Select Topic:
Browse by Series:

Waldenstrom Macroglobulinemia: Diagnostic Criteria

Insights From: Meletios A. Dimopoulos, MD, the National and Kapodistrian University of Athens School of Medicine; Steven P. Treon, MD, PhD, Dana-Farber Cancer Institute
Published: Friday, Mar 22, 2019



Transcript: 

Meletios A. Dimopoulos, MD:
The hallmark of Waldenström macroglobulinemia is the presence of a monoclonal IgM protein in the serum, along with a lymphoplasmacytic infiltration in the bone marrow of the patient. So we need both of these findings to make the diagnosis of Waldenström. Thus, whenever we suspect this condition, we need to perform a serum protein electrophoresis, a quantitation of serum immunoglobulins by nephelometry, and an immunofixation in order to classify the type of monoclonal protein. Furthermore, we need to check the urines for the presence of protein because sometimes there may be, although rarely, involvement of the kidney. Finally, free light chains in the serum have been helpful in some patients. And of course, the diagnosis of the disease will require a bone marrow biopsy and aspiration, along with flow cytometry. In the bone marrow biopsy we will see small lymphocytes, plasma cells, lymphoplasmacytic cells, and the flow cytometry will typically show a pattern of CD5-positive cells, CD20-positive cells, CD23-positive cells, and in a minority of the patients, CD5  and CD10 positivity.

Steven P. Treon, MD, PhD: In terms of the work-up of a patient with Waldenström, you’d want, of course, to get a CBC [complete blood count] so you understand what type of cytopenias you’re facing. If you have a patient who is anemic—in most cases, patients will be anemic—it’s important to understand what the mechanism of the underlying anemia is. Is it because of crowding of the bone marrow? Is it because the patient has some type of hemolytic process? You’d want to check for cold agglutinins in that particular case.

But also, we’re seeing that hepcidin production also contributes to anemia in many of these patients, so you want to get iron indices. You want to get a total iron level as well as a TIBC [total iron-binding capacity] and look at the iron saturation level.

Of course you’re going to want to know what the patient’s IgM level is. And you should also check the IgG and IgA levels because they tend to be lower in patients with Waldenström. You’d want to get a serum protein electrophoresis. You can see if the patient has an IgM monoclonal protein. That’s important to be able to establish the diagnosis of Waldenström. You’d want to get CT [computed tomography] scans to look at the presence of adenopathy. And essentially, you want to get a bone marrow biopsy. That will help you understand whether or not this is Waldenström, and it will also give you a sense of what the genomic status of this patient is.

The MYD88 mutation is very important. It helps us discern the patients who have Waldenström from those who don’t. There are a lot of other disease entities that overlap with Waldenström. The MYD88 mutation is seen in about 95% of patients with Waldenström. So it helps you right off the bat to be able to separate out the Waldenström diagnosis from other IgM-secreting entities. And of course, if you can get the CXCR4 mutation status, that’s important because, as we mentioned earlier, it can help you understand the disease presentation as well as help you in your therapeutic decision making.

Meletios A. Dimopoulos, MD: In Waldenström macroglobulinemia, oftentimes the disease is spreading outside the bone marrow. So it is advised to perform CT scans of the chest, abdomen, and pelvis in order to detect enlarged lymph nodes, hepatomegaly, or splenomegaly. Also, the physical exam is necessary in order to see if there are any palpable lymph nodes or a palpable spleen or liver. So this should be part of the initial work-up of a patient with this disease.


Transcript Edited for Clarity
 
Slider Left
Slider Right


Transcript: 

Meletios A. Dimopoulos, MD:
The hallmark of Waldenström macroglobulinemia is the presence of a monoclonal IgM protein in the serum, along with a lymphoplasmacytic infiltration in the bone marrow of the patient. So we need both of these findings to make the diagnosis of Waldenström. Thus, whenever we suspect this condition, we need to perform a serum protein electrophoresis, a quantitation of serum immunoglobulins by nephelometry, and an immunofixation in order to classify the type of monoclonal protein. Furthermore, we need to check the urines for the presence of protein because sometimes there may be, although rarely, involvement of the kidney. Finally, free light chains in the serum have been helpful in some patients. And of course, the diagnosis of the disease will require a bone marrow biopsy and aspiration, along with flow cytometry. In the bone marrow biopsy we will see small lymphocytes, plasma cells, lymphoplasmacytic cells, and the flow cytometry will typically show a pattern of CD5-positive cells, CD20-positive cells, CD23-positive cells, and in a minority of the patients, CD5  and CD10 positivity.

Steven P. Treon, MD, PhD: In terms of the work-up of a patient with Waldenström, you’d want, of course, to get a CBC [complete blood count] so you understand what type of cytopenias you’re facing. If you have a patient who is anemic—in most cases, patients will be anemic—it’s important to understand what the mechanism of the underlying anemia is. Is it because of crowding of the bone marrow? Is it because the patient has some type of hemolytic process? You’d want to check for cold agglutinins in that particular case.

But also, we’re seeing that hepcidin production also contributes to anemia in many of these patients, so you want to get iron indices. You want to get a total iron level as well as a TIBC [total iron-binding capacity] and look at the iron saturation level.

Of course you’re going to want to know what the patient’s IgM level is. And you should also check the IgG and IgA levels because they tend to be lower in patients with Waldenström. You’d want to get a serum protein electrophoresis. You can see if the patient has an IgM monoclonal protein. That’s important to be able to establish the diagnosis of Waldenström. You’d want to get CT [computed tomography] scans to look at the presence of adenopathy. And essentially, you want to get a bone marrow biopsy. That will help you understand whether or not this is Waldenström, and it will also give you a sense of what the genomic status of this patient is.

The MYD88 mutation is very important. It helps us discern the patients who have Waldenström from those who don’t. There