Plasma Cell Neoplasms

Question 1

**What is an M spike?

Answer 1

• Sharp spike of a single type of Antibody on Serum Electrophoresis

(In a normal person you would expect to see rounded peaks)

Question 2

**What does an IFE tell you?

Answer 2

Immunofixation Electrophoresis tells you if the antibodies being produced are kappa or lambda restricted

**Note: kappa or lambda restriction implies monoclonal proliferation

Question 3

**Name the four components of CRAB?

Answer 3

C - Calcium
R - Renal Insufficiency
A - Anemia
B - Hypogammaglobulinemia

Question 4

**Describe the mechanism of bone destruction in myeloma.

Answer 4

1. Myeloma Cells Produce DKK1
2. DKK1 stimulates STROMAL cells and OSTEOBLASTS to release RANKL and IL6
3. RANKL and IL6 Impair osteoblast and STIMULATE OSTEOCLAST maturation

Question 5

**What is the Durie Salmon Muliple Myeloma Staging System?

Answer 5

STAGE 1:
Hemoglobin > 10 g/dL
Calcium less than 12 mg/dL
Normal Skeletal Survey (or solidary plasmacytoma)
IgG less than 5 g/dL (IgA less than 3 g/dL)
Bence Jones Proteins less than 4 g/24 hrs

STAGE 3:
Hemoglobin less than 8 g/dL
Calcium greater than 12 mg/dL
IgG greater than 7 g/dL (IgA greater than 5g/dL)
Bence Jones Proteins greater than 12g/24hrs

***Stage 2 is in between

Question 6

**What is the ISS staging system?

Answer 6

STAGE 1:
ß2Microglobulin and Albumin less than 3.5 g/dL
Median Survival 5 years

STAGE 2:
In between (~4 years survival) 

STAGE 3:
B2Microlglobulin greater than 5.5 g/dL
Multiple Lytic Lesions
~ 2 years survival

Question 7

**What is the worst prognostic chromosome abnormality in Myeloma

Answer 7

del17p - WORST prognostic indicator

**t(4,14) and t(14, 16) also poor prognostic indicators

Question 8

**What two classification of drugs have changed the way we treat myeloma.
• Mechanism of Action

Answer 8

IMiDs
• Act on Immune System to Target Plasma Cells, Activate NK cells, and prevent angiogenesis

Proteosome Inhibitors:
• Block the Proteosome that targes IkB the inhibitor of NFkB, effectively inhibiting the NFkB pathway

Question 9

**When is an autologous transplant indicated in Myeloma?

Answer 9

• Under 70 years old

* Fairly Healthy

Question 10

**Why do Waldenstrom patients become hyperviscous more commonly than myeloma patients?

Answer 10

IgM (produced by this disease is much larger than IgG produced in most plasma cell lymphomas

Question 11

**Name Three causes of Amyloidosis.

Answer 11

Light Chain Amyloid
• Secondary to Myeloma or Primary

Transthyretin Amyloidosis
• Familial

AA amyloid
• Chronic Inflammatory disorders like osteomyelitis

Question 12

What is a hallmark of Multiple Myeloma on the Peripheral Smear?
• What causes this

Answer 12

Rouleaux

• Excess antibodies secreted by plasma cells causes platelets to stick through electrostatic forces

Question 13

What can serum protein electrophoresis (SPEP) used for in cases of mutiple myeloma?
• What parameters can it determine?

Answer 13

SPEP:

• Look for an M-spike that can be used to 1. IDENTIFY PRESENCE OF ABNORMAL Ig 2. QUANTIFY abnormal Ig

Question 14

What does serum and urine electrophoresis with immunofixation do that SPEP can’t do?

Answer 14

Tells you TYPE, whether its Kappa or Lambda restricted

Question 15

What test would you do to assess the degree of cytopenia in a newly diagnosed multiple myeloma?

Answer 15

CBC with Differential

•You would expect Anemia and/or Pancytopenia because the disease is knocking out all of the bone marrow

Question 16

Why would you expect calcium to be high in multiple Myeloma?

Answer 16

• Bone is being actively degraded by osteoclast upregulation and osteoblast down regulation

Question 17

T or F: ß2-microglobulin is used as a prognostic factor in Multiple myeloma.

Answer 17

True

Question 18

Why would you look at a UPEP?

Answer 18

Looking for Light Chain in the urine (Bence Jones Bodies) is important because it indicates that the Kidneys may begin to fail

Question 19

How are cytogenetics and FISH important in plasma cell lymphomas (multiple myeloma)?

Answer 19

These are good indicators of the prognosis of multiple myeloma

Question 20

What criteria do you need to diagnose multiple myeloma?

