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Molecular Basis Of Disease > Intro To Lymphoma And Myeloma > Flashcards

Intro To Lymphoma And Myeloma Flashcards

1
Q

What is lymphoma and state the 2 key risk factors?

A
  • Cancer of mature WBCs (lymphocytes) -> B (mostly) + T LP -> heterogenous group
  • Risk factors: Specific genetic mutations + Chromosomal translocations
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2
Q

State the 4 main functions of the lymphatic system and what it is aided by? VD

A
  • Blood filtration
  • Removal of excess fluids from tissues
  • Absorption, Transport of lipids
  • Immune system activation
  • Occurs within lymph nodes throughout body
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3
Q

Describe the difference in function between primary + secondary lymph organs and state organ examples

A
  • Primary: SC divide + become immunocompetent -> thymus + bone marrow
  • Secondary: Where most of the immune responses occur -> tonsils, lymph nodes, appendix, spleen
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4
Q

Describe how chromosomal translocation leads to lymphoma?

A
  • Affects lymphocytes in different maturation stages - uncontrolled division
  • Organ size increases (adenopathy = LN) (splenomegaly = other L organs)
  • Lymphoma spread to other tissues through lympathic system
  • May infiltrate in bone marrow (detectable in blood) and/or organs
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5
Q

State key symptoms of lymphoma?

A
  • Fever
  • Itchiness
  • breathlessness
  • Swelling of the face and neck
  • Lump in your neck, armpits or grain
  • Excessive sweating at night
  • Unexpected weight loss
  • Feeling of weakness
  • Loss of appetite
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6
Q

Describe the full diagnostic process behind lymphoma? VD

A
  • Symptoms -> lymph node biopsy (presence of informer) -> analyse via microscope (detect LP) - identify genetic alteration + subtype of lymphoma (via FISH, flow cytometry, NGS OR immunophenotyping) - Identify stage (I-IV) of LP via PET
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7
Q

Describe the aetiology of lymphoma and the main trigger?

A
  • Aetiology: multifactorial disorder -> malfunctioning of immunity + exposure to certain infections
  • Main trigger: Unknown -> Mostly due to B cell mutation
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8
Q

State the traditional + updated (WHO) classification?

A
  • Traditional: Non Hodgkin’s (<) + Hodgkin lymphoma
  • WHO: Mature B-cell neoplasms, mature T-cell & NK neoplasms + Hodgkin lymphoma
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9
Q

Describe hodgkin lymphoma, its presentation + risk factors?

A
  • Hodgkin lymphoma: Clonal B-cell malignancy
  • Presentation: Non-painful enlarged lymph node(s)
  • Risk factors: Epstein-barr virus (50%), family history + HIV/AIDs
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10
Q

Describe the diagnosis and treatment of hodgkin lymphoma?

A
  • Diagnosis: Excisional lymph node biopsy -> Reed-Sternberg cells present
    Treatment: Chemotherapy, radiotherapy, SC transplant
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11
Q

Briefly describe Reed sternberg cells

A
  • Hodgkin lymphoma is diagnosed by the detection of Reed Sternberg cells
  • They’re derived from B lymphocyte mutations
  • Key marker of Hedgkin lymphoma
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12
Q

Non-hodgkin lymphoma
State the presentation, cause + risk factors of non-hodgkin lymphoma?

A
  • Presentation: Enlarged lymph node + general lymphoma symptoms
  • Cause: Chromosome translocations
  • Risk factors: Virus infections -> EBV (Burkitt’s lym.). Human T-cell leukaemia virus (adult T-cel lym)
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13
Q

Describe how virus infections become a risk factor of non-hodgkin lymphoma?

A
  • Directly transforms B-lymp. via viral oncogene LMP-1 -> over half of all normal individuals carry latent EBV infection -> no lymphoma development -> effective immunity via Tc cells
  • Highly immunosuppressed individuals -> latent EB may transform B-cells -> no longer be eliminated via Tc cells -> development of high grade lymphoma
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14
Q

Describe the low grade classification and features of them for non-hodgkin lymphoma?

