105 Essential Monoclonal Gammopathy Flashcards
Two important characteristics of essential monoclonal gammopathy
Monoclonal gammopathy of unknown significance (MGUS) is ensconced as a designation, replacing benign monoclonal gammopathy because approximately one-quarter of patients eventually progress to myeloma, macroglobulinemia, amyloidosis, or a B-cell lymphoma over 2 decades of observation.
Thus, it is monoclonal gammopathy of indeterminate progression or MGIP, not MGUS
- Plasma immunoglobulin (Ig) or Ig light chain that has the molecular features of the product of a single clone of B lymphocytes or plasma cells: homogeneous electrophoretic migration and a single Ig light-chain type
- Absence of evidence of an overt neoplastic disorder of B lymphocytes or plasma cells, such as lymphoma, macroglobulinemia, myeloma, or amyloidosis.
TRUE OR FALSE
Monoclonal gammopathy can occur at any age, but it is unusual before puberty, and its frequency increases with age.
TRUE
Monoclonal gammopathy can occur at any age, but it is unusual before puberty, and its frequency increases with age.
The frequency of a serum paraprotein using zonal electrophoresis is approximately 1% in persons older than age 25 years, approximately 3% in those older than age 70 years, and approximately 10% in those older than age 80 years
Males are more frequently affected than females.
_________________ monoclonal gammopathy arises from somatically mutated postswitch preplasma cells and may have translocations involving the Ig heavy-chain region on chromosome 14.
IgG or IgA monoclonal gammopathy
_________________ monoclonal gammopathy arises from a mutated postgerminal center lymphocyte that does not have evidence of isotype switching.
IgM monoclonal gammopathy
IgG and IgA monoclonal gammopathies tend to evolve into ________________________, and IgM monoclonal gammopathies tend to evolve into __________________________
IgG and IgA monoclonal gammopathies : myeloma or plasmacytoma (plasma cell phenotypes)
IgM monoclonal gammopathies:lymphomas and Waldenstrom macroglobulinemia (lymphocytic phenotypes)
A protein associated with inherited increased risk of IgA and IgG monoclonal gammopathy and myeloma
Paratarg-7 (also known as STOML2, HSPC108, and SLP-2)
A somatic mutation found in approximately 50% of individuals with IgM monoclonal gammopathy and in more than 90% of patients with Waldenström macroglobulinemia.
MYD88 L265
“Low-risk” monoclonal gammopathy:
(a) those with less than 1.5 g/dL IgG and a normal serum free Ig light-chain ratio or
(b) less than 1.5 g/dL of IgM or light-chain monoclonal gammopathy with a normal serum free light-chain ratio accompanied by an absence of unexplained symptoms (eg, back pain) or other laboratory features of concern
A marrow examination and skeletal imaging may be omitted because they have been shown to be very unlikely to be informative in these settings
Blood cell and marrow findings in essential monoclonal gammopathy
Anemia is not present
The proportion of plasma cells in marrow is less than 10%
Microvessel density on average is threefold greater than in normal persons but far less than in patients with myeloma,
Frequent binucleate plasma cells and large plasma cell nucleoli, is a finding more specific for myeloma
Patients with essential monoclonal gammopathy categorized risk of progression into four categories:
High:
Intermediate:
Standard:
Low:
High-risk patients: t(4;14) and del 17p
Intermediate-risk: trisomies without translocation
Standard-risk: t(11;14), translocations other than t(4;14) with or without trisomies or chromosome 13 abnormalities
Low-risk: normal results or an insufficient marrow plasma cell sample
Percentage of types of monoclonal gammopathy:
IgG:
IgM:
IgA:
Percentage of types of monoclonal gammopathy:
IgG: 70%
IgM: 20%
IgA: 10%
A low percentage of persons may have biclonal or triclonal gammopathy
Most patients with essential monoclonal gammopathy have a monoclonal protein concentration of less than _____ g/L, but exceptions occur.
Less than 30 g/L
Diagnosis of essential monoclonal gammopathy
- The monoclonal protein level
- The marrow plasma cell concentration (<10%)
- The absence of other features of progressive plasma cell neoplasm (eg, hypercalcemia, osteolysis, otherwise unexplained anemia, otherwise unexplained renal disease)
- The absence of progression on periodic long-term follow-up.
The normal range of the κ-to-λ ratio of free light chains in serum is
0.26–1.65
> 1.65: excess κ light chains
< 0.26: excess λ light chains
Used to confirm a monoclonal protein found on gel electrophoresis
Immunofixation electrophoresis
May also detect a monoclonal protein not evident on serum protein gel electrophoresis, usually because the protein is in too low a concentration or is embedded in the normal polyclonal α- or β-globulin peak.
Monoclonal proteins identified by immunofixation electrophoresis may be transient (~15–20%) and have a greater likelihood to progress to a disease if they are of an IgA or IgM isotype.
May be a more sensitive and specific method to identify monoclonal proteins
Mass spectroscopy
In a patient with a presumptive diagnosis of essential monoclonal gammopathy, reexamination should be made at_______months to confirm the diagnosis of a stable clone
3–6 months
A term to denote a monoclonal gammopathy that can produce disease, often quite serious, without lymphoproliferation and progression of the neoplastic cell population.
