Myeloma

Question 1

What is multiple myelooma?

Answer 1

A disease of plasma cells characterised by uncontrolled replication of a single plasma cell clone, leading to overproduction of one type of immunoglobulin.

A type of bone marrow cancer.

Question 2

What is a plasma cell?

Answer 2

An antibody-producing B lymphocyte

Note - antibodies are also called immunoglobulins

Question 3

Pathophysiological of multiple myeloma?

Answer 3

1) Normally a large variety of plasma cells produce various forms of immunoglobulin, however, in myeloma one particular plasma cell clone begins to replicate in an uncontrolled manner.

2) This results in one specific type of immunoglobulin being massively overproduced by the large group of identical plasma cell clones.

3) These plasma cell clones accumulate in the bone marrow, causing reduction in normal blood cell production –> anaemia, leukopenia & thrombocytopniea

Question 4

How can this spike in a specific form of immunoglobulins be seen on serum and urine electrophoresis?

Answer 4

As a monoclonal band

Question 5

In addition to crowding out the bone marrow and interfering with normal blood cell production, what can abnormal plasma cells cause?

Answer 5

1) Produce paraprotein –> cause damage to the kidneys by forming protein casts in the renal tubules

2) Secrete factors which activate osteoclasts to break down bone –> widespread lytic lesions, bone pain and hypercalcaemia.

Question 6

What is a paraprotein (or M protein)?

Answer 6

Abnormal immunoglobulin light chains i.e. an abnormal antibody or part of an antibody

Question 7

Myeloma vs multiple myeloma?

Answer 7

Multiple myeloma is where the myeloma affects multiple bone marrow areas in the body.

Question 8

What is monoclonal gammopathy of undetermined significance (MGUS)?

Answer 8

This involves the production of a specific paraprotein without other features of myeloma or cancer.

MGUS is often an incidental finding in an otherwise healthy person.

It has a small risk of progression to myeloma (about 1% per year).

Question 9

What is smouldering myeloma?

Answer 9

Involves abnormal plasma cells and paraproteins but no organ damage or symptoms.

It has a greater risk of progression to myeloma (about 10% per year).

Question 10

What are the 5 types of antibodies?

Answer 10

A, G, M, D and E.

Question 11

Structure of an immunoglobulin?

Answer 11

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

Question 12

What does the Bence Jones protein refer to?

Answer 12

Free light chains in the urine

Question 13

How is myeloma classified?

Answer 13

based on which type of immunoglobulin is produced

Question 14

What mnemonic can be used to remember the four key features of myeloma?

Answer 14

C - hyperCalcaemia

R - renal failure

A - anaemia

B - bone lesions and bone pain

Question 15

What is the most common symptom of myeloma?

Answer 15

Bone pain (common areas include the spine and ribs).

Pain typically worsens with activity.

Question 16

What should persistent pain in a particular area in myeloma raise suspicion of?

Answer 16

A pathological fracture

Question 17

Cause of bone pain in myeloma?

Answer 17

Due to increased osteoclast activity within the bones creating lytic lesions (and suppressed osteoblast activity).

Question 18

How are lytic lesions best visualised?

Answer 18

Plain XR

Question 19

Appearance of lytic lesions on XR?

Answer 19

Punched-out areas (the skull can appear to have a “pepper pot” appearance)

Question 20

Cause of hypercalcaemia in myeloma?

Answer 20

Due to the resorption of bone

Question 21

Cause of anaemia & thrombocytopenia in myeloma?

Answer 21

Production of RBCs and platelets is inhibited by plasma cells invading the bone marrow.

Question 22

Symptoms of anaemia?

Answer 22

Include SOB & fatigue

Question 23

What type of anaemia is typically seen in myeloma?

Answer 23

Typically normocytic and normochromic

Question 24

What is often required to maintain an adequate haemoglobin level in myeloma?

Answer 24

repeated transfusions

Question 25

Symptoms of thrombocytopenia in myeloma?

Answer 25

Often asymptomatic

If platelets reach critically low levels (e.g. <10), symptoms such as petechiae, bruising and bleeding develop

Question 26

Patients with myeloma often develop renal impairment.

What are some various causes of this?

Answer 26

1) Paraproteins deposited in the kidneys

2) Hypercalcaemia affecting kidney function

3) Dehydration

4) Glomerulonephritis (inflammation around the glomerulus and nephron)

5) Medications used to treat the condition

Question 27

Symptoms of hypercalcaemia?

Answer 27

constipation, nausea, anorexia and confusion etc

Question 28

Why are those with myeloma at increased risk of infection?

Answer 28

Patients have abnormally high levels of immunoglobulin, due to the diseased plasma cells. However despite this, the immunoglobulin is mutated, faulty and ineffective.

Production of normal immunoglobulin is also impaired and as a result, patients are significantly immunocompromised.

Question 29

What neurological symptoms may be seen in myeloma?

Answer 29

1) Confusion, weakness and fatigue – hypercalcaemia

2) Headaches and visual disturbances – hyperviscosity (present in some paraproteinaemia)

3) Peripheral neuropathy – amyloid deposition

4) Limb weakness and loss of bowel/bladder control – spinal cord compression

Question 30

How is viscosity of the blood affected in myeloma?

Answer 30

Plasma viscosity increases when more proteins are in the blood, such as the paraproteins found in myeloma.

Question 31

Complications of hyperviscosity of blood?

Answer 31

Hyperviscosity syndrome is considered an emergency. It can cause many issues:

1) Bleeding (e.g., nosebleeds and bleeding gums)

2) Visual symptoms and eye changes (e.g., retinal haemorrhages)

3) Neurological complications (e.g., stroke)

4) Heart failure

Question 32

Investigations in myeloma?

Answer 32

1) FBC –> anaemia, leukopenia & thrombocytopenia

2) Calcium –> raised

3) ESR –> raised

4) Plasma viscosity –> increased

5) U&Es –> renal impairment

6) Serum protein electrophoresis –> detect paraproteinaemia

7) Serum-free light-chain assay –> detect abnormally abundant light chains

8) Urine protein electrophoresis –> to detect the Bence-Jones protein

Question 33

What is required to confirm the diagnosis of myeloma?

Answer 33

Bone marrow biopsy