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Haematology > Introduction to Lymphoid Malignancies > Flashcards

Introduction to Lymphoid Malignancies Flashcards

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1
Q

What is lymphoma?

A

Lymphoma: cancer of the white blood cells (lymphocytes)

  • Group of heterogeneous cancers of mature lymphocytes that develop in lymph organs.
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2
Q

Which cells does lymphoma affect?

A

Affects mature blood cells, mostly B lymphocytes but also less commonly T lymphocytes.

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3
Q

What causes lymphoma?

A

Heterogeneous group.

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

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4
Q

Which step of the haematopoiesis process does lymphoma affect?

A

It affects mature lymphocytes and natural killer cells of lymphoid lineage in haematopoiesis process

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5
Q

What is lymph?

A

Lymph is a fluid composed of lipids, proteins and immune cells present in interstitial spaces between tissues

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6
Q

Outline the main functions of lymph

A

Main functions:

a) blood filtration/purification
b) removal of excess fluids from tissues
c) absorption and transport of lipids
d) Immune system activation

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7
Q

What are lymph nodes?

A

Lymph nodes are small organs responsible for the aforementioned functions and are located throughout the body

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8
Q

What are the primary lymph organs?

A

Thymus & bone marrow

sites where stem cells can divide and become immunocompetent.

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9
Q

What are the secondary lymph organs?

A

Tonsils, adenoids, lymph nodes, spleen, peyer’s patches, appendix

sites where most of the immune responses occur.

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10
Q

Outline the progression of lymphomas

A
  1. Affect lymphocytes in different maturation stages
  2. Uncontrolled division
  3. Organ size increase:
    • Lymph node (adenopathy)
    • Other lymph organs (splenomegaly)
  4. Spread to other tissues through lymphatic system
  5. Might infiltrate bone marrow (detectable in blood)
    and / or other organs
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11
Q

How are lymphomas classified

A

Non-hodgkin Lymphoma

Hodgkin lymphoma

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12
Q

What are the warning signs of lymphoma?

A
  • Fever
  • Face + neck swelling
  • Lump in neck, armpits or groin
  • Excessive sweating at night
  • Unexpected weight loss
  • Loss of appetite
  • Feeling of weakness
  • Breathlessness
  • Itchiness
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13
Q

How is lymphoma diagnosed?

A
  1. lymph node biopsy
  2. analyse under microscope
  3. immunophenotyping
  4. NGS, FISH or flow cytometry
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14
Q

Describe stage 1 lymphoma

A

1 - localised disease

single lymph node region or single organ

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15
Q

Describe stage 2 lymphoma

A

2 - 2+ lymph node regions on same side of diaphragm

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16
Q

What is defined as stage 3 lymphoma?

A

3 - 2+ lymph node regions above and below the diaphragm

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17
Q

What is stage 4 lymhpoma?

A

4 - widespread disease; multiple organs with or without lymph node involvement

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18
Q

Describe lymphoma aetiology

A

Multifactorial disorder:

  • Malfunctioning of immune system
  • Exposure to certain infections
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19
Q

What causes lymphoma?

A

The triggers are unknown but… most lymphomas occur when a B cell develops/acquires a mutation in its DNA.

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20
Q

Describe the WHO classifications of lymphoma

A

According to WHO 2016

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

67 subtypes of mature lymphoid neoplasm

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21
Q

What is hodgkin lymphoma?

A

Clonal B-cell malignancy.

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22
Q

What are the signs of hodgkin lymhoma?

A

Presentation- non-painful enlarged lymph node(s).

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23
Q

What are the risk factors for hodgkin lymphoma?

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A

Risk factors: ~50% cases due to Epstein-Barr virus (EBV)-Classic form.
Other risk factors: Family history and HIV/AIDS.

24
Q

How is hodgkin lymphoma diagnosed?

