Multiple Myeloma + Paraproteinaemias Flashcards
What is Multiple Myeloma?
Neoplasia of plasma cells: accumulation of abnormal plasma cells in the BM interfere with the production of normal blood cells.
What is a ‘paraprotein’ (aka ‘Myeloma Protein’)?
An abnormal/monoclonal immunoglobulin fragment or immunoglobulin light chain, produced in excess by an abnormal clonal proliferation of plasma cells, typically in multiple myeloma.
Which cell differentiates into a plasma cell? What activates this differentiation?
B lymphocyte cell.
Encountering an antigen drives a virgin B cell to generate a low affinity plasma cell or migrate to the germinal center, where it matures before migrating to the bone marrow and becoming a long-lived plasma cell (produces antibodies)
Multiple Myeloma:
What age group is most at risk? What ethnicity group has increased incidence? What is the median survival?
65-70yo
Afro-Caribbean
3-4 years
What are the clinical features of Multiple Myeloma?
CRAB:
Calcium High (thirst, moans, groans, stones, bones)
Renal failure (+ amyloidosis and nephrotic syndrome)
Anaemia (+ pancytopenia)
Bones: pain, osteoporosis, osteolytic lesions, fractures (wedge compression, pepper pot skull)
+ Hyperviscosity syndrome
What Ix would you request for a patient with suspected Multiple Myeloma? What would they show if the patient did in fact have Multiple Myeloma?
FBC: high ESR, U&E: high Ca, maybe high creatinine
Blood Film: Rouleaux (RBC stacking)
Blood electrophoresis: dense narrow band (presence of paraprotein, most of IgG paraprotein)
Urine electrophoresis: Bence-Jones protein
LP: over 10% plasma cells in BM
What system is used to stage Multiple Myeloma?
Durie-Salmon Staging System
What is the treatment for Multiple Myeloma?
Supportive for CRAB symptoms (inc Bisphosphonates)
Chemo combination: Melphalan, Bortezomib (proteasome inhibitor), Lenalidomide, Thalidomide +/- auto SCT
Steroids: dex or pred
How does Multiple Myeloma cause kidney injury? (basic Pathophysiology)
Filtered Light Chains activate inflammatory mediators in the proximal tubule epithelium –> proximal tubule necrosis
FLCs and Tamm Horsfall proteins lead to cast injury in thick ascending limb
What is Monoclonal Gammaglobinopathy of Unknown Significance (MGUS)?
Condition where a paraprotein is found in blood, so resembles MM, but levels of paraprotein are lower and there are no other symptoms
under 10% plasma cells in BM, under 30g/L monoclonal paraprotein, no CRAB symptoms
What percentage of MGUS progress to MM?
1-2% progression/year
What is Smoldering Myeloma?
Very slow growing type of myeloma, characterized by a proliferation of malignant plasma cells and monoclonal paraproteins in blood, but no symptoms.
>10% plasma cell in BM, >30g/L monoclonal paraprotein, no CRAB, no organ/tissue involvement.
What is Waldenstrom’s Macroglobinaemia?
A low grade Non Hodgkins Lymphoma: lymphoplasmacytoid cells produce monoclonal serum (IgM) that infiltrates the lymph nodes and bone marrow
What are the symptoms of Waldenstrom’s Macroglobinaemia? Who is most commonly effected?
Weight loss, fatigue, hyperviscosity syndrome (visual problems, confusion, CCF, muscle weakness)
Elderly men are most affected
What is the treatment for Waldenstrom’s Macroglobinaemia?
Plasmapheresis for hyperviscosity, chlorambucil, cyclophosphamide and other chemo.
