Monoclonal Gammopathies, Plasma Cell Dyscrasias, and Amyloidoses

Question 1

Most common myeloma related siorders

Answer 1

MGUS

Question 2

Monoclonal gammopathies

Answer 2

Plasma cells neoplasms characterized by secretion of monoclonal Ig…detected by electrophoresis

Question 3

Electrophoresis gammopathies

Answer 3

Normally see broad band
Will now see a huge peak because less diversity and more of one type

May also see in urine if excess

Question 4

Immunofixation electrophoresis

Answer 4

Shows the subclass of monoclonal antibody protein

Question 5

MGUS Pop, clinically, diagnosis

Answer 5

Increases with age (males>females, black>white)
Asymptomatic 
Monoclonal immunogobluin (<3 g/dl)
<10% marrow plasma cells 
no lytic bone lesions or symptoms

Question 6

MGUS prognosis, progression

Answer 6

1-1.5% progression to other things per year

Very good prognosis

Question 7

Multiple myeloma diagnosis

Answer 7

Marrow clonal plasma cells >10% or plasmacytoma
Calcium increased
Renal insuffieicny
Anemia
Bone lytic lesions (more than 1 on CT or MRI)
clonal plasma cell pop on bone marrow>60%
abnormal serum free light chain ration >100 OR

Question 8

Asymptomatic myeloma diagnosis

Answer 8

No CRAB symptoms
M proteins at least 3g/dL OR B-J protein >500 AND/OR Cloncal plasma cells in marrow 10-60%

Risk of transforming to symptomatic is 10% in first 2 years

Also called smoldering myeloma

Question 9

Disease manifestations of MM

Answer 9

Bone pain and Hypercalcemia from cytokine release
Anemia from cytokine release and marrow infiltration
Immune deficiency from antibody
Everything else from the monoclonal protein

Question 10

What is most likely symptoms in multiple myeloma

Answer 10

Anemia

Question 11

Staging of MM

Answer 11

1) Serum b2 <3.5, serum albumin >3.5, no chromosomal, normal LDH
2) not 1 or 3
3) Serum B2>5.5 AND increased LDH or high risk chromosomal abnormalities

Question 12

High risk MM

Answer 12

FISH - t(14;16), t(4;14) or del 17p

Cytogenetic - hypodiploidy or del 13

Question 13

Waldenstrom macroglobulinemia

Answer 13

Excess IgM production
Lymphoplasmacytic lymphoma in the bone marrow with IgM monoclonal gammopathy in the blood
Strong genetic correlation
64 age median diagnosis

Question 14

Waldenstroms macroglobulinemia risk factors

Answer 14

Male sex
Increasing age
Caucasians
IgM monoclonal gammopathy of undetermined significance (IgM MGUS)

Question 15

Waldenstroms macroglobulinemia genetics

Answer 15

6q deletion
Mutations of hypermutation region in V regions of IgM genes (t(9;14), (p13;p32)
Trisomy 4

Question 16

WM clinical presentation

Answer 16

Funduscopic, symptoms secondary to hyper viscosity, LAD, regales, neuro, B symptoms

Question 17

Prognostics for waldenstroms

Answer 17

Age>65
Hb<11.5
Platelet less than 100*10^9
B2>3 
Serum monoclonal protein >70

Question 18

Amyloidosis

Answer 18

Beta pleated sheet

Congo red stain and polarizes with apple green birefringence

Question 19

Amyloid pathogenesis

Answer 19

Kidneys - obliterate glomeruli
Heart - impair conduction contraction
GI - malabsorption/motility
Tongue - speech.swalloing

Question 20

Chemical types of amyloid

Answer 20

AL - from light chains (L>K), made by plasma cells
AA - from serum protein SAA (from liver, acute phase reactant), complicate chronic diseases
Beta - from beta protein precursor in CNS

Question 21

Clinical types of amyloid

Answer 21

Primary - Plasma cell dycrasias (AL, most common)
Secondary - also called reactive systemic amyloidosis, chronic inflammatory conditions (AA), can become neoplastic
Hemodialysis associated - B2 micro globulin, carpal tunnel/joints/synovium

Question 22

AL amyloid

Answer 22

Most common systemic type in US
Monoclonal gammopathy…could be myeloma but often not

Involves Kidneys, heart, liver, nerves (not brain) and lungs

Prognosis - about 18 months and depends on circulating light chain level

Question 23

AA amyloid

Answer 23

Most common cause of systemic worldwide
Associated strongly with inflammatory arthritis

Renal dysfunction in almost all
Some liver involvement

Poor prognosis is higher SAA, older age, end stage renal, Crohn’s, chronic sepsis

Question 24

Hereditary, senile systemic, and localized amyloidosis

Answer 24

Familial mediterranean fever- AA from increased inflammation from increased IL-1
Cardiac involvement - transthyretin
Cerebral amyloidosis associated with alzeihmers (beta-amyloid)