Plasma Dyscriasis Flashcards
• Terminally differentiated B cells• Function– Antibody secretion
Plasma Cells
• 2 heavy chains:• 2 light chains:
• 2 heavy chains: μ, γ, α, δ, ε• 2 light chains: κ, λ
Describe Plasma cell on HE
Has clock faced nuclei
Below is an image of reactive plasma cells, When would we see them?
• Chronic infections (eg. Hpylori gastritis,osteomyelitis,endometritis)• Autoimmune processes(lupus, hepatitis)
• Multiple myeloma• Monoclonal gammopathy of undeterminedsignificance (MGUS)• Plasmacytoma– Extramedullary plasmacytoma– Solitary plasmacytoma of bone• Lymphoplasmacytic lymphoma• AmyloidosisAll exmaples of:
Neoplastic plasma cell conditions
How do we differentiate between reactive and neoplastic plasma cell conditions?
• 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)
Normally, the production andcoupling of heavy and lightchains is
tightly balanced.
Monoclonal antibodies = M protein– Serum• Plasma cells actively secreting antibodies: what are we looking for in the serum?
intactimmunoglobulins and free light chains when performing clonality assessment
What do we look for in clonality assesment of Uring?
• Antibodies may be filtered when kidney damage• Free light chains (small) may pass through glomerulus– Bence Jones proteins = free light chains
–Bence Jones proteins=
free light chains
– Identification is donewith electrophoresis– _______May be present in plasma cell disorders and B-celllymphomas (monoclonal gammopathy); rarelyreactive states
Clonality assesment of M protein
What isSerum/Urine Electrophoresis(SPEP/UPEP)
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
What is Immunofixation?
Take pt serum and run itall should stain a little bitoverabundace or over-represented stain most likely pathologic
• Most common plasma cellneoplasm• Malignant• Epidemiology– 15% of all heme malignanciesin US– ♂ > ♀– AAs > Caucasians– 50-70 y/o• Median age 68-70 y/o
Multiple Myeloma
Three key Dx critera for multiple myeloma
Diagnostic criteria1. Clonal plasma cells2. M protein3. End organ damage
Wha tis the Dx critera for MM as far as Clonal plasma cells are concerned?
- Clonal plasma cells• Bone marrow• Plasmacytoma
What are Dx criteria in MM as far as M protein is concerned?
- M protein• Serum and/or Urine• Intact immunoglobulin OR
What end organ damage do we see in MM (CRAB)
• HyperCalcemia• Renal insufficiency• Anemia• Bone disease
What is true of the plasma cells in picture below of Multpile Myeloma?
The are clonal
Why is it important to obtain both electrophoresis on theserum and urine for the diagnosis of myeloma?
– 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
Multiple Myeloma causes this as a result of end organ damage
Lytic bone lesions– Bone pain– Pathologic fractures– Most common sites:– Vertebrae (66%)– Ribs (44%)– Skull (41%)-Pelvis (28%)– Femur (24%)– Osteopenia
MM causes hypercalcemia secondary to:
Secondary to bone resorption– Signs and symptoms:– Weakness, lethargy → Coma– Polyuria, stones, renal failure– Constipation, abd pain– Depression– Arrythmias
Renal insufficiency, 50% of patients with MM, this is due to:
– Bence Jones (light chain) proteinuria• Direct nephrotoxicity• Formation of tubular casts» Obstruction» Secondary inflammation(also from HyperC, amyloidosis and light chain gammapoathy)
MM can lead toAnemia– May be associated with______– Secondary to marrow replacement by plasma cells and/orrenal disease
rouleaux
MM can lead toImmunosuppression… How and what are the negative consequences?
– Production of normal Igs suppressed with M protein– Humoral immune system affected– Leads to recurrent infections, particularly bacterial– Most common cause of death
Prognosis of Multiple Myeloma:
– Incurable– Median survival of 4-6 years, treated• Chemotherapy• Tandem autologous bone marrow transplants
• Localized growth of monoclonal plasma cells• May be seen in multiple myeloma or as distinct entity
Plasmacytomas
If Plasmacytoma is seen as distinct entity:No clonal plasma cells in______– ____M protein– Usually treated with ______
– No clonal plasma cells in bone marrow– +/- M protein– Usually treated with radiation therapy
Classification of Plasmacytomas
• Extramedullary plasmacytoma– 80% occur in the upper respiratory tract (URT)• Solitary plasmacytoma of bone
Lymphoma with plasmacytic differentiation (Bcells and plasma cells are neoplastic)• IgM paraprotein• Characterized by Waldenstrom’smacroglobulinemia
Lymphoplasmacytic lymphoma
– Visual/neurologicimpairment– Cryoglobulinemia–>• Raynaud phenomenon–>• BleedingAll from:
Waldenstrom’smacroglobulinemia
• Most common form of monoclonal gammopathy– 2% in >50y/o; 3% in >70y/o
Monoclonal Gammopathy ofUndetermined Significance (MGUS)
Dx for MGUS
Diagnostic criteria*:– – – No myeloma-related end organ damage
Considered “benign” plasma cell proliferation, butprecursor lesion– ___% develop malignant transformation over 10-20 yrs.–________»_space;» Lymphoplasmacytic lymphoma ±Waldenstrom’s macroglobulinemia > Primary amyloidosis– Indefinite follow-up, monitoring of ____
25%MMM protein
Diseases characterized by deposition of amyloid• Disorder of protein misfolding• Inherited and acquired forms
Amyloidosis
- an extracellular,proteinaceous misfolded substance• Variable chemical composition• Non-branching, 7.5-10nm fibrils• Similar staining properties:Congo Red (+)
AMyloid
Most common forms:
Amyloid light chain, Amyloid-associated, and β-amyloid
Amyloidosis seen in ____% of MM
5-10
