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Molecular Basis of Disease(Sem 4) > Introduction to Lymphoma and Myeloma > Flashcards

Introduction to Lymphoma and Myeloma Flashcards

1
Q

Define and outline Lymphoma

A

Lymphoma is a cancer of white blood cells (lymphocytes )

Affects to mature blood cells , mostly B lymphocytes but also T lymphocytes

Heterogeneous group

Many known to be due to specific genetic mutations and chromosomal translocations

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2
Q

What are the main functions 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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3
Q

What are the lymph nodes ?

A

small glands that filter lymph, the clear fluid that circulates through the lymphatic system.

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4
Q

What are lymph organs ?

A

Primary lymph organs :
sites where stem cells can divide and become immunocompetent

Secondary lymph organs : sites where most of the immune response occur

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5
Q

What are the primary lymph organs ?

A

Thymus

Bone Marrow

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6
Q

What are the secondary lymph organs ?

A 
Tonsils and adenoids
Lymph nodes
Spleen
Peyer's patches 
Appendix
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7
Q

How do Lymphomas develop ?

A

They affect lymphocytes in different maturation stages which leads to uncontrolled divison .

Organ size increase :
Lymph node ; Adenopathy
Other lymph organs: Splenomegaly

Spread to other tissues through the lymphatic system

Might infiltrate in bone marrow (detectable in blood ) and other organs

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8
Q

How is Lymphoma classified ?

A

Non Hodgkin’s (more common) (80-84)

Hodgins (75-79 years old)

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9
Q

What is the presentation of lymphoma ?

A 
Fever 
Swelling on face 
Lump in neck,armpit or groin 
Excessive sweating at night
Unexpected weight loss
Loss of appetite
Weakness
Breathlessness
Itchiness
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10
Q

How is lymphoma diagnosed ?

A

Through taking a lymph node biopsy using a biopsy needle

Following this :
Flow cytometry
FISH
NGS
Immunophenotyping
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11
Q

What is the staging of Lymphoma ?

A

This is a series of tests carried out by PET to identify where in the body is affected .

Stage 1: Localised disease , single lymph node region or single organ

Stage 2: Two or more lymph node regions on the same side of the diaphragm

Stage 3: Two or more lymph nodes regions above and below diaphragm

Stage 4 : Widespread disease multiple organs with/without lymph node involvement

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12
Q

What is the aetiology of Lymphoma ?

A

Multifactorial disorder :
Malfunctioning of the bodys immune system
Exposure to certain infections

Most lymphomas occur when a B cell develops/acquires mutations in its DNA

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13
Q

What is the traditional classification of Lymphoma ?

A

Hodgkin’s and Non Hodgkin’s with Hodgkin’s being the larger group.

Non Hodgkin’s -
Diffuse / Follicular

Hodgkin’s

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14
Q

What are the aspects does the WHO 2016 take into account ?

A

Mature B-cell neoplasms
Mature T-cell and NK neoplasms
Hodgkin lymphoma

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15
Q

What is Hodgkin lymphoma ?Outline the disease and its presentation

A

Clonal B-Cell malignancy
Presentation: Non-Painful enlarged lymph node

Risk factors : approx. 50% cases are due to Epstein Barr virus (EBV)

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16
Q

How can we diagnose Hodgkin’s Lymphoma ?

A

Excisional lymph node biopsy :
Observing Reed Sternberg cell which arise from normal B lymphocytes
These are bilobed nucleus

These are only present in Hodgkins lymphomas

17
Q

What is the treatment of Hodgkin’s lymphoma ?

A

-Chemotherapy /radiotherapy and stem cell transplant

-Prognosis- 5 year survival
good results in young adults

18
Q

What are Non -Hodgkin lymphomas ?

A

These are all lymphomas aprt from hodgkins lymphoma

19
Q

Outline Non-Hodgkins Lymphoma

A

Presentation : Enlarged lymph nodes

Causes: Chromosome translocations

Risk factors : Virus infections in Burkitt’s lymphoma , Human T-cell leukaemia virus in adult T-cell lymphoma

20
Q

What are the chromosome translocations which occour in Non-Hodgkins Lymphoma ?

