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Fundamentals of P > Introduction to Lymphoid Malignancies > Flashcards

Introduction to Lymphoid Malignancies Flashcards

1
Q

Define Lymphoma

A
  • Lymphoma: cancer of the white blood cells (lymphocytes).
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2
Q

Lymphoma - affect and cause

A
  • Affects to 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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3
Q

Lymph nodes - function

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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4
Q

Primary lymph organs - function

A
  • Primary lymph organs: sites where stem cells can divide and become immunocompetent
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5
Q

Secondary lymph organs - function

A
  • Secondary lymph organs: sites where most of the immune responses occur
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6
Q

Describe process of infiltration of bone marrow in lymphoma

A

Affect lymphocytes in different maturation stages

Uncontrolled division

Organ size increase:
Lymph node (adenopathy)
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

Lymphoma - warning signs

A 
Swelling of face/neck
Fever
Lump in your neck, armpits and groin
Excessive sweating at night
Unexpected weight loss
Loss of apetite
Itchiness
Breathlessness
Feeling of weakness
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8
Q

Lymphoma - diagnosis

A

Lymph node biopsy - (make a small cut, remove the lymph node or portion of the lymph node, stitch the biopsy site close, then bandage)

Then immunophenotyping

NGS carried out after

FISH analysis for the detection of lymphoma-associated chromosomal abnormalities and flow cytometry

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9
Q

Describe the PET for stage I of lymphoma

A

Localized disease, single lymph node or single organ

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10
Q

Describe the PET for stage II of lymphoma

A

Two or more lymph node regions on the same side of the diaphragm

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11
Q

Describe the PET for stage III of lymphoma

A

Two or more lymph node regions above and below the diaphragm

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12
Q

Describe the PET for stage IV of lymphoma

A

Widespread disease, multiple organs, with/without lymph node involvement

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13
Q

Describe the factors causing lymphoma

A

Malfunctioning of the body’s immune system

Exposure to certain infections

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14
Q

Explain effect of factors causing lymphoma

A

Infection = transformed B cells

Leading to:
Deregulated cell cycle 
Inhibition of apoptosis
Genomic instability
Increased metastasis

= higher angiogenesis

= lymphoma (along w/other infections including HIV)

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15
Q

Describe the certainty of the knowledge of the causing factors for lymphoma

A

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

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16
Q

Describe classification of lymphoma according to WHO

A

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

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17
Q

Hodgkin lymphoma - what type

A
  • Clonal B-cell malignancy.
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18
Q

Hodgkin lymphoma - presentation

A
  • Presentation- non-painful enlarged lymph node(s)
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19
Q

Hodgkin lymphoma - risk factors

A
  • Risk factors: ~50% cases due to Epstein-Barr virus (EBV)- Classic form.
  • Other risk factors: Family history and HIV/AIDS.
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20
Q

Hodgkin lymphoma - diagnosis

A

Excisional lymph node biopsy

Cut skin to remove lymph node

If whole lymph node is removed = excisional biopsy

If a small part of a larger tumor or node is removed = incisional

Look for Hodgkin lymphoma cells (called Reed-Sternberg cells)

21
Q

Hodgkin lymphoma - treatment

A

Treatment: Chemotherapy +/- radiotherapy. Stem cell transplant

22
Q

Hodgkin lymphoma - prognosis

A

Prognosis = 5 year survival ~50-90% depending on age, stage and histology. Especially good results in young adults (97%)

23
Q

Non-Hodgkin lymphoma - high grade classification

A

Diffuse large B cell lymphoma

Burkitt lymphoma

24
Q

Non-Hodgkin lymphoma - low grade classification

A

Marginal zone lymphoma
Follicular lymphoma
Mantle cell lymphoma

25
Q

Non-Hodgkin lymphoma - high and low grade classification

A

T cell lymphoma (all subtypes)

26
Q

Non-Hodgkin lymphoma - presentation

A
  • Presentation: enlarged lymph node(s). Some forms are slow and others grow faster. General lymphoma symptoms
27
Q

