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Haematology > Introduction to Lymphoid Malignancies > Flashcards

Introduction to Lymphoid Malignancies Flashcards

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?

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?

A

Diagnosis: Excisional lymph node biopsy

25
Q

What are the treatment options for hodgkin lymphoma?

A

Treatment: Chemotherapy +/- radiotherapy. Stem cell transplant.

26
Q

Describe hodgkin lymphoma prognosis

A

Prognosis 5 year survival ~50-90% depending on age, stage and histology

Especially good results in young adults (97%)

27
Q

Describe the signs of non-hodgkin lymphomas

A

enlarged lymph node(s)
Some forms are slow and others grow faster
General lymphoma symptoms.

28
Q

What causes non-hodgkin lymphomas?

A

Causes: Chromosome translocations

29
Q

What are the risk factors for non-hodgkin lymphomas?

A

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
Q

What chromosomal translocation causes lymhpomas?

A

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

31
Q

Describe the normal IgG expression

A

Ig genes are highly expressed in B-cells.

Each Ig gene has a powerful tissue specific enhancer (high expression levels).

32
Q

What is the normal role of Ig genes

A

Normal role: activating the promoter of the rearranged V segment

33
Q

What is a common chromosomal translocation in lymphomas?

A

Most cases of follicular lymphoma carry t(14;18)(q32;q21)

34
Q

Outline the translocation often seen in Burkitts Lymphoma

A

t(8;14)(q24;q32) is frequently observed in Burkitt’s lymphoma.
c-myc is a potent oncogene

35
Q

How does EBV (HHV4) viral infection lead to lymhpoma?

A

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
Q

Why don’t all EBV infected people develop lymhpomas?

A

Over half of normal individuals carry latent EBV infection

They don’t develop lymphomas due to effective immune surveillance by cytotoxic T-cells

37
Q

Describe how EBV in immunosuppressed patients causes lymphoma

A

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

No longer eliminated by cytotoxic T-cells.
Develop high grade lymphoma.

38
Q

What are low grade non-hodgkin lymphomas?

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 indolent fashion

39
Q

What are high grade non-hodgkin lymphomas?

A

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
Q

What are the diagnostic techniques used for non-hodgkin lymphoma?

A
  • Immunophenotyping
  • Cytogenetics: FISH; For chromosome translocations
    (e. g. t(14;18) Ig : Bcl-2)
  • Light chain restriction
  • PCR; For clonal Ig gene rearrangement
41
Q

Outline the treatment options for non-hodgkin lymphoma patients

A
  • Chemotherapy
  • Radiotherapy
  • Stem cell transplant
  • Monoclonal Ab therapy -Rituximab (anti-CD20)
42
Q

What is the prognosis of non-hodgkin lymphoma?

A

Prognosis: Overall five-year survival rate ~70%

43
Q

What is multiple myeloma?

A

Tumour of the bone marrow that involves plasma cells (antibodies production).

44
Q

What are the signs of myeloma?

A

Absence of initial symptoms. Later: bone pain, bleeding, frequent infections, and anaemia.

45
Q

What causes multiple myeloma?

A

Unknown cause

46
Q

What are the identified risk factors for myeloma?

A

Obesity, radiation exposure, family history, and certain chemicals

47
Q

What clinical features are altered in multiple myeloma?

A
  1. Suppression of normal bone marrow, blood cell and immune cell function
  2. Bone resorption release of calcium
  3. Pathological effects of paraprotein –
48
Q

What is the effect of pathological paraprotein?

A

Single monoclonal Igɣ in the serum- high levels – malignancy

49
Q

What are the consequences of abnormal bone marrow, blood and immune cell function?

A
  • Anaemia
  • Bleeding tendency
  • Recurrent infections
50
Q

What is the consequence of bone resorption release of Ca2+?

A

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
Q

What does calcium release from bones cause?

A

Calcium released from bone causes hypercalcaemia (multiple symptoms including mental disturbance).

52
Q

What is the consequence of pathological paraprotein?

A
  • 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
Q

How is myeloma diagnosed?

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 RBC
  • Flow cytometry + cytogenetics detect cause
  • Radiological investigation of skeleton for lytic lesions
54
Q

How is myeloma treated?

A

Radiotherapy, chemotherapy, allogeneic hematopoietic stem cell transplantation (ASCT) in young patients.

55
Q

describe myeloma prognosis

A

Prognosis: Chemo+ASCT-overall 5-year survival rate ~35%

56
Q

Describe multiple myeloma

A

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
Q

Give examples of blood cell cancers

A

Leukaemia, lymphoma and myeloma are cancers of the blood cells.

Haematology (8 decks)

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