Myeloma

Question 1

what is myeloma?

Answer 1

cancer of the plasma cells (a type of B lymphocyte that produce antibodies)

specific type of plasma cell results in large quantities of a single type of antibody being produced

Question 2

what is multiple myeloma?

Answer 2

where the myeloma affects multiple areas of the body

Question 3

what is Monoclonal gammopathy of undetermined significance (MGUS)

Answer 3

there is an excess of a single type of antibody or antibody components without other features of myeloma or cancer.

often an incidental finding in an otherwise healthy person and as the name suggests the significance is unclear

may progress to myeloma and patients are often followed up routinely to monitor for progression

Question 4

what is smouldering myeloma?

and what is Waldenstrom’s macroglobulinemia?

Answer 4

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.

Question 5

what is the pathophysiology of myeloma?

Answer 5

genetic mutation causing a specific type of plasma cell rapidly and uncontrollably multiply

they produce 1 type of antibody aka immunoglobulins

Question 6

what are antibodies/immunoglobulins?

what are the 5 main types

Answer 6

complex molecules made up of two heavy chains and two light chains arranged in a Y shape.

help the immune system recognise and fight infections by targeting specific proteins on the pathogen

come in 5 main types: A, G, M, D and E

Question 7

what will you find when you measure immunoglobulins in a patient with myeloma?

Answer 7

one of those types either A, G, M, D & E, will be significantly abundant.

More than 50% of the time this is immunoglobulin type G (IgG).

Question 8

what is a monoclonal paraprotein?

Answer 8

single type of antibody that is produced by all the identical cancerous plasma cells

Question 9

what is a Bence Jones protein and where is it found?

Answer 9

part (subunit) of the antibody called the light chains

can be found in the urine of many patients with myeloma

Question 10

why do patients get anaemia in myeloma?

Answer 10

cancerous plasma cells invade the bone marrow - BM infiltration

causes suppression of development of other blood cell lines = anaemia, neutropenia, thrombocytopenia

Question 11

what is myeloma bone disease?

Answer 11

decreased osteoclast activity and suppressed osteoblast activity

osteoclasts absorb bone and osteoblasts deposit bone

more bone is being reabsorbed than constructed

caused by cytokines released from the plasma cells and stromal cells when they are in contact with plasma cells

Question 12

where are some common places for myeloma bone disease to happen?

Answer 12

skull

spine

long bones

ribs

Question 13

what are osteolytic lesions

Answer 13

abnormal bone metabolism is patchy, meaning that in some areas the bone becomes very thin whereas others remain relatively normal.

osteolytic lesions are the patches of thin bone

Question 14

what happens at areas with osteolytic lesions?

Answer 14

weak points = pathological fractures

eg vertebral body in spine may collapse or femur may break under minimal force

Question 15

why do patients with myeloma have high blood calcium - hypercalcaemia?

Answer 15

osteoclast activity causes a lot of calcium to be reabsorbed from the bone into the blood = hypercalcaemia

Question 16

what are plasmacytomas?

Answer 16

can develop with multiple myeloma

individual tumours made up of cancerous plasma cells

can occur in bones, replacing normal bone tissue or can occur outside bones in the soft tissue of body

Question 17

Patients with myeloma often develop renal impairment. what are some factors that impact this?

Answer 17

1. High levels of immunoglobulins (antibodies) can block the flow through the tubules
2. Hypercalcaemia impairs renal function
3. Dehydration
4. Medications used to treat the conditions such as bisphosphonates can be harmful to the kidneys

Question 18

describe hyperviscocity

Answer 18

plasma viscosity increases when then 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.

Question 19

what are some issues caused by plasma viscosity?

Answer 19

1. Easy bruising
2. Easy bleeding
3. Reduced or loss of sight due to vascular disease in the eye
4. Purple discolouration to the extremities (purplish palmar erythema)
5. Heart failure

Question 20

what are the 4 key features of myeloma?

Answer 20

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

Question 21

what are the risk factors for myeloma?

Answer 21

1. Older age
2. Male
3. Black African ethnicity
4. Family history
5. Obesity

Question 22

when should you suspect myeloma and what investigations should you do?

Answer 22

considering myeloma in anyone >60 with persistent bone pain, particularly back pain, or an unexplained fractures. Perform initial investigations:

• 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.

Question 23

what initial investigations are done for myeloma? - BLIP

Answer 23

• B – Bence–Jones protein (request urine electrophoresis)
• L – Serum‑free Light‑chain assay
• I – Serum Immunoglobulins
• P – Serum Protein electrophoresis

bone marrow biopsy - to confirm dx

imaging - to assess for bone lesions - whole body MRI or CT or skeletal survey (in order of preference)

Question 24

what are some x ray signs for myeloma?

Answer 24

• 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

Question 25

what is the management of myeloma?

Answer 25

aim to control disease

1st line = combination chemotherapy

• Bortezomid
• Thalidomide
• Dexamethasone

stem cell transplantation can be used as part of clinical trial where patients are suitable

VTE prophylaxis with aspirin or LMWH - higher risk of thrombus development

Question 26

how is myeloma bone disease managed?

Answer 26

• Myeloma bone disease can be improved using bisphosphonates - 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

Question 27

what are some complications of myeloma?

Answer 27

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