Monoclonal Gammopathies, Plasma Cell Dyscrasias, and Amyloidoses Flashcards
Most common myeloma related siorders
MGUS
Monoclonal gammopathies
Plasma cells neoplasms characterized by secretion of monoclonal Ig…detected by electrophoresis
Electrophoresis gammopathies
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
Immunofixation electrophoresis
Shows the subclass of monoclonal antibody protein
MGUS Pop, clinically, diagnosis
Increases with age (males>females, black>white) Asymptomatic Monoclonal immunogobluin (<3 g/dl) <10% marrow plasma cells no lytic bone lesions or symptoms
MGUS prognosis, progression
1-1.5% progression to other things per year
Very good prognosis
Multiple myeloma diagnosis
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
Asymptomatic myeloma diagnosis
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
Disease manifestations of MM
Bone pain and Hypercalcemia from cytokine release
Anemia from cytokine release and marrow infiltration
Immune deficiency from antibody
Everything else from the monoclonal protein
What is most likely symptoms in multiple myeloma
Anemia
Staging of MM
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
High risk MM
FISH - t(14;16), t(4;14) or del 17p
Cytogenetic - hypodiploidy or del 13
Waldenstrom macroglobulinemia
Excess IgM production
Lymphoplasmacytic lymphoma in the bone marrow with IgM monoclonal gammopathy in the blood
Strong genetic correlation
64 age median diagnosis
Waldenstroms macroglobulinemia risk factors
Male sex
Increasing age
Caucasians
IgM monoclonal gammopathy of undetermined significance (IgM MGUS)
Waldenstroms macroglobulinemia genetics
6q deletion
Mutations of hypermutation region in V regions of IgM genes (t(9;14), (p13;p32)
Trisomy 4
WM clinical presentation
Funduscopic, symptoms secondary to hyper viscosity, LAD, regales, neuro, B symptoms
Prognostics for waldenstroms
Age>65 Hb<11.5 Platelet less than 100*10^9 B2>3 Serum monoclonal protein >70
Amyloidosis
Beta pleated sheet
Congo red stain and polarizes with apple green birefringence
Amyloid pathogenesis
Kidneys - obliterate glomeruli
Heart - impair conduction contraction
GI - malabsorption/motility
Tongue - speech.swalloing
Chemical types of amyloid
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
Clinical types of amyloid
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
AL amyloid
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
AA amyloid
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
Hereditary, senile systemic, and localized amyloidosis
Familial mediterranean fever- AA from increased inflammation from increased IL-1
Cardiac involvement - transthyretin
Cerebral amyloidosis associated with alzeihmers (beta-amyloid)