Answer 20

1. M-protein in serum or Urine
2. Marrow Clonal plasma cells or Plasmacytoma
3. Related organ or tissue impairment (e.g. lytic lesions)

Question 21

What are some common side effects of bone destruction secondary to Multiple Myeloma?

Answer 21

• Pain
• Fractures
• Spinal Cord Compression

Question 22

What are some common side effects of Hypercalcemia secondary to Multiple Myeloma?

Answer 22

• Altered Mental Status

* Renal Insufficiency

Question 23

Why do people with Plasma Cell Lymphoma (aka multiple myeloma) get renal insufficiency?

Answer 23

• Light Chain Nephropathy
• Amyloid
• Uric Acid
• Hypercalcemia
• Infection

Question 24

Why would people with an increased release in antibody in mutliple myeloma be at an increased risk of infection?

Answer 24

*They are only producing monoclonal antibody while stamping out other antibody populations

Question 25

What Lymphoma is associated with amyloidosis and Hyperviscosity?

Answer 25

Multiple Myeloma

Question 26

In what population are you most likely to see MGUS? | • would you expect to see Bence Jones Bodies in the urine of these patients?

Answer 26

MGUS is most commonly seen in Old People • 1% of people over 60 • 5% of people over 80 Bence Jones Bodies (Ig light chain) are not typically found in the urine of people with MGUS

Question 27

What is the rate of progression to malignancy in Monoclonal Gammopathy of Unspecified Significance?

Answer 27

1% per year progress to B cell malignancy

Question 28

Differentiate MGUS from Smoldering Myeloma and Multiple Myeloma?

Answer 28

(essentially) Asymptomatic Conditions = NO CRAB: MGUS: • M-protein in serum less than 3 mg/dL (30 g/L) • Bone marrow clonal plasma cells less than 10% Smoldering Myeloma: • M-protein in serum greater than 3mg/dL (30g/L) • Bone marrow clonal cells greater than 10% Symptomatic (most likely) = CRAB!! MULTIPLE MYELOMA: • M-protein in serum or URINE • Organ impairment, Tissue Injury (bone erosion)

Question 29

What morphologic features are important to identifying plasma cells?

Answer 29

* Eccentric Nucleus * Perinuclear Clear Zone * ROYAL BLUE COLOR

Question 30

What are some Poor Prognostic Indicators outside of translocations for Multiple Myeloma?

Answer 30

``` B2Microglobulin > 4 LDH > 190 CRP > 4 Creatinine > 2 Focal Lesions > 5 ```

Question 31

What are some unique treatment options for Plasma Cell Lymphomas?

Answer 31

* IMiDs - IMMUNE MODULATORY DRUGS * Proteosome Inhibitors * Bisophosphonates

Question 32

What are 2 important IMiDs?

Answer 32

* Thalidimide | * Linalidimide

Question 33

What are 2 important proteosome inhibitors?

Answer 33

* Bortezomib | * Carfilzomib

Question 34

What are the steps to treating someone with Multiple Myeloma that is Transplant Eligible?

Answer 34

1. IMiD + Dex or Bortezomib + Dex 2. Collect Stem Cells 3. Knock down bone marrow, DO NOT USE ALKYLATING AGENTS 4. Put cells back in 5. Treat with IMiD+Dex

Question 35

What makes someone ineligible for Autologous transplant?

Answer 35

* too old (greater than 70) | * Too sick

Question 36

**What is the major difference in symptoms produced by IgM Multiple Myelomas from the others?

Answer 36

HYPERVISCOSITY of blood is a big one

Question 37

You have a patient with Waldenstrom Macrolglobulinemia. | • How old do you suspect they are?

Answer 37

• At least over 40 y/o More than 97% of cases occur in people over 40

Question 38

What sydrome is unique to people with plasma cell neoplasms that produce IgM? • what are some symptoms

Answer 38

Hyperviscosity Syndrome ``` Symptoms: • Headache • Ataxia • Blurred vision • Mental Status Change ```

Question 39

What therapies are most commonly used for Waldenstroms Macrogammaglobulinemia?

Answer 39

* Purine Analogues - Fludarabine * Bortezomib * Rituximab (anti-CD20) * PLASMAPHERESIS with viscosity > 4

Question 40

What systems are affected by Light Chain Amyloidosis? | • What other Amyoid affects the same systems?

Answer 40

Liver Heart G.I. Nervous System *Transthyretin affects the same systems

Question 41

What systems are primarily affected by AA amyloid?

Answer 41

Renal Hepatic G.I.

Question 42

Where would you biopsy to detect amyloid? • Prognosis • Treatment?

Answer 42

Px. | 1-2 years with standard treatment