Bhl Week 3: Multiple Myeloma

Front 1

What is the most common monoclonal gammamopathy?

What is the most clinically significant monoclonal gammamopathy?

Back 1

Monoclonal gammamopathy of undetermined significance (MGUS)
*By far the most common! 2/3 cases

*Multiple myeloma is the most common clinically significant one
(second most common overall)

Front 2

Which monoclonal gammamopathy is associated with an Ig or Ig fragment that precipitates in tissues as an amoprhous eosinophilic material?

Back 2

Primary (AL) amyloidoisis

Front 3

Which condition is associated with a monoclonal IgM in the blood?

Back 3

Waldenstrom's macroglobinemia

Front 4

Which subtype of non-Hodgkin lymphoma is typically associated with a significant monoclonal protein in the serum, and is often grouped with the gammamopathies?

Back 4

Waldentrom's macroglobinemia

Front 5

What is the multiple myeloma triad?

Back 5

1. Accumulation of plasma cells in bone marrow
2. Bone lesions
3. Monoclonal immunoglobulin protein in serum and/or urine

Front 6

What is the most common lymphoid malignancy in African Americans?

Back 6

Multiple myeloma
(twice as common in African Americans as Caucasians)

Front 7

What general age population is more at risk for multiple myeloma-- younger or older?

Back 7

Older population
(median age: 70)

Front 8

Although there is no obvious predisposing factor in the majority of multiple myeloma cases, what are some possible etiologies?

Back 8

1. Occupational exposures (farmers, petroleum workers, wood and leather industries)
2. Ionizing radiation

Front 9

How is the diagnosis of multiple myeloma made?

Back 9

1. Presence of monoclonal protein in serum and/or urine (measure and determine type)
2. Increased plasma cells in marrow
3. Presence of end-organ or tissue damage due to plasma cell proliferation or monoclonal Ig.

Front 10

What is the key to the diagnosis of symptomatic multiple myeloma versus asymptomatic?

Back 10

Presence of myeloma-related organ damage or tissue infiltration

Front 11

Why is it important to distinguish between symptomatic and asymptomatic multiple myeloma?

Back 11

Patients with symptomatic multiple myeloma are probably going to be treated right away; Whereas patients with asymptomatic myeloma are probably not going to be treated until they develop symptoms

Front 12

What is the minimum size of monoclonal protein required for the diagnosis of myeloma if the patient has organ damage related to the plasma cell clone?

Back 12

There is NO minimum size required for diagnosis

Front 13

List the signs of myeloma-related end-organ damage included in the diagnostic criteria.

Back 13

CRAB!

1. HyperCalcemia
2. Renal abnormalities
3. Anemia
4. Bone lesions

*Infections are also common, but not included in the diagnostic criteria

Front 14

How is asymptomatic myeloma distinguished from monoclonal gammamopathy of undetermined significance (MGUS)?

Back 14

Based on the presence of a large monoclonal population in the:
1. Marrow (> 10%)
2. Blood or urine (>3 grams)

Front 15

List some common laboratory findings associated with multiple myeloma.

Back 15

1. Anemia
2. Hypercalcemia
3. Renal insufficiency
4. Elevated total serum protein

Front 16

What are the two types of bone lesions seen in cases of multiple myeloma?

Back 16

1. "Punched out" osteolytic lesions
2. Diffuse osteopenia

Front 17

What causes hypercalcemia in multiple myeloma?

Back 17

Myeloma cells produce factors which stimulate osteoclasts to resorb bone--> "Osteoclast Activating Factor" (OAF)

Liberation of calcium from bone causes hypercalcemia

Front 18

Along with the common myeloma-related symptoms, which other clinical symptom is often associated with myeloma?

Back 18

BACK PAIN

*Consider multiple myeloma in any elderly patient with back pain, anemia, renal insufficiency, and elevated serum protein!

Front 19

What type of monoclonal proteins are most common in multiple myeloma?

