Waldenstrom macroglobulinemia

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Waldenstrom macroglobulinemia


Coagulation disorders


Vitamin K deficiency

Leukemoid reaction

Leukemoid reaction


Waldenstrom macroglobulinemia


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Waldenstrom macroglobulinemia

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USMLE® Step 1 style questions USMLE

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A 62 year-old man presents to his outpatient provider’s office because of two months of persistent headaches, blurry vision, and numbness in the hands bilaterally. The headache is unresponsive to over the counter pain-killers. He also reports 10 lbs (4.5 kg) weight loss over the same period. Past medical history is notable for hypertension. Family history is significant for multiple sclerosis in his mother. His temperature is 37.1°C (98.8°F), pulse is 75/min and blood pressure is 148/97 mmHg. Cardiopulmonary examination is noncontributory. Abdominal examination reveals hepatosplenomegaly. On peripheral smear, red blood cells are seen to clump together when placed in a 5°C (41°F) refrigerator. Which of the following best explains the pathophysiology of the patient’s condition? 


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.

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.

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.

Although commonly asymptomatic, the symptoms that do occur are mainly attributed to hyperviscosity syndrome, which leads to mucosal bleeding from the nose and gums.


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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