Introduction to Lymphoma and Myeloma Flashcards Preview

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Flashcards in Introduction to Lymphoma and Myeloma Deck (40)
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What are lymphomas?

  • Lymphomas are a group of heterogeneous cancers of mature lymphocytes (mainly B) that develop in lymph organs
  • Many known due to specific genetic mutations and chromosomal translocations


What are the roles of the lymphatic system?

  • Blood filtration and purification
  • Removal of excess tissue fluid from tissues
  • Absorption and transport of lipids
  • Immune system activation


What are primary lymph organs?

Site where stem cells can divide and become immunocompetent

e.g Thymus and bone marrow


What are secondary lymph organs?

Site where most of the immune responses occur

e.g Lymph nodes, appendix, spleen, tonsils + adenoids, Peyer's patches


What effect does lymphoma have on other organs? (uncontrolled division of B and T cells) 

  • Growth of certain lymph organs 
  • Cancer cells can spread to other tissues via the lymphatic system 
  • Can infiltrate the bone marrow (detectable in blood) and/or other organs 


What is the aetiology of lymphoma? 

Lymphoma is a multifactorial disorder (causes are not well known) 

  • Malfunctioning of the bodies immune system 
  • Exposure to certain infections (Epstein Barr Virus) 

The triggers are mostly unknown however most of the lymphomas occur due to a B cell developing/ acquiring a mutation in its DNA 


What does adenopathy and splenomegaly mean in terms of lymphoma?

Adenopathy = enlarged lymph nodes

Splenomegaly = enlargement spleen or other lymphatic organ


List some warning signs of lymphoma

  • Fever
  • Swelling of face + neck
  • Lump in neck armpits or groin -
  • Excessive sweating at night
  • Unexpected weight loss
  • Breathlessness
  • Itchiness


What is the general diagnosis for lymphoma?

  • Lymph node biopsy 
    • Analyse the microscopic sample further through 
      • Immunophenotyping, Flow cytometry, FISH and NGS 
  • PET Scans 


What is staging PET?

Another way of classifying lymphoma according to the level of spread of lymphoma

  • Stage 1 – Localised, only a single lymph node region is affected 
  • Stage 2 – Two or more lymph node regions on the same side of the diaphragm
  • Stage 3 – Two or more lymph node regions above and below diaphragm
  • Stage 4 – Widespread disease, multiple organs, with or without lymph node involvement


How can lymphoma be classified?

  • Hodgkin's and Non-Hodgkin's lymphoma -
    • Hodgkins is not very prevalent and has two peaks of incidence (1 in adolescence + 1 over 50)
    • Non-Hodkins is more prevalent in older ages 6th most common cancer in UK



What is Hodgkin Lymphoma?

Clonal B-cell malignancy which develops in your lymphatic system


What is the presentation of Hodgkin's Lymphoma?

Non-painful enlarged lymph nodes


What are risk factors of Hodgkin's Lymphoma?

- 50% of cases are due to Epstein Barr Virus (EBV)

- Other risk factors are family history and HIV


What is the diagnosis of Hodgkin's Lymphoma?

From carrying out a lymph node biopsy there will be a presence of REED-STERNBERG CELLS

These contain:

1) Bi-lobal nucleus

2) Usually sit in a sea of B-lymphocytes


What is the treatment and prognosis of Hodgkin's Lymphoma?

Treatment = Chemotherapy +/- radiotherapy, Stem cell transplant Prognosis = 5 year survival 50-90% depending on age and histology, especially good results in young adults (97%)


What is Non-Hodgkin's Lymphoma?

A group of blood cancer which occurs due to over proliferation of lymphocytes

Can be divided into high grade, low grade and high and low grade 

Include all types of lymphoma (e.g Burkitt and Mantel cell) except for Hodgkin's Lymphoma


What is the presentation of Non-Hodgkin's Lymphoma?

Enlarged lymph nodes

  • Some forms are slow, others grow faster,
  • Also general lymphoma symptoms (fever, sweating, swelling of face and neck, loss of appetite, weight loss, breathlessness, feeling weak) 


What are the causes of Non-Hodgkin's Lymphoma?

Chromosomal translocations

  • Many lymphomas will carry chromosome translocations involving the Ig heavy chain or light chain loci (loci is located in Chr14)
  • Ig genes are highly expressed in B-cells
  • Each Ig gene has a powerful tissue specific ENHANCER.
    • Normally it will have the role of activating the promoter of the rearranged V segment
    • In the chromosome translocation the enhancer will start regulating the promoter of another gene


What happens due to chromosomal translocation in follicular lymphoma?

  • In follicular lymphoma t(14;18)(q32;q21) cases the translocation between chromosome 14 (contains locus for Ig) and chromosome 18 will bring together the BCL-2 gene and the enhancer of the immunoglobulin (Ig). 
  • This enhancer will start regulating the activity of the BCL-2 gene, normally BCL-2 is an apoptosis inhibitor, the enhancer will cause high levels of BCL-2 meaning there is no programmed cell death leading to many cells and a high-level lymphoma


How does chromosomal translocation lead to Burkitt's Lymphoma?

  •  In Burkitt’s lymphoma t(8;14)(q24;q32) there is another common translocation between chromosome 8 (c-myc protooncogene is located here) and chromosome 14 (where the Ig gene enhancer resides) 
  • Ig enhancer will start to regulate the proto-oncogene promoter c-myc
  • Enhancer will upregulate expression of c-myc = cell proliferation and lymphoma 


What are risk factors of Non-Hodgkin's Lymphoma?

Viral infections (EBV infection in Burkitt’s Lymphoma, Human T-cell leukaemia virus in adult T-cell lymphoma)


What oncogene causes lymphoma following infection from the EBV (Epstein Barr Virus) (HHSV4)? 

Viral Oncogene LMP-1 (It has been observed that B-lymphocytes in culture can be transformed via the viral infection with EBV virus)


Why so some individuals following infection of EBV get lymphomas and other don't?

Normal individuals = will carry latent EBV infection but will not develop lymphomas due to effective immune surveillance via cytotoxic T-cells

PROBLEM - immunosuppressed patients (organ transplant/HIV patients), virus cannot be eliminated by cytotoxic T cells and endogenous latent EEBV may transform B-cells This happens in high grade lymphoma


What is the classification of non-Hodgkin's lymphoma?

  • Low grade and high grade lymphoma can be observed under a microscope following the lymph node biopsy.
  • This is because the classification is based on the characteristics of the cells/tissues. 


What are the characteristics of low grade lymphoma?

  • 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


What are characteristics of high grade lymphoma?

  • 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


What further diagnosis is carried out following classification of high/low grade non-Hodgkin's lymphoma?

  • Immunophenotyping
  • Cytogenetics – FISH o For chromosome translocations (e.g. t(14;18) Ig : Bcl-2)
  • Light chain restriction
  • PCR (This detects for clonal immunoglobulin gene rearrangement)


List some treatment options for Non-Hodgkin's Lymphoma?

  • Chemotherapy
  • Radiotherapy
  • Stem Cell Transplant
  • Monoclonal Ab therapy = Rituximab (Anti-CD20)


Give an example of a monoclonal Ab therapy used to treat Non-Hodgkins Lymphoma and its mechanism of action. 

  • RITUXIMAB (Anti-CD20)
    • Binds and labels all CD20 molecules present in cell surface of abnormal B-cells
    • Causes the immune system to recognise these and kill them

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