Myeloma and other plasma cell disorders Flashcards
Where are B cells derived from and what is their role?
- Derived in bone marrow from pluripotent haemopoietic stem cells
- Part of the adaptive immune system
- Dual roles - antibody production, acting as antigen presenting cells
What are immunoglobulins?
- Antibodies produced by B cells and plasma cells
- Proteins made up of 2 heavy and 2 light chains
- Each antibody recognises a specific antigen
Where do B cells travel in the periphery?
- Travel to the follicle germinal centre of the lymph node
- Identify the antigen and improve the fit by somatic mutation or be deleted
- May return to the marrow as plasma cell or circulate as memory B cell
What is a plasma cell and what are some of its features?
- A factory cell
- Pumps out antibody
- Eccentric clock face nucleus on H&E
- Open chromatin - synthesising mRNA
- Plentiful blue cytoplasm - laden with protein
- Pale perinuclear area - Golgi apparatus
There is an associated rise in monoclonal immunoglobulins in myeloma. What are monoclonal immunoglobulins?
- Monoclonal immunoglobulin = paraprotein
- All derived from clonal expansion of a single B cell
- Identical antibody structure and specificity
What does serum electrophoresis do?
Separates serum proteins into distinct bands or zones which allows detection of abnormal proteins
What does serum immunofixation do?
Classifies the abnormal protein band
What paraprotein is shown in this serum immunofixation?
IgGK - band of IgG kappa
What paraprotein is shown in this serum immunofixation?
IgAK - band of IgA kappa
What is Bence-Jones protein?
- Immunoglobulin light chains (excess)
- Detected by urine electrophoresis
What is the major cause of paraproteinaemia?
MGUS - monoclonal gammopathy of undetermined significance
What are some of the direct tumour cell effects of myeloma?
- Bone lesions
- Hypercalcaemia
- Bone pain
- Replace normal bone marrow -> marrow failure
What are some paraprotein mediated effects of myeloma?
Renal failure, immune suppression, hyperviscocity, amyloid
What are the symptoms of hypercalcaemia?
Stones, bones, abdominal groans, psychiatric moans, thirst, dehydration, renal impairment
Myeloma can cause renal impairment, what are the features of this?
- Tubular cell damage by light chains
- Light chain deposition - cast nephropathy
- Sepsis
- Hypercalcaemia and dehydration
- Hyperuricaemia
- Amyloid
How can cast nephropathy be treated?
- Damage may be reversible with prompt treatment
- Hydration, stop nephrotoxic drugs
- Switch off light chain production with steroids/chemo
How is myeloma treated?
- Combination chemotherapy the mainstay
- Corticosteroids e.g. dexamethasone, alkylating agents e.g. cyclophosphamide, novel agents e.g. thalidomide
- High dose chemo/autologous stem cell transplant in suitable patients
What is used to monitor response in myeloma?
Paraprotein level
What are some medications used for symptom control?
- Opiate analgesia - avoid NSAIDs
- Local radiotherapy - good for pain relief or spinal cord compression
- Bisphosphonates - corrects hypercalcaemia and bone pain
- Vertebroplasty - inject sterile cement into fractured bone to stabilise
How is MGUS defined?
- Paraprotein <30g/L
- Bone marrow plasma cells <10%
- No evidence of myeloma end organ damage - normal calcium, renal function, Hb, no lytic lesions or increase in infections
What is AL amyloidosis and how is it treated?
- Rare disorder
- Small plasma cell clone
- Mutation in the light chain -> altered structure
- Precipitates in tissues as an insoluble beta pleated sheet
- Often presents late with organ damage
- Slowly progressive
- Multi-system disease
- Poor prognosis especially if cardiac amyloid
- Treatment with chemo similar to myeloma to switch off light chain supply
What organ damage can occur in AL amyloid?
- Kidney - nephrotic syndrome
- Heart - cardiomyopathy
- Liver - organomegaly deranged LFTs
- Neuropathy - autonomic, peripheral
- GI tract - malabsorption
How is AL amyloid diagnosed and staged?
- Organ biopsy confirming AL amyloid deposition - congo red stain, rectal or fat biopsy may be done if high clinical suspicion
- Evidence of deposition in other organs - echo/cardiac MRI, nephrotic range proteinuria
What is used to measure disease burden in AL amyloid?
SAP scan - localises rapidly and specifically to amyloid deposits in proportion to the quantity of amyloid present
