Plasma Cell Dyscrasias Flashcards
Where do B cells come from and what is their function?
Derived from stem cells in the bone marrow
- produce antibodies
What are antibodies and how are they structured?
Immunoglobulins
- -> proteins made of 2 heavy chains + 2 light chains
- monomers = IgD, IgE + IgG
- dimer = IgA
- pentamer = IgM
Describe the progression of a stem cell into a plasma cell
Stem cell –> lymphoid progenitor –> pro B cell –> pre B cell –> (leaves marrow) –> IgM B cell –> IgM plasma cell
(may return to marrow as plasma cell or circulate as memory B cell)
What is the function of a plasma cell and what does it look like?
Factory cell –> pumps out antibody
Clock-face nucleus, plentiful blue cytoplasm, pale patch next to nucleus
What might cause a polyclonal rise in Ig?
Reactive to –> infection, AI, malignancy, liver disease
What would cause a monoclonal rise in Ig?
Underlying clonal B cell disorder
What is another term for monoclonal Ig?
Paraprotein
Which investigations defect monoclonal Ig?
Serum electrophoresis –> detects abnormal protein bands
Serum immunofixation –> classifies abnormal band e.g. IgG, IgM
What is Bence Jones protein and how is it detected?
Excess Ig light chains in urine
–> detected by urine electrophoresis
What are the possible causes of paraproteinaemia?
MGUS (monoclonal gammaopathy of uncertain significance) Myeloma Amyloidosis Lymphoma Plasmacytoma CLL Waldenstrom's
What is myeloma?
Malignant proliferation of plasma cells in bone marrow
–> large amount of identical Ig (paraprotein) + free light chains (Bence Jones proteins if in urine)
How is myeloma classified?
By Ig class:
- 2/3 are IgG
- 1/3 are IgA
- rest are IgM or IgD
What happens to the other classes of Ig in myeloma?
Other classes will be low –> immunoparesis
What are the key features of myeloma?
Osteolytic bone lesions --> fractures + bone pain --> HYPERCALCAEMIA Pancytopenia (marrow infiltration) Infection (immunoparesis) Renal disease Hyperviscosity
What is the mechanism of kidney injury in myeloma?
Light chains (BJPs) deposit in kidneys –> tubular obstruction + kidney failure = cast nephropathy
What are the features of hypercalcaemia?
Stones Bones Abdo groans Psychiatric moans Thirst Dehydration Renal impairment
What would be seen on bloods in myeloma?
Normocytic anaemia
Raised ESR + plasma viscosity
Raised urea + creatinine
Bone profile: hypercalcaemia + normal ALP
What would be seen on the blood film in myeloma?
Rouleaux formation (stacked RBCs)
Which investigations should be done for myeloma?
Bloods + film
Serum + urine electrophoresis
Imaging to detect bony lesions (whole body MRI)
What is diagnostic criteria for myeloma?
Both:
- marrow aspirate/biopsy showing clonal plasma cells >10%
- 1 or more organ dysfunction –> CRAB (Calcium, renal, anaemia, bone)
How should myeloma be screened for in a patient > 50 with new back pain?
Electrophoresis + ESR
What is the symptomatic treatment for myeloma?
Bisphosphonates + analgesia (NOT NSAIDs) for bone
- RT +/- surgery if fractures or high risk
Transfusions +/- Epo for anaemia
Fluids +/- bisphosphonates for hypercalcaemia
Antibiotic prophylaxis, vaccines, Ig
What is the specific treatment for myeloma?
Combination chemotherapy
- high dose chemo + autologous stem cell transplant in fit patients
How is response to treatment monitored in myeloma?
Paraprotein level
What are some of the complications of myeloma?
Hyperviscosity syndrome
Spinal cord compression
Death usually due to infection or kidney failure
What is hyperviscosity syndrome?
Increase in PV usually due to raised Ig/paraproteins, RBCs or WBCs
(note: raised PV is also an inflammatory marker)
What are the causes of hyperviscosity syndrome?
Myeloma
Waldenstrom’s macroglobulinaemia
Polycythaemia vera
Leukaemia
What are the clinical features of hyperviscosity syndrome?
Classic triad:
- neuro symptoms: impaired cognition, headaches, seizures
- visual changes from retinopathy
- mucosal bleeding
How is hyperviscosity syndrome managed?
Plasmapharesis
When would a patient be considered to have MGUS?
Paraprotein < 30g/l, bone marrow plasma cells < 10%
No evidence of myeloma end organ damage
- normal calcium, renal function, Hb, bones
- no increase in infections
What is AL amyloidosis?
Rare disorder
Mutation in light chain –> altered structure
Precipitates in tissues as an insoluble beta pleated sheet –> organ damage
How is AL amyloidosis diagnosed?
Organ biopsy showing amyloid deposition: - congo red stain --> apple green birefringence under polarised light Evidence of deposition in other organs: - SAP scan (serum amyloid P) - echo/cardiac MRI - nephrotic range proteinuria
How is AL amyloidosis treated?
Chemotherapy similar to myeloma (switch off light chain supply)
How is Waldenstrom’s macroglobulinaemia characterised?
IgM paraprotein
What are the clinical features of Waldenstrom’s?
Lymphadenopathy Splenomegaly Marrow failure Hyperviscosity syndrome Night sweats, weight loss
How is Waldenstrom’s treated?
Chemotherapy Plasmapheresis (removes paraprotein from circulation)
