Plasma Cell Myeloma and Amyloid Flashcards
what is multiple myeloma?
Cancer of the BM plasma cells, terminally differentiated and Ig secreting B cells
What kind of tumours do myeloma plasma cells produce?
Bone expansile / soft tissue tumours
What kind of Ig do myeloma plasma cells produce?
MONOCLONAL Ig
either IgA or IgG
What is the most important structure produced by myeloma plasma cells?
Excess of monoclonal (K/lambda) serum free light chains
aka BENCE JONES PROTEIN
What condition can predispose to MM?
Pre-malignant condition called:
Monoclonal Gammopathy of Uncertain Significance (MGUS)
What is median survival for MM?
4-7 years
POOR prognosis
Explain pathophysiology of MM
Early in plasma cell, error occurs in genome
This leads to monoclonal accumulation of plasma cells (MGUS)
1% of people every year acquire extra mutations (KRAS, NRAS) which transform MGUS into MM
What is the average age for myeloma?
67
What are RF for myeloma?
Age
Obesity
Genetic (sporadically familial)
Black
What proportion of patients a year go from MGUS too MM?
1%
What disease occurs if from MGUS there is excess IgM production?
Lymphoma
What bone marrow plasma cell percentage is required for MGUS classification?
<10%
What disease sits between MGUS and MM?
Smouldering myeloa
What is the progression of MM?
Incurable
Periods of remission-relapse
Becomes refractory to tx
Becomes extramedullary disease, with circulating plasma cells
What is the most common primary event that causes MM?
HYPERPLOIDY (additional odd number chromosome)
What is another primary event that causes MM?
heavy immunoglobulin chain rearrangement
What occurs genetically in each pt with MM’
In each patient there are multiple subclones with genetic lesions
As tumour develops, more lesions accumulate in linear /branching fashion
This creates evolutionary pressure
Selects either indolent or aggressive clones
What is the aetiology of MM causing bone destruction?
MM releases cytokines
cytokines stimulate osteoclasts to induce bone resorptiìon
What percentage of plasma cells in bone marrow are required for MM dx?
> =10% plasma cells in bone marrow
What are the clinical presentations of MM? ACRONYM
CRAB
Calcium elevated
Renal impairment
Anaemia
Bone lesions
What diagnosis is a good indicator that pt will develop myeloma in coming months?
MDE (Myeloma Defining Event)
What cellular markers is MM positive for?
CD138
CD38
CD56
CD58
What cellular markers in MM negative for?
CD19
CD20
Surface IgG
What does bone disease present like in MM?
Proximal skeleton affected Spine, chest wall, pelvic pain OsteoLYTIC lesions Osteopoenia Pathological fractures Hypercalcaemia
What is the key bone emergency in MM?
Cord compression
Due to spine fracture > soft tissue enters spinal canal or soft tissue mass forms
What is tx for cord compression in MM?
Dexamethasone
Radiotherapy
Neurosurgery
How do you image MM bone lesions?
MRI or CT scan (or PET)
NOT plain X ray film. obsolete as low sensitivity
What is the key cause of kidney injury in MM’
FLC and Bence Jones Proteins
How do light chains cause kidney injury in MM?
High quantity of free light chains produced
Proximal tubule can no longer uptake them, as under high stress
FLC travel to distal tubule
Here they bind to THP
This complex obstructs the tubule and eventually destroys the nephron
How do you treat kidney disease in MM?
BORTEXOIB
What marker of mM do you look for in bone marrow aspirate?
CD138
What does AL amyloidosis occur due to?
Misfolded free light chains aggregate into amyloid fibrils in target organs
What kind of stain do you use for AL amyloidosis?
CONGO red
What are 2 common target organs of AL amyloidosis=?
Kidney - nephrotic syndrome
Heart - heart failure
What are the 4 key domains for MM treatment=?
Cytostatic drugs e.g. melphalan, cycophosphamide
Steroids
Immunomodulators e.g. thalidomide
Proeasome inhibitors
What are other immunomodulators that are used for M M?
Lenalidomide
Pomalidomide
What are examples of protease inhibitors?
Bortezomib
