Introduction to Lymphomas and Myeloma Flashcards
Define lymphoma and what cells does it affect
Is it heterogenous and why?
cancer of the 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 4 main functions of lymph nodes?
a) blood filtration/purification
b) removal of excess fluids from tissues
c) absorption and transport of lipids
d) Immune system activation
Define primary and secondary lymph organs
Primary lymph organs: sites where stem cells can divide and become immunocompetent.
Secondary lymph organs: sites where most of the immune responses occur.
What are the 5 stages of lymphoma?
Affect 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 (detectable in blood)
and/or other organs
How do we classify lymphoma?
Non-Hodgkins (diffuse and follicular) and hodgkins
What are the warning signs of lymphoma?
fever
swelling of face and neck
sweating
lump in armpit or groin
weight loss
appetite loss
itchness
How do we diagnose lymphoma?
On image
What are the stages of THE diagnosis lymphoma?
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Describe the aetiology of lymphoma
o Multifactorial disorder:
- Malfunctioning of the body’s immune system
- Exposure to certain infections
o The triggers are unknown but… most of lymphomas occur when a B cell develops/acquires a mutation in its DNA.
o Different Lymphoid malignancies correspond to normal stages of lymphoid development
What causes Hodgkin’s lymphoma?
How does it present?
How do we diagnose it?
What is the treatment?
Clonal B-cell malignancy.
Presentation- non-painful enlarged lymph node(s).
Excisional lymph node biopsy and…
Treatment: Chemotherapy +/- radiotherapy. Stem cell transplant.
What causes non-Hodgkin lymphoma?
How does it present itself?
What are the risk factors?
How do we diagnose and treat it?
Chromosome translocations
- Presentation: enlarged lymph node(s). Some forms are slow and others grow faster. General lymphoma symptoms.
Risk factors: virus infections (e.g. EBV (HHV4) in Burkitt’s lymphoma; Human T-cell leukaemia virus in adult T-cell 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).
o Chemotherapy
o Radiotherapy
o Stem cell transplant
o Monoclonal Ab therapy -Rituximab (anti-CD20)
Describe Chromosome translocations and lymphoma
o Many lymphomas carry chromosome translocations involving the Ig heavy chain or light chain loci (chr14).
o Ig genes are highly expressed in B-cells
o Each Ig gene has a powerful tissue specific enhancer (high expression levels) near to the constant (C) segment
o Normal role: activating the promoter of the rearranged V segment
o Most cases of follicular lymphoma carry t(14;18)(q32;q21)
- t(8;14)(q24;q32) is frequently observed in Burkitt’s lymphoma.
- c-myc is a potent oncogene
What are the types of Non-Hodgkin’s Lymphomas
o Low grade
o High grade
How do we diagnose Non-Hodgkin’s Lymphomas
o Immunophenotyping o Cytogenetics –FISH o For chromosome translocations (e.g. t(14;18) Ig : Bcl-2) o Light chain restriction o PCR o For clonal Ig gene rearrangement
How do we treat Non-Hodgkin’s Lymphomas
o Chemotherapy
o Radiotherapy
o Stem cell transplant
o Monoclonal Ab therapy -Rituximab (anti-CD20)
Compare low and high 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
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 Multiple Myeloma?
How does it present itself?
What are the risk factors?
Tumour of the bone marrow that involves plasma cells (antibodies production).
Absence of initial symptoms. Later: bone pain, bleeding, frequent infections, and anaemia.
Obesity, radiation exposure, family history, and certain chemicals.
How do we diagnose Multiple Myeloma?
How do we treat it?
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
Radiotherapy, chemotherapy, allogeneic hematopoietic stem cell transplantation (ASCT) in young patients.
What are the Three aspects of myeloma give rise to different clinical features?
- Suppression of normal bone marrow, blood cell and immune cell function
- Anaemia
- Recurrent infections
- Bleeding tendency - 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 the paraprotein –(single monoclonal Igɣ 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
Heart failure
