Immunoproliferative Disorders Flashcards
What type of cell produces most of the immunoglobulin G or A in normal adult serum?
Plasma Cells
Are hypergammaglobulinemias monoclonal or polyclonal in nature?
They are both monoclonal and polyclonal
What are a few key factors about Monoclonal gammopathy?
Can be benign or malignant
results from single clone of plasma cells producing a single class elevation of immunoglobulins (ex. monoclonal protein/paraprotein)
Multiple myeloma and Waldentrom macroglobulinemias
What are some key factors about Polyclonal Gammopathy?
classified as a secondary disease
characterized by the elevation of two or more immunoglobulins of several clones of plasma cells
General Characteristics of Monoclonal Gammopathies include…?
production of monoclonal immunoglobulins
associated w/ suppressed uninvolved immunoglobulins and dysfunctional t cell responses
MM-prototypical monoclonal gammopathy
Serum and urine electrophoresis can show abnormal results
Do symptomatic pt show characteristic monoclonal band/spike in protein patterns?
some pt do not show characteristic monoclonal spike in protein patterns - seen with light chain disease
what is a common abnormality in polyclonal gammopathies?
common protein abnormality
What is increased in general characteristics of polyclonal gammopathies?
there is an increase in more than one immunoglobulin, involving several clones of plasma cells
True or false: Polyclonal Gammopathies consist of one or more heavy chain classes and both light chain types.
true
What are some secondary manifestations of infection or inflammation of Polyclonal Gammopathies?
chronic infections, chronic liver disease, lymphoproliferative disorders and rheumatoid connective diseases
Multiple Myeloma is characterized by?
Plasma cell Neoplasms.
accumulation of malignant plasma cells within the bone marrow microenvironment, monoclonal protein in blood or urine, associated organ dysfunction
What is the normal % of plasma cells in Bone Marrow vs Multiple Myeloma?
BM -1%
MM -90%
MM Etiology
cause is uncertain, possible causes include radiation, viral, environmental stim: LIKELY A GENETIC FACTOR
true or false: plasma cells produce one of five heavy-chain types together with K and lambda (no key for that rip) molecules
true
True or false: There is approximately 30% excess production of free LC over HC synthesis to allow proper conformation of intact immunoglobulin molecules
False: it is approximately 40%
What is the most likely cause of MM?
Most likely is Genetic factors that cause Multiple myeloma
What cells do myelomas arise from?
They arise from asymptomatic premalignant proliferation of monoclonal plasma cells
True or false: MM myelomas arise from cells that are often immature and may have the appearance of plasmablasts
true
In MM, most patients have what kind of abnormality? (Pathophysiology)
most pt have complex karyotype abnormalities - chromosomal gains, deletions and translocations
Do myeloma cells proliferate slowly or quickly? Where do they proliferate?
They proliferate slowly in the marrow - absolute number of these cells correlates with disease activity and predicts progression in SMOLDERING MM (wtf is smoldering mm)
Smoldering MM made me think of the Flynn Rider smolder lol
What Interleukin is essential for survival and growth of myeloma cells?
IL-6 - promotes survival of myeloma cells and prevents apoptosis
What is the most common form of dysproteinemia?
Multiple myeloma
What is the average age of onset of MM? When is the peak?
onset is around 40-70 yrs with a peak incidence in 70s, less than 2% under 40yrs old
What is the most common immunoglobulin in MM?
IgG is the most common (IgG3 likely to experience hyperviscosity syndrome)
What is the most common cause of death in pt with MM?
Most patients die from infections and renal insufficiency, MM is progressive and pt usually die within 1-3 yrs :(
What are the most common signs/symptoms of MM?
bone pain in chest/back is the most common
also weakness, fatigue, pallor, renal issues
20% hepatomegaly
5% splenomegaly
What are some hematologic features of MM?
Increased plasma cells in BM or biopsy
Bleeding, abnormal PLTs and thrombocytopenia
What % of pt have broadly disseminated destruction of the skeleton in MM?
90% of pts, responsible for the bone pain (how does it hurt if you dont have bones?) 80% of pt have punched out bones/lytic areas
True or false: Renal failure is common and occurs more with IgD and light chain myeloma in MM?
True
Proteinuria is common in MM. Over half of MM pt’s excrete what protein abnormally to cause this?
half of all MM pt excrete abnormal amounts of Bence-Jones Proteins (light chains)
What are the two ways Bence Jones proteins cause issues in MM?
