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4 pathology > introduction to lymphoma and myeloma > Flashcards

introduction to lymphoma and myeloma Flashcards

1
Q

what is lymphoma?

A

group of heterogeneous cancers of the mature lymphocytes that develop in lymph organs

cancer of the white blood cells (lymphocytes)

  • Affects mature blood cells, mostly B lymphocytes but also T lymphocytes
  • Heterogeneous group
  • Many known to be due to specific genetic mutations and chromosomal translocations
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2
Q

functions of lymph node?

A

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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3
Q

what does the lymphatic system consist of?

A

fluid (lymph), lymph nodes and secondary organs

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4
Q

primary lymph organs?

A

sites where stem cells can divide and become immunocompetent

-thymus, bone marrow

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5
Q

secondary lymph organs?

A

sites where most of the immune responses occur

-spleen, toenails and adenoids, lymph nodes, appendix, peyers patches

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6
Q

stages of lymphoma?

A
  • lymphocytes in different maturation stages are affected
  • uncontrolled division
  • organ size increase: lymph node (adenopathy) and other lymph organs (splenomegaly)
  • spread to other tissues through lymphatic system
  • might infiltrate in bone marrow (detectable in blood)
    and/or other organs
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7
Q

Lymphomas are classified in two main types - what are they?

A

Hodgkin (HL) and Non-Hodgkin lymphomas (NHL).

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8
Q

is Hodgkin or Non-Hodgkin lymphoma more common?

A

Non-Hodgkin lymphoma much more common

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9
Q

what are the warning signs of lymphoma?

A
  • unexpected weight loss
  • loss of appetite
  • feeling of weakness
  • breathlessness
  • swelling of neck and face
  • lump in neck
  • excessive sweating at night
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10
Q

how is lymphoma diagnosed?

A

Lymph node biopsy

  • extraction of lymph node
  • check the sample under the microscope, and then you’ll get an idea of which type of lymphoma it is

In order to classify to subtype you’ll need to do further tests like NGS, FISH and flow cytometry

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11
Q

stages of lymphoma detected via a PET scan?

A

STAGE 1 - localised disease, single lymph node region or signal organ

STAGE II - 2 or more lymph node regions on the same side of the diaphragm

STAGE III - 2 or more lymph node regions above and below the diaphragm

STAGE IV - widespread disease, multiple organs, with or without lymph node involvement

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12
Q

what type of disease is lymphoma?

A

multifactorial

  • Malfunctioning of the body’s immune system
  • Exposure to certain infections
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13
Q

triggers of lymphoma?

A

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

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14
Q

describe Hodgkin lymphoma

-presentation, risk factors

A

Clonal B-cell malignancy

  • Presentation- non-painful enlarged lymph node(s)
  • Risk factors: 50% cases due to Epstein-Barr virus (EBV)- Classic form
  • Other risk factors: Family history and HIV/AIDS
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15
Q

describe Hodgkin lymphoma further

-diagnosis, treatment and prognosis

A
  • Excisional lymph node biopsy
  • Treatment: Chemotherapy +/- radiotherapy. Stem cell transplant.
  • Prognosis 5 year survival ~50-90% depending on age, stage and histology. Especially good results in young adults (97%)
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16
Q

types of non-Hodgkin lymphoma

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

  • diffuse large B cell lymphoma
  • Burkitt lymphoma

low grade
Normal tissue architecture partially preserved -normal cell of origin recognisable
Divide slowly
May be present for many months before diagnosis
Behave in an indolent fashion

-marginal zone lymphoma, follicluar lymphoma and mantle cell lymphoma

high and low grade
-T cell lymphoma

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17
Q

describe non-Hodgkin lymphoma

-presentation, causes and risk factors

A
  • Presentation: enlarged lymph node(s). Some forms are slow and others grow faster. General lymphoma symptoms
  • Causes: Chromosome translocations
  • Risk factors: virus infections (e.g. EBV (HHV4) in Burkitt’s lymphoma; Human T-cell leukaemia virus in adult T-cell lymphoma)
18
Q

with non-hodgkins lymphoma, what do many lymphomas carry?

