Myelomas Flashcards
diagnosis: This is a pathological fracture of the femur
cause: multiple myeloma
Older person with osteoporosis-fractures at neck of femur
Fractures in shaft of femur without osteoporosis-2 options: 1)heavy trauma=broken leg 2)pathological fracture=fracture with only moderate trauma and happens through a weakened/pathological form of the bone.
lymphohaemopoietic cancers-how common?
About 9% of adult cancers
But much more common in children. Don’t see myeloma in children but do see leukaemias
Blood cancers-are caused by an acquired somatic change in DNA
- More time DNA is replicated, the greater the chance of a mutation.
- May be inherited predisposition, but it’s usually just a random acquired mutation.
- Humans due to adaptive immune response can develop antibodies to various antibodies
- To have this we need instability in lymphoid genome in order to have this, which means if mistakes happen you can get mutations, and this instability can predispose to lymphoid cancers
Cancer requires a tissue diagnosis:
How do we get the tissue sample/biopsy
- Aspirate-stick needle and suck out free cells from BM-liquid which you spread out on slide. With this, you get great detail on individual cells
- Trephine will take out a core. Doesn’t give great detail but gives good idea of structure of cells
Bone marrow trephine:
In leuakaemia fat spaces are replaced by cells. In aplastic lots of fat spaces and few cells
Lymph node biopsy-what is best?
Core biopsy-don’t need GA
Haemato-oncology diagnosis
Core biopsy-don’t need GA
Why haematology complicated
Because malignancies can happen at different stages of maturation and affecting different lineages
Compared to prostate cancer where you just have adenocarcinoma
T-cell ontogeny:
B-cell ontogeny:
If malignancy of precursor b lymphocytes we call it:
B cell acute cell lymphoma (childhood ALL)
Name cancers on the cell at the stage they occur.
Mature plasma cell returns to bone marrow and they produce antibodies against some previously encountered antigen.
What happens in multiple myeloma?
Plasma cells return to BM but there are far more plasma cells
Normal plasma will secrete an antibody and malignant plasma cells do the same but they produce only one type of immunoglobulin.
Each individual immunoglobulin molecule has a charge and weight so produces a line when you run an electrophoresis strip. So if lots of the same immunoglobulin, you get a paraprotein band.
Malignant cell cannot maintain balance of heavy chain and light chain to from immunoglobulin and they produce too much light chains which are unpaired and end up in urine.
Introduction to multiple myeloma:
Incurable
Myeloma statistics
Cause of myeloma?
Key features of myeloma:
pancytopenia-once eliminated b12 or folate then you are thinking something infiltrating the bone marrow.
ESR high due to vast excess of globulins
Hypercalcaemia and renal failure
Get monoclonal excess of immunoglobulins
Diagnosis of MM
Anaemia-reflects infiltration of the bone marrow by the plasma cells
Diagnosis on aspirate showing excess of plasma cells or on trephine showing excess of plasma cells.
MM cell morphology:
pale golgi aparatus where protein is synthesised
Blue dye-shows protein
Vast excess of Ig G
paraprotein-when you have an excess of a
immune paresis-as BM gets taken over and body only produces malignant immunoglobulin you get lower levels of igm and iga
free light chains-imbalance between heavy and light chains and they pass out into urine through GBM where they can be detected in serum free light chain assay.
Bence jones protein-free light chains in urine
The tumour cells:
As well as secreting immunoglobulins the plasma cells secrete soluble factors activating osteoclasts
Clinical presentation-bone disease
Pepper pot skull
Prostate boney metastases causes osteoblastic activity but with this just erosions, no associated blastic activity.
Bone disease and emergencies in myeloma
-First presentation may be paralysis due to vertebral body collapse due to MM
=Cast nephropathy
Is most common causes because at time of diagnosis man had serum free light chains and lots of kappa light chains
Never get myeloma invading kidney, it stays in BM in contrast to lymphoma or leukaemia.
Kidney injury in myeloma:
-High levels of free light chains can be deposited in distal convoluted tubule and cause cast nephropathy which is cause of acute renal failure in MM.
Treatments in myeloma:
- High doses of steroids
- Proteasome inhibitors try to reduce protein production seen in myeloma
Melphalan-alkylating agent was a first drug used
Immunomodulatory drugs are also used in MM. Eg Thalidomide which impacts plasma cell and BM microevironment and improves outcome of MM patients.
To intensify treatment, can give an autologous haemopoeitic stem cell transplant
No-
need FBC to check for pancytopenia
Check kidney function-creatinine normal
No hypercalcaemia
Everything excludes myeloma
BUT sometimes can get light chain only myeloma so plasma cells don’t secrete any heavy chain so can’t get paraprotein
So look in urine for bence jones protein or look in blood for free light chains.
- management of hypercalcaemia
- management of acute renal failure
- Initial management of multiple myeloma
IV fluids for calcium and renal failure, steroids are fast acting so give these, bisphosphonates (but be cautious with renal failure),