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 (lazy) fashion
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15
Q

Describe the high grade classification and features of them for 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
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16
Q

State the diagnostic methods for non-hodgkin lymphoma?

A
  • Diagnosis:
  • Immunophenotyping
  • Cytogenetics - FISH (For chromosome translocations (e.g. t(14;18) Ig : Bcl-2))
  • Light chain restriction (k>^)
  • PCR (clonal Ig gene rearrangement)
17
Q

State the treatments for non-hodgkin lymphoma?

A
  • Treatment:
  • Chemotherapy
  • Radiotherapy
  • SC transplant
  • Monoclonal Ab therapy - Rituximab (anti-CD20)
18
Q

Describe the main cause of non-hodgkin lymphoma?

A
  • Chromosomal translocation - involve lg heavy or light chain loci (Cr 14) - Ig genes highly expressed in B-cells - Ig gene has tissue specific enhancer (increase expression)
  • Enhancer role - promotor activation of rearranged V segment of lg
  • However, in lymphoma, this enhancer translocates to a different chromosome and begins enhancing the expression of a different unwanted gene through its promoter.
19
Q

Describe how follicular lymphoma arises?

A
  • Chromosomal translocation -> enhancer (cr14) + BCL-2 (apoptosis inhibitor) (cr18) brought together -> Enhancer causes increased BCL-2 -> Increased inhibition of apoptosis
20
Q

Describe how Burkitt’s lymphoma arises?

A
  • Chromosomal translocation -> c-myc (potent proto-oncogene) (cr8) + enhancer (cr-14) brought together -> E causes increased c-myc expression -> oncogene -> Increased cell proliferation
21
Q

What is multiple myeloma?

A
  • Tumour of the bone marrow
  • Involving plasma cells (AB production).
22
Q

Describe the presentation + risk factors of multiple myeloma?

A
  • Presentation: Absence of initial symptoms -> Later: bone pain, bleeding, frequent infections + anaemia -> unknown cause
  • Risk factor: Obesity, radiation exposure, family history, + certain chemicals.
23
Q

Describe methods of diagnosis of multiple myeloma (6)

A
  • Serum electrophoresis for paraprotein
  • Urine electrophoresis
  • Bone marrow biopsy for increased levels of plasma cells
  • Erythrocyte sedimentation rate (ESR) - increased due to stacking of the RBC Myeloma
  • Flow cytometry + cytogenetics to detect causes
  • Radiological investigation of skeleton for lytic lesions
24
Q

Describe the treatments for multiple myeloma?

A
  • Radiotherapy, chemotherapy combinations (thalidomide, lenalidomide and bortezomib)
  • targeted therapies
  • immunotherapy (CAR-T)
  • allogeneic hematopoietic SC transplantation (ASCT) in young patients
25
Q

State the 3 major clinical features of multiple myeloma?

A
    1. Suppression of normal bone marrow, blood cell + immune cell function-> anaemia, recurrent infections + bleeding tendency
    1. Bone resorption + release of calcium
    1. Pathological effects of the paraprotein
26
Q

Describe the bone resorption effect from multiple myeloma?

A
  • Myeloma cells produce cytokines (esp. IL-6)
  • BM stromal cells release RANKL
  • Osteoclasts activation
  • Calcium released from bone causes hypercalcaemia
  • Multiple symptoms (including mental disturbance)
27
Q

Describe the pathological effects of the paraprotein?

A
  • Abnormal WBC (myeloma cell) -> contains paraprotein -> single monoclonal Ig in serum -> Increased levels = malignancy
  • Precipitates in kidney tubules - renal failures
  • Deposited as amyloid
  • Can develop into hyperviscosity syndrome -> stroke + heart failure

Molecular Basis Of Disease (30 decks)

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