Myeloma

Question 1

What is a myeloma?

Answer 1

A neoplastic disorder of plasma cells (post germinal B cells). They show normal plasma biomarkers but an abnormal phenotype. Clones either express kappa or lambda light chains

Question 2

Describe the presentation of myeloma

Answer 2

CRAB HAI:
- Hypercalcaemia: increased osteoclast bone resorption
- Renal impairement: due to light chain deposition and hypercalcaemia
- Anaemia: bone marrow infiltration by tumour
- Bone pathology: Pain and pathological fractures
- Hyperviscosity
- Amyloidosis
- Infection: due to leukopenia

Question 3

What is the classsic triad of myeloma?

Answer 3

1. Increased plasma cells in th ebone marrow,
2. Clonal immunoglobulin/paraprotein
3. Lytic bone lesions

Question 4

How is myeloma diagnosed?

Answer 4

1. Blood tests (FBC, ESR, U&Es, Ca, serum protein electrophoresis to detect high paraproteins and serum free light chain quantity).
2. Urine electrophoresis (look for light chains in urine (Bence-jones protein)
3. Bone marrow aspirate (RBC rouleaux and lots of plasma cells)
4. Imaging/skeletal survay

BLIP: Bence-jones proteins (urine electrophoresis), serum-free Light chain assay, serum Immunoglobulins, serum Protein electrophoresis

Question 5

What type of imaging is used in myeloma?

Answer 5

MRI/CT as these are far better at detecting lytic lesions which occur due to the activation of osteoclasts

Question 6

What is the diagnostic criteria for myeloma?

Answer 6

Neoplastic plasma cells in the bone marrow that account for a minimum of 10% of cells and one of the following evidence of end organ damage: CRAB.
C - hypercalcaemia,
R - Renal insufficiency,
A - Anaemia,
B - Bone lesions (must have at least 1)
or biomarkers of malignancy:
1. Clonal plasma cell percentage>60%.
2. Serum free light chain ration >100
3. 1 focal lesion on MRI

Question 7

What is paraprotein?

Answer 7

Where the clonal neoplastic plasma cells produce a monoclonal protein (immunoglobulin). Mainly IgG or IgA (just another name for the antibodies produced by the malignant plasma cells)

Question 8

What is the treatment for myeloma?

Answer 8

• Asymptomatic (watch and wait)
• Symptomatic patients are given supportive treatment and chemotherapy and combination of Dexamethasone, thalidomide or Bortezomib. Stem cell transplant.

Question 9

What is the supportive treatment given to myeloma patients

Answer 9

• Bisphosphonates (reduce pain, reduce pathological fractures, reduce hypercalcaemia and reduce need for radiotherapy)
• Blood transfusion/epo,
• Good fluid intake,
• Prophylactic antibiotics,
• Vaccinations,
• Radiotherapy,
• Surgery
• Interventional radiotherpay

Question 10

What is the difference between myeloma and monoclonal gammopathy of undetermined significance?

Answer 10

While both have an increased percentage of plasma cells in bone marrow and high serum paraprotein. MGUS will rarely have bence jones protein and immune paresis and don’t have lytic bone lesions and other non specific symptoms.

MGUS - excess of a single type of antibody without features of cancer

Question 11

What is the significance of MGUS?

Answer 11

It has the potential to develop into a myeloma

Question 12

What is Smouldering Myeloma?

Answer 12

Progression of MGUS with high levels of antibodies. It is premalignant and is more likely to progress to myeloma than MGUS

Question 13

What is waldenstrom’s macroglobinemia

Answer 13

A type of smouldering myeloma where there is specifically an excess of IgM

Question 14

What are the causes of myeloma renal disease?

Answer 14

High levels of immunoglobulins which can block the tubules,
Hypercalcaemia due to increased osteoclast activity,
Dehydration

Question 15

Explain the pathophysiology of myeloma bone disease

Answer 15

Cytokine release from plasma cells stimulate osteoclasts

Question 16

Why do patients with myeloma have plasma hyperviscocity and what can this cause?

Answer 16

because the excess proteins cause hyperviscosity. This can result in:
Easy bruising, easy bleeding, vascular eye changes, purple discoloration in extremities and heart failure

Question 17

When should you suspect myeloma?

Answer 17

In patients over 60 with persistant lower back/bone pain or unexplained fracturs

Question 18

What are the initial investigations for suspected myeloma?

Answer 18

• FBC (low WCC)
• Hypercalcaemia
• Raised ESR
• Raised plasma viscosity
• BLIP - Bence-Jones proteins, serum free Light chain assay, serum Immunoglobulins, serum Protein electrophoresis
• Bone marrow biopsy
• Whole body MRI

Question 19

What are the X ray signs for Myeloma?

Answer 19

Punched out lesions, lytic lesions and perpperpot skull

Question 20

What are the complications of myeloma?

Answer 20

Infection, pain, renal failure, anaemia, hypercalcaemia, peripheral neuropathy, spinal cord compression and hyperviscosity

Question 21

When should you suspect myeloma?

Answer 21

• Anyone around age 60 with persistent bone pain or unexplained fracture.
• The do following: FBC (low WCC), calcium, ESR and plasmaviscosity. If these are abnormal do a serum protein electrophoresis and bence-jones protein test

Question 22

What are the X-ray signs for myeloma?

Answer 22

• Punched out lesion,
• Lytic lesions,
• Raindrop skull

Question 23

What is the blood film appearence for myeloma?

Answer 23

Rouleaux formation

Question 24

What is the diagnostic criteria for myeloma?

Answer 24

1 major an 1 minor or 3 minor.
Major: Plasmacytoma, 30% plasma cells in bone marrow sample or elevated levels of M protein in blood/urine.
Minor: 10-30% plasma cells in bone marrow, minor elevation of M protein, osteolytic lesions, low levels of other antibodies in blood.