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MBD > Introduction To Lymphomas And Myelomas > Flashcards

Introduction To Lymphomas And Myelomas Flashcards

1
Q

What is lymphoma?

A

Cancer of the white blood cells (lymphocytes).

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2
Q

What does lymphoma affect?

A

Mature blood cells

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3
Q

What are lymphomas due to?

A

Specific genetic mutations and chromosomal translocations

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4
Q

Name some of the functions of the lymphatic system

A
  • blood filtration/purification
  • removal of excess fluid from tissues
  • absorption and transport of lipids
  • immune system activation
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5
Q

Describe the structure and function of the lymph nodes

A
  • Filter the lymph fluid
  • Are formed from multiple lymph nodules that have a capillary bed inside each one
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6
Q

What are primary lymph organs? - Name them

A

Sites where stem cells can divide and become immunocompetent

  • bone marrow and thymus
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7
Q

What are secondary lymph organs? - Name them

A

Sites where most of the immune responses occur

  • spleen, lymph nodes, appendix, tonsils and Peyer’s patches
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8
Q

What is an adenopathy?

A

When lymph nodes increase in size

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9
Q

What organs does lymphoma usually spread to?

A

Lungs, bone marrow, liver

  • if it infiltrates the bone marrow it may be seen in the blood - this makes it complicated as it is between a leukaemia and a lymphoma
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10
Q

What are the types of lymphoma?

A
  • Non-hodgkins
  • Hodgkins
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11
Q

Between Hodgkin’s and non-Hodgkin’s lymphoma - which is most common?

A

Non-Hodgkin’s (83%)

Hodgkin’s is rare (is not in top 20 cancers in the UK) but non-Hodgkin’s is top 6 so is much more common

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12
Q

What are non-hodgkins lymphomas characterised by?

A

Mature B-cell, T-cell and NK neoplasms

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13
Q

What two ways can we group non-Hodgkin’s lymphoma?

A

Diffuse and follicular

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14
Q

What is a neoplasm?

A

Abnormal tissue growth

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15
Q

Describe the difference in age (incidence) of the two types (Non-Hodgkin’s vs Hodgkin’s)

A
  • Non-Hodgkin’s increases with age
  • Hodgkin’s peaks in adolescence and people over 50
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16
Q

Describe how lymphomas tend to present

A
  • Fever
  • Swelling of the face and neck
  • Lump in neck, armpits or groin
  • Excessive sweating at night
  • Unexpected weight loss
  • Breathlessness
  • Itchiness
  • Feeling of weakness
  • Loss of appetite
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17
Q

How can you diagnose lymphoma?

A
  • Lymph node biopsy to check for lymphoma
  • Then flow cytometry, FISH or NGS to check the type
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18
Q

What are the stages of lymphoma called?

A
  • I
  • II
  • III
  • IV
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19
Q

What does stage I lymphoma look like?

A
  • Localised disease
  • Single lymph node region or organ
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20
Q

What does stage II lymphoma look like?

A

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

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21
Q

What does stage III lymphoma look like?

A

Two or more lymph node regions above and below the diaphragm

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22
Q

What does stage IV lymphoma look like?

A
  • Widespread disease
  • Multiple organs with or without lymph node involvement
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23
Q

What do we do to figure out what stage the lymphoma is?

A

PET

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24
Q

Broadly, describe the drivers and type of disease that lymphomas are

A

Multifactorial disease due to the malfunctioning of the body’s immune system

  • could be due to exposure to certain infections
  • most lymphomas occur when a B cell develops a mutation possibly due to a viral infection
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25
Q

According to WHO, describe their different classification as opposed to the traditional classification

A

The WHO one takes into account if it is a B or T cell, and the site from which it arises as well as other factors is as follows:

  • Mature B cell neoplasms
  • Mature T cell and NK neoplasms
  • Hodgkin lymphoma
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26
Q

What cell is cloned in Hodgkin lymphoma?

A

B cells

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27
Q

How does Hodgkin lymphoma present?

A

non-painful enlarged lymph nodes

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28
Q

What are 50% of Hodgkin lymphomas caused by?

A

Epestein-Barr infection - this is the classic form

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29
Q

What else is hodgkin lymphoma caused by?

A
  • Family history
  • HIV/AIDS
30
Q

How do we diagnose Hodgkin lymphoma (what do we look for?)?

A

By finding a hodgkin cell in a lymph node biopsy

31
Q

What does a hodgkin cell look like?

A
  • Bilobed nucleus
  • So big you can see by a light microscope
32
Q

How do you treat hodgkin lymphoma?

A
  • Chemotherapy with/without radiotherapy
  • Stem cell transplant
33
Q

What is the prognosis for hodgkin lymphoma?

A

5 year survival of 50-90%

34
Q

What do non-hodgkin lymphomas present with?

A
  • Enlarged lymph nodes
  • general lymphoma symptoms
35
Q

What are the risk factors for non-hodgkins lymphoma?

A
  • viral infections in Burkitt’s lymphoma
  • Human T-cell leukaemia virus = risk factor for adult T cell lymphoma
36
Q

What is the cause of non-Hodgkin lymphoma?

A

Chromosome translocations

37
Q

Which type of genes are often involved in non-Hodgkin lymphoma chromosomal translocations?

A

Immunoglobulin (Ig) heavy chain or light chain loci on chromosome 14

38
Q

Why do these genes (Ig )in particular cause non-Hodgkin lymphoma in translocation?