Dangerous small B-cell clone
Functional impairment from a monoclonal protein
Examples: red cell aplasia, TEMPI (telangiectasia, erythrocytosis, monoclonal gammopathy, perinephric fluid, intrapulmonary shunting) syndrome, immune hemolytic anemia, acquired von Willebrand disease,acquired thrombasthenia, immune neutropenia,insulin autoimmune syndrome, and other functional manifestations
Medications favored for renal injury in monoclonal gammopathy
Cyclophosphamide, thalidomide, bortezomib, and bendamustine
A glucocorticoid (eg, dexamethasone) and rituximab can also be useful
Plasmapheresis in an effort to decrease plasma monoclonal Igs quickly has been used as an adjunct to chemotherapy
One should also consider the possibility that the monoclonal protein may be secreted by a solitary plasmacytoma, which would be amenable to local radiation therapy.
TRUE OR FALSE
IgM monoclonal gammopathy has a significantly higher frequency of neuropathy than does IgG or IgA monoclonal gammopathy.
TRUE
IgM monoclonal gammopathy has a significantly higher frequency of neuropathy than does IgG or IgA monoclonal gammopathy.
Mechanisms of nerve damage in IgM monoclonal gammopathy
Monoclonal antibodies can react with peripheral nerve myelin, specifically with myelin-associated glycoprotein, glycolipids, or sulfatides.
The monoclonal antibodies reactive with nerve antigens usually are of the _____type
IgM type
Patients with _________ monoclonal gammopathy usually have chronic inflammatory demyelinating polyneuropathy; a minority have sensory axonal or mixed neuropathy
IgG or IgA monoclonal gammopathy
____ gammopathy is associated with dysautonomia
IgA gammopathy
Seven treatment approaches have been used to ameliorate the neuropathies:
(a) immunoglobulin (IVIG) administration;
(b) glucocorticoids alone;
(c) immunoadsorption of perfused blood with staphylococcal protein A;
(d) plasma exchange or plasmapheresis;
(e) immunosuppressive cytotoxic chemotherapy, such as cyclophosphamide, chlorambucil, or fludarabine with or without added glucocorticoids;
(f) rituximab (anti–cluster of differentiation [CD] 20 antibody) to deplete B cells; and
(g) high-dose cytotoxic therapy with autologous hematopoietic cell rescue
A recommendation has been made to start therapy with IVIG, especially in essential monoclonal IgM-associated neuropathy, because of the relative safety of this approach.
In monoclonal gammopathy of the IgG type, the concentration of monoclonal Ig usually is less than __________
less than 3 g/dL
Patients with monoclonal gammopathy usually have normal polyclonal Ig levels, and if a decrease of their polyclonal Ig levels is present, it is usually not as severe as in myeloma.
In the IgA or IgM type, the concentration usually is less than _______
less than 2.5 g/dL
Patients with monoclonal gammopathy usually have normal polyclonal Ig levels and if a decrease of their polyclonal Ig levels is present, it is usually not as severe as in myeloma.
The concentration of plasma cells in the marrow is less than ____%, and the incorporation of tritiated thymidine into marrow plasma cells is negligible (<1%) in essential monoclonal gammopathy.
Less than 10%
TRUE OR FALSE
Marrow plasma cells in monoclonal gammopathy express neural cell adhesion molecule (CD56), myeloma cells strongly express this surface protein as well
FALSE
Marrow plasma cells in monoclonal gammopathy do not express neural cell adhesion molecule (CD56), myeloma cells strongly express this surface protein
Blood T-lymphocyte subset levels are normal
Blood B-cell concentration is normal
β2M concentration is (low, normal, elevated) in essential monoclonal gammopathy.
Normal
Ophthalmic injury from a monoclonal proteins results from what element deposits on the eye
Copper
Prognosis of essential monoclonal gammopathy:
Do not progress to a lymphocytic neoplasm over 25–30 years:
Die of an unrelated cause:
Develop a plasmacytoma, myeloma, amyloidosis, macroglobulinemia, lymphoma, or chronic lymphocytic leukemia over several decades of observation:
Prognosis of essential monoclonal gammopathy:
Do not progress to a lymphocytic neoplasm over 25–30 years: 25%
Die of an unrelated cause: 50%
Develop a plasmacytoma, myeloma, amyloidosis, macroglobulinemia, lymphoma, or chronic lymphocytic leukemia over several decades of observation:25%
The actuarial risk of progressing to a clonal B-cell malignancy for all classes of monoclonal protein is approximately _____% per year depending on the population studied.
0.75% per year
Drug that may decrease the risk of progression of monoclonal gammopathy to myeloma.
Metformin
Clinical trials have not been reported, and the drug is not approved for that purpose.
Patients with low risk of progression to a malignant disorder (eg, myeloma) need not be followed at least _________
Some authorities have suggested that after the diagnosis of essential monoclonal gammopathy is confirmed by a second analysis 3–6 months after the presumptive diagnosis
Once a year
The most efficient method of follow-up is to assess three of several factors that may inform the time to progression:
(a) a serum monoclonal protein concentration greater than 1.5 g/dL
(b) an IgM or IgA isotype, and
(c) an abnormal free light-chain ratio
There are two considerations that argue for less frequent follow-up of those deemed less likely to progress based on the height of their monoclonal Ig, the normality of serum light-chain ratio, and an IgG isotype