A

Many lymphomas carry chromosome translocations involving the Ig heavy chain or light chain loci (chr14)

  • Ig genes are highly expressed in B-cells
  • Each Ig gene has a powerful tissue specific enhancer (high expression levels )
21
Q

What are the consequences of these chromosome translocations in Non-Hodgkin lymphoma ?

A

The normal role of the enhancer is to activate the promoter of the rearranged V segment of the Ig

Due to the translocation between chromosome 14 and other chromosomes , the enhancer starts regulating the transcription of the other genes of the chromosome which has fused with chromosome 14.

There is an overexpression of the BCL-2 gene which is an apoptosis inhibitor.

Most cases of follicular lymphoma carry ty(14:18)(q32:q21)

22
Q

What is Follicular Lymphoma ?

A

Follicular lymphoma is a type of non-Hodgkin lymphoma

23
Q

What is the translocation observed in Burkitt’s lymphoma ?

A

t(8;14)(q24;q32)

c-myc is a potent proto-oncogene

24
Q

What are the risk factors of Non-Hodgkin lymphoma ?

A

Virus infections

  • It directly transforms B-lymphocytes in culture. Due to viral oncogene LMP-1
  • Over half of all normal individuals carry latent EBV infection. They do not develop lymphomas due to effective immune surveillance by cytotoxic T-cells.
25
Q

If over half of normal individuals carry the latent EBV virus why do some people develop lymphoma ?

A

In highly immunosuppressed individuals , the endogenous latent EBV may transform B-cells.

No longer eliminated by cytotoxic T-cells

Develop high grade lymphoma

26
Q

What is the classification of Non-Hodgkin Lymphoma ?

A

Low grade :

  • 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

High grade :

  • Loss of normal tissue architecture -normal cell or origin hard to determine
  • Divide rapidly
  • Present for a matter f weeks before diagnosis
  • May be life threatening
27
Q

How is Non-Hodgkin lymphoma diagnosed ?

A

-Immunophenotyping
-Cytogenetics-FISH
(For chromosome translocations (e.g.t(14;18)Ig : Bcl-2)
-Light chain restriction
-PCR
(For clonal Ig gene rearrangement)

28
Q

How is Non-Hodgkin lymphoma treated ?

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

Targets CD20 cell surface molecules which are usually present in Leukaemia and Lymphoma B cells. The antibody will bind to all the CD20 proteins and the immune system will then kill them by releasing cytotoxins

29
Q

What is multiple myeloma ?

A

This is a tumour of the bone marrow that involves plasma cells.Plasma cells are a type of leukocytes which secrete antibodies.

30
Q

What is the presentation of multiple myeloma ?

A

Absence of initial symptoms , later bone pain , bleeding , frequent infections and anaemia

Unknown cause :
Risk factors :
Obesity 
Radiation exposure 
Family history 
Certain chemicals
31
Q

What is the difference between healthy bone marrow and bone marrow in myeloma ?

A

Bone marrow produces white blood cells (B cells).
These become plasma cells and secrete normal antibodies

Bone Marrow in Myeloma:
Damaged white blood cell ,becomes myeloma cell and secretes paraprotein (M component)

32
Q

What three aspects of myeloma give rise to clinical features ?

A
  1. Suppression of normal bone marrow , blood cells and immune cell function :
    - Anaemia
    - Bleeding tendency
    - Recurrent infections

2.Bone reabsorption and release of calcium
-Myeloma cells produce cytokines (esp IL-6) bone marrow stromal cells to release the cytokine RANKL - osteoclast activation (lytic lesions of bone, bone pain and fractures
Calcium released from bone causes hypercalcaemia

3.PAthological effects of the paraprotein

33
Q

Outline what the pathological effects of the paraprotein

A

Single monoclonal Ig gamma in the serum -high levels =malignancy

Precipitates in kidney tubules cause renal failure
-Deposited as amyloid in many tissues
-2% of cases develop hyperviscosity syndrome:
Increased viscosity of blood leading to :
stroke and heart failure

34
Q

How 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

35
Q

Outline the treatment of Multiple Myeloma

A

Radiotherapy
Chemotherapy combinations (thalidomide ,lenalidomide and bortezomib),
Targeted therapies Immunotherapy (CAR-T) and allogenic hematopoietic stem cell transplantation (ASCT) young patients

Molecular Basis of Disease(Sem 4) (28 decks)

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