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Haematology > Introduction To Lymphoma And Myeloma > Flashcards

Introduction To Lymphoma And Myeloma Flashcards

1
Q
  1. What is lymphoma?
A

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

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2
Q
  1. What is lymphoma caused by?
A

Specific gene mutations and chromosomal translocations

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3
Q
  1. What is the function of the lymphatic system?
A
  • blood filtration/purification
  • removal of excess fluids from tissues
  • absorption and transport of lipids
  • Immune system activation
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4
Q
  1. What is the difference between primary and secondary lymph organs?
A

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.

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5
Q
  1. Explain the process of how lymphoma can affect so many lymph organs?
A
  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.
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6
Q
  1. Explain the traditional classification of Lymphoma?
A

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

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

Hodgkin = 17%

Non-Hodgkin = 83%

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

Hodgkin’s:

  • 1% of all cases
  • 2000 new cases

Non-Hodgkin’s

  • 4% of all cases
  • 13,800 new cases
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9
Q
  1. What is the peak rate age range for Hodgkin and Non-Hodgkin?
A

Hodgkin:
-Peak rate in 75-79 year olds

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

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

Hodgkin:
-+36% in incidence rates

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

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11
Q
  1. What are the main symptoms of lymphoma?
A
  • Fever
  • Swelling of neck,face
  • Lumps in neck,armpit,groin
  • Excessive Sweating at night
  • Itchiness
  • Breathlessness
  • Unexpected Weight loss
  • Appetite Loss
  • Feeling of weakness
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12
Q
  1. In what ways can we diagnose lymphoma?
A 
•	Flow cytometry
•	FISH
•	NGS
•	Biopsy needle- immunophenotyping. 
o	PET staging: Step I to Step IV.
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13
Q
  1. Explain what you see in from stages I through to IV?
A

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

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14
Q
  1. What is the Aetiology of lymphoma?
A

-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.

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

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

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

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).

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

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

18
Q
  1. What is the diagnosis for Hodgkin Lymphoma?
A

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

19
Q
  1. What is the treatment for Hodgkin Lymphoma?
A

Chemotherapy +/- radiotherapy and stem cell transplant.

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

o Prognosis 5 year survival.

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

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

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

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

B Cells

23
Q
  1. What do all Ig gene contain
A

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)

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

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

25
Q
  1. One risk factor is virus infections (e.g. EBV (HHV4) driven lymphomas in immunosuppressed patients)
    How does virus infection —-> Lymphoma?
A
  • 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.
26
Q
  1. Explain the characteristics of low grade lymphoma?
A
  • 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
27
Q
  1. Explain the characteristics of high grade lymphoma?
A
  • 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
28
Q
  1. In what ways can we diagnose lymphoma?
A
  • 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.
29
Q
  1. What treatment is there for lymphoma?
A

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

30
Q
  1. Overall 5 year survival rate is approx. what %
A

70

31
Q
  1. What is Multiple Myeloma?
A

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

32
Q
  1. What are the symptoms of multiple myeloma?
A

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

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

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.

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

causes anaemia, recurrent infections and tendency to bleed.

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

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

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

• 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).

37
Q
  1. 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?
A

-high levels cause malignancy

• Precipitates in kidney tubules to cause renal failure and is deposited as amyloid in many tissues.

38
Q
  1. 2% of multiple myeloma cases have hyper-viscosity syndrome-what is this? what can it cause?
A

Increased blood viscosity leading to stroke/heart failure

39
Q
  1. In what ways can we diagnose multiple myeloma?
A
  • 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.
40
Q
  1. What is the treatment of multiple myeloma?
A

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

41
Q
  1. What is the prognosis for multiple myeloma?
A

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

Haematology (8 decks)

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