Via intratubular precipitation and intrarenal obstruction (referred to as myeloma kidney)
or Via direct tubular cell injury (renal acidification is observed)
True or false: MM causes compression of the spinal cord and or nerves, as well as bladder incontinence
True
Immunologic manifestations of MM include defects in what type of immunity?
Humoral but not cellular immunity
What is the most consistent immunologic manifestation of MM?
incessant synthesis of dysfuncional single monoclonal protein or immunoglobulin chains of fragments
True or false: Normochromic normocytic anemia is present in 2/3rd of pt at diagnosis of MM
True
What is a common rbc morphology found in MM pts?
Rouleaux rbcs
What CD classes (ex CD4+ or CD8+) are increased/decreased in MM?
CD4+ is reduced (helper) and CD8+ is increased (Cytotoxic)
What is a molecular testing method used in the identification of MM?
FISH (fluorescent in situ hybridization) test of bone marrow ESSENTIAL
One is an important diagnostic marker in MM?
Bence jones proteins are an important marker, seen with typical monoclonal gammopathy and in free LCD
True or false: Very small amounts of BJ proteins in serum are not associated with clinical significance in MM
False they are very significant
Bence jones proteins are soluble at RT, become insoluble (form precipitate) at ____ degrees, then dissolve at ____ degrees. (this is unique to BJ proteins)
become insoluble at 60 degrees celsius and dissolve at 100 degrees celsius and the pattern reverses when cooled
FLC (free light chains) occurs in what cells?
B cell development and plasma cells, normally rapidly cleared and metabolized by the kidneys
Immunoelectrophoresis for MM determines the blood levels of what immunoglobulin classes?
IgM, IgA, IgG
(also 90% of pt will have a monoclonal protein)
Assume the diagram on the left is normal, what disease is present in the diagram on the right?
MM
Treatment of MM includes what three supportive treatments?
biophosphonates to reduce risk of fractures
Plasmaphoresis to remove abnorm proteins
Surgery to remove tumors/prevention of fractures
What kind of cell disorder is associated with Waldenstrom Macroglobulinemia?
B cell disorder characterized by infiltration of lymphoplasmacytic cells and IgM monoclonal gammopathy
True or false: Waldenstrom Macroglobulinemia is considered a lymphoplasmacytic lymphoma
True
What is the cause of Waldenstrom Macroglobulinemia?
Unknown cause- possibly genetic, but has malignant lymphs-plasma cells with abnormal amounts of IgM
What age does Waldenstrom Macroglobulinemia mostly occur in?
mostly 60-64yr olds, disease onset is insidious and survival is approx 3yrs post diagnosis
The pace of manifestation of Waldenstrom Macroglobulinemia is determined by the rate of profileration of what clone?
IgM-secreting Clones
In Waldenstrom Macroglobulinemia, bleeding from what areas causes the most concern?
Bleeding from the gums/nose
What are some hematologic abnormalities associated with Waldenstrom Macroglobulinemia?
chronic anemia/bleeding, bruising, disturbed PLT function, increases ESR..etc (idk how important this is so i picked the most important sounding ones)
True or false: Pickles are good
true (if you said false you’re dead to me)
What is the predominant form of renal injuries in Waldenstrom Macroglobulinemia?
Glomerular lesions
What is the basic abnormality in Waldenstrom Macroglobulinemia?
Uncontrolled prolif of B lymphs and plasma cells, heavy accum of IgM in plasma and plasmacytoid in BM
Assume left is normal, what disease is present on the right?
Waldenstrom Macroglobulinemia
What are some treatment methods for Waldenstrom Macroglobulinemia?
Plasmapheresis, drugs, and various therapies
Monoclonal Gammopathy of Undetermined Significance (MGUS) has presence of what kind of Protein? What gender is it most frequent in?
Monoclonal proteins, increases with age and more common in males
What is the most common Ig class in MGUS?
IgG followed by IgM
What are some facts about Light-Chain disease?
10-15% of monoclonal gammopathies
only K or lambda light chains or BJ proteins produced
What are some facts about Heavy-Chain disease?
Franklins disease - IgG heavy chain disease
Alpha Heavy-chain is most common (men w mediterranean descent)
Mu heavy-chain disease is rare
