Myeloma and lymphoma Flashcards
Where does B cell maturation take place?
Bone marrow
What does B cell maturation comprise?
Gain surface immunoglobins
What happened during B cell differentiation?
Mature B cells are exposed to antigens and become either…
- apoptose
- differentiate into plasma cell
- enter germinal centre
What produced immunoglobins?
Plasma cells in response to immunogen
Wha t is the structure of an immaunogen? How are they classified?
4 polypeptide chains - 2 light, 2 heavy held together by disulphide bonds
Heavy chain - IgG, IgM, IgE, IgD, IgA
Light chain kappa or lama
What are the techniques by which myeloma is identified?
Protein electrophoresis - serum placed in gel and exposed to electric current
Immunofixation
Bone marrow biopsy
What is the group of interest when investigating myeloma using electrophoreses?
Gamma globulins
What is produced with myeloma? How is this different to normal plasma cells?
Produce just one type of immunoglobin
Usually plasma cells produce a variety
What is myeloma? What is myeloma’s aetiology?
incurable malignant condition of clonal plasma cells
No know aetiology
What condition is myeloma always preceeded by?
Monoclonal gammopathy of undetermined Significance (MGUS)
No features of myeloma
What is diagnostic of myeloma?
> 10% plasma cells are neoplastic AND any one/more of…
- CRAB features
- Myeloma defining events
What are the CRAB features?
C - hyperCalcaemia - due to promoted osteoclastic activity)
R - Renal insufficiency - free light chains damage kidney (BENCE JONES protein - proteinuria)
A - Anaemia
B - bone lesions
What are the myeloma defining events?
> 60% clonal plasma cells in BM biopsy
- Focal lesions on MRI scan
What other factors, other than myeloma, could box out the kidney?
- Hyperviscocity
- Renal vein thrombosis
- CT contrast
- Dehydration
- NSAIDs/ACEi
- Hypercalcaemia
- Biaphosphonates
What should you treat individuals with suspected myeloma in first instance?
Steroids (delays damage to kidney)
What does intensive therapy for myeloma involve?
VCD (chemo) - extract stem cells - chemo (melphalan) - replace stem cells (allows bone marrow to recover)
What is the aim for intensive chemotherapy
Myeloma = incurable, put into remission for as long as possible
Also allow bone marrow to recover and reduce symptoms
What are the first line treatments for myeloma?
thalidomide/ lenalidomide in
combination with dexamethasone.
What are the diagnostic criteria for MGUS?
-Paraproteins (M proteins/light chains)
What is amyloidosis caused by?
Light chain fragments released from monoclonal plasma cells misfiled and aggregate, form Beta pleated fibrils
- deposit into organs
- Cause liver/cardiac enlargement, proteinuria, peripheral neuropathy
What is follicular lymphoma? What is it characterised by/
Neoplastic disorder of the lymph tissue (non-hopkin’s)
Slowly enlarging lymph node
What is the genetic component occurring in the majority of cases in follicular lymphoma?
Translocation between chromosome 14 to 18
What is Hogkin lymphoma characterised by?
Presence of Hodgkin Reed Sternberg cells - giant cells (usually originate from B germinal cells) which lack antibodies, do not undergo apoptosis and are surrounded by non-malignant infiltrates (i.e. T cells, plasma cells, B cells)
What is Hodgkins disease caused by? i.e. pathogenesis
Resistance to apoptosis
Genetic mutation/transciption error to Ig genes - no longer express Ig antibodies
Environmental - EBV virus
What are the clinical features of Hodkin lymphoma
Enlarged lymph nodes
B cell symptoms - night sweats, cachexia, fever
Hepatosplenomegaly
Lung involvement - breathlessness
How is Hodkins lymphoma managed?
Chemotherapy and radiotherapy
What is non Hodkins lymphoma?
Malignant tumours of lymphoid tissues WITHOUT Reed Sternberg cells
What is the clinical presentation of non-hoskins Lymphoma?
- Superficial lymph enlargement
- B cell symptoms - night sweats, fever, cachexia
- pancytopenia - anaemia of RBCs, WBCs, and platelets
