segment however after chromosome translocation, the enhancer regulated the promoter of another gene(not its own)

Question 24

24. Explain what happens in these chromosome translocations, particularly giving examples of Burkitts Lymphoma and Follicular Lymphoma

Answer 24

The IGH gene on chromosome 14 gains another gene from a different chromosome for eg:

Burkitts Lymphoma:
c-MYC gene( potent oncogene) from chromosome 8 translocated to chromosome 14 with IGH gene

Follicular lymphoma:
BCL-2 (an apoptosis inhibitor) from chromsome 18 , with IGH gene on chromosome 14

Question 25

25. One risk factor is virus infections (e.g. EBV (HHV4) driven lymphomas in immunosuppressed patients) How does virus infection ----> Lymphoma?

Answer 25

* It directly transforms B-lymphocytes due to the viral oncogene LMP-1. * In immunosuppressed individuals, these cells are no longer eliminated by cytotoxic T-cells so the patients develop high grade lymphoma. * More than half the normal cells carry the latent EBV infection but they don’t all develop lymphomas due to effective immune surveillance by cytotoxic T-cells.

Question 26

26. Explain the characteristics of low grade lymphoma?

Answer 26

* Normal tissue architecture is partially preserved so the normal cell of origin is recognisable. * Divide slowly and may be present for many months before diagnosis. * Behave in an indolent (lazy/avoiding activity) fashion

Question 27

27. Explain the characteristics of high grade lymphoma?

Answer 27

* Loss of normal tissue architecture so the normal cell of origin is hard to determine. * Divide rapidly and may be life-threatening. * Present for a matter of weeks before diagnosis

Question 28

28. In what ways can we diagnose lymphoma?

Answer 28

* Immunophenotyping and Light chain restriction. * Cytogenetics (how chromosomes relate to cell behaviour) e.g. FISH - For chromosome translocations (e.g. t(14;18) Ig : Bcl-2). * PCR for clonal Ig gene rearrangement.

Question 29

29. What treatment is there for lymphoma?

Answer 29

• Chemotherapy and Radiotherapy • Stem cell transplant • Monoclonal Ab therapy -Rituximab (anti-CD20)

Question 30

30. Overall 5 year survival rate is approx. what %

Answer 30

70

Question 31

31. What is Multiple Myeloma?

Answer 31

o Tumour of the bone marrow that involves plasma cells (antibodies production) of the lymphoid lineage.

Question 32

32. What are the symptoms of multiple myeloma?

Answer 32

initial symptoms are absent and later symptoms include bone pain, bleeding, frequent infections, and anaemia.

Question 33

33. What is the cause and risk factors of multiple myeloma?

Answer 33

o Cause is unknown but risk factors include obesity, radiation exposure, family history, and certain chemicals. o DNA damage damages the white blood cells and transform them into myeloma cells.

Question 34

34. Aspect no1 of myeloma is the suppression of normal bone marrow,blood cell and immune cell function. What is the clinical significance of this?

Answer 34

causes anaemia, recurrent infections and tendency to bleed.

Question 35

35. Aspect no2 of myeloma is bone reabsorption and release of calcium. What is the clinical significance of this?

Answer 35

causes hypercalcaemia which has multiple symptoms e.g. mental disturbance.

Question 36

36. Myeloma cells produce cytokines, what is the clinical significance of this?

Answer 36

• Myeloma cells produce cytokines (esp. IL-6) which act on bone marrow stromal cells causing them to release the cytokine RANKL. RANK causes osteoclasts activation which leads to lytic lesions of bone, bone pain, fractures).

Question 37

37. Aspect no3 of multiple myeloma is the pathological effects of the paraprotein which is a single monoclonal Ig in the serum, what is the clinical significance of this?

Answer 37

-high levels cause malignancy | • Precipitates in kidney tubules to cause renal failure and is deposited as amyloid in many tissues.

Question 38

38. 2% of multiple myeloma cases have hyper-viscosity syndrome-what is this? what can it cause?

Answer 38

Increased blood viscosity leading to stroke/heart failure

Question 39

39. In what ways can we diagnose multiple myeloma?

Answer 39

* Serum electrophoresis for paraprotein. * Urine electrophoresis * Bone marrow biopsy for increased levels of plasma cells * Erythrocyte sedimentation rate (ESR)- high due to stacking of the RBC * Flow cytometry and cytogenetics to detect cause * Radiological investigation of skeleton for lytic lesions.

Question 40

40. What is the treatment of multiple myeloma?

Answer 40

Radiotherapy, chemotherapy, allogeneic hematopoietic stem cell transplantation (ASCT) in young patients.

Question 41

41. What is the prognosis for multiple myeloma?

Answer 41

Chemo + ASCT - overall 5-year survival rate ~35%.