Back 19

Intact immunoglobulin +/- free light chain
IgG ~50%, IgA ~25%

Light chain only = ~10%

Front 20

What is the standard screening test for multiple myeloma?

Back 20

Serum protein electrophoresis (SPEP)

Front 21

Which test is used to identify the type of immunoglobulin in multiple myelomas?

Back 21

Immunofixation

Front 22

Which test is useful in the diagnosis of "non-secretor" myeloma or "light chain only" myeloma?

Back 22

Free light chain assay

Front 23

List 3 tests used for the detection of monoclonal proteins.

Back 23

1. Serum protein electrophoresis
2. Immunofixation
3. Free light chain assay

Front 24

Why are light chain-only myelomas missed by routine SPEP?

Back 24

Light chains are cleared by kidneys ("Bence Jones" protein). They do not accumulate in plasma

*Can be detected by urine protein electrophoresis

Front 25

What is one of the most important prognostic factors in myeloma patients?

Back 25

Cytogenetics:
1. Abnormality of chromosome number (aneuploidy)
2. Reciprocal translocations

*Detected by FISH

Front 26

What are the three major complications of multiple myeloma?

Back 26

1. Bone pain and fractures
2. Infections
3. Renal failure

*Hypercalcemia also common

Front 27

What is the most common cause of death in patients with multiple myeloma?

Back 27

Infections

Front 28

Which infections are common in patients with multiple myeloma?

Patients are prone to infections by which bacteria?

Back 28

1. Pneumonitis
2. Pyelonephritis

Bacteria:
1. Strep. pneumoniae
2. Staph. aureus

Front 29

What is the term used for free immunoglobulin light chains in the urine?

Back 29

Bence Jones protein

Front 30

Do urine dipsticks detect light chains in a urine sample?

Back 30

NO.
They primarily detect albumin

Front 31

What is the SECOND most common cause of death in patients with multiple myeloma?

Back 31

Renal insufficiency

Front 32

What is the most common cause of renal damage in patients with multiple myeloma?

Back 32

Myeloma cast nephropathy
(precipitation of the monoclonal Ig in large casts in the renal tubules-- plug up tubules)

Front 33

Why should you be careful using radiographic contrast in elderly patients?

Back 33

In the case that they have multiple myeloma, radiographic contrast agents can induce renal shutdown

Front 34

Is there a curative treatment plan for multiple myeloma?

Back 34

No.
Patients respond to therapy for months or years, but eventually develop resistance. Survival thereafter is poor.

Front 35

What is the conventional therapy for treating multiple myeloma?

Back 35

Phenylalanine mustard (Melphalan) + Prednisone

Front 36

What type of treatment is useful in controlling the bone disease in myeloma?

Back 36

Bisphosphonates (Pamidronate)

Front 37

List the available treatments for multiple myeloma.

Back 37

1. Phenylalanine + Prednisone
2. Thalidomide + Dexamethasone
3. Dexamethasone alone
4. Proteosome inhibitor
5. Immunomodulatory drugs (Lenalidomide)
6. Combination chemo
7. Bisphosphonates

Front 38

Which type of stem cell transplant has become a very popular therapy in myeloma-- autologous or allogenic?

Is this procedure curative?

Back 38

Autologus

*Appear to prolong survival in mutiple myeloma, but the procedure doesn't appear to be curative; the myeloma lamost always comes back eventually

Front 39

What is the most common site of extramedullary plasmacytoma?

Back 39

Upper respiratory tract

Front 40

Can a solitary extramedullary plasmacytoma be curable with local therapy?

What is the significance of this?

Back 40

Yes.

*Must exclude disseminated disease because patients with multiple myeloma also can have extramedullary tumors. Multiple myeloma is incurable with conventional therapy. If it truly is solitary extramedullary, then it is curable.

Front 41

What is the definition of MGUS?

Back 41

Monoclonal protein in the absence of signs or symptoms of multiple myeloma.

