L26: Intro To Lymphomas & Myeloma Flashcards
Which cells are involved in lymphomas?
→mostly B lymphocytes
→ T lymphocytes
→natural killers
What are the main functions of the lymph nodes?
→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
When lymphomas spread to the bone marrow, how are they detected?
→detectable in blood
What are the traditional classifications of lymphomas?
→Non-Hodgkin’s
→Hodgkins
What are the two types of Non-Hodgkin’s lymphomas?
→diffuse
→follicular
What is the age of onset of HK and NHK lymphomas?
→HK= 75-79 →NHK= 80-84
What are the warning signs of lymphomas?
→swelling of face and neck →excessive sweating at night →unexpected weight loss →breathlessness itchiness →loss of appetite
How are lymphomas diagnosed?
→lymph node biopsy →immunophenotyping →NGS →FISH →flow cytometry
What are the PET stages of lymphomas?
→Stage 1= localized disease, single lymph node
→Stage 2= two or more lymph nodes on the same of the diaphragm
→Stage 3= two or more nodes above and below diaphragm
→Stage 4= widespread disease, multiple organs
How do most lymphomas occur?
→when a B cell develops/acquires a mutation in its DNA
What is Hodgkin lymphoma?
→Clonal B-cell malignancy
What is the presentation of HK lymphomas?
→Presentation- non-painful enlarged lymph node(s)
What are the risk factors of HK lymphomas?
→50% cases due to Epstein-Barr virus
→Family history
→HIV/AIDS
How is HK lymphomas diagnosed?
→Excisional lymph node biopsy
→Reed-Sternberg cell present
→observed by light microscope
What are the features of Reed-Sternberg cells?
→multinucleated
→condensed cytoplasm
What is the treatment for HK lymphomas?
→Chemotherapy +/- radiotherapy
→Stem cell transplant
What is the prognosis for HK lymphomas?
→5 year survival ~50-90% depending on age, stage and histology
What are two high grade NHK lymphomas?
→diffuse large B cell
→Burkitt
What is the main presentation of HK lymphomas?
→enlarged lymph node
What is a cause of NHK lymphomas?
→Chromosome translocations detected using FISH
What are the risk factors for NHK?
→virus infection
What are viral risk factors for NHK?
→EBV (HHV4) in Burkitt’s lymphoma
→ Human T-cell leukaemia virus in adult T-cell lymphoma
→H.Pylori in gastric lymphoma
What is the chromosome translocations in NHK?
→Ig heavy chain or light chain loci (chr14)
How does Ig-BCL-2 fusion created?
→Ig gene has a powerful tissue specific enhancer in B-cells
→translocation brings BCL-2 which is an apoptosis inhibitor under the influence of Ig enhancer
Which chromosomes are involved in IG-BCL-2 fusion of follicular lymphoma?
→14 and 18
Which chromosomes are involved in Ig-C-MYC fusion of Burkitt’s lymphoma?
→t(8;14)(q24;q32)
What does the Epstein Barr virus due to B-cells in those immunosuppressed?
→directly transforms B-lymphocytes in culture.
→Due to viral oncogene LMP-1
→high grade lymphoma.
What are the features of low grade NHK?
→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
What are the features of high grade NHK?
→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 are the diagnostic techniques for NHK?
→Immunophenotyping
→Cytogenetics –FISH
→Light chain restriction
→PCR-For clonal Ig gene rearrangement
What is NHK diagnosis similar to?
→chronic myeloid leukaemia
What are the treatments for NHK?
→Chemotherapy
Radiotherapy
Stem cell transplant
Monoclonal Ab therapy
Example of MAb for NHK
→Rituximab (anti-CD20)
What is normally found on surface of lymphoma cells?
→CD20
→Antibodies mark the CD20 and then is killed by releasing cytotoxin
What is the survival rate in nHK?
→70%
What is myeloma?
→Tumour of the bone marrow that involves plasma cells
What are the initial symptoms of myeloma?
→Absence of initial symptoms
What are the later symptoms of myeloma?
→bone pain,
→bleeding,
→frequent infections,
→anaemia
What do abnormal plasma cells produce?
→paraprotein
What are paraproteins?
→monoclonal immunoglobulin or light chain
How are Bence-Jones proteins detected?
→blood or urine
→homogeneous gel migration
Why is there hypercalcaemia observed in myelomas?
→Myeloma cells produce cytokines (esp. IL-6)
→ bone marrow stromal cells to release the cytokine RANKL
→ osteoclasts activation
→Calcium released
What are the three features of myelomas that give rise to 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)
Why is there hyper viscosity syndrome in myeloma?
→paraprotein precipitates in kidney
→renal failure
→Deposited as amyloid in many tissues
What are the diagnostic techniques of multiple myeloma?
→Serum electrophoresis for paraprotein
→Urine electrophoresis
→Bone marrow biopsy for increased levels of plasma cells
→Erythrocyte sedimentation rate (ESR)-
Why is ESR performed for myeloma?
→high due to stacking of the RBC- forms Rouleaux’s due to increased paraprotein
→Flow cytometry and cytogenetics to detect cause
→Radiological investigation of skeleton for lytic lesions
What are the treatments for MM?
→Radiotherapy
→chemotherapy combinations →targeted therapies
→immunotherapy (CAR-T),
→allogeneic hematopoietic stem cell transplantation (ASCT) in young patients.
What is the survival rate for MM?
→35%
Which type of cancers are stem cells and bone marrow transplants mainly used for?
→AML
What are the two types of stem cell transplants?
→allogenic
→autologous
What is CART cell therapy?
→treatment of haematological cancers
→T cells produce chimeric antigen receptors on their surface
