Multiple Myeloma

Question 1

What is rouleaux on peripheral blood film?

Answer 1

Linear stacking RBCs during preparation of blood smear due to altered viscosity of serum due to increased proteins

Seen in any condition causing hypergammaglobulinemia (e.g. multiple myeloma)

Question 2

What is multiple myeloma?

Answer 2

Clonal proliferation of plasma cells in the bone marrow that produce an abnormal amount of immunoglobulin, resulting in end organ dysfunction (CRAB)

Question 3

What kinds of end organ dysfunction is seen in multiple myeloma?

Answer 3

CRAB

Hypercalcemia
Renal failure (high Cr)
Anemia
Bony lesions (lytic or osteoporosis)

Question 4

What are signs and symptoms of multiple myeloma?

Answer 4

Hypercalcemia: N/V, confusion, constipation, polyuria, polydipsia due to increased bone turnover

Renal failure due to cast nephropathy

Anemia: weakness, fatigue, pallor due to bone marrow suppression

Bone disease: back pain, bony tenderness, fractures due to increased bone resorption

Question 5

How does amyloidosis occur in multiple myeloma?

Answer 5

Accumulation of insoluble Ig light chain protein that can be deposited in any tissue, but most commonly in kidneys

Question 6

What does SPEP demonstrate in multiple myeloma?

Answer 6

Serum Protein Electrophoresis

Shows monoclonal protein spike in serum (i.e. presence of M protein in serum)

Question 7

What does UPEP demonstrate in multiple myeloma?

Answer 7

Urine Protein Electrophoresis

Shows presence of light chains (Bence Jones proteins) in the urine

Question 8

What are Bence-Jones proteins?

Answer 8

Light chains fragments excreted in urine

15-20% of multiple myeloma cases secrete only light chains, which can only be detected on UPEP

Question 9

What is required to diagnose multiple myeloma?

Answer 9

M protein seen on SPEP or UPEP
Clonal plasma cells in bone marrow (traditionally 10% of bone marrow)
Signs of end organ damage (CRAB)

Note that rarely (3%), multiple myelomas are non-secretory (no protein in serum or urine)

Question 10

What is the prognosis of multiple myeloma?

Answer 10

Incurable, median survival is 5-7 years

Question 11

How is multiple myeloma treated?

Answer 11

Improve QOL, prevent progression complications, improve survival

Autologous stem cell transplant if 65 or ineligible for transplant

Question 12

How do bony lesions occur in multiple myeloma?

Answer 12

Direct invasion and replacement of bone marrow by plasma cells

Induction of RANKL (enhanced osteoclast activity)

Multimodal suppression of osteoblast activity

Question 13

How does hypercalcemia occur in multiple myeloma?

Answer 13

Due to increased bone turnover due to increased osteoclast activity

Question 14

How does anemia occur in multiple myeloma?

Answer 14

Due to bone marrow suppression secondary to proliferation of plasma cells

Question 15

How does renal failure occur in multiple myeloma?

Answer 15

Light chains “poison” renal tubules causing light chain nephropathy

Hypercalcemia can lead to nephrocalcinosis and calcium stones leading to obstruction

Light chain amyloidosis in kidneys

Question 16

What is monoclonal gammoapthy of undetermined significance (MGUS)?

Answer 16

Presence of monoclonal immunoglobulin protein (whole or light chain) in the SERUM, little or no M protein in the urine, less than 10% plasma cells in the bone marrow and no end organ dysfunction (no CRAB)

30% of MGUS develops into myeloma