Myeloma Flashcards
What is myeloma?
Myeloma is a cancer of the plasma cells.
Cancer in a specific type of plasma cell results in large quantities of a single type of antibody being produced.
What are plasma cells?
These are a type of B lymphocyte that produce antibodies.
What % of all cancers does myeloma account for?
Myeloma accounts for around 1% of all cancers.
What is multiple myeloma?
Multiple myeloma is where the myeloma affects multiple areas of the body.
What is monoclonal gammopathy of undetermined significance (MGUS)?
Monoclonal gammopathy of undetermined significance (MGUS) is where there is an excess of a single type of antibody or antibody components without other features of myeloma or cancer. This is often an incidental finding in an otherwise healthy person and as the name suggests the significance is unclear. It may progress to myeloma and patients are often followed up routinely to monitor for progression.
What is smouldering myeloma?
Smouldering myeloma is where there is progression of MGUS with higher levels of antibodies or antibody components. It is premalignant and more likely to progress to myeloma than MGUS.
What is Waldenstrom’s macroglobulinemia?
Waldenstrom’s macroglobulinemia is a type of smouldering myeloma where there is excessive IgM specifically.
Briefly describe the pathophysiology of myeloma
Plasma cells are B cells (B lymphocytes) of the immune system that have become activated to produce a certain antibody. They are called B cells because they are found in the bone marrow. Myeloma is a cancer of a specific type of plasma cell where there is a genetic mutation causing it to rapidly and uncontrollably multiply.
These plasma cells produce one type of antibody. Antibodies are also called immunoglobulins. They are complex molecules made up of two heavy chains and two light chains arranged in a Y shape. They help the immune system recognise and fight infections by targeting specific proteins on the pathogen. They come in 5 main types: A, G, M, D and E. When you measure the immunoglobulins in a patient with myeloma, one of those types will be significantly abundant. More than 50% of the time this is immunoglobulin type G (IgG). This single type of antibody that is produced by all the identical cancerous plasma cells can be called a monoclonal paraprotein. This means a single type of abnormal protein.
The “Bence Jones protein” that can be found in the urine of many patients with myeloma is actually a part (subunit) of the antibody called the light chains.
Out of all the immunoglobulins, myeloma affecting which one is predominantly affected?
More than 50% of the time this is immunoglobulin type G (IgG).
Why does anaemia present in myeloma?
The cancerous plasma cells invade the bone marrow. This is described as bone marrow infiltration. This causes suppression of the development of other blood cell lines leading to anaemia (low red cells), neutropenia (low neutrophils) and thrombocytopenia (low platelets).
What is myeloma bone disease? What causes it?
Myeloma bone disease is a result of increased osteoclast activity and suppressed osteoblast activity. Osteoclasts absorb bone and osteoblasts deposit bone. This results in the metabolism of bone becoming imbalanced as more bone is being reabsorbed than constructed. This is caused by cytokines released from the plasma cells and the stromal cells (other bone cells) when they are in contact with the plasma cells.
How does myeloma bone disease present?
Common places for myeloma bone disease to happen are the skull, spine, long bones and ribs. The abnormal bone metabolism is patchy, meaning that in some areas the bone becomes very thin whereas others remain relatively normal. These patches of thin bone can be described as osteolytic lesions. These weak points in bone lead to pathological fractures. For example, a vertebral body in the spine may collapse (vertebral fracture) or a long bone such as the femur may break under minimal force.
All the osteoclast activity causes a lot of calcium to be reabsorbed from the bone into the blood. This results in hypercalcaemia (high blood calcium).
People with myeloma can also develop plasmacytomas. These are individual tumours made up of the cancerous plasma cells. They can occur in the bones, replacing normal bone tissue or can occur outside bones in the soft tissue of the body.
Why do patients with myeloma develop renal disease?
Patients with myeloma often develop renal impairment. This is due to a number of factors:
- High levels of immunoglobulins (antibodies) can block the flow through the tubules
- Hypercalcaemia impairs renal function
- Dehydration
- Medications used to treat the conditions such as bisphosphonates can be harmful to the kidneys
Why does hyperviscosity occur in myeloma?
The normal plasma viscosity, or internal friction in the flow of blood, is between 1.3 and 1.7 times that of water. To oversimplify it: blood is 1.3 to 1.7 times thicker than water. Plasma viscosity increases when there are more proteins in the blood. These are proteins like immunoglobulins and fibrinogen, both of which increase with inflammation. In myeloma there are large amounts of immunoglobulins in the blood causing the plasma viscosity to be significantly higher.
What does raised plasma viscosity in myeloma lead to?
Raised plasma viscosity can cause many issues:
- Easy bruising
- Easy bleeding
- Reduced or loss of sight due to vascular disease in the eye
- Purple discolouration to the extremities (purplish palmar erythema)
- Heart failure
