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TI2 > Intro to lymphoid malignancies > Flashcards

Intro to lymphoid malignancies Flashcards

1
Q

What is ALL? What is it characterised by? What is the corresponding normal cell?

A

Acute lymphoblastic leukaemia

  • Infiltration of blood and bone marrow
  • B-cell precursors in the bone marrow
  • T-ALL is T-cell precursors
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2
Q

What is CLL? What is it characterised by? What is the corresponding normal cell?

A

Chronic lymphocytic leukaemia

  • Infiltration of blood and bone marrow
  • Mature circulating B cells
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3
Q

What are lymphomas? What is it characterised by? What is the corresponding normal cell?

A
  • Tumours of lymph nodes and other secondary lymphoid organs
  • B cells in secondary lymphoid organs
  • T-cell lymphoma = T cells in secondary lymphoid)
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4
Q

What is myeloma? What is it characterised by? What is the corresponding normal cell?

A
  • Foci of malignant cells in the bone marrow

- Ig secreting plasma cells in the bone marrow

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5
Q

What are the two pathways that can be taken from HSCs?

A
  • Common myeloid progenitor -> neutrophils, red cells, platelets etc
  • Common lymphoid progenitor -> Pre-T and Pre-B
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6
Q

Where are lymphocytes produced?

A
  • All lymphocytes start in the bone marrow
  • Pre-T cells then go to the thymus where they mature and undergo TCR gene rearrangement. They then go to the secondary lymphoid organs
  • Pre-B cells stay in the bone marrow longer, here they can undergo Ig gene rearrangement. When they are mature, they go to the secondary lymphoid organs
  • in the lymph nodes, you have follicles with resting lymphocytes and germinal centres with proliferating ones
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7
Q

What are secondary lymphoid organs?

A
  • Lymph nodes
  • Spleen
  • Peyers patches
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8
Q

What is light chain restriction?

A
  • Normal B cells have Ig with heavy and light chains
  • The light chains are either kappa or lambda
  • Because malignancies are clonal disease, if a cell with lambda light chains becomes malignant, all the descendants will also be lambda
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9
Q

How does ALL present?

A
  • Usually non-specific symptoms of bone marrow suppression

- Will get symptoms of organ filtration in advanced disease

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10
Q

What is the epidemiology of ALL?

A
  • Commonest leukaemia in children under 10

- Majority of patients are over 40

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11
Q

How do we investigate and diagnose ALL?

A
  • Bone marrow morphology - infiltration by undifferentiated blasts
  • Immunophenotyping - B-cell surface markers (T for T-ALL); light chain restriction; TdT (terminal deoxynucleotidyl transferase) positive
  • Cytogenetics - look at flow cytometry
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12
Q

How do we treat ALL?

A
  • Chemotherapy - induction, intensification, CNS directed chemo, maintenance
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13
Q

What is the prognosis for ALL?

A
  • Children - cure more than 90%
  • Adults - much lower survival because of different cell of origin, different oncogene mutations and older patients dont tolerate intensive treatment
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14
Q

What is Hodgkin’s lymphoma?

A
  • Enlarged lymph nodes from accumulation of lymphocytes
  • Presence of large Reed-Sternberg cells - malignant B-cells
  • Typically 99% of cells are reactive non-malignant cells
  • Peak incidence in young adults and possibly associated with EBV
  • treated with chemo/radiotherapy
  • 5 year survival ~50-90% dependent on age, stage and histology
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15
Q

What are the different types of NHL?

A
  • Low grade
  • High grade
  • T-cell lymphoma
  • EBV driven lymphoma in immunosuppressed patientss
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16
Q

What happens when there are chromosomal translocations in lymphoma?

A
  • Each Ig gene has a powerful tissue specific enhancer near to the constant segment
  • They activate the promoter of the rearranged V segment
  • If a chromosome translocation brings another gene close to the Ig enhancee, it will increase the expression of the gene
  • So if it gets closer to the BCL-2 gene, there will be increased production of BCL-2 (which inhibits apoptosis)
  • So follicular lymphoma is caused by cells failing to die rather than increased proliferation
17
Q

What happens in some cases of high grade lymphoma?

