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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
According to WHO, describe their different classification as opposed to the traditional classification
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
26
What cell is cloned in Hodgkin lymphoma?
B cells
27
How does Hodgkin lymphoma present?
non-painful enlarged lymph nodes
28
What are 50% of Hodgkin lymphomas caused by?
Epestein-Barr infection - this is the classic form
29
What else is hodgkin lymphoma caused by?
* Family history * HIV/AIDS
30
How do we diagnose Hodgkin lymphoma (what do we look for?)?
By finding a hodgkin cell in a lymph node biopsy
31
What does a hodgkin cell look like?
* Bilobed nucleus * So big you can see by a light microscope
32
How do you treat hodgkin lymphoma?
* Chemotherapy with/without radiotherapy * Stem cell transplant
33
What is the prognosis for hodgkin lymphoma?
5 year survival of 50-90%
34
What do non-hodgkin lymphomas present with?
* Enlarged lymph nodes * general lymphoma symptoms
35
What are the risk factors for non-hodgkins lymphoma?
* viral infections in Burkitt’s lymphoma * Human T-cell leukaemia virus = risk factor for adult T cell lymphoma
36
What is the cause of non-Hodgkin lymphoma?
Chromosome translocations
37
Which type of genes are often involved in non-Hodgkin lymphoma chromosomal translocations?
Immunoglobulin (Ig) heavy chain or light chain loci on chromosome 14
38
Why do these genes (Ig )in particular cause non-Hodgkin lymphoma in translocation?
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
Which cell are these genes (Ig )normally highly expressed in?
B cells
40
As an example, name the genes/chromosomes translocated in most cases of follicular lymphoma
* 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
What happens to the epstein barr virus in highly immunosuppressed individuals?
Endogenous latent EBV transform B cells as no cytotoxic T cells
42
Name the translocation in Burkitt’s lymphoma (a type of non-Hodgkin lymphoma) name the proto-oncogene involved
* chromosome 14 + chromosome 8 * brings together enhancer + c-myc (a potent proto-oncogene)
43
Name a risk factor for non-Hodgkin lymphoma
Also viral infections such as EBV in immunosuppressed patients
44
How does this risk factor (EBV) cause non-Hodgkin lymphoma - name the oncogene involved?
* 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
What are the classifications of non-hodgkins lymphoma?
Low and high grade
46
What are the features of low grade non-hodgkin lymphoma?
* Normal tissue architecture partially preserved * Slow division * May be present for many months before diagnosis
47
What are the features of high grade lymphoma?
* Loss of normal tissue architecture * Divide rapidly * Present for a matter of weeks before diagnosis * Life threatening
48
How can you diagnose non-hodgkin lymphoma?
* Immunophenotyping * Cylogenics-FISH * Light chain restriction * PCR
49
How can you treat non-hodgkins lymphoma?
* Monoclonal antibody therapy * Chemotherapy * Radiotherapy * Stem cell transplant
50
How does the monoclonal antibody therapy work?
* Targets CD20 antigen on B cells that are cancerous for leukaemia or lymphoma * Then natural killer cells will kill these abnormal B cells
51
What is the prognosis for non-hodgkin lymphoma?
Overall 5 year survival rate = 70%
52
What is the difference of Hodgkin vs non-Hodgkin lymphoma?
Hodgkin - clonal B cell malignancy Non-Hodgkin - all of the other lymphomas (?)
53
What is a multiple myeloma?
Tumour of the bone marrow that involves B plasma cells (antibody production)
54
What does multiple myeloma present as?
Absence of initial symptoms, later there is bone pain, bleeding, frequent infections and anaemia
55
When does multiple myeloma present?
Much later
56
What are the causes and risk factors for multiple myeloma?
* Unknown cause * Risk factors are normal cancer risk factors
57
What are the three aspects associated with multiple myeloma?
* Suppression of normal bone marrow, blood cell and immune cell function * Bone resorption and release of calcium * Pathological effects of the paraprotein
58
What is a paraprotein?
Single monoclonal immunoglobulin in the serum
59
What does high levels of paraprotein mean?
Malignancy
60
Name the 3 clinical (pathological) features of multiple myeloma that cause disease
* suppression of normal bone marrow * bone resorption and release of calcium * accumulation of paraproteins
61
What does supression of noraml bone marrow, blood cell and immune function cause?
* Anaemia * Bleeding * Recurrent infections
62
Why do multiple myelomas cause bone resorption and release of calcium?
lytic lesions of the bone and bone pain and fractures and hypercalcaemia
63
What is a lytic lesion?
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
**Outline the mechanism of bone resorption in multiple myeloma**
Myeloma cells produce IL-6 which stimulates bone marrow stromal cells to release RANKL which activates osteoclasts for resorption * also suppresses OPG
65
What symptoms are caused by calcium release from the bone?
Mental disturbance
66
Describe the pathological effects of the accumulation of paraprotein (high paraprotein)
* Precipitates in kidney tubules causing renal failure * Deposited as amyloid in tissues * Hyperviscosity syndrome (rare - 2%)
67
What is hyperviscosity syndrome?
Increased viscosity of blood leading to stroke and heart failure
68
How can you diagnose multiple myeloma?
* 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
Why is the erythrocyte senimentation rate high in multiple myeloma?
Stalking of the RBC
70
How do you treat multiple myeloma?
* Radio/chemo combination * Targeted therapies * Immunotherapy * Haematopoetic stem cell transplantation in young patients
71
What is the prognosis for multiple myeloma?
35% survival for 5 yrs

MBD (23 decks)

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