Myeloma

Question 1

What is the link between amyloidosis and myeloma?

Answer 1

Link between myeloma and AL amyloidosis

AL amyloidosis and multiple myeloma share several clinical features such as clonal plasma cells and the production of monoclonal immunoglobulins

Diagnosis of AL amyloidosis requires histological confirmation with a biopsy specimen staining positive with Congo red and demonstrating apple green birefringence under polarissed light

Diagnosis of AL amyloidosis is made at presentation or some time during the course of the myeloma in 10–15% of patients

Question 2

Is amyloidosis common?

Answer 2

No, it is rare, affects 500-600 people each year in the UK

Question 3

What is AL amyloidosis?

Answer 3

Amyloidosis Light chain - it is this form of amyloidosis that is associated with myeloma

Question 4

What are the common symptoms of myeloma?

Answer 4

Calcemia

Renal failure

Anaemia

Bone lesions

Question 5

What is multiple myeloma/ myeloma?

Answer 5

Malignant disease of plasma cells

2nd most common blood cancer

Characterised by the production of abnormal antibody/ immunoglobulin

Question 6

What are plasma cells?

Answer 6

Terminally differentiated B-cells which produce immunoglobulins

Question 7

What are the signs and symptoms of myeloma?

Answer 7

• Back pain
• Anaemia
• Renal failure
• Proteinuria
• Fractures
• Dehydration
• Resp. tract infections

Question 8

What are haemopoietic stem cells?

Answer 8

Stem cells that give rise to blood cells

Give rise to common lymphoid progenitors which give rise to B lymphocytes which produce plasma cells

Question 9

In the bone marrow of a normal person, what % of the bone marrow is plasma cells?

Answer 9

5%

Question 10

What % of the bone marrow is made up of plasma cells in patients with myeloma?

Answer 10

>10%

Question 11

What are paraproteins?

Answer 11

An abnormal immunoglobulin found in the blood as a result of myeloma

AKA M-proteins

The antibodies made by malignant plasma cells in myeloma are abnormal and light chains are produced by themselves

Question 12

What is the most common type of heavy chain produced in myeloma?

Answer 12

IgG, followed by IgA and then IgD

Question 13

Elevated IgM in the blood would be most likely caused by what?

Answer 13

Waldenstrom’s macroglobulinemia

Question 14

What is Bence Jones myeloma?

Answer 14

20% of people with myeloma only produce the light chains of immunoglobulins (either kappa or lambda)

The light chains show up in the urine and are known as Bence Jones proteins

Question 15

How does myeloma cause hypercalcemia and bone fractures?

Answer 15

Myeloma cells secrete cytokines

• IL-3: reduces osteoblastic activity
• DKK1: increases osteoclast activity
• M1P1 alpha: increases osteoclast activity

Question 16

How does myeloma cause renal failure?

Answer 16

Paraproteins in the blood get stuck in he neprhons and cause renal damage

Hypercalcemia also causes calcification of the nephrons

Question 17

How does myeloma cause anaemia?

Answer 17

There is a shift from myeloid progenitor cell production to lymphoid progenitor cell production - over production of plasma cells clogs the bone marrow and there is no room for RBC production

Kidney failure potentiates this as there is no EPO for RBC production

Question 18

Outline investigations for myeloma

Question 19

Discuss the clinical features of myeloma

Answer 19

• Disease of the elderly
• Mean age of presentation is 60+
• More common in men and black Africans
• Bone destruction
• Kidney injury
• Recurrent infections
• Lytic bone lesions
• Increased osteoclast function without increase in osteoblast function

Question 20

Where are lytic bone lesions seen in myeloma?

Answer 20

Skull - pepper pot skull

Spine

Long bones

Ribs

80% of patients have lytic lesions at time of presentation

Question 21

Other than myeloma, where can a pepper pot skull be seen?

Answer 21

Hyperparathyroidism

Question 22

Discuss immunoglobulin levels in myeloma

Answer 22

• 60% IgG
• 20% IgA
• 20% light chain only

Question 23

Discuss laboratory features of myeloma

Answer 23

Routine biochemistry: raised calcium, raised urea and creatinine, raised total protein

Bone marrow: increased plasma cells that are abnormal, >10% plasma cells is diagnositc of myeloma

Plasma cells often show an enlarged golgi apparatus

Binucleated plasma cells can also be seen

Question 24

What is beta-2 microglobulin?

Answer 24

Low molecular weight proteins found on the surface of all nucleated cells

Increased levels in patients with myeloma has been associated with poor prognosis

Question 25

Which mutations are associated with worse outcomes in myeloma?

Answer 25

Anything involving chromosomes 14 or 17

Question 26

What is smouldering myeloma?

Answer 26

Type of plasma cell dyscrasia

Precancerous condition

50% will develop mutliple myeloma within 5yrs

Question 27

Discuss staging of myeloma

Answer 27

Prognosis determined by International Staging System (ISS) and cytogenetics.

Stage 1 Beta-2 microglobulin <3.5mg/l, Albumin >35g/l. OS 62 months.

Stage 2 Beta-2 microglobulin 3.5-5.5mg/l and/or Albumin <35g/l. OS 44 months.

Stage 3 Beta-2 microglobulin >5.5mg/l. OS 29 months.

Question 28

Discuss management of myeloma

Answer 28

5-10% have no symptoms and do not require immediate therapy

Patients <70yrs: thalidomide/ lenalidomine/ bortezomib combination therapy (induction therapy)

/ stem cell transplantation with high dose melphalan if not successful

Bisphosphonates for myeloma bone disease

Question 29

What is diagnostic of myeloma?