Non-Hodgkin lymphoma - cause

A
  • Causes: 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.
28
Q

Non-Hodgkin lymphoma - risk factors

A
  • Risk factors: virus infections (e.g. EBV (HHV4) in Burkitt’s lymphoma; Human T-cell leukaemia virus in adult T-cell lymphoma)
29
Q

Non-Hodgkin lymphoma - cause = explain

A
  • Many lymphomas carry chromosome translocations involving the Ig heavy chain or light chain loci (chr14).
  • Ig genes are highly expressed in B-cells.
  • Each Ig gene has a powerful tissue specific enhancer (high expression levels).
30
Q

BCL-2 gene = function

A
  • BCL-2 is an apoptosis inhibitor
31
Q

Non-Hodgkin lymphoma - explain high grade development

A

Virus infections (e.g. EBV (HHV4) driven lymphomas in immunosuppressed patients)

  • 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.
  • Develop high grade lymphoma.
32
Q

Non-Hodgkin lymphoma - low grade description

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 an indolent fashion

33
Q

Non-Hodgkin lymphoma - high grade description

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

34
Q

Non-Hodgkin lymphoma - diagnosis

A

Diagnosis:

Immunophenotyping

Cytogenetics –FISH = for chromosome translocations (e.g. t(14;18) Ig : Bcl-2)

Light chain restriction

PCR = for clonal Ig gene rearrangement

35
Q

Non-Hodgkin lymphoma - treatment

A

Chemotherapy
Radiotherapy
Stem cell transplant
Monoclonal Ab therapy -Rituximab (anti-CD20)

36
Q

Non-Hodgkin lymphoma - prognosis

A

Prognosis:

Overall five-year survival rate ~70%

37
Q

Multiple Myeloma - define

A
  • Tumour of the bone marrow that involves plasma cells (antibodies production).
38
Q

Multiple Myeloma - presentation

A
  • Presentation: Absence of initial symptoms. Later: bone pain, bleeding, frequent infections, and anaemia.
39
Q

Multiple Myeloma - risk factors

A
  • Unknown cause. Risk factors: obesity, radiation exposure, family history, and certain chemicals.
40
Q

Multiple Myeloma - comparison w/healthy bone marrow

A

Healthy = WBC detect antigens, plasma cells produce normal antibodies

Myeloma = DNA damage in bone marrow, damaged WBC leads to myeloma cell expressing paraprotein (M component)

41
Q

Multiple Myeloma - effect of suppression of bone marrow as a clinical feature

A

Suppression of normal bone marrow, blood cell and immune cell function

Anaemia
Recurrent infections
Bleeding tendency

42
Q

Multiple Myeloma - describe bone resorption as a clinical feature

A

Bone resorption and release of calcium.

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).

43
Q

Multiple Myeloma - describe pathological effects of paraprotein as a clinical feature

A

Pathological effects of the paraprotein –(single monoclonal Igɣ in the serum- high levels – malignancy)

  • 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
44
Q

Multiple Myeloma - diagnosis

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

45
Q

Multiple Myeloma - treatment

A
  • Treatment: Radiotherapy, chemotherapy, allogeneic hematopoietic stem cell transplantation (ASCT) in young patients.
46
Q

Multiple Myeloma - prognosis

A
  • Prognosis: Chemo+ASCT-overall 5-year survival rate ~35%
47
Q

CAR-T cell therapy- treatment of haematological cancers

A

Remove blood from patient to get T cells

Make CAR T cells in lab = insert gene for CAR, now chimeric antigen receptor (CAR) present

Grow millions of CAR T cells

Infuse CAR T cells into patient

CAR T cells bind to cancer cells and kills them

48
Q

Autologous vs allogeneic stem cell transplant

A

An autologous transplant uses a person’s own stem cells

An allogeneic transplant uses stem cells from a donor whose human leukocyte antigens (HLA) are acceptable matches to the patient’s

Regardless process is:

Collection - stem cells from pt/donor’s BM/blood

Processing = blood/BM processed to purify/concentrate stem cells

Cryopreservation = blood/BM frozen to preserve

Chemo = high dose/radiation given to pt

Reinfusion = thawed stem cells reinfused into pt from donor or themselves

Fundamentals of P (62 decks)

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