other monoclonal disorders

7/31/2019 Other Monoclonal Disorders

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1. Monoclonal gammophathy of undeterminedsignificance (Mgus)2. Light-Chain disease3. Heavy-chain disease4. Gammopathies with more than one band

Other Monoclonal Disorders


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Monoclonal gammopathy of undeterminedsignificance (MGUS)

Definition

Condition in which an abnormal protein

(monoclonal protein, or M protein) is inthe blood.


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M protein

In myeloma, a single B- lymphocyte in thebone marrow undergoes a geneticmutation which causes it to over produceplasma cells in an uncontrolled manner.These clone plasma cells will continue to

produce the same immunoglobulinproteins as the original cancerous cell inlarge quantities.


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M Protein

These clone plasma cells will continue to

produce the same Ig proteins as theoriginal cancerous cell in large quantities.As a result, an excessive amount of a singletype of immunoglobulin is created. The

accumulation of this single variety ofimmunoglobulin is called the M-protein.


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Definition

Benign (non-cancerous) condition that may

be a precursor to developing myeloma. InMGUS, there is a slight elevation in plasmacells in the marrow and a low M-proteinlevel, but there are no other disease

symptoms such as bone destruction orkidney damage.


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Charcteristic

Serum M-protein concentration


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Considered a benign monoclonal

gammopathy. Can evolve into a malignancy

monoclonal gammopathy


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MGUS SmolderingMM

MM WM

BM plasma

cells

10%

and

Circulatin

M-protein


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Symptoms

Rarely causes signs or symptoms

nerve problems, such as numbness ortingling, associated with the abnormalprotein.


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Causes

In the majority of people with MGUS, theprotein isn't harmful. But when too much

M protein accumulates, it crowds outhealthy cells in your bone marrow and candamage other tissues in your body


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Risk factors

Age 25y/o 1% , 70y/o 5% Race More often in blacks

than in whites Sex Frequently in men thanwomen

Family history Hereditary Weight BMI >30


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Complication

10 and 25 percent of people with MGUSdevelop a more serious condition, such as

multiple myeloma or other cancers orblood disorders.

Other complications include fractures andblood clots.


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Factors determing risk

The amount of M protein in your blood The type of M protein The amount of another small protein (free

light chain) in your blood The number of plasma cells in your bone

marrow The presence of protein in your urine


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Laboratory test

Hb concentration Creatinine concentration

BM aspiration examination Total serum protein concentration and serumelectrophoresis

24h urine protein execretion concentration and erineelectrophoresis

Serum and urine immunofixation Determinarion of serum FLC ratio( & ), for assesment of

prognosis


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MGUS doesn't require treatment, but your doctor is likelyto recommend frequent checkups to monitor your health

Treatments and drugs

Prevention

The cause of monoclonal gammopathy of undetermined

significance is unknown, so there is no way to preventmonoclonal gammopathy of undetermined significanceand no way to stop it from progressing to a more seriouscondition.



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Light-Chain Disease

Light-Chain Deposition Disease

(LCDD)


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Light chain deposition disease involves our immune system. It is caused by an excess buildup of Ig light chain in our

tissues and organs. While an important part of our immune system, if these

proteins become trapped in the tissues of the kidneys, lungs,skin, joints, or blood vessels, they can set off reactions thatlead to tissue or organ inflammation (swelling) and damage.

Early signs and symptoms of LCDDmay include protein in theurine, high BP, decreased kidney function, and nephrotic

syndrome. LCDD is often associated with MM, MGUS, or other disorders

of abnormal overgrowth of lymph nodes.


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10-15% of Monoclonal gammopathiesIn Light-Chaid Deposition Disease (LCDD) only

or monoclonal light chain are produced.



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Diagnostic evaluation

High resolution protein electrohoresis of serum andurine (total protein concentration)

24h urine specimen

Visual examination

q Observation

1. Typical well defined monoclonal band, g region

2. Diffuse band caused by polymerization ofmonoclonal protein

3. H o amma lobulinemia



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Heavy-Chain Diseases (HCDs)

Heavy-Chain Deposition Disease


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Heavy chain diseases (HCDs) are rare B-cellproliferative disorders characterized by the synthesisand secretion of incomplete immunoglobulin heavychains. These disorders initially were recognized as

gammopathies due to the presence of monoclonalproteins in the patient's serum or urine. The disorders

were defined in terms of the production of structurallyaberrant immunoglobulin molecules.



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Plasma cell disorderscharacterized by ananomalous serum andurinary protein that is

immunochemically relatedto the Fc fragment of theimmunoglobulin moleculeare known as HCDs.


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The heavy chain diseases are divided according toimmunoglobulin type.

alpha chain disease (Seligmann's disease) HCD

gamma chain disease (Franklin's disease) HCD

mu chain disease HCD



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Epidemiology

?



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Gammopathies with more than one band

Gammopathies with more thanone band


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Gammopathies with more than one band

Cases more than one monoclonal band is produced.

2 bands may rapresent a true biclonal condition

The appearance of more than one band onelectrophoresis is often associated with an advancedgammopathy

other monoclonal disorders

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