12-1: 1/17 - Plasma Cell Dyscrasias

Front 1

Plasma cells officially come from ___-cells.

Back 1

B cells!

Front 2

What is a plasma cell dyscrasia?

Back 2

Proliferation of a clone of plasma cells that will either synthesize a homogenous Ig or Ig fragment

monoclonal Ig production

Front 3

Multiple Myeloma:
What is it?
Diagnostic triad

Back 3

Masses of plasma cells scattered trough skeletal system

1) M-protein in serum and/or urine

2) Clonal plasmal cells in BM

3) Evidence of damage from clone (organ tissue impairment):
CRAB:
HyperCa2+
Renal Insuff
Anemia
Bone Lzns

Front 4

What's on chromosome 14?

Back 4

Immunoglobulin heavy chain

Front 5

Serum Protein Electrophoresis:
Diagnostic utility
What would you look for?

Back 5

Note: Gamma-globulin is where Ig's migrate

Normal Serum Protein Electrophoresis (SPEP): gamma should be diffuse

Would see a gamma spike in Multiple Myeloma (M-protein!)

Front 6

What is the most common Ig monoclonal protein made in multiple myeloma?

Other Ig's?

Back 6

IgG kappa is most common

Also see IgA

Or JUST light chains (kappa or lambda)--Bence Jones Proteins

Front 7

Multiple Myeloma:
Diagnostics

Back 7

-SPEP

-If SPEP negative-->24 hour urine for light chains and/or serum free light chains

Front 8

Mott Cells:
What are they?
Indicative of?

Back 8

Mott Cells are plasma cells containing multiple Ig globules (vacuoles)

Indicates multiple myeloma

Front 9

Bone symptoms of MM.

Back 9

Bone pain, pathologic fractures (lytic lesions) in axial skeleton.

Front 10

How does bone destruction occur in MM?

Back 10

Osteoclast Activating Factor

Myeloma cells secrete RANK Ligand which stimulates diff of osteoclasts (bone resorption)

Myeloma cells inhibit osteoprotegerin (OPG) production (which blocks RANK-L)

Front 11

Most important factor in MM renal insufficiency?

Back 11

Bence Jones proteinuria

Front 12

How does anemia develop in MM?

Back 12

Multifactorial:
Invasion by myeloid cells
EPO deficiency due to renal failure
Anemia of chronic dz

Front 13

What is an erythrocyte sedimentation rate?

What would it be like in someone with MM?

Back 13

Erythrocyte Sedimentation Rate; how far go down tube RBCs in an hour.

Rate of fall is higher if proteins present in plasma (in someone with MM)

Front 14

What is amyloidosis?

Where can it occur?

Back 14

Result of number of unrelated dz processes that lead to abnormal depositino of amyloid proteins in organs/tissues.

Occurs ANYWHERE IN BODY

Front 15

Amyloidosis Related to Monoclonal Light Chains:
How is it a plasma cell dyscrasia?

Back 15

AL amyloidosis = plasma cell dyscrasia of unknown cause

Ig light chain produced by plasma cell clones deposits as extracell amyloid fibers.

Front 16

Amyloidosis:
Diagnosis

Back 16

Aspiration of abdominal fat and stain with Congo red, if negative, do a rectal biopsy.

Front 17

Monoclonal Gammopathies of Undetermined Significance (MGUS):
What is it?
Clinical significance?

Back 17

-<3g/dl of monoclonal protein in serum
-No Bence-Jones proteinuria
-BM plasma cells <10%

ACCOUNTS for 70% of monoclonal gammopathies.

No CRAB!

Clin Sig: 1% per year progress to multiple myeloma

Front 18

What is smoldering myeloma?

Back 18

MGUS-->Smoledering Myeloma-->MM

Asymptomatic MM:
>3g M-protein OR >10% plasma cells (no CRAB)

10% per year go on to multiple myeloma

Front 19

Solitary Myeloma:
What is it?

Back 19

Single area of plasma cell dyscrasia, everything else normal.

No serum protein production.

Can progress to MM.

Tx w/localized XRT

Front 20

Multiple Myeloma:
Treatment with drug classes

Back 20

Thalidomide-dexamethasone (immunomodulatory)
Lenalidomide-dexamethasone (immunomodulatory)
Bortezomib (proteasome inhibitor)

Front 21

What occurs in stage III of MM?

Back 21

Advanced lytic bone lesions!

This doesn't occur in stage I or II.

Front 22

Waldenstrom's Macroglobulinemia:
What is it?
How does it differ from other MM's?

Back 22

Indolent, Clone of plasma cells making IgM

Do not form tumor masses or lytic lesions!

LAD, hepatosplenomegaly.

IgM buildup-->hyperviscosity syndrome.

Front 23

What causes hyperviscosity syndrome?

Back 23

Waldenstrom's Macroglobulinemia: lots of IgM (pentameric) clumps up

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