266 - Multiple Myeloma

Question 1

What is the therapy for myeloma?

Answer 1

High dose combination therapy with autologous stem cell transplant

• Prognosis variable*
• Do more chemo if pt not elligible for stem cell transplant*

Question 2

What is the significance of Ig light chains in multiple myeloma?

Answer 2

Myeloma cells produce more light chain than heavy chain

-> extra light chains floating around

• Excreted in urine as Bence-Jones proteins
  
  • Can be nephrotoxic
• Misfolded light chains -> amyloid
  
  • -> Nephrotic syndrome

Question 3

What is the normal kappa:lamba ratio in plasma cells?

What is the significance of a deviation from this ratio?

Answer 3

Kappa:Lambda = 2:1

Deviation => Clonal population (possible malignancy, cannot diagnosis without consistent clinical features)

• Note: Dr. Gao’s lecutre (264) says ~1:1, and Dr. Wolniak’s lecture (266) says ~2:1*
• Wikipedia says normal is 0.26 - 1.65 so pick your poison here I guess!*

Question 4

What hematologic malignancy arises from plasma cells?

Answer 4

Multiple myeloma

Question 6

What cytokine drives myeloma cell growth, survival, and Ig production?

Answer 6

IL-6

Question 7

What is the most frequent cause of death in multiple myeloma?

Answer 7

Infection

Malignant plasma cells

• > no healthy/functional plasma cells
• > not enough working antibody
• > cannot protect against infection

Question 8

What testing method do we use to find monoclonal gammopathies?

Answer 8

SPEP or UPEP

• If <10% clonal plasma cells = monoclonal gammopathy of undetermined significance (MGUS)*
• If >10% clonal plasma cells = may be multiple myeloma (need to have consistent clinical features though)*

Question 9

What are the characteristics of plasma cells?

(2 morphologic features, 2 markers)

Answer 9

• Fried egg appearance
• Clock-face chromatin
• CD38+
• CD138+

Markers are cytoplasmic => detected on immunostain, not flow

Question 10

What do plasma cells produce in abundance that can have pathologic effects on organs (especially the kidney)?

Answer 10

Immunoglobulins (antibodies) -> deposition -> tissue damage

Ig Light chains can also form amyloid -> tissue damage

Question 11

What finding on peripheral blood smear may be concerning for multiple myeloma?

Answer 11

Roleaux formation (stack of coins)

• Immunoglobulins in serum alter normal (-) charge of RBCs -> they stick together
• Not specific, but warrants further screening*

Question 12

What is the diagnosis if a patient has 10-60% monotypic plasma cells but no clinical sings of myeloma?

Answer 12

Smolering myeloma

75% chance of turning into myeloma

Question 13

What will plasma cells look like on flow cytometry?

Answer 13

CD 19+

CD56-

If CD19- and CD56+, likely a neoplastic plasma cell

Immunostain will show CD138+, CD38+ (but cytoplasmic)

Question 14

What are the diagnostic criteria for multiple myeloma?

Answer 14

≥ 10% clonal plasma cells in the bone marrow, in the setting of myeloma-defining clinical criteria

• Myeloma-defining criteria
  
  • Hypercalcemia
  • Renal insufficiency
  • Anemia
  • Bone lesions

Monoclonal gammopathy is not sufficient to diagnose - need clinical criteria

Question 15

What do Bence Jones protiens in the urine indicate?

Answer 15

Multiple myeloma

If consistent clinical picture (ex: lytic bone lesions, hypercalcemia)

Ig Light Chains enter the urine -> Bence Jones proteins

Question 16

How does the presentation of Waldenstrom’s macroglobulinemia differ from that of myeloma?

Answer 16

Waldenstrom will have:

• Hyperviscosity syndrome 2/2 IgM penatmers
  
  • Dizziness, blurred vision, Raynaud’s
• Bleeding 2/2 platelet dysfunction
• No lytic bone legions

Waldenstrom is an IgM monoclonal gammopathy

Question 17

List the clinical findings of myeloma (6)

Answer 17

• Anemia
• Hypercalcymia
• Lytic bone lesions
• Renal insufficiency
• Amyloidosis
• Hypogammaglobulinemia / infections

Question 18

How does multiple myeloma lead to bone destruction?

Answer 18

Myeloma cells produce factors that drive bone destruction

• Expression of MIP1-alpha
• -> Activation of RANKL
• -> RANKL activates osteoclasts
• Osteoclasts absorb bone