Multiple Myeloma (MM) And Detection Methods Part I and II

What is a tumor

An abnormal mass of tissue caused by cancer, inflammation, or infection

What are neoplasms

Tumors caused by uncontrolled cellular growth. They may form a mass or may not (Multiple Myeloma in the blood)

What is cancer

It refers to malignant neoplasms that invade surrounding tissues aggressively

What is multiple myeloma

A neoplasm of proliferating plasma cells that secrete Ig uncontrollably

How are plasma cells best distinguished from other populations

By their membrane expression of syndecan-1 which is CD138 a marker unique to plasma cells

What is CD138 and discuss the clinical utility of CD138 of syndecan-1

It is a surface marker expressed on mature plasma cells, playing a critical role in cell adhesion and antibody secretion. Clinically, CD138 is used to ID and quantify plasma cells in conditions like MM

What are the plasma cells dyscrasias or disorders of plasma cells

1. Monoclonal gammopathy of undetermined significance

2. Multiple Myeloma

3. Immunoglobulin Light Chain (AL) amyloidosis

4. Waldenstrom macroglobulinemia

What characterizes plasma cell dyscrasias

Overproduction of Ig, leading to hypergammaglobulinemia

What is hypergammaglobulinemia

The overproduction of Ig by plasma cells

What are the two types of hypergammaglobulinemia

Monoclonal and Polyclonal

Which hypergammaglobulinemia is this

Monoclonal

Which hypergammaglobulinemia is this

Polyclonal

What is elevated in monoclonal gammopathy

A single class of Ig

What types of cells are involved in monoclonal gammopathy

A single clone of B cells or plasma cells

What characterizes monoclonal gammopathy

The presence of an excessive amount of paraprotein or M protein

What does a discrete band in monoclonal gammopathy indicate

Excessive single monoclonal gamma globulin in the blood

What is elevated in polyclonal gammopathy

More than one class of Ig

What types of cells are involved in polyclonal gammopathy

Several clones of B cells or plasma cells

What characterizes polyclonal gammopathy

A broad diffuse band with no sharp or discrete band W

What are some causes of polyclonal gammopathy

1. Chronic infection

2. Hepatic cirrhosis

3. Decreased clearance of endotoxins/antigens

What is an example of an autoimmune disorder associated with polyclonal gammopathy

Rheumatoid

Is polyclonal gammopathy a primary or secondary disease

Secondary

What kind of band is this and what is it associated with

Discrete band. monoclonal gammopathy

What kind of band is this and what is it associated with

Broad diffused band, polyclonal gammopathy

What is the benign form of hypergammaglobulinemia

MGUS

What does a small spike in the gamma zone indicate

MGUS

What is the severe form of hypergammaglobulinemia

MM

What does a large spike in the gamma zone indicate

MM

What type of Ig is involved in Waldenstroms Macrogloublinemia

IgM

What does Waldenstrom’s Macroglobulinemia involve

Lymphoplasmacytic lymphoma (a mix of lymphocytes and plasma cells)

What is heavy chain disorder

Synthesis and secretion of incomplete Ig heavy chains

What is light chain disease

Synthesis and secretion of incomplete immunoglobulin light chains.

What is amyloidosis

Deposit of abnormal protein in multiple organs

What is AL amyloidosis caused by

Overproduction and misfolding of Ig light chains

What is AA amyloidosis caused by

Overproduction of amyloid A (acute phase proteins) in the liver during chronic inflammation (joint arthritis)

Is MGUS a premalignant condition

Yes a premalignant form and a precursor to myeloma

Does MGUS show the triad of MM

No

What is the level of M-protein in serum in MGUS

Less than 3g/dL

What is the percentage of marrow plasma cells in MGUS

Less than 10%

Are bone lesions present or end stage damage present in MGUS

No

Are Bence Jones Proteins present in MGUS

No

What is an important consideration for MGUS management

Long term follow-up is required, but no treatment is given

What % of asymptomatic MM cases does smoldering myeloma account for

About 15%

What is smoldering myeloma

It is an indolent (slow progressing) myeloma that exists in a concealed state

What is it important to follow cases of MGUS

To monitor if it develops into multiple myeloma

How long should cases of monoclonal protein be followed?

