Introduction To Lymphoma And Myelanoma Flashcards
Define lymphoma
A cancer of the white blood cells (lymphocytes)
Affects mature blood cells, mostly B lymphocytes but also T lymphocytes
Heterogeneous group
Many known to be due ti 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 primary lymph organs?
Sites where stem cells can divide and become immunocompetent
What are secondary lymph organs?
Sites where most of the immune responses occur
Eg. Bone marrow and thymus
How do lymphomas develop?
- Mutation occurs in lymphocytes in different maturation stages
- Uncontrolled division
- Organ size increase:
Lymph node (adenopathy)
Other lymph organs (splenomegaly) - Spread to other tissues through lymphatic system
- Might infiltrate in bone marrow and/or other organs
How are lymphomas classified?
Non Hodgkins (more common)
Hodgkins
What are the warning signs of lymphoma?
Fever
Swelling of the face and neck
Lump in your neck, armpits or groin
Excessive sweating at night
Unexpected weight loss
Loss of appetite
Feeling of weakness
Breathlessness
Itchiness
What can be done to confirm the presence of a lymphoma?
Lymph node biopsy
Then :
- flow cytometry
- FISH
- NGS
- immunophenotyping
What is the staging in PET of lymphomas?
Stage 1 - localised disease (single lymph node or organ)
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 the diaphragm
Stage 4 - widespread disease (multiple organs or without lymph node involvement)
What are the causes of lymphomas?
Multifactorial disorder:
- malfunctioning of the body’s immune system
- exposure to certain infections
Triggers are unknown - what causes the mutations in the DNA?
What is Hodgkin lymphoma?
Presentation: non-painful enlarged lymph node
Risk factors:
- 50% of cases due to Epstein Barr virus (EBV) - classic form
- HIV
- Family history
Diagnosis: excisional lymph node biopsy and Hodgkin cells (Reed sternberg cell) are seen.
Treatment: chemotherapy +/- radiotherapy. Stem cell transplant.
Prognosis: 5 year survival (50-60% depending on age and histology), especially good results in young adults
What is non Hodgkin’s lymphoma?
Presentation: enlarged lymph nodes + general lymphoma symptoms
Causes: chromosome translocations
Risk factors: virus infection
Describe how translocations can cause non Hodgkin lymphoma (FOLLICULAR LYMPHOMA)
Lymphomas carry chromosome translocations involving ig heavy chain or light chain loci
Ig genes are highly expressed in B-cells
Each Ig gene has a powerful tissue specific enhancer (high expression levels)
Translocation between chromosome 14 and 18
On chromosome 18 BCL2 is present
BCL2 is a apoptosis inhibitor and becomes over expressed after translocation
High rates of proliferation and survival
Describe how translocations can cause non Hodgkin lymphoma (BURKITTS LYMPHOMA)
Chromosome 8 and 14
C-myc is a potent proto-oncogene present on chromosome 8
After translocation it becomes a oncogene
How can viral infections be risk factors for non Hodgkin lymphoma?
It directly transforms B-lymphocytes in culture due to viral oncogene LMP-1
over half of all normal individuals carry latent EBV infection but do not develop lymphoma due to immune surveillance by cytotoxic T cells.
Highly immunosuppressive individuals the EBV is no longer eliminated by cytotoxic T cells
Develop high grade lymphoma
What is classifies as LOW GRADE non Hodgkin lymphoma?
Normal tissue architecture partially preserved - normal cell of origin recognised
Divide slowly
May be present for many months before diagnosis
Behave in an indolent fashion
What classifies as HIGH grade non Hodgkin lymphoma?
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
What is diagnosis of non Hodgkin’s lymphoma?
Immunophenotyping
Cytogenetics - FISH (for chromosome translocation)
Light chain restriction
PCR - for clonal ig rearrangement
How is non Hodgkin’s lymphoma treated?
Chemotherapy
Radiotherapy
Stem cell therapy
Monoclonal Ab therapy - Rituximab (anti-CD20)
What is the prognosis non Hodgkin’s lymphoma?
Overall five year survival rate ~ 70%
What is multiple myeloma?
Tumour of the bone marrow that involves plasma cells (antibodies production)
How is multiple myeloma presented in patients?
Absence on initial symptoms
Later:
- bone pain
- bleeding
- frequent infections
- anaemia
What are the risk factors of multiple myeloma?
Obesity
Radiation exposure
Family history
Certain chemicals
What is a paraprotein?
Monoclonal immunoglobulin which a light chain
Can be detected in blood or urine
Characterised by homogenous migration
What are the three aspects of myeloma that give rise to different clinical features?
- Suppression of normal bone marrow, blood cell and immune cell function
- Bone resorption and release of calcium
- Pathological effects of the paraprotein - single monoclonal ig in the serum - high levels - malignancy)
What clinical features in multiple myeloma arise due to suppression of normal bone marrow, blood and immune cell function?
Anaemia
Recurrent infections
Bleeding tendency
What clinical features in multiple myeloma arise due to bone resorption and release of calcium?
- Myeloma cells produce cytokines
- Bone marrow stromal cells to release the cytokine RANKL
- Osteoclasts activation
(Lyric lesions of bone, bone pain, fractures)
Calcium released from bone causes hypercalcaemia (multiple symptoms including mental disturbance)
What clinical features in multiple myeloma arise due to the pathological effects of the paraprotein?
Precipitates in kidney tubules cause renal failure
Deposited as amyloid in many tissues
2% of cases develop hyper viscosity syndrome (increased viscosity of blood)
- stroke
- heart faliure
How is multiple myeloma diagnosed?
Serum electrophoresis for paraprotein
Urine electrophoresis
Bone marrow biopsy for increased level 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 lyric lesions
What is the treatment for multiple myeloma?
Radiotherapy
Chemotherapy combinations
Targeted therapies
Immunotherapy
Allogenic haematopoietic stem cell transplant in young patients (ASCT)
What is the prognosis of multiple myeloma?
Chemo + ASCT overall 5 year survival rate ~ 35%
