Myeloma Flashcards
What is multiple myeloma and what is the effect of it on the body?
MM is a B-cell malignancy derived from Ab-producing plasma cells in the bone marrow
Myeloma cells interfere w bone marrow function
The abnormal production of M-protein affect the blood, skeleton, and kidneys
Give the presenting symptoms for MM
Also, MM cells produce a single monoclonal Ab, this can vary between patients. Usually IgG or IgM
What does this show?
Give some other clinical indications of a patient with myeloma
What is the clinical significance associated with myeloma symptoms- ie what emergencies can they lead to?
What are the common sites for myeloma?
Emergencies associated with myeloma:
-Hyperviscosity
-Hypercalcaemia
-Infection
-Pathological fractures
-Spinal cord compression
-Renal failure
Common sites for myeloma:skull, spine, pelvis and long bones (mostly axial skeleton)
What are the myeloma defining events?
How is FISH (Fluorescence in situ hybridisation) used to aid a patient’s diagnosis/prognosis w myeloma?
Looking at known specific high risk translocations in patients, eg abnormalities w chromosome 14 or 17P deletion
In FISH, Plasma cells (CD138+ cells) are isolated from a bone marrow aspirate
Specific fluorescent probes bind comp DNA sequences to highlight location of genes
Compare these 2 X rays. Which patient has MM and why?
X ray A: Each of the vertebral bodies have a defined edge, there is symmetry
x RAY B: Less definition, more difficult to see the bones on the x ray bc hay menos bone density. 5 vertebrae from the bottom, one of them appears whiter- this is a vertical compression fracture
X ray B=myeloma. Also, you can have holes/lytic lesions- lytic bone disease
How would you check for bone disease in MM?
The preferred way is a low dose CT which is more sensitive, or diffusion weighted MRI scans
May need additional imaging in certain situations including PET-CT or whole spine MRI
Describe Myeloma Bone disease
Osteoclasts resorb bone, osteoblasts produce bone.
Bone marrow stromal cells activate this process
Myeloma cells produce cytokines which stimulate bone marrow stromal cells, which stimulate the plasma cells
In myeloma, hay down regulation of osteoprotegerin and increased osteoclast activation
Describe the management of bone disease (6 things)
Bisphosphonates: - bind Ca in bone, taken up by the osteoclast and cause its premature death
- eg Pamidronate & Zoledronic acid have an additional effect on bone metabolism - also induce OPG secretion by osteoblasts, blocking RANK-l
Non nitrogenous BP’s - induce apoptosis directly, while Nitrogenous BP’s interfere with actin/ cytoskeletal elements important for ruffling the active osteoclast border
RANK ligand inhibitors, eg Denosumab: monoclonal Ab to treat osteoporosis. It binds RANK-L, blocking its binding to RANK on osteoclasts, thus mimicking osteoprotegerin action
Analgesia, Orthopaedic Input, Chemo, radiotherapy
Why do renal stones form in patients with myeloma?
In myeloma pts, hypercalcaemia–>hypercalcuria and precipitation of excess calcium in the urine
This leads to the development of Ca phosphate renal stones
What is the impact of myeloma on the kidney?
Obstruction of urine flow leading to stagnant urine w increased infection risk
Backpressure on Kidney from obstructed urine (hydronephrosis) causing pressure atrophy
Failing kidney causing hypertension via RAAS
What does this show?
Cast Nephropathy
Renal tubules filled w precipitated light chain
Build up of this protein damages the renal tubules
Inflammatory response (interstitial nephritis)
Progressive damage can lead to scarring and renal failure
Explain what is meant by deposition of light chains- where does it occur, what are the types, what can it lead to?
Can occur in plasma cell dyscrasia (MGUS, Myeloma). 2 types:
Light chain deposition disease: abnormal light chains produced by plasma cells deposit in tissues
Amyloidosis (AL type): Abnormal light chain deposition causes amyloidosis. This type is seen in myeloma pts
Can lead to proteinuria and renal failure
Most pts w amyloidosis have lambda light chain secreting tumours
What does this show?
What is this caused by?
A renal biopsy showing amyloidosis
Monoclonal protein-producing plasma cells can cause Ig light chain (AL) amyloidosis, buildup of which causes kidney damage below
Draw a diagnosistic diagram to show investigation of a case of bacterial lobar pneumonia
What is the positive optochin test for strep pneumonia?
How can you use immunofluourescence to diagnose VZV?
A microscopy slide is made of the tissue scrapings, fixed and incubated with a panel of fluorescently labelled VZ antibodies
If the antibody binds to the cells= virus is present
