3 - myeloma & plasma cell disorders Flashcards
give a small summary of B cell maturation process?
B cells in bone marrow go from stem cells →IgM B cells leave bone marrow and go to lymph node →encounter antigen →pick best B cells and keep them (somatic hypermutation) →then decide which class to produce (gG, IgE, IgA) →plasma cells or memory cells
what is a plasma cell?
B cells dedicated to producing lots of circulating immunoglobulins (ones that circulate in blood not on B cell surface)
what is appearance of plasma cell on histology?
big fried eggs - cytoplasm dark blue (since making lots protein) and nucleus purple ish
what can cause polyclonal increase in immunoglobulins? (what trigger lots different antibodies to be made)
infection, malignancy, autoimmune disease, liver disease
(it’s normal reaction to underlying trigger)
what is paraprotein?
marker of underlying monoclonal B cell or plasma disorder = it shows that single antibody being produced over & over by 1 dysfunctional B/plasma cell
what 2 tests is done to detect abnormal immunoglobulins?
FIRST:
serum electrophoresis = apply voltage & proteins are separated by size & charge (detects if there are abnormal proteins)
SECOND:
serum immunofixation = more detailed test to classify abnormal proteins (detects which specific faulty immunoglobulin)
what is bence jones protein?
excess immunoglobulin leaked into urine
what is myeloma?
cancer of plasma cells (bone marrow cells that churn out antibodies)
- faulty plasma cells make too much of 1 antibody (causes problems)
what is MGUS (monoclonal gammopathy of undetermined significance)?
benign premalignant clone = they have faulty antibody but not causing any problems yet
- it’s very common, you’re at increased risk of progression to myeloma (but uncommon)
what is clinical presentation of myeloma?
- bone pain & problems = faulty plasma cell makes cytokines which stimulate osteoclasts & suppress osteoblast
- hypercalcaemia (from bone breakdown) = bones, stones, abdominal groans & psychiatric moans
- bone marrow failure (from build up plasma cells) = pancytopenia
- hyperviscosity (from paraprotein making increased plasma viscosity) = headaches
- amyloid
- renal failure (light chains aggregate & block tubules in kidneys)
what is cast nephropathy?
light chains that blocked in kidney - some shed in urine and are seen as cast nephropathy
what is treatment of myeloma?
- switch off light chain production with chemo & steroids (dexamethasone)
- monoclonal antibodies e.g. daratumumab (stick to monoclonal antibodies & kill)
- stem cell transplant if young & fit
symptom control:
- opiate analgesia (avoid NSAIDs)
- bisphosphonates (inhibit osteoclasts)
- vertebroplasty or local radiotherapy for spine issues
what is amyloidosis?
group of diseases which share feature of faulty proteins that stick together - they build up in tissues causing multisystem organ disease
(AL amyloidosis is important subtype - this is seen as presentation in myeloma)
what is done for diagnosis of amyloidosis?
ideally biopsy of affected organ with congo red stain = amyloid looks apple green birefringence in polarised light
what is waldenstrom’s macroglobulinaemia?
= rare disease which is like hybrid of features of lymphoma & myeloma, can be called lymphoplasmacytoid neoplasm
