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CLINICAL PATHOLOGY > Introduction to Lymphoma and Myeloma > Flashcards

Introduction to Lymphoma and Myeloma Flashcards

1
Q

What are lymphomas?

A
  • 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
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2
Q

What are the roles of the lymphatic system?

A
  • Blood filtration and purification
  • Removal of excess tissue fluid from tissues
  • Absorption and transport of lipids
  • Immune system activation
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3
Q

What are primary lymph organs?

A

Site where stem cells can divide and become immunocompetent

e.g Thymus and bone marrow

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4
Q

What are secondary lymph organs?

A

Site where most of the immune responses occur

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

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5
Q

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

A
  • 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
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6
Q

What is the aetiology of lymphoma?

A

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

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7
Q

What does adenopathy and splenomegaly mean in terms of lymphoma?

A

Adenopathy = enlarged lymph nodes

Splenomegaly = enlargement spleen or other lymphatic organ

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8
Q

List some warning signs of lymphoma

A
  • Fever
  • Swelling of face + neck
  • Lump in neck armpits or groin -
  • Excessive sweating at night
  • Unexpected weight loss
  • Breathlessness
  • Itchiness
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9
Q

What is the general diagnosis for lymphoma?

A
  • Lymph node biopsy
    • Analyse the microscopic sample further through
      • Immunophenotyping, Flow cytometry, FISH and NGS
  • PET Scans
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10
Q

What is staging PET?

A

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
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11
Q

How can lymphoma be classified?

A
  • 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
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12
Q

What is Hodgkin Lymphoma?

A

Clonal B-cell malignancy which develops in your lymphatic system

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13
Q

What is the presentation of Hodgkin’s Lymphoma?

A

Non-painful enlarged lymph nodes

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14
Q

What are risk factors of Hodgkin’s Lymphoma?

A
  • 50% of cases are due to Epstein Barr Virus (EBV)
  • Other risk factors are family history and HIV
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15
Q

What is the diagnosis of Hodgkin’s Lymphoma?

A

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

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16
Q

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

A

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

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17
Q

What is Non-Hodgkin’s Lymphoma?

A

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

18
Q

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

A

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)
19
Q

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

A

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
20
Q

What happens due to chromosomal translocation in follicular lymphoma?

A
  • 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
21
Q

How does chromosomal translocation lead to Burkitt’s Lymphoma?

A
  • 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
22
Q

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

A

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

23
Q

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

A

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

24
Q

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

A

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

25
Q

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

A
  • 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.
26
Q

What are the characteristics of low grade lymphoma?

A
  • 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
27
Q

What are characteristics of high grade lymphoma?

A
  • 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
28
Q

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

A
  • 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)
29
Q

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

A
  • Chemotherapy
  • Radiotherapy
  • Stem Cell Transplant
  • Monoclonal Ab therapy = Rituximab (Anti-CD20)
30
Q

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

A
  • 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
31
Q

What is a multiple myeloma?

A
  • Tumour of the bone marrow that affects the plasma cells
    • Antibodies are produced by plasma cells are abnormal
    • Plasma cells will synthesise a single monoclonal antibody called paraprotein (M component)
32
Q

What is the normal role of plasma cells?

A

Plasma cells will produce antibodies

33
Q

What is the presentation of multiple myeloma?

A

Absence of initial symptoms

Later: Bone pain Bleeding Frequent Infections Anaemia

34
Q

Describe some risk factors of multiple myeloma

A
  • Obesity
  • Radiation exposure
  • Family History
  • Certain chemicals
35
Q

What are three aspects of myeloma that give rise to different clinical features?

A
  1. Suppression of normal bone marrow, blood cells and immune cell function
  2. Bone resorption and release of calcium
  3. Pathological effects of the PARAPROTEIN
36
Q

How is there bone resorption and release of calcium in multiple myeloma’s?

A
  • a. Myeloma cells produce cytokines (esp. IL-6)  bone marrow stromal cells will release the cytokine RANKL  osteoclasts activation (lytic lesions of bone, bone pain, fractures)
  • b. Calcium will be released from bone causing hypercalcaemia (multiple symptoms including mental disturbance)
37
Q

What is paraprotein?

A
  • Paraprotein is a single monoclonal gamma immunoglobulin antibody secreted by abnormal plasma cells
  • Secreted at high levels in serum = Malignancy
38
Q

What are the effects of high levels of paraprotein in serum?

A
  • Precipitates in kidney tubules and causes renal failure
  • Deposited as amyloid in many tissues
  • 2% of cases develop hyper viscosity syndrome
  • Increased viscosity of blood leading to = Stroke and Heart failure
39
Q

What is the diagnosis of multiple myeloma’s?

A
  • Serum electrophoresis for paraprotein -
  • Urine electrophoresis
  • Bone marrow biopsy (increased levels of plasma cells)
  • ESR (Erythrocyte sedimentation rate) = high due to stacking of RBCs
    • ESR + observation under a microscope can detect for stacking of RBCs which is a key characteristic of multiple myelomas
  • Flow cytometry and cytogenetics to detect cause - Radiological investigation of skeleton for lytic lesions
40
Q

What are treatments of multiple myeloma’s?

A

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

CLINICAL PATHOLOGY (52 decks)

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