A
  • many lymphomas carry chromosome translocations involving the Ig heavy chain or light chain loci (chr14)
19
Q

where are Ig genes highly expressed?

A

B-cells

20
Q

what does Ig gene have?

A

a powerful tissue specific enhancer (high expression levels)

21
Q

causes of non-hodgkins lymphoma?

A

Chromosome translocations

  • Normal role: activating the promoter of the rearranged V segment
  • Most cases of follicular lymphoma carry t(14;18)(q32;q21)
  • t(8;14)(q24;q32) is frequently observed in Burkitt’s lymphoma
  • BCL-2 is an apoptosis inhibitor
  • c-myc is a potent oncogene
22
Q

effect of EBV?

A

viral infection
-directly transforms B-lymphocytes in culture. Due to viral oncogene LMP-1.

  • Over half of all normal individuals carry latent EBV infection. They do not develop lymphomas due to effective immune surveillance by cytotoxic T-cells
  • In highly immunosuppressed individuals the endogenous latent EBV may transform B-cells
  • No longer eliminated by cytotoxic T-cells, and so develop high grade lymphoma.
23
Q

how is non-hodgkins lymphoma diagnosed?

A 
Immunophenotyping
Cytogenetics –FISH
For chromosome translocations (e.g. t(14;18) Ig : Bcl-2)
Light chain restriction
PCR
24
Q

how is non-hodgkins lymphoma treated?

A
  • Chemotherapy
  • Radiotherapy
  • Stem cell transplant
  • Monoclonal Ab therapy -Rituximab (anti-CD20)
25
Q

prognosis of non-hodgkins lymphoma?

A

Overall five-year survival rate ~70%

26
Q

what is multiple myeloma?

A
  • Tumour of the bone marrow, affects plasma cells (antibodies production)
  • characterised by suppression of normal bone marrow, bone resorption and release of calcium and production of paraprotein
27
Q

presentation of multiple myeloma?

A

Absence of initial symptoms

Later: bone pain, bleeding, frequent infections, and anaemia.

28
Q

is there a cause of multiple myeloma?

A

Unknown cause

29
Q

risk factors of multiple myeloma?

A

obesity, radiation exposure, family history, and certain chemicals

30
Q

name the 3 aspects of myeloma that give rise to different clinical features

A
  1. Suppression of normal bone marrow, blood cell and immune cell function
  2. Bone resorption and release of calcium
  3. Pathological effects of the paraprotein –(single monoclonal Ig in the serum- high levels – malignancy)
31
Q

what does suppression of normal bone marrow, blood cell and immune cell function cause?

A
  • Anaemia
  • Recurrent infections
  • Bleeding tendency
32
Q

bone resorption and release of calcium causes?

A

a) Myeloma cells produce cytokines (esp. IL-6) → bone marrow stromal cells to release the cytokine RANKL→ osteoclasts activation (lytic lesions of bone, bone pain, fractures)
b) Calcium released from bone causes hypercalcaemia (multiple symptoms including mental disturbance)

33
Q

effects of paraprotein?

A
  • Precipitates in kidney tubules cause renal failure
    • Deposited as amyloid in many tissues
    • 2% of cases develop hyperviscosity syndrome
  • Increased viscosity of blood leading to stroke
  • Heart failure
34
Q

where are abnormal paraprotein levels found?

A

myeloma

35
Q

diagnosis of myeloma?

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 the RBC
  • Flow cytometry and cytogenetics to detect cause
  • Radiological investigation of skeleton for lytic lesions
36
Q

treatment of myeloma?

A

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

37
Q

prognosis of myeloma?

A

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

38
Q

name some cancers of blood cells?

A

Leukaemia, lymphoma and myeloma

39
Q

where are chromosomal translocations commonly observed?

A

NHL

40
Q

main risk factor of both HL and NHL types?

A

virus infection (e.g. EBV (HHV4))

4 pathology (14 decks)

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