Front 42

How frequently does MGUS transform to overt myeloma?

Back 42

~25% transform
(median time ~8yrs; patients with higher M-protein levels are at higher risk)

Front 43

How do physicians monitor patients with MGUS?

Back 43

Monitor serum and urine proteins, CBC, chemistry panel periodically

Front 44

Which condition is characterized by a monoclonal IgM protein with lymphoplasmacytic lymphoma?

Back 44

Waldenstrom's Macroglobulinemia (WM)

Front 45

Hyperviscosity syndrome is seen in which hematologic condition?

What causes the hyperviscosity?

Back 45

Waldentrom's macroglobinemia

*High levels of IgM protein increases blood viscosity

Front 46

What symptoms are associated with hyperviscosity syndrome?

Back 46

1. Fatigue
2. Dizziness
3. Blurred vision
4. Shortness of breath

Front 47

An exam of a patient with hypervisosity syndrome may show what?

Back 47

Dilated, "sausage-shaped" retinal veins

Front 48

What is the treatment for Waldenstrom's macroglobinemia?

Back 48

1. Plasmapheresis for hyperviscosity <-- IMMEDIATE treatment of choice
2. Chemotherapy needed to prevent reaccumulation

Front 49

Which condition is associated with deposition of protein with beta-pleated sheet configuration in tissues?

Back 49

Amyloidosis

Front 50

Macroglossia is a relatively specific physical examination finding for which condition?

Back 50

Amyloidosis

Front 51

List the classifications of amyloidosis.

Back 51

1. AL = immunoglobulin light chain or fragment
2. AA = Amyloid-associated protein
3. AF = Familial; usually prealbumin
4. AE = Endocrine (calcitonin, insulin, etc.)
5. AB2M: Hemodialysis-associated

Front 52

What is the most common type of amyloidosis in the U.S.?

What is the second most common type?

Back 52

AL (immunoglobulin light chain or fragment)

AA (amyloid-associated protein)

Front 53

Which type of amyloidosis is associated with chronic infection, chronic inflammation, or some neoplasms?

Back 53

AA (amyloid-associated protein)

Front 54

What is the classic stain to diagnosis amyloidosis?

Back 54

Congo red stain
(when viewed under polarized light, it has a sort of "apple green" color)

Front 55

What is a very useful test to help diagnose AL amyloidosis?

Back 55

Serum free light chain analysis

Front 56

What are some complications of AL amyloidosis?

Back 56

1. Heart (congestive failure, arrhythmias)
2. Kidney (nephrotic syndrome, renal failure)
3. Skin (purpura)

Front 57

Is the overall survival rate of amyloidosis generally high or low?

Which patients have the worst prognosis?

Back 57

Low, but varies.

*Patients who presented with congestive hart failure have the worse prognosis, with a median survival rate of < 1yr.

Front 58

What is the most common cause of secondary amyloidosis in the U.S.?

Back 58

Rheumatoid arthritis
(Secondary amyloidosis = AA)

Front 59

What two factors are required for the development of secondary amyloidosis?

Back 59

1. Chronic increase in SAA protein (due to chronic inflammation)
2. Defective macrophage processing or breakdown of SAA

Front 60

What is the treatment for AA (Secondary) amyloidosis?

Back 60

Treat the primary condition

Front 61

Familial (AF) amyloidosis is due to a mutation in which protein?

Back 61

Prealbumin protein
(broken down into fragments which participate as B-pleated sheet)

Front 62

Which form of amyloidosis may present as peripheral neuropathy?

Back 62

Familial (AF) amyloidosis

Front 63

List some procedures that can be done to diagnose amyloidosis. Which one is considered the procedure of choice?

Back 63

1. Abdominal fat pad aspiration <-- PROCEDURE OF CHOICE
2. Rectal biopsy
3. Skin lesion biopsy
4. Kidney biopsy
5. Stain with congo red stain