Follow up is required for years in some cases

How is smoldering myeloma initially diagnosed

It is initially diagnosed as MGUS

What is the percentage of marrow plasma cells in Smoldering myeloma

Greater than or equal to 10%

What is another name for MM

Plasma cell myeloma

What is multiple myeloma also known as, named after a doctor

Kahler’s disease, named after Austrian doctor Otto Kahler

What type of gammopathy is MM

Monoclonal gammopathy

What is the cause of MM

The exact cause is unknown

What are the suggested causes or risk factors for MM

1. Radiation

2. Viral Causes

3. Environmental stimulants

4. Genetic factors

What is the level of M-protein in serum in Smoldering Myeloma

Greater than or equal to 3g/dL

Are bone lesions present or end stage damage present in Smoldering myeloma

No

What is the percentage of marrow plasma cells in MM

Up to 90%

Are bone lesions present or end stage damage present in MM

Yes, there is a presence of end organ damage

What is the level of M-protein in serum in MM

M protein in serum and urine

What is the most common form of dysproteinemia

MM

What does dysproteinemia refer to

Excessive synthesis of Ig molecules or subunits

How common is MM

It accounts for 5-10 per 100,000 people

How does MM prevalence vary by ethnicity and sex

It is 2 times common in African Americans than whites and 1.6 times more common in males than females

What % of all malignancies does MM represent

1%

What % of hematological malignancies does MM account for

It accounts for 10% of hematological malignancies

What is the tumor burden in MM

Marrow plasma cells are 10%, and the tumor burden can increase up to 90%

What type of bone lesions are seen in MM

1. Ribs

2. Vertebrae

3. Skull

4. Long bones

What symptoms commonly accompanies bones lesions in MM

Bone pain and pathological fractures

What blood abnormality is present in MM related anemia

Normochromic, normocytic anemia

What causes fatigue in MM patients

Anemia and elevated ESR due to infection or inflammation

What protein damages kidney in MM

Free light chains, also known as Bence Jones Protein

What is a common cause of death in MM patients

Kidney failure due to free light chain deposition

What is another major cause of death in MM patients

Overwhelming infection or sepsis

What electrolyte balance is associated with MM

Hypercalcemia

What % of MM cases involve IgM

12%

Which Ig type is most common in MM

IgG, 52%

What % of cases involve IgA

22%

Are IgE and heavy chains common in MM

No they are rare

What % of MM cases involve light chains

11%

What type of disorder is Waldenstrom’s Macroglobulinemia

A low grade B cell lymphoplasmacytic disorder involving both lymphocytes and plasma cells

What type of lymphoma is WM classified as

Indolent lymphoma

What organ enlargements are associated with WM

Lymphadenopathy and Splenomegaly

What causes anemia in WM

Lymphoplasmacytic marrow infiltration disrupting erythropoiesis and increasing B cell proliferation

What are two common complications associated with WM

Hyper viscosity and Cryoglobulinemia

What type of anemia is seen in WM

Cold agglutinin hemolytic anemia

What is the main Ig implicated in WM

IgM

What bleeding disorder is associated with WM

Thrombocytopenic purpura (low platelet count)

What neurological condition is linked with WM

Peripheral neuropathy, present in 10% of patients with M-proteins

What patient population is WM more common in

Diabetes patients

What happens in cryoglobulinemia

Serum proteins precipitate at lower than normal body temperatures

What are the main tissue complications of cryoglobulinemia

Vasculitis and ischemic injury to peripheral tissue, which can lead to ischemic gangrene

What is “cold related gelling”

It refers to the blocking of blood vessels due to protein precipitation in cryoglobulinemia

What is Type I cryoglobulinemia

It involves monoclonal proteins, often IgM

What is type II cryoglobulinemia

It involves a mix of polyclonal and monoclonal Ig

What is type III cryoglobulinemia

It involves polyclonal Ig without monoclonal components

What is important when handling cryoglobulinemia lab specimens

The specimens must be transported, clotted, and centrifuged at temperatures near body temperature

A condition where abnormal misfolded protein produced in the bone marrow are deposited in tissues, leading to organ failure

Amyloidosis

What is the protein type involved in AL

Monoclonal light chain Ig, also known as monoclonal LC Ig deposition disease

What are the consequences of amyloid proteins deposition in tissue

1. Nephrosis

2. Cardiomyopathy

3. Pulmonary failure

4. Malabsorption

What are common physical signs of amyloidosis

1. Macroglossia (enlarged tongue)

2. Skin purpura

3. Vessel fragility

4. Carpal tunnel syndrome

What neurological symptoms may occur with amyloidosis

Peripheral neuropathy and autonomic insufficiency