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Clinical pathology specialities: Haematology > Haematology: Introduction to Lymphoid Malignancies > Flashcards

Haematology: Introduction to Lymphoid Malignancies Flashcards

1
Q

What is lymphoma?

A
  • A group of cancers that affect lymphocytes
  • They mainly affect B lymphocytes but can also affect T lymphocytes
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2
Q

What are the main functions of the lymphatic system?

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

The lymphatic system contains lymph organs. What are the different types of lymph organ?

A
  • Primary lymph organ - sites where stem cells can divide and become immunocompetent (have ability to produce normal immune response)
  • Secondary lymph organ -
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4
Q

Name the primary lymph organs

A
  • Thymus
  • Bone marrow
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5
Q

Name the secondary lymph organs

A
  • Lymph nodes
  • Spleen
  • Appendix
  • Tonsils and adenoids
  • Peyer’s patches
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6
Q

Briefly explain the effect how lymphoma has on lymphocytes and the effects this has on other organs

A
  • Lymphocytes affected as a result of lymphoma begin to undergo uncontrolled cell division
  • Uncontrolled cell division leads to lymph organ enlargement, e.g. lymph nodes (adenopathy) or spleen (splenomegaly)
  • Lymphoma cells can then travel from lymph organs and affect other tissues, e.g. liver, bone marrow or lungs
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7
Q

What other things can cause adenopathy apart from lymphoma?

A
  • Autoimmune response
  • Infection
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8
Q

Why does it become difficult to identify what type of blood cancer a person has if lymphoma imflitrates into the bone marrow?

A
  • Lymphoma cells won’t be present in lymphatic system and will be in bone marrow instead
  • This means that lymphoma may be identified as leukaemia because the lymphoma cells from bone marrow will eventually be released into blood and be detectable there
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9
Q

What are the 2 main types of lymphoma?

A
  • Hodgkin’s lymphoma
  • Non-Hodgkin’s lymphoma
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10
Q

What are some of the common symptoms of lymphoma?

A
  • Swelling of the face and neck
  • Lumps on the neck, armpit or groin
  • Excessive sweating, especially at night
  • Feeling of weakness
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11
Q

What are some of the ways in which lymphoma can be diagnosed?

A
  • Lymph node biopsy - lymph sample taken is then viewed under microscope to determine which type of lymphoma a persopn has (Hodkins or Non-Hodgkin’s)
  • The following techniques are all used to dteremine the sub-type of lymphoma:
    • Immunophenotyping
    • Next generation sequencing (NGS)
    • Fluorescence in situ hybridisation (FISH)
    • Flow cytometry
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12
Q

What other techniques can be used to determine the type of treatment used against lymphoma?

A
  • Staging of lymphoma using positron-emission tomography (PET) also used to determine course of treatment
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13
Q

Explain the concept of staging using PET

A
  • Staging is used to classify lymphoma into different stages based on how much the lymphoma has spread
  • PET is used to determine how much the lymphoma has spread throughout the body
  • There are 4 stages:
    • Stage 1 - Localised, only one lymph node affected
    • Stage 2 - Two or more lymph nodes affected on same side of diaphragm
    • Stage 3 - Two or more lymph nodes affected on different sides of diaphragm
    • Stage 4 - Widespread, multiple organs affected
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14
Q

What are the causes of lymphoma?

A
  • Causes mostly unknown but it is a multifactorial disorder.
  • Some of the causes may include:
    • Malfunctioning of the body’s immune system
    • Exposure to certain infections
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15
Q

Non-hogdkin’s lymphoma can be further classified into two main subtypes. What are these subtypes?

A
  • Mature B-cell neoplasms
  • Mature T-cell and natural killer (NK) neoplasms
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16
Q

What is Hodgkin’s lymphoma?

A
  • Clonal B-cell malignancy
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17
Q

What is the main symptom of Hodgkin’s lymphoma?

A
  • Non-painful enlarged lymph nodes (adenopathy)
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18
Q

Name some of the risk factors of Hodgkin’s lymphoma

A
  • Epstein-Barr virus (50% of cases due to virus)
  • Family history
  • HIV/Aids
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19
Q

What is the main feature of Hodgkin’s lymphoma?

