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SEM 4: Haematology > Introduction to Lymphoid Malignancies > Flashcards

Introduction to Lymphoid Malignancies Flashcards

1
Q

What are the 3 types of blood cancers?

A
  • Leukaemia
  • Lymphoma
  • Myeloma
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2
Q

What is lymphoma?

A

Cancer of the white blood cells (lymphocytes)

Affects to mature white blood cells such as B lymphocytes and T lymphocytes

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3
Q

Lymphomas are heterogenous. What does this mean?

A

It is heterogenous and so there are multiple types of lymphomas and many are known to be due to specific genetic mutation and chromosomal translocation

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4
Q

What causes lymphomas?

A
  • Due to specific genetic mutations and chromosomal translocations
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5
Q

Describe the action of lymphomas

A
  1. Lymphocytes in different staged get affected leading to abnormal cell division and therefore organ sizes increases such as adenopathy or splenomegaly.
  2. The cancer cells can then spread to other tissues via the lymphatic system or the blood
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6
Q

What are the 2 types of lymphoma?

A

Hodgkin and non-Hodgkin

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7
Q

What are the cells involved in non-hodgkin lymphomas?

A

Includes mature B cell neoplasms, mature T cell and NK neoplasms

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8
Q

What is the lymphatic system?

A
  • Composed of lymph and lymph nodes
  • Lymph nodes located throughout the whole body -> neck, chest etc
  • Lymph is immune cells, lipids, proteins present between cell tissues
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9
Q

What are the main functions of lymph nodes and organs?

A
  • Help filter and purify the blood
  • Remove excess fluids from the tissues
  • Active the immune system
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10
Q

What are primary lymph organs?

A

Sites where stem cells divide and become immunocompetent, such as thymus and bone marrow

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11
Q

What are secondary lymph organs?

A

Sites where most of the immune response occurs, such as tonsils, adenoids, lymph nodes, spleen, Peyere’s patches and appendix

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12
Q

What is hodgkin lymphoma?

A
  • Clonal B cell malignancy leading to painless enlarged lymph nodes
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13
Q

What are the risk factors of hodgkin lymphoma?

A

EBV, family history and AIDS.

The other risk factors are family history and HIV/AIDs.

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14
Q

How are hodgkin lymphoma diagnosised?

A

Include excisional lymph node biopsy where a Reed Sternberg cell under a microscope should be seen in a sea of normal B cells and abnormal lymphocytes

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15
Q

What is the treatment of Hodgkin lymphoma?

A

Chemotherapy, radiotherapy and stem cell transplant

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16
Q

What is non-hodgkin lymphoma?

A

A complex group of blood cancers which include all types of lymphomas apart from Hodgkin’s.

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17
Q

What is the staging (PET) of cancer?

A

Classifies lymphoma at different stages according to the level of spread of the lymph.

Stage 1: Localised disease; single lymph node region or single organ

Stage 2: Two or more lymph node regions on the same side of the diaphragm

Stage 3: Two or more lymph node region above and below the diaphragm

Stage 4: Widespread disease; multiple organs, with or without lymph node involvement

18
Q

How is lymphomas diagnosed?

A

Take a lymph node biopsy:

  • Take lymph
  • Under microscope
  • Type cells give an idea of type of lymphoma
  • Flow cytometry to fully diagnosis
19
Q

What is cause of most lymphomas?

A

The acquisition of a mutation in DNA

20
Q

How is lymphoma a multfactorial disease?

A
  • Malfunctioning of the body’s immune system

- Exposure to certain infections

21
Q

What are the traditional classifications of lymphomas?

A

Lymphomas are divided into: non-hodgkin’s and hodgkin’s.
Then non-hodgkin’s are divided into: diffuse and follicular lymphomas.
Then hodgkin’s are many types.

22
Q

What are the classifications of WHO?

A
  • Mature B-cell neoplasms
  • Mature T-cell and NK neoplasms
  • Hodgkin lymphoma
23
Q

What are high grade, low grade and a combination of high and low grade non-hodgkin lymphomas?

A
  • High grade: diffuse large B cell lymphoma and burkitt lymphoma - loss of normal tissue architecture and so the cell of origin cannot be traced, the cells divide rapidly, present in a matter of weeks before diagnosis
  • Low grade: marginal zone lymphoma, follicular lymphoma and mantle cell lymphoma - normal tissue architecture present so the normal cell of origin can be determined, the cells divide slowly, may be present months before diagnosis
  • High and low grade: T cell lymphoma (all subtypes)
24
Q

What is the presentation of non-hodgkin lymphoma?

A
  • Present with enlarged lymph node(s). Some forms are slow and others grow faster. General lymphoma symptoms
25
Q

What causes non-hodgkin lymphoma?

