Other Monoclonal Disorders

1.

2. 3. 4.

Monoclonal gammophathy of undetermined significance (Mgus) Light-Chain disease Heavy-chain disease Gammopathies with more than one band

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Monoclonal gammopathy of undetermined significance (MGUS)

Definition

Condition in which an abnormal protein (monoclonal protein, or M protein) is in the blood.

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Monoclonal gammopathy of undetermined significance (MGUS)

M protein

In myeloma, a single B- lymphocyte in the bone marrow undergoes a genetic mutation which causes it to over produce plasma cells in an uncontrolled manner. These clone plasma cells will continue to produce the same immunoglobulin proteins as the original cancerous cell in large quantities.
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Monoclonal gammopathy of undetermined significance (MGUS)

M Protein

These clone plasma cells will continue to produce the same Ig proteins as the original cancerous cell in large quantities. As a result, an excessive amount of a single type of immunoglobulin is created. The accumulation of this single variety of immunoglobulin is called the M-protein.
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Monoclonal gammopathy of undetermined significance (MGUS)

Definition

Benign (non-cancerous) condition that may be a precursor to developing myeloma. In MGUS, there is a slight elevation in plasma cells in the marrow and a low M-protein level, but there are no other disease symptoms such as bone destruction or kidney damage.
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Monoclonal gammopathy of undetermined significance (MGUS)

Charcteristic

Serum M-protein concentration <3g/dl <10% plasma cell in the BM Absence of lytic bone lesions Anemia Hypercalcemia Renal insufficiency No clinical signs or symptoms related to the monoclonal gammopathy
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Monoclonal gammopathy of undetermined significance (MGUS)

Considered a benign monoclonal gammopathy. Can evolve into a malignancy monoclonal gammopathy

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Diagnostic Criteria for MGUS, MM and WM

MGUS Smoldering MM 10%
and/or

MM

WM

BM plasma cells Circulatin M-protein

<10%
and

10%
and/or

>10%
and

<3g/dL

3g/dL

3g/dL

(<10% lymphoplas macytoid cell) >3g/dL Present

Clinical sign and

Absent

Absent

Present
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Monoclonal gammopathy of undetermined significance (MGUS)

Symptoms

Rarely causes signs or symptoms

nerve problems, such as numbness or tingling, associated with the abnormal protein.

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Monoclonal gammopathy of undetermined significance (MGUS)

Causes

In the majority of people with MGUS, the protein isn't harmful. But when too much M protein accumulates, it crowds out healthy cells in your bone marrow and can damage other tissues in your body

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Monoclonal gammopathy of undetermined significance (MGUS)

Risk factors

Age 25y/o 1% , 70y/o 5% Race More often in blacks than in whites Sex Frequently in men than women Family history Hereditary Weight BMI >30
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Monoclonal gammopathy of undetermined significance (MGUS)

Complication

10 and 25 percent of people with MGUS develop a more serious condition, such as multiple myeloma or other cancers or blood disorders. Other complications include fractures and blood clots.
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Monoclonal gammopathy of undetermined significance (MGUS)

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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Monoclonal gammopathy of undetermined significance (MGUS)

Laboratory test

Hb concentration Creatinine concentration BM aspiration examination Total serum protein concentration and serum electrophoresis 24h urine protein execretion concentration and erine electrophoresis Serum and urine immunofixation Determinarion of serum FLC ratio( & ), for assesment of prognosis

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Monoclonal gammopathy of undetermined significance (MGUS)

Treatments and drugs

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

Prevention

The cause of monoclonal gammopathy of undetermined significance is unknown, so there is no way to prevent monoclonal gammopathy of undetermined significance and no way to stop it from progressing to a more serious condition.
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Light-Chain Disease

Light-Chain Deposition Disease (LCDD)

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Light-Chain Deposition Disease

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 that lead to tissue or organ inflammation (swelling) and damage. Early signs and symptoms of LCDDmay include protein in the urine, 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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Light-Chain Deposition Disease

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

or monoclonal light chain are produced.

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Light-Chain Deposition Disease

Diagnostic evaluation
High resolution protein electrohoresis of serum and

urine (total protein concentration)

24h urine specimen Visual examination q Observation 1.

Typical well defined monoclonal band, g region band caused monoclonal protein by polymerization
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2. Diffuse

of

3. Hypogammaglobulinemia

Heavy-Chain Deposition Disease

Heavy-Chain Diseases (HCDs)

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Heavy-Chain Deposition Disease

Heavy chain diseases (HCDs) are rare B-cell proliferative disorders characterized by the synthesis and secretion of incomplete immunoglobulin heavy chains. These disorders initially were recognized as gammopathies due to the presence of monoclonal proteins in the patient's serum or urine. The disorders were defined in terms of the production of structurally aberrant immunoglobulin molecules.

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Heavy-Chain Deposition Disease

Plasma cell disorders characterized by an anomalous serum and urinary protein that is immunochemically related to the Fc fragment of the immunoglobulin molecule are known as HCDs.

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Heavy-Chain Deposition Disease

The heavy chain diseases are divided according to immunoglobulin type.
alpha chain disease (Seligmann's disease) HCD gamma chain disease (Franklin's disease) HCD mu chain disease HCD

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Heavy-Chain Deposition Disease

Epidemiology

?
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Gammopathies with more than one band

Gammopathies with more than one 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 on

electrophoresis is often associated with an advanced gammopathy

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