A
  • Presence of Reed-sternberg cells (abnormal B lymphocytes) in lymph
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20
Q

What are some of the characteristics of Reed-sternberg cells?

A
  • Very large compared to normal B lymphocytes
  • Contain 2 nuclei
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21
Q

Name the different treatments for Hodgkin’s lymphoma

A
  • Chemotherapy (may be in combination with radiotherapy)
  • Stem cell transplant
22
Q

Describe what the usual outcome is for someone with Hodgkin’s lymphoma

A
  • 5 year survival rate between 50-90% depending on age, stage and histology.
  • Especially good results in young adults (97% survival rate)
23
Q

What are the different types of Non-Hodgkin’s lymphoma?

A
  • High grade
    • Diffuse large B cell lymphoma
    • Burkitt lymphoma
  • Low grade
    • Marginal zone lymphoma
    • Follicular lymphoma
    • Mantle cell lymphoma
  • High and low grade
    • T cell lymphoma (all subtypes)
24
Q

What is the main symptom of non-Hodgkin’s lymphoma?

A
  • Enlarged lymph node/s
25
Q

Name some of the risk factors for Non-Hodgkin’s lymphoma

A
  • Viral infections - e.g. EBV (HHV4) in Burkitt’s lymphoma or Human T-cell leukaemia virus in adult T-cell lymphoma
26
Q

What is the main cause of Non-Hodgkin’s lymphoma?

A
  • Chromosomal translocations of the immunoglobulin heavy chain or light chain on chromsome 14
27
Q

Why is it that most types of Non-Hodgkin’s lymphoma are caused by a chromosomal translocation involving the Ig light or heavy chain?

A

*

28
Q

Describe the normal function of the enhancer found associated with each immunoglobulin gene

A
  • The enhancer activates the promoter of the gene that encodes for the V segment of present in both the heavy and light chains of immunoglobulins
29
Q

Most cases of follicular lymphoma are caused by a translocation between chromosomes 14 and 18. Explain what occurs as a result of this translocation

A
  • Chromosomal translocation between chromosome 14 and chromosome 18 brings together the BCL-2 gene, on chromosome 18, and the enhancer for the Ig, on chromosome 14.
  • This results in the enhancer activating the promoter of the BCL-2 gene
  • BCL-2 encodes for a protein that inhibits apoptosis so increased expression of BCL-2 leads to decreased apoptosis
  • Eventully leads to follicular lymphoma
30
Q

Most cases of Burkitt’s lymphoma are caused by a translocation between chromosomes 8 and 14. Explain how this translocation lkeads to development of burkitt’s lymphoma

A
  • Chromosomal translocation between chromosomes 8 and 14 brings together c-myc proto-oncogene and enhancer for Ig gene
  • Translocation results in c-myc beoming an oncogene
  • Translocation results in enhancer activating promoter of c-myc leading to increased c-myc expression
  • This leads to increased cell proliferation eventually leading to burkitt’s lymphoma
31
Q

How is the EBV viral infection able to cause Non-Hodgkin’s lymphoma?

A
  • EBV virus directly transforms B-lymphocytes in culture due to it containing the viral oncogene LMP-1.
32
Q

If over half of all normal individuals carry a latent EBV infection why don’t more people develop lymphoma?

A
  • Don’t develop lymphomas due to effective immune surveillance by cytotoxic T-cells.
33
Q

What individuals are at risk of developing non-hodgkin’s lymphoma due to EBV infection? Why is this?

A
  • Immunosuppressed individuals
  • Individuals with HIV
  • These people are at risk because their immune systems are restrained so the EBV infected B lymphocytes are no longer eliminated by cytotoxic T-cells.
  • As a result they may develop high grade lymphoma.
34
Q

What are the differences between high grade and low grade Non-Hodgkin’s lymphoma?