A

Mostly chromosomal translocations

26
Q

What are the risk factors of non-hodgkin lymphomas?

A
  • Virus infections (e.g. EBV (HHV4) in Burkitt’s lymphoma; Human T-cell leukaemia virus in adult T-cell lymphoma)
27
Q

How are non-hodgkin lymphoma’s diagnosised?

A

Via immunophenotyping, FISH, light chain restriction or PCR

28
Q

What is the treatment of non-hodgkin’s lymphomas?

A

Chemotherapy
Radiotherapy
Stem cell transplant
Monoclonal antibody therapy Rituximab (antibody bind to B cell so immune system recognises it)

29
Q

How do chromosomal translocations cause non-hodgkin lymphomas?

A
  1. Lymphomas carry chromosomal translocations in the Ig heavy or light chain present on Chromosome 14.
  2. This area contains an enhancer which is meant to increase the expression of rearranged segment V area which codes for the Ig chains for B cells.
  3. However, when translocation occurs, this enhancer upregulates the wrong genes leading to abnormal proliferation or inhibition of apoptosis.
  4. In follicular lymphoma, translocation of chromosome 14 and 18 brings about the upregulation of the BLC-2 gene causing the inhibition of apoptosis. In Burkett’s lymphoma translocation between chromosome 14 and 8 which upregulates the expression of a C-MYC proto-oncogene leading to uncontrolled cell proliferation.
30
Q

How does EMV infections in immunosuppressed patients affect non-hodgkin lymphoma?

A
  1. The virus injects LMP-1 viral oncogene which transforms B lymphocytes. This is common in most people but doesn’t cause lymphoma due to immunosurveillance by cytotoxic T cells.
  2. In immunosuppressed patients do not have cytotoxic T cells and therefore the B cells get transformed causing lymphoma.
  3. This will develop a high-grade lymphoma.
31
Q

How are non-hodgkin lymphoma’s diagnosised?

A
  • Immunophenotyping
  • Cytogenetics - FISH for chromosomal translocations (e.g. t(14,18); Ig: Bcl-2)
  • Light chain restriction
  • PCR: For clonal Ig gene rearrangement
32
Q

How does a monoclonal Ab therapy - Rituximab (anti-CD20) work?

A
  • This monoclonal antibody binds all the CD20 molecules on the cell surface of B-cell.
  • Immune system will recognise and kill it.
33
Q

What is a multiple myeloma?

A

Tumour of the bone marrow that involves plasma cells (antibodies production). It is second most prevalent after leukaemia - plasma cells responsible for antibody production.

34
Q

What is the presentation of multiple myeloma?

A
  • Asymptomatic at first: absence of initial symptoms

- Later: presents with bone pain, bleeding, frequent infections, and anaemia

35
Q

What are the risk factors of multiple myeloma?

A
  • Obesity
  • Radiation exposure
  • Family history
  • Certain chemicals
36
Q

How is multiple myeloma diagnosised?

A

Done via serum and urine electrophoresis for paraprotein, bone marrow biopsy for increased levels of plasma cells, erythrocyte sedimentation rate, flow cytometry and radiological investigation of bone lytic lesions

37
Q

How are multiple myeloma produced?

A
  1. B-cells produce antibodies in myeloma.

2. The antibodies are abnormal and synthesis paraprotein which is a characteristic of a myeloma.

38
Q

What are the 3 aspects of clinical features in myeloma?

A
  1. Suppression of normal bone marrow, blood cell and immune cell function: anaemia, recurrent infections and bleeding tendency
  2. Bone resorption and release of calcium
  3. Pathological effects of the paraprotein
39
Q

How does bone resorption and release of calcium result in a myeloma?

A
  1. Myeloma cells produce cytokines (esp. IL-6).
  2. Bone marrow stromal cells to release the cytokine RANKL that leads to osteoclasts activation causing lytic lesions of bone, bone pain and fractures.
  3. Calcium is released from the bone causing hypercalcaemia (multiple symptoms including mental disturbance).
40
Q

What is paraprotein?

A
  • A single monoclonal Ig in the serum and urine. Higher levels are found during myeloma leading to precipitations in the kidney which causes renal failure and sometimes hyperviscosity. This can also be depositied as amyloid.
41
Q

What is the stem cells and bone marrow transplants (SCBMTs) for blood cancers?

A
  • Used mainly for treatment of AML
  • Haematopoiesis is reconstituted from the quiescent stem cell pool
  • It is either allogenic vs autologous
  • Elderly unable to tolerate aggressive chemotherapy or SCBMT

SEM 4: Haematology (8 decks)

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