intro to Lymphomas and Myeloma Flashcards
1
Q
What do lymphoid malignancies include?
A
- lymphomas
- lymphoid
- leukaemias
- myeloma
2
Q
Define Lymphoma
A
- a cancer of WBC
- affects mature cells, mostly B lymphocytes
- Heterogeneous group
- many known to be due to specific genetic mutations and chromosomal translocation
3
Q
What is the main function of lymphatic system?
A
- blood filtration/purification
- removal of excess fluids from tissues
- absorption and transport of lipids
- immune system activation
4
Q
What are primary lymph organs?
A
- sites where stem cells can divide and become immunocompetent
- eg: Thymus and bone marrow
5
Q
What are secondary lymph organs?
A
- sites where most of the immune response occurs
- eg: tonsils and adenoids, lymph nodes , appendix, peyer’s patches
6
Q
How do lymphomas develop?
A
- affect lymphocytes in different maturation stages
- uncontrolled division
- organ size increase: lymph node (adenopathy), other lymph organs (splenomegaly)
- spread to toher tissues through lymphatic system
- might infiltrate in bone marrow (detectable in blood) and/or other organs
7
Q
What is the traditional classification
A
- Non -Hodkin’s : diffuse and follicular.
- Hodkins
8
Q
Compare Hodgkin and non Hodkin lymphomas.
A
- Hodkin
- less common (<1%)
- age: 75 -79 y/o
- trend over time: 36% - Non - Hodkin
- more common (4%)
- age: 80-84 y/o
- trend over time : 39%
9
Q
What are signs and symptoms of lymphomas?
A
- fever
- swelling of the face and neck
- lump in your neck, armpits, or groin
- excessive sweating at night
- unexpected weight loss
- loss of appetite
- breathlessness
- itchiness
- feeling of weakness
10
Q
How do you diagnose lymph node?
A
- lymph node biopsy
- study and identify using FISH, flow cytometry
11
Q
What are stages of PET?
A
- stage 1 : localised disease, single lymph node region or single organ
- stage 2: 2 or more lymph node regions on the same side of diaphragm
- stage 3: two or more lymph node regions above and below the diaphragm
- stage 4: widespread disease, multiple organs with or without lymph node.
12
Q
What is aetiology of lymphoma?
A
- multifactorial disorder:
-malfunctioning of the body’s immune system
-exposure to certain infections
=> triggers are unknown but most of lymphomas occur when a B cell develops/acquires a mutation in its DNA.
13
Q
Hodkin Lymphoma
A
- 1832 - Thomas Hodkin
- clonal B-cell malignancy
- presentation : non-painful enlarged lymph nodes
- Risk factors: 50% cases due to Epstein -Barr virus (EBV) classic form
14
Q
Diagnosis of Hodkin lymphoma
A
Excisional lymph node biopsy and :
- normal B lymphocytes
- Reed-sternberg cell
15
Q
What is the treatment for Hodgkin lymphoma?
A
- chemotherapy +/- radiotherapy
- stem cell transplant
16
Q
What is the prognosis of Hodgkin lympoma?
A
- 5 year survival ~ 50-90% depending on age, stage and histology.
- Especially good results in young adults (97%)
17
Q
What are 3 grades of non -Hodgkin 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)
18
Q
Non- Hodgkin
A
- Presentation:
- enlarged lymph nodes. some form are slow and others grow faster. Symptoms. - Causes: chromosome translocations
- Risk Factors: virus infections (eg; EBV (HHV4) in Brkitt’s lymphoma; human T cell leukaemia virus in adult T cell lymphoma)
19
Q
What causes Non-Hodgkin lymphoma?
A
- chromosome translocations
- many lymphoma carry chromosome translocations involving the Ig heavy chain or light chain loci (chr14)
- Ig genes are highly expressed in B-cells
- Each Ig gene has a powerful tissue specific enhancer (high expression levels)
20
Q
How does translocation observed in follicular lymphoma lead to decreased apoptosis and increased proliferation leading to cancer?
A
- due to translocation enhancer starts regulating and enhancing the transcription of genes that are located in other chromosomes.
- Example: in follicular lymphoma translocation between chr14 and chr18.
- the promoter of new adjacent gene becomes regulated by immunoglobulin enhancer.
- in chr18 there is an important gene called BCL-2 gene which is an apoptosis inhibitor so when there is translocation to chr18 the apoptosis inhibitor causes inhibition in apoptosis thus more proliferation.
21
Q
How does translocation observed in Burkitt’s lymphoma lead to cancer?
A
- translocation between chr8 and chr14
- chr8 has a myc gene
- c-myc is a potent proto-oncogene
22
Q
What are risk factors of Npn-Hodgkin lymphoma?
A
- virus infections (eg: EBV (HHV4) driven lymphomas in immunosuppressed patients)
- it directly transforms B-lymphocytes in culture. Due to viral oncogene LMP-1.
- over half of all normal individuals carry latent EBV infections. They do not develop lymphomas due to effective immune surveillance by cytotoxic T- cells
23
Q
How is Non - Hodgkin Lymphoma classified?
A
- Low grade
- normal tissue architecture partially perserved normal cell of origin recognisable
- divide slowly
- may be present for many months before diagnosis
- behave in indolent fashion - High grade
- loss of normal tissue architecture- normal cell origin hard to determine
- divide rapidly
- present for a matter of weeks before diagnosis
- maybe life threatening
24
Q
How do you diagnose Non-Hodgkin lymphoma?
A
- immunophenotyping
- cytogentics - FISH : for chromosome translocations (eg. t(14, 18) Ig: Bcl -2)
- Light Chain restriction
25
Q
What are treatments for Non-Hodgkin lymphoma?
A
- chemotherapy
- radiotherapy
- stem cell transplant
- monoclonal Ab therapy - Rituximab(anti-CD20)
26
Q
What is prognosis for non- hodgkin lymphoma?
A
- overall 5 year survival rate `70%
27
Q
What is multiple myeloma?
A
- tumour of the bone marrow that involves plasma cells (antibodies production)
=> Presentation:
-absence of initial symptoms . Later: bone pain, bleeding, frequent infection, and anaemia.
=> Unknown cause (genetics)
=> Risk factors: obesity, radiation exposure, family history, and certain chemicals
28
Q
What are 3 aspects of multiple myeloma?
A
- suppression of normal bone marrow, blood cell and immune cell function :
- anemia
- bleeding tendency
- recurrent infections - Bone resorption and release of calcium:
(a) myeloma cells produce cytokines (esp. IL-6) -> bone marrow stromal cells to release the cytokine RANKL -> osteoclasts activation (lytic lesions of bone, bone pain, fractures)
(b) Calcium released from bone causes hypercalcaemia (multiple symptoms including mental disturbance) - Pathological effects of paraprotein - (single monoclonal Ig in the serum - high levels - malignancy)
29
Q
What are treatments for multiple myeloma?
A
- radiotherapy
- chemotherapy combinations (thalidomide, lenalidomide and Bortzezomib) , targeted therapies, immunotherapy (CAR- T), and allogeneic hematopoietic stem cell transplantation (ASCT)
30
Q
What is prognosis for multiple myeloma?
A
- chemo + ASCT - overall 5 year survival rate ~ 35%