A
  • With low grade Non-Hodgkin’s lymphoma the normal tissue architecture is partially preserved, normal cell of origin recognisable, while with high grade there’s a loss of normal tissue architecture, normall cell of origin is unrecognisable
  • With low grade cells divide slowly while with high grade cells divide rapidly
  • Symptoms of low grade may present for many months before diagnosis while symptoms of high grade present for a few weeks before diagnosis
  • Low grade doesn’t cause a lot of pain (non-life threatening) while high grade may be life-threatening
35
Q

How can you diagnose Non-Hodgkin’s lymphoma?

A
  • Immunophenotyping
  • Fluorescence in situ hybridisation (FISH) - used to detect chromosomal translocations
  • Light chain restriction
  • PCR - used to detect clonal Ig gene rearrangement
36
Q

How can Non-Hodgkin’s lymphoma be treated?

A
  • Chemotherapy
  • Radiotherapy
  • Stem cell transplant
  • Monoclonal Ab therapy -Rituximab (anti-CD20)
37
Q

Explain the mechanism of action of Rituximab

A
  • Rituximab is a binds to the CD20 molecules present on the surface of the abnormal B lymphocytes
  • This results in the abnormal B lymphocytes being destroyed in a no. of different ways:
    • Macrophages can use Rituximab to recognise abnormal B lymphocytes and phagocytose them
    • Natural killer cells can also use Rituximab to recognise abnormal B lymphocytes and kill them
    • Binding of Rituximab to CD20 molecules can induce apoptosis in abnormal B lymphocytes
38
Q

Describe what the usual outcome is for someone with Non-Hodgkin’s lymphoma

A
  • Overall five-year survival rate of 70%
39
Q

What is multiple myeloma?

A
  • A type of cancer that develops in the bone marrow and affects plasma cells and therefore antibody production.
40
Q

What are some common symptoms of multiple myeloma?

A
  • Absence of initial symptoms.
  • Eventually symptoms will include:
    • Bone pain
    • Bleeding
    • Frequent infections
    • Anaemia
41
Q

What are some risk factors for multiple myeloma?

A
  • Obesity
  • Radiation exposure
  • Family history
  • Certain chemicals
42
Q

Normally the plasma cells produced by B cells produce normal antibodies, what do myeloma cells, abnormal plasma cells, produce instead?

A
  • They produce M protein (paraprotein) which is an abnormal antibody
43
Q

What are the 3 aspects of myeloma that give rise to its clinical features?

A
  • Suppression of normal bone marrow, blood cells and immune cell function
  • Bone resorption and release of calcium
  • Pathological effects of the paraprotein
44
Q

What are the effects of the suppression of normal bone marrow, blood cells and immune cell function as a result of myeloma?

A
  • Anaemia
  • Recurrent infections
  • Bleeding tendencies
45
Q

Explain how myeloma leads to bone resportion

A
  • Myeloma cells produce cytokines, especially IL-6) which causes bone amrrow stromal cells to release the cytokine RANKL
  • RANKL leads to activation of oestoclasts
  • Activated oesteoclasts cause bone resorption as they break down the bone
  • This results in lytic lesions, bone pain and fractures
46
Q

Myleoma cells also result in calcium being released from bone. What condition does this lead to?

A
  • Hypercalcaemia - High calcium blood level
47
Q

What problems can be caused as a result of the paraprotein that’s released by myeloma cells?

A
  • Paraprotein can precipitate in kidney tubules which causes renal failure
  • It can accumulate as amyloid in many tissues
  • 2% of multiple myeloma cases can develop hyperviscosity syndrome as a result of the paraprotein, which leads to:
    • Increased viscosity of blood leading
    • Stroke
    • Heart failure
48
Q

How can multiple myeloma be diagnosed?

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 which is a symptom of multiple myeloma (Rouleaux)
  • Flow cytometry and cytogenetics to detect cause
  • Radiological investigation of skeleton for lytic lesions
49
Q

How can multiple myeloma be treated?

A
  • Radiotherapy
  • Chemotherapy
  • Allogeneic hematopoietic stem cell transplantation (ASCT) in young patients.
50
Q

Describe what the usual outcome is for someone with multiple myeloma

A
  • Patients treated with Chemotherapy and ASCT only have 5-year survival rate of 35%

Clinical pathology specialities: Haematology (8 decks)

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