Plasma Dyscriasis

Question 1

• Terminally differentiated B cells• Function– Antibody secretion

Answer 1

Plasma Cells

Question 2

• 2 heavy chains:• 2 light chains:

Answer 2

• 2 heavy chains: μ, γ, α, δ, ε• 2 light chains: κ, λ

Question 3

Describe Plasma cell on HE

Answer 3

Has clock faced nuclei

Question 4

Below is an image of reactive plasma cells, When would we see them?

Answer 4

• Chronic infections (eg. Hpylori gastritis,osteomyelitis,endometritis)• Autoimmune processes(lupus, hepatitis)

Question 5

• Multiple myeloma• Monoclonal gammopathy of undeterminedsignificance (MGUS)• Plasmacytoma– Extramedullary plasmacytoma– Solitary plasmacytoma of bone• Lymphoplasmacytic lymphoma• AmyloidosisAll exmaples of:

Answer 5

Neoplastic plasma cell conditions

Question 6

How do we differentiate between reactive and neoplastic plasma cell conditions?

Answer 6

• Monoclonal antibodies in theserum or urine• Light chain restriction in cellcytoplasm (kappa v lambda) byflow cytometry orimmunohistochemistry• Immunophenotypic aberrancy(i.e. CD56 on plasma cells)

Question 7

Normally, the production andcoupling of heavy and lightchains is

Answer 7

tightly balanced.

Question 8

Monoclonal antibodies = M protein– Serum• Plasma cells actively secreting antibodies: what are we looking for in the serum?

Answer 8

intactimmunoglobulins and free light chains when performing clonality assessment

Question 9

What do we look for in clonality assesment of Uring?

Answer 9

• Antibodies may be filtered when kidney damage• Free light chains (small) may pass through glomerulus– Bence Jones proteins = free light chains

Question 10

–Bence Jones proteins=

Answer 10

free light chains

Question 11

– Identification is donewith electrophoresis– _______May be present in plasma cell disorders and B-celllymphomas (monoclonal gammopathy); rarelyreactive states

Answer 11

Clonality assesment of M protein

Question 12

What isSerum/Urine Electrophoresis(SPEP/UPEP)

Answer 12

Fractionate the serum and apply with electric fieldpeaks show most abundant proteinalbumin is always high, but others should all be present and lowerif one is overexpressed, will peak

Question 13

What is Immunofixation?

Answer 13

Take pt serum and run itall should stain a little bitoverabundace or over-represented stain most likely pathologic

Question 14

• Most common plasma cellneoplasm• Malignant• Epidemiology– 15% of all heme malignanciesin US– ♂ > ♀– AAs > Caucasians– 50-70 y/o• Median age 68-70 y/o

Answer 14

Multiple Myeloma

Question 15

Three key Dx critera for multiple myeloma

Answer 15

Diagnostic criteria1. Clonal plasma cells2. M protein3. End organ damage

Question 16

Wha tis the Dx critera for MM as far as Clonal plasma cells are concerned?

Answer 16

1. Clonal plasma cells• Bone marrow• Plasmacytoma

Question 17

What are Dx criteria in MM as far as M protein is concerned?

Answer 17

2. M protein• Serum and/or Urine• Intact immunoglobulin OR

Question 18

What end organ damage do we see in MM (CRAB)

Answer 18

• HyperCalcemia• Renal insufficiency• Anemia• Bone disease

Question 19

What is true of the plasma cells in picture below of Multpile Myeloma?

Answer 19

The are clonal

Question 20

Why is it important to obtain both electrophoresis on theserum and urine for the diagnosis of myeloma?

Answer 20

– 99% of myelomas have an M protein* (IgG>IgA) and/orBence Jones protein– 60-70% have a serum M protein* and Bence Jonesproteins– 20% have only Bence Jones protein

Question 21

Multiple Myeloma causes this as a result of end organ damage

Answer 21

Lytic bone lesions– Bone pain– Pathologic fractures– Most common sites:– Vertebrae (66%)– Ribs (44%)– Skull (41%)-Pelvis (28%)– Femur (24%)– Osteopenia

Question 22

MM causes hypercalcemia secondary to:

Answer 22

Secondary to bone resorption– Signs and symptoms:– Weakness, lethargy → Coma– Polyuria, stones, renal failure– Constipation, abd pain– Depression– Arrythmias

Question 23

Renal insufficiency, 50% of patients with MM, this is due to:

Answer 23

– Bence Jones (light chain) proteinuria• Direct nephrotoxicity• Formation of tubular casts» Obstruction» Secondary inflammation(also from HyperC, amyloidosis and light chain gammapoathy)

Question 24

MM can lead toAnemia– May be associated with______– Secondary to marrow replacement by plasma cells and/orrenal disease

Answer 24

rouleaux

Question 25

MM can lead toImmunosuppression… How and what are the negative consequences?

Answer 25

– Production of normal Igs suppressed with M protein– Humoral immune system affected– Leads to recurrent infections, particularly bacterial– Most common cause of death

Question 26

Prognosis of Multiple Myeloma:

Answer 26

– Incurable– Median survival of 4-6 years, treated• Chemotherapy• Tandem autologous bone marrow transplants

Question 27

• Localized growth of monoclonal plasma cells• May be seen in multiple myeloma or as distinct entity

Answer 27

Plasmacytomas

Question 28

If Plasmacytoma is seen as distinct entity:No clonal plasma cells in______– ____M protein– Usually treated with ______

Answer 28

– No clonal plasma cells in bone marrow– +/- M protein– Usually treated with radiation therapy

Question 29

Classification of Plasmacytomas

Answer 29

• Extramedullary plasmacytoma– 80% occur in the upper respiratory tract (URT)• Solitary plasmacytoma of bone

Question 30

Lymphoma with plasmacytic differentiation (Bcells and plasma cells are neoplastic)• IgM paraprotein• Characterized by Waldenstrom’smacroglobulinemia

Answer 30

Lymphoplasmacytic lymphoma

Question 31

– Visual/neurologicimpairment– Cryoglobulinemia–>• Raynaud phenomenon–>• BleedingAll from:

Answer 31

Waldenstrom’smacroglobulinemia

Question 32

• Most common form of monoclonal gammopathy– 2% in >50y/o; 3% in >70y/o

Answer 32

Monoclonal Gammopathy ofUndetermined Significance (MGUS)

Question 33

Dx for MGUS

Answer 33

Diagnostic criteria*:– – – No myeloma-related end organ damage

Question 34

Considered “benign” plasma cell proliferation, butprecursor lesion– ___% develop malignant transformation over 10-20 yrs.–________&raquo_space;» Lymphoplasmacytic lymphoma ±Waldenstrom’s macroglobulinemia > Primary amyloidosis– Indefinite follow-up, monitoring of ____

Answer 34

25%MMM protein

Question 35

Diseases characterized by deposition of amyloid• Disorder of protein misfolding• Inherited and acquired forms

Answer 35

Amyloidosis

Question 36

• an extracellular,proteinaceous misfolded substance• Variable chemical composition• Non-branching, 7.5-10nm fibrils• Similar staining properties:Congo Red (+)

Answer 36

AMyloid

Question 37

Most common forms:

Answer 37

Amyloid light chain, Amyloid-associated, and β-amyloid

Question 38

Amyloidosis seen in ____% of MM

Answer 38

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