A
  • Some cases carry t(8:14)(q24;32)
  • This brings together the myc gene on chr18 with the IgH locus on chr14
  • Myc is a powerful oncogene - so cell has fast replication of cells, which also fail to die
18
Q

How does low grade NHL present?

A
  • enlarged lymph nodes
  • Normal tissue architecture partially preserved
  • Normal cell of origin recognisable
19
Q

How do we diagnose low grade NHL?

A
  • Histology
  • Immunocytochemistry - take a section of the tumour, stain it, see that kappa cells stain - shows clonal and malignant
  • Cytogenetics
  • Light chain restriction
  • PCR
20
Q

How do we use PCR to look at NHL?

A
  • Look at the Ig genes
  • Do PCR between the V and J regions - gives different sized bands
  • Would usually see a smear do to the polyclonal response
  • However if it is malignant and clonal, there will be separate bands
21
Q

How do we treat low grade NHL?

A
  • Chemo
  • Glucocorticoids - can induce death of lymphocytes
  • Radiotherapy
  • MoAb therapy - rituximab (anti-CD20)
22
Q

What is the prognosis for low grade NHL?

A
  • Doesnt proliferate much
  • Responds well to therapy
  • But hard to cure
23
Q

What is different about high grade NHL?

A
  • Low grade - relatively normal cells

- High grade - undifferentiated, abnormal cells

24
Q

What is the main risk factor for acute t-cell leukaemia/ lymphoma?

A
  • Infection with retrovirus HTLV-1

human T-cell leukaemia/lymphoma virus 1

25
Q

How does EBV cause lymphomas?

A
  • EBV (HHV4) directly transforms B-lymphocytes in culture
  • This is caused by the viral oncogene LMP-1
  • Over half of all normal indivuiduals carry latent EBV, but dont develop lymphomas due to immune surveillance by CTLs
  • So causes lymphoma in highly immunosuppressed individuals
26
Q

What is paraproteinaemia?

A
  • Presence of a single monoclonal Ig in the serum
  • If you take plasma, allow it to clot to get serum, and then run electrophoresis, you will see a series of bands
  • Bands will be albumin, alpha globulins, beta globulins and then a fuzzy band of gamma globulins
  • Usually it would be a faint blur of gamma globulins (polyclonal)
  • In malignancies, it will show a dark, thick bands as the clonal cells will produce a single type of Ig
27
Q

What is the most common disease that you find paraprotein?

A

Multiple myeloma

28
Q

What three aspects of myeloma give rise to different clinical features?

A
  • Suppression of normal bone marrow, blood cells and immune cell function
  • Bone resorption and release of calcium
  • Pathological effects of the paraprotein
29
Q

What does the blood cell/ immune suppression cause?

A
  • Anaemia
  • Recurrent infections
  • Bleeding tendency
30
Q

What causes the bone resorption?

A
  • Myeloma produces cytokines - especially IL-6
  • These stimulate bone marrow stromal cells to release RANKL
  • This activates osteoclasts, causing lytic lesions of bone, bone pain, and fractures
  • The calcium released from the bone causes hypercalcaemia -> mental disturbance
31
Q

What is the effect of the paraprotein?

A
  • Precipitates in the kidney tubules and causes renal failure
  • Deposited as amyloid in many tissues
  • 2% of cases develop hyperviscosity syndrome leading to stroke and heart failure
32
Q

How do we diagnose MM?

A
  • Serum electrophoresis for paraprotein
  • urine electrophoresis - Bence-Jones protein represents free monoclonal light chains
  • Increased plasma cells in the bone marrow
  • ESR (very high due to rouleaux formation) - RBCs stack together due to high protein
  • Radiological investigation of skeleton for lytic lesions
33
Q

How do we treat myeloma?

A
  • Chemo - cytotoxic drugs, glucocorticoids, thalidomide analogues, Bortezomib
  • Allogenic bone marrow transplant

TI2 (20 decks)

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