Waldenstrom macroglobulinemia

Definitions & Key takeaways

Waldenstrom Macroglobulinemia, or Waldenstrom syndrome, is a rare type of malignant lymphoma that's characterized by the overproduction of an antibody called immunoglobulin M, or IgM, in the blood, which can lead to hyperviscosity syndrome and a collection of symptoms including bleeding, visual changes, headaches, and weakness.

Diagnosis is typically made through serum electrophoresis and immunofixation, which can identify elevated levels of immunoglobulin M. Treatment is mainly done through the removal of these large immunoglobulin M proteins via plasmapheresis, but chemotherapeutic agents may also be used. Stem cell transplantation may also be considered in certain cases.

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Introduction0:00–0:16

Waldenstrom Macroglobulinemia, or Waldenstrom syndrome, is a rare type of malignant lymphoma. It is characterized by the overproduction of an antibody called immunoglobulin M, or IgM, in the blood.

Physiology0:16–0:55

Like all antibodies, IgM is produced by a subpopulation of white blood cells called B lymphocytes, or B-cells for short.
B-cells start off as stem cells within the bone marrow, where they undergo a series of developmental phases. When they’re mature enough, they leave the bone bone marrow and enter the blood, and from there, they go into secondary lymph organs such as the spleen and lymph nodes.
Within the secondary lymph organs,these B-cells can then further differentiate into plasma cells which ultimately give rise to the immunoglobulins.
Thus, Waldenstrom’s macroglobulinemia is more specifically referred to as a lymphoplasmacytic lymphoma. Now, IgM is actually composed of 5 separate antibodies bound together, thus creating a pentamer, which is a very large, or MACRO-globulin.

Pathology0:55–1:53

These macroglobulins increase the thickness of blood and aggregate with one another causing a condition known as hyperviscosity syndrome.
Hyperviscosity causes blood vessels to become engorged, causes hypercoagulability, and reduces the overall rate of blood flow.
Like with many cancers, the exact cause of this overproduction is not well understood but it is hypothesized to be due to mutations in the MYD88 and CXCR4 genes.
When mutated, these genes allow lymphoplasmacytic cells to avoid programmed cell death, so they end up proliferating excessively.
The overproduction of lymphoplasmacytic cells in the bone marrow can also crowd out and interfere with the production of normal red blood cells and platelets.

Symptoms1:53–2:33

Although commonly asymptomatic, the symptoms that do occur are mainly attributed to hyperviscosity syndrome, which leads to mucosal bleeding from the nose and gums.
In the eyes, distension of retinal veins causes retinopathy or blurring and loss of vision. The sluggishness of blood flow also leads to neurological symptoms such as peripheral neuropathy, headache, fatigue, and general weakness.
Lastly, the immunoglobulins tend to accumulate in the lymph nodes, spleen and liver, making these organs enlarge, and causing lymphadenopathy, splenomegaly, and hepatomegaly, respectively.

Diagnosis2:33–3:05

Diagnosis of Waldenstrom's macroglobulinemia is done via serum protein electrophoresis which looks for increased globulin concentration in the blood, known as an M spike, and immunofixation, which is when antibodies against specific globulins are used, may be done to detect increased IgM levels specifically.
Bone marrow biopsies are also done, as well as CT scans of the chest and abdomen to look for enlarged lymph nodes, liver, and spleen.
Complete blood counts usually show low red blood cell and platelet counts as well. Asymptomatic individuals don’t require treatment, but should be monitored closely.

Treatment3:05–3:32

Those who experience symptoms are usually treated with plasmapheresis, where a machine filters out the large immunoglobulins from the person's plasma, and then the filtered, less viscous plasma is returned back into the body.
Chemotherapeutic agents such as rituximab, chlorambucil, and fludarabine may also help treat Waldenstrom’s Macroglobulinemia.
All right, as a quick recap… Waldenstrom Macroglobulinemia is a malignant lymphoma caused by the overproduction IgM antibodies.

Review3:32–4:12

IgM is a very large molecule, so this mainly causes a collection of symptoms known as hyperviscosity syndrome, which includes bleeding, visual changes, headaches, and weakness.
Diagnosis is done through serum electrophoresis which detects M-spikes of immunoglobulin proteins and immunofixation which specifically identifies elevated levels of immunoglobulin M.
Treatment is mainly done through the removal of these large immunoglobulin M proteins via plasmapheresis, but chemotherapeutic agents may also be used.