A

Each Ig gene has a very powerful tissue specific enhancer causing high expression levels so can increase expression of an oncogene

  • so there is a translocation between chromosome 14 and one other chromosome
39
Q

Which cell are these genes (Ig )normally highly expressed in?

A

B cells

40
Q

As an example, name the genes/chromosomes translocated in most cases of follicular lymphoma

A
  • chromosome 14 + chromosome 18
  • enhancer from one of the Ig genes enhances the promoter of the BCL-2 gene which is an apoptosis inhibitor
41
Q

What happens to the epstein barr virus in highly immunosuppressed individuals?

A

Endogenous latent EBV transform B cells as no cytotoxic T cells

42
Q

Name the translocation in Burkitt’s lymphoma (a type of non-Hodgkin lymphoma) name the proto-oncogene involved

A
  • chromosome 14 + chromosome 8
  • brings together enhancer + c-myc (a potent proto-oncogene)
43
Q

Name a risk factor for non-Hodgkin lymphoma

A

Also viral infections such as EBV in immunosuppressed patients

44
Q

How does this risk factor (EBV) cause non-Hodgkin lymphoma - name the oncogene involved?

A
  • Directly transforms B-lymphocytes in culture due to the viral oncogene LMP-1
  • Mostly in immunosuppressed patients due to not enough immune surveillance of cytotoxic T cells.
  • Causes high grade non-Hodgkin lymphoma.
45
Q

What are the classifications of non-hodgkins lymphoma?

A

Low and high grade

46
Q

What are the features of low grade non-hodgkin lymphoma?

A
  • Normal tissue architecture partially preserved
  • Slow division
  • May be present for many months before diagnosis
47
Q

What are the features of high grade lymphoma?

A
  • Loss of normal tissue architecture
  • Divide rapidly
  • Present for a matter of weeks before diagnosis
  • Life threatening
48
Q

How can you diagnose non-hodgkin lymphoma?

A
  • Immunophenotyping
  • Cylogenics-FISH
  • Light chain restriction
  • PCR
49
Q

How can you treat non-hodgkins lymphoma?

A
  • Monoclonal antibody therapy
  • Chemotherapy
  • Radiotherapy
  • Stem cell transplant
50
Q

How does the monoclonal antibody therapy work?

A
  • Targets CD20 antigen on B cells that are cancerous for leukaemia or lymphoma
  • Then natural killer cells will kill these abnormal B cells
51
Q

What is the prognosis for non-hodgkin lymphoma?

A

Overall 5 year survival rate = 70%

52
Q

What is the difference of Hodgkin vs non-Hodgkin lymphoma?

A

Hodgkin - clonal B cell malignancy

Non-Hodgkin - all of the other lymphomas (?)

53
Q

What is a multiple myeloma?

A

Tumour of the bone marrow that involves B plasma cells (antibody production)

54
Q

What does multiple myeloma present as?

A

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

55
Q

When does multiple myeloma present?

A

Much later

56
Q

What are the causes and risk factors for multiple myeloma?

A
  • Unknown cause
  • Risk factors are normal cancer risk factors
57
Q

What are the three aspects associated with multiple myeloma?

A
  • Suppression of normal bone marrow, blood cell and immune cell function
  • Bone resorption and release of calcium
  • Pathological effects of the paraprotein
58
Q

What is a paraprotein?

A

Single monoclonal immunoglobulin in the serum

59
Q

What does high levels of paraprotein mean?

A

Malignancy

60
Q

Name the 3 clinical (pathological) features of multiple myeloma that cause disease

A
  • suppression of normal bone marrow
  • bone resorption and release of calcium
  • accumulation of paraproteins
61
Q

What does supression of noraml bone marrow, blood cell and immune function cause?

A
  • Anaemia
  • Bleeding
  • Recurrent infections
62
Q

Why do multiple myelomas cause bone resorption and release of calcium?

A

lytic lesions of the bone and bone pain and fractures and hypercalcaemia

63
Q

What is a lytic lesion?

A

An osteolytic lesion is a softened section of a patient’s bone formed as a symptom of specific diseases, including breast cancer and multiple myeloma.

64
Q

Outline the mechanism of bone resorption in multiple myeloma

A

Myeloma cells produce IL-6 which stimulates bone marrow stromal cells to release RANKL which activates osteoclasts for resorption

  • also suppresses OPG
65
Q

What symptoms are caused by calcium release from the bone?

A

Mental disturbance

66
Q

Describe the pathological effects of the accumulation of paraprotein (high paraprotein)

A
  • Precipitates in kidney tubules causing renal failure
  • Deposited as amyloid in tissues
  • Hyperviscosity syndrome (rare - 2%)
67
Q

What is hyperviscosity syndrome?

A

Increased viscosity of blood leading to stroke and heart failure

68
Q

How can you diagnose multiple myeloma?

A
  • Serum electrophoresis for paraprotein
  • Urine electrophoresis
  • Bone marrow biopsy for increased levels of plasma cells
  • Erythrocyte sedimentation rate
  • Flow cytometry and cytogenesis
  • Radiological investigation
69
Q

Why is the erythrocyte senimentation rate high in multiple myeloma?

A

Stalking of the RBC

70
Q

How do you treat multiple myeloma?

A
  • Radio/chemo combination
  • Targeted therapies
  • Immunotherapy
  • Haematopoetic stem cell transplantation in young patients
71
Q

What is the prognosis for multiple myeloma?

A

35% survival for 5 yrs

MBD (23 decks)

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