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A

Diagnosis: Excisional lymph node biopsy

25
What are the treatment options for hodgkin lymphoma?
Treatment: Chemotherapy +/- radiotherapy. Stem cell transplant.
26
Describe hodgkin lymphoma prognosis
Prognosis 5 year survival ~50-90% depending on age, stage and histology Especially good results in young adults (97%)
27
Describe the signs of non-hodgkin lymphomas
enlarged lymph node(s) Some forms are slow and others grow faster General lymphoma symptoms.
28
What causes non-hodgkin lymphomas?
Causes: Chromosome translocations
29
What are the risk factors for non-hodgkin lymphomas?
Virus infections (e.g. EBV (HHV4) in Burkitt's lymphoma driven lymphomas in immunosuppressed patients; Human T-cell leukaemia virus in adult T-cell lymphoma)
30
What chromosomal translocation causes lymhpomas?
Many lymphomas carry chromosome translocations involving the Ig heavy chain or light chain loci (chr14).
31
Describe the normal IgG expression
Ig genes are highly expressed in B-cells. | Each Ig gene has a powerful tissue specific enhancer (high expression levels).
32
What is the normal role of Ig genes
Normal role: activating the promoter of the rearranged V segment
33
What is a common chromosomal translocation in lymphomas?
Most cases of follicular lymphoma carry t(14;18)(q32;q21)
34
Outline the translocation often seen in Burkitts Lymphoma
t(8;14)(q24;q32) is frequently observed in Burkitt’s lymphoma. c-myc is a potent oncogene
35
How does EBV (HHV4) viral infection lead to lymhpoma?
Viral infections (e.g. EBV (HHV4)) is a risk factor because It directly transforms B-lymphocytes in culture. Due to viral oncogene LMP-1
36
Why don't all EBV infected people develop lymhpomas?
Over half of normal individuals carry latent EBV infection They don't develop lymphomas due to effective immune surveillance by cytotoxic T-cells
37
Describe how EBV in immunosuppressed patients causes lymphoma
In highly immunosuppressed individuals endogenous latent EBV may transform B-cells. No longer eliminated by cytotoxic T-cells. Develop high grade lymphoma.
38
What are low grade non-hodgkin lymphomas?
Low grade - Normal tissue architecture partially preserved - normal cell of origin recognisable - Divide slowly - May be present for many months before diagnosis - Behave in indolent fashion
39
What are high grade non-hodgkin lymphomas?
High grade - Loss of normal tissue architecture -normal cell of origin hard to determine - Divide rapidly - Present for a matter of weeks before diagnosis - May be life-threatening
40
What are the diagnostic techniques used for non-hodgkin lymphoma?
- Immunophenotyping - Cytogenetics: FISH; For chromosome translocations (e. g. t(14;18) Ig : Bcl-2) - Light chain restriction - PCR; For clonal Ig gene rearrangement
41
Outline the treatment options for non-hodgkin lymphoma patients
- Chemotherapy - Radiotherapy - Stem cell transplant - Monoclonal Ab therapy -Rituximab (anti-CD20)
42
What is the prognosis of non-hodgkin lymphoma?
Prognosis: Overall five-year survival rate ~70%
43
What is multiple myeloma?
Tumour of the bone marrow that involves plasma cells (antibodies production).
44
What are the signs of myeloma?
Absence of initial symptoms. Later: bone pain, bleeding, frequent infections, and anaemia.
45
What causes multiple myeloma?
Unknown cause
46
What are the identified risk factors for myeloma?
Obesity, radiation exposure, family history, and certain chemicals
47
What clinical features are altered in multiple myeloma?
1. Suppression of normal bone marrow, blood cell and immune cell function 2. Bone resorption release of calcium 3. Pathological effects of paraprotein –
48
What is the effect of pathological paraprotein?
Single monoclonal Igɣ in the serum- high levels – malignancy
49
What are the consequences of abnormal bone marrow, blood and immune cell function?
- Anaemia - Bleeding tendency - Recurrent infections
50
What is the consequence of bone resorption release of Ca2+?
Myeloma cells produce cytokines (esp. IL-6) Il-6 goes to bone marrow stromal cells Causes release of cytokine RANK Osteoclasts activation (lytic lesions of bone, bone pain, fractures).
51
What does calcium release from bones cause?
Calcium released from bone causes hypercalcaemia (multiple symptoms including mental disturbance).
52
What is the consequence of pathological paraprotein?
- Precipitates in kidney tubules = renal failure - Deposited as amyloid in many tissues - 2% of cases develop hyperviscosity syndrome Increased viscosity of blood leading to Stroke + Heart failure
53
How is myeloma diagnosed?
- Serum electrophoresis for paraprotein - Urine electrophoresis - Bone marrow biopsy for increased levels of plasma cells - Erythrocyte sedimentation rate > (ESR)-high due to stacking of RBC - Flow cytometry + cytogenetics detect cause - Radiological investigation of skeleton for lytic lesions
54
How is myeloma treated?
Radiotherapy, chemotherapy, allogeneic hematopoietic stem cell transplantation (ASCT) in young patients.
55
describe myeloma prognosis
Prognosis: Chemo+ASCT-overall 5-year survival rate ~35%
56
Describe multiple myeloma
Multiple myeloma is a tumour of the bone marrow that affects plasma cells characterised by suppression of normal bone marrow, bone resorption and release of calcium and production of paraprotein.
57
Give examples of blood cell cancers
Leukaemia, lymphoma and myeloma are cancers of the blood cells.

Haematology (8 decks)

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