Waldenstrom's Macroglobulinaemia Flashcards
Waldenstrom’s Macroglobulinaemia
Waldenstrom's macroglobulinaemia is an uncommon condition seen in older men. It is a lymphoplasmacytoid malignancy characterised by the secretion of a monoclonal IgM paraprotein (WaldenstroM - IgM) Features monoclonal IgM paraproteinaemia systemic upset: weight loss, lethargy hyperviscosity syndrome e.g. visual disturbance hepatosplenomegaly lymphadenopathy cryoglobulinaemia e.g. Raynaud's
Waldenstrom’s Macroglobulinaemia - Diagnosis: Example Question
A 67 year old female presents with 4 month history of increasing lethargy and malaise. She has no past medical history and travels widely, last visiting the Middle East one week prior to this admission, returning with a respiratory tract infection that appears to be resolving. She is a lifelong non-smoker and does not drink alcohol to excess. Over the past two weeks, she reports increasing bilateral persistent headache associated with binocular visual blurring. In addition, she describes a non-specific abdominal discomfort without any changes in bowel habit.
On examination, you note bilateral axillary lymphadenopathy and conjunctival pallor. Cardiovascular and respiratory system examinations were unremarkable. Neurological examination is unremarkable. Fundoscopy reveals dilated tortous retinal veins. Abdominal examination reveals hepatosplenomegaly. Lastly, you note areas of purpura around her left anterior shin and her right upper arm. A chest radiograph is unremarkable.
Her blood results are as follows:
Hb 8.7 g/dl MCV 79 fl Platelets 190 * 109/l WBC 3.4 * 109/l Na+ 142 mmol/l K+ 4.5 mmol/l Urea 7.6 mmol/l Creatinine 89 µmol/l Adj Calcium 2.47 mmol/l Phosphate 1.34 mmol/l LDH 1890 (normal range 140-280 units/L) Serum electrophoresis IgM paraprotein band at 5.4 g/L
A bone marrow biopsy demonstrates 14% infiltration of lymphoplasmacytic cells
What is the diagnosis?
> Waldenstrom's macroglobulinaemia Multiple myeloma Monoclonal gammopathy of unknown significance (MGUS) Chronic lymphocytic leukemia (CLL) Upper respiratory tract infection (URTI)
There is an enormous IgM paraprotein band on serum eletrophoresis, immediately suggesting the differentials to narrow to Waldenstrom’s macroglobulinaemia, multiple myeloma and MGUS.
The patient is symptomatic, has bone marrow involvement of greater than 10% with IgM band greater than 3g/L, ruling out MGUS.
The key to this diagnosis is differentiating between myeloma and Waldenstrom’s: it is particularly rare (but not impossible) for a IgM secreting plasma cell clone in myeloma but this accounts for only 0.5% of all multiple myelomas. Secondly, clinically, the patient demonstrates signs of hyperviscosity syndrome and splenomegaly, both of which are much more common in Waldenstrom’s than myeloma. Thirdly, there is a lack of bone symptoms and renal involvement with normal serum calcium: bone lesions are significantly more common in multiple myeloma. Fourthly, fundoscopic tortuous and dilated veins are classical in hypervisous patient with Waldenstrom’s macroglobulinaemia. The diagnosis is clinched on bone marrow biopsy, demonstrating lymphoplasmacytic cells instead of plasma cells, confirmed by cell immunophenotyping.
CLL should not result in a paraprotein band.
URTI may result in a rise in IgA but should not result in bone marrow involvement.
Waldenstrom’s Macroglobulinaemia vs Multiple Myeloma
WM = IgM!
MM = IgG!
Waldenstrom’s vs Myeloma
- it is particularly rare (but not impossible) for a IgM secreting plasma cell clone in myeloma but this accounts for only 0.5% of all multiple myelomas.
- Secondly signs of hyperviscosity syndrome and splenomegaly are much more common in Waldenstrom’s than myeloma.
- Thirdly, there is a lack of bone symptoms and renal involvement with normal serum calcium in Waldenstroms: bone lesions are significantly more common in multiple myeloma.
- Fourthly, fundoscopic tortuous and dilated veins are classical in hypervisous patient with Waldenstrom’s macroglobulinaemia.
- The diagnosis is clinched on bone marrow biopsy, demonstrating lymphoplasmacytic cells instead of plasma cells, confirmed by cell immunophenotyping.
Hyperviscosity Syndrome
‘Over the past two weeks, she reports increasing bilateral persistent headache associated with binocular visual blurring. In addition, she describes a non-specific abdominal discomfort without any changes in bowel habit.
Fundoscopy reveals dilated tortous retinal veins. Abdominal examination reveals hepatosplenomegaly. Lastly, you note areas of purpura around her left anterior shin and her right upper arm’
Example of Hyperviscosity Syndrome Presentation
