Multiple Myeloma Flashcards

1
Q

What is myeloma?

A

Myeloma is a cancer of the plasma cells. These are a type of B lymphocyte that produce antibodies. Cancer in a specific type of plasma cell results in large quantities of a single type of antibody being produced. Myeloma accounts for around 1% of all cancers.

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2
Q

what is multiple myeloma?

A

where the myeloma affects multiple areas of the body

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3
Q

what is monoclonal gammopathy of undetermined significance?

A

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.

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4
Q

What is smouldering myeloma?

A

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. Waldenstrom’s macroglobulinemia is a type of smouldering myeloma where there is excessive IgM specifically.

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5
Q

What do plasma cells normally do?

A

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.

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6
Q

What will be foundwhen measuring immunoglobulins in a patient with myeloma?

A

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.

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7
Q

What can be found in urine of patients with myeloma?

A

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.

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8
Q

How does anaemia occur?

A

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).

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9
Q

What is myeloma bone disease?

A

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.

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10
Q

Where are common places for myeloma bone disease to occur?

A

Common places for myeloma bone disease to happen are the skull, spine, long bones and ribs.

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11
Q

what are osteolytic lesions?

A

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.

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12
Q

What electrolyte imbalance occurs?

A

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).

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13
Q

What are plasmacytomas?

A

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.

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14
Q

What causes myeloma renal disease?

A

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

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15
Q

What happens to plasma viscocity in myeloma?

A

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.

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16
Q

What issues arise with an increased plasma viscosity?

A

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

17
Q

Important features to remember for exams!

A

C – Calcium (elevated)
R – Renal failure
A – Anaemia (normocytic, normochromic) from replacement of bone marrow.
B – Bone lesions/pain

18
Q

Rf for myeloma

A
Older age
Male
Black African ethnicity
Family history
Obesity
19
Q

When suspicious of myeloma

A
FBC (low white blood cell count in myeloma)
Calcium (raised in myeloma)
ESR (raised in myeloma)
Plasma viscosity (raised in myeloma)
If any of these are positive or myeloma is still suspected do an urgent serum protein electrophoresis and a urine Bence-Jones protein test.
20
Q

Testing for myeloma

A

B – Bence–Jones protein (request urine electrophoresis)
L – Serum‑free Light‑chain assay
I – Serum Immunoglobulins
P – Serum Protein electrophoresis
Bone marrow biopsy is necessary to confirm the diagnosis of myeloma and get more information on the disease.

Imaging is required to assess for bone lesions. The order of preference to establish this is:

Whole body MRI
Whole body CT
Skeletal survey (xray images of the full skeleton)
Patients only require one investigation but may not tolerate or be suitable for MRI or CT.

21
Q

signs on x-ray

A

Punched out lesions
Lytic lesions
“Raindrop skull” caused by many punched out (lytic) lesions throughout the skull that give the appearance of raindrops splashing on a surface

22
Q

Managing myeloma

A

First line treatment usually involves a combination of chemotherapy with:

Bortezomid
Thalidomide
Dexamethasone
Stem cell transplantation can be used as part of a clinical trial where patients are suitable.

Patients require venous thromboembolism prophylaxis with aspirin or low molecular weight heparin whilst on certain chemotherapy regimes (e.g. thialidomide) as there is a higher risk of developing a thrombus.

23
Q

Managing myeloma bone disease

A

Myeloma bone disease can be improved using bisphosphonates. These suppress osteoclast activity.
Radiotherapy to bone lesions can improve bone pain.
Orthopaedic surgery can stabilise bones (e.g. by inserting a prophylactic intramedullary rod) or treat fractures.
Cement augmentation involves injecting cement into vertebral fractures or lesions and can improve spine stability and pain

24
Q

Complications arising from myeloma

A
Infection
Pain
Renal failure
Anaemia
Hypercalcaemia
Peripheral neuropathy
Spinal cord compression
Hyperviscocity