What are the reactive plasma cell conditions?
Chronic infections (H. pylori gastritis, osteomyelitis, endometris)
Autoimmune processes (lupus, hepatitis)
What are the plasma cell neoplastic conditions?
Monoclonal gammopathy of undetermined significance (MGUS)
Plasmacytoma (Extramedullary or solitary of bone)
How do we assess clonality of plasma cell?
Monoclonal antibodies in the serum or urine
Light chain restriction in cell cytoplasm (kappa v lambda) by flow cytometry or immunohistochemistry
Immunophenotypic aberrancy (e.g. CD56 on plasma cells)
What are M proteins?
How do they appear in serum?
How do they appear in urine?
What else can they be assocciated with?
Intact immunoglobulins and free light chains
Full antibodies are filitered with kidney damage, free light chains may pass through glomerulus (Bence-Jones proteins
B-cell lymphomas (monoclonal gammopathy), rarely reactive states
How are M proteins IDed?
Most important spikes in electrophoresis?
What does a gamma-globulin spike indicate?
What does the immunofixation do?
Identification with electrophoresis and immunofixation
Most important spikes in electrophoresis are the albumin fraction (positive lead) and gamma fraction (negative lead)
Spike means that there is one dominant Ab
Allows specific ID of the gammaglobulin
What is multiple myeloma?
Male or female dominant?
Most common plasma cell neoplasm
Males greater than female
AAs greater than caucasians
What are the diagnostic criteria for MM?
Clonal plasma cells - Bone marrow and plasmacytoma
M protein - Serum and/or Urine
Need to check for Bence Jones protein (kidney disease results in complete excretion, 20% have no serum findings)
End organ damage: hyperCalcemia, Renal insufficiency, Anemia, Bone Disease (CRAB
Which bone lesions are associated with MM?
Why is there an association with hypercalcemia?
Pathologic fractures in Vertebrae, Ribs, Skull, Pelvis, Femur
Hypercalcemia is secondary to the bone resorption
What is this?
Clonal plasma cells in myeloma
What effect does M protein have on immune system?
Elevated risk for recurrent infections due to abnormal Ig production
Most common cause of death
What is the prognosis of multiple myeloma?
How is it treated?
Incurable, median survival of 4-6 years treateed (chemo and tandem autologous bone marrow transplants)
What is a plasmacytoma?
How is it treated when distinct (non-systemic)?
Are there clonal plasma cells in marrow? M protein?
Localized growth of monoclonal plasma cell
No clonal plasma cells in marrow.
+/- M protein
What is lymphoplasmacytic lymphoma?
What protein is associated with it?
What syndrome is associated with it?
Lymphoma with plasmacytic differentiation (B cells and plasma cells are neoplastic)
What are the symptoms of Waldenstrom's macroglobulinemia?
Cryoglobulinemia - Raynaud phenomenon, Bleeding
Monoclonal Gammopathy of Undetermined Significance
What is it?
What is the diagnostic criteria?
Most common form of monoclonal gammopathy (2% in >50y/o; 3% in >70y/o)
<3 g/dL serum M protein
<10% clonal plasma cells in bone marrow
No myeloma-related end organ damage
What is the progression of MGUS?
Which specific diseases can it result in?
What is the follow-up?
"Benign" plasma cell proliferation, but precursor lesion
25% develop malignant transformation over 10-20 year
Multiple myeloma >>>> Lymphoplasmacytic lymphoma +/- Waldenstrom's macroglobulinemia > Primary amyloidosis
Indefinite follow-up, monitoring of M protein
What is amyloidosis?
What is the etiology?
What is amyloid?
Diseases characterized by deposition of amyloid
Disorder of protein misfoldings: inherited and acquired forms
Extracellular, proteinaceous misfolded substance
What is the most common forms of amyloidosis?
What are the most common deposits and what do they cause?
Amyloid light chain, amyloid associated, and beta-amyloid
Heart - Conduction abnormalities
Kidney - Glomerular damage, nephrotic syndrome
Liver - Hepatomegaly
Nerves - Polyneuropathy
GI Tract - Malabsorption, diarrhea
Tongue - Macroglossia
Clinical categories and subtypes of amyloidosis
Primary amyloidosis from multiple myeloma (5-10%), other plasma cell disorders
Secondary amyloidosis from chronic inflammatory conditions
Hemodialysis-associated amyloidosis from chronic renal failure