Plasma Cell Disorders Flashcards
What is a plasma cell? What is its function?
A fully differentiated B cell / to pump out soluble antibodies
Antibodies are produced by what?
B cells and plasma cells
What are antibody proteins made up of?
2 heavy chains and 2 light chains
Name antibodies which are each of the following shapes: a) monomer? b) dimer? c) pentamer?
a) IgD, IgE, IgG b) IgA c) IgM
Normally, B cells and plasma cells will be polyclonal. What does this mean?
They will be diverse, with thousands of small clones all producing different antibodies
What is meant by a cell being monoclonal?
One clone develops and expands so there is overexpression of one particular clone of plasma cells - lots of similar antibodies will be produced
Monoclonal antibodies are derived from what?
Clonal expansion of a single B cell
A monoclonal antibody can also be known as what? What is the use of this?
Paraprotein / can be used as a marker of underlying clonal B cell disorders
What are the two stages of detecting immunoglobulins?
Serum electrophoresis detects abnormal protein bands / serum immunofixation is used to classify the abnormal protein band
A band on serum electrophoresis which shows up bright suggests the presence of what?
A monoclonal antibody
What are Bence-Jones proteins?
Immunoglobulin light chains detected by urine electrophoresis
When immunoglobulins are synthesised in plasma cells, more light chains than heavy chains are produced. What happens to the excess free light chains?
Secreted into the plasma, along with intact immunoglobulin
In Bence-Jones proteins, which type of free light chain will be seen as each of the following: a) monomers? b) dimers?
a) Kappa free light chains b) Lambda free light chains
Why do Bence-Jones proteins occur?
If there is an increase in the number of plasma cells then the amount of free light chains in the plasma increase and excess can leak into the urine
What is myeloma?
A plasma cell malignancy
What are the 3 stages of the development of myeloma?
MGUS, asymptomatic myeloma, myeloma
What are some direct tumour effects of myeloma?
Bone lesions/pain, hypercalcaemia, pancytopenia due to marrow failure
What are some paraprotein mediated effects of myeloma?
Renal failure, immunosuppression, hyperviscosity, amyloid
How does myeloma cause lytic bone disease?
Interacts with bone marrow stromal cells to produce IL-6 to suppress osteoblasts but activate osteoclasts causing a net loss of bone
How can lytic bone disease of myeloma manifest?
As osteoporosis, or as focal lesions
What are some features of hypercalcaemia which may be seen in myeloma?
Stones, bones, abdominal groans, psychiatric moans / dehydration, thirst, renal impairment
What effects do light chains in myeloma have on the kidneys?
Tubular cell damage and cast nephropathy
Are the renal effects of myeloma reversible? What are some treatment options?
Yes, if treated promptly / hydrate, stop nephrotoxic drugs, steroids and chemotherapy
What is the median age at diagnosis of myeloma?
65
What is the mainstay of treatment for myeloma?
Combination chemotherapy
What other drug should always be given alongside chemotherapy for myeloma?
Corticosteroids (activity against plasma cells)
In myeloma treatment, alkylating agents can be used. Give an example?
Cyclophosphamide
In myeloma treatment, novel agents can be used. Give some examples?
bortezomib and lenalidomide
What is a treatment option for myeloma which is only used in younger, fitter patients?
High dose chemotherapy and autologous stem cell transplant
What is used to monitor response to myeloma treatment?
Paraprotein levels
What are some treatments which can be used for symptom control in myeloma?
Opiate analgesics, local radiotherapy, bisphosphonates, vertebroplasty
What are the survival outcomes of myeloma?
5-10 years for younger patients, though relapse is inevitable
What happens every . time there is a remission of myeloma?
The period of remission becomes less
In terms of paraproteins and plasma cells, what is seen in MGUS?
Paraproteins present at a level of < 30g/L and the bone marrow plasma cells are < 10%
What are the clinical features of MGUS?
None
Prevalence of MGUS increases with what? It is twice as common in who?
Age / Black people
What is the risk of progression to myeloma from MGUS?
1% risk every year
What is the mechanism behind AL amyloidosis?
Mutations in the light chains lead to altered structure. They then precipitate in tissues as an insoluble beta pleated sheet.
What is the clinical presentation of AL amyloidosis?
Causes organ damage which is slowly progressive - often presents late with end organ failure
How should AL amyloidosis be treated? What is its prognosis?
Chemotherapy to switch off the light chains / poor prognosis
What is used to diagnose AL amyloidosis? What will this show under polarised light?
Organ biopsy with Congo red stain / apple green birefringence
What is Waldenstrom’s macroglobulinaemia? What type of paraprotein is seen?
Clonal disorder of cell intermediates between a lymphocyte and plasma cell / IgM
What are the tumour effects of Waldenstrom’s macroglobulinaemia?
Lymphadenopathy, splenomegaly, marrow failure
What are the paraprotein effects of Waldenstrom’s macroglobulinaemia?
Hyperviscosity and neuropathy
What are some ‘B symptoms’ of Waldenstrom’s macroglobulinopathy?
Night sweats and weight loss
How is Waldenstrom’s macroglobulinaemia treated?
Plasmapheresis and possible chemotherapy
