Introduction to Lymphoma and Myeloma Flashcards
Define and outline Lymphoma
Lymphoma is a cancer of white blood cells (lymphocytes )
Affects to mature blood cells , mostly B lymphocytes but also T lymphocytes
Heterogeneous group
Many known to be due to specific genetic mutations and chromosomal translocations
What are the main functions of the lymphatic system ?
Blood filtration /purification
Removal of excess fluids from tissues
Absorption and transport of lipids
Immune system activation
What are the lymph nodes ?
small glands that filter lymph, the clear fluid that circulates through the lymphatic system.
What are lymph organs ?
Primary lymph organs :
sites where stem cells can divide and become immunocompetent
Secondary lymph organs : sites where most of the immune response occur
What are the primary lymph organs ?
Thymus
Bone Marrow
What are the secondary lymph organs ?
Tonsils and adenoids Lymph nodes Spleen Peyer's patches Appendix
How do Lymphomas develop ?
They affect lymphocytes in different maturation stages which leads to uncontrolled divison .
Organ size increase :
Lymph node ; Adenopathy
Other lymph organs: Splenomegaly
Spread to other tissues through the lymphatic system
Might infiltrate in bone marrow (detectable in blood ) and other organs
How is Lymphoma classified ?
Non Hodgkin’s (more common) (80-84)
Hodgins (75-79 years old)
What is the presentation of lymphoma ?
Fever Swelling on face Lump in neck,armpit or groin Excessive sweating at night Unexpected weight loss Loss of appetite Weakness Breathlessness Itchiness
How is lymphoma diagnosed ?
Through taking a lymph node biopsy using a biopsy needle
Following this : Flow cytometry FISH NGS Immunophenotyping
What is the staging of Lymphoma ?
This is a series of tests carried out by PET to identify where in the body is affected .
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 nodes regions above and below diaphragm
Stage 4 : Widespread disease multiple organs with/without lymph node involvement
What is the aetiology of Lymphoma ?
Multifactorial disorder :
Malfunctioning of the bodys immune system
Exposure to certain infections
Most lymphomas occur when a B cell develops/acquires mutations in its DNA
What is the traditional classification of Lymphoma ?
Hodgkin’s and Non Hodgkin’s with Hodgkin’s being the larger group.
Non Hodgkin’s -
Diffuse / Follicular
Hodgkin’s
What are the aspects does the WHO 2016 take into account ?
Mature B-cell neoplasms
Mature T-cell and NK neoplasms
Hodgkin lymphoma
What is Hodgkin lymphoma ?Outline the disease and its presentation
Clonal B-Cell malignancy
Presentation: Non-Painful enlarged lymph node
Risk factors : approx. 50% cases are due to Epstein Barr virus (EBV)
How can we diagnose Hodgkin’s Lymphoma ?
Excisional lymph node biopsy :
Observing Reed Sternberg cell which arise from normal B lymphocytes
These are bilobed nucleus
These are only present in Hodgkins lymphomas
What is the treatment of Hodgkin’s lymphoma ?
-Chemotherapy /radiotherapy and stem cell transplant
-Prognosis- 5 year survival
good results in young adults
What are Non -Hodgkin lymphomas ?
These are all lymphomas aprt from hodgkins lymphoma
Outline Non-Hodgkins Lymphoma
Presentation : Enlarged lymph nodes
Causes: Chromosome translocations
Risk factors : Virus infections in Burkitt’s lymphoma , Human T-cell leukaemia virus in adult T-cell lymphoma
What are the chromosome translocations which occour in Non-Hodgkins Lymphoma ?
Many lymphomas 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 )
What are the consequences of these chromosome translocations in Non-Hodgkin lymphoma ?
The normal role of the enhancer is to activate the promoter of the rearranged V segment of the Ig
Due to the translocation between chromosome 14 and other chromosomes , the enhancer starts regulating the transcription of the other genes of the chromosome which has fused with chromosome 14.
There is an overexpression of the BCL-2 gene which is an apoptosis inhibitor.
Most cases of follicular lymphoma carry ty(14:18)(q32:q21)
What is Follicular Lymphoma ?
Follicular lymphoma is a type of non-Hodgkin lymphoma
What is the translocation observed in Burkitt’s lymphoma ?
t(8;14)(q24;q32)
c-myc is a potent proto-oncogene
What are the risk factors of Non-Hodgkin lymphoma ?
Virus infections
- It directly transforms B-lymphocytes in culture. Due to viral oncogene LMP-1
- Over half of all normal individuals carry latent EBV infection. They do not develop lymphomas due to effective immune surveillance by cytotoxic T-cells.
If over half of normal individuals carry the latent EBV virus why do some people develop lymphoma ?
In highly immunosuppressed individuals , the endogenous latent EBV may transform B-cells.
No longer eliminated by cytotoxic T-cells
Develop high grade lymphoma
What is the classification of Non-Hodgkin Lymphoma ?
Low grade :
- 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
High grade :
- Loss of normal tissue architecture -normal cell or origin hard to determine
- Divide rapidly
- Present for a matter f weeks before diagnosis
- May be life threatening
How is Non-Hodgkin lymphoma diagnosed ?
-Immunophenotyping
-Cytogenetics-FISH
(For chromosome translocations (e.g.t(14;18)Ig : Bcl-2)
-Light chain restriction
-PCR
(For clonal Ig gene rearrangement)
How is Non-Hodgkin lymphoma treated ?
- Chemotherapy
- Radiotherapy
- Stem cell transplant
- Monoclonal Ab therapy-Rituximab (anti-CD20)
Targets CD20 cell surface molecules which are usually present in Leukaemia and Lymphoma B cells. The antibody will bind to all the CD20 proteins and the immune system will then kill them by releasing cytotoxins
What is multiple myeloma ?
This is a tumour of the bone marrow that involves plasma cells.Plasma cells are a type of leukocytes which secrete antibodies.
What is the presentation of multiple myeloma ?
Absence of initial symptoms , later bone pain , bleeding , frequent infections and anaemia
Unknown cause : Risk factors : Obesity Radiation exposure Family history Certain chemicals
What is the difference between healthy bone marrow and bone marrow in myeloma ?
Bone marrow produces white blood cells (B cells).
These become plasma cells and secrete normal antibodies
Bone Marrow in Myeloma:
Damaged white blood cell ,becomes myeloma cell and secretes paraprotein (M component)
What three aspects of myeloma give rise to clinical features ?
- Suppression of normal bone marrow , blood cells and immune cell function :
- Anaemia
- Bleeding tendency
- Recurrent infections
2.Bone reabsorption and release of calcium
-Myeloma cells produce cytokines (esp IL-6) bone marrow stromal cells to release the cytokine RANKL - osteoclast activation (lytic lesions of bone, bone pain and fractures
Calcium released from bone causes hypercalcaemia
3.PAthological effects of the paraprotein
Outline what the pathological effects of the paraprotein
Single monoclonal Ig gamma in the serum -high levels =malignancy
Precipitates in kidney tubules cause renal failure
-Deposited as amyloid in many tissues
-2% of cases develop hyperviscosity syndrome:
Increased viscosity of blood leading to :
stroke and heart failure
How can we diagnose Multiple Myeloma ?
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
Flow cytometry and cytogenetics to detect cause
Radiological investigation of skeleton for lytic lesions
Outline the treatment of Multiple Myeloma
Radiotherapy
Chemotherapy combinations (thalidomide ,lenalidomide and bortezomib),
Targeted therapies Immunotherapy (CAR-T) and allogenic hematopoietic stem cell transplantation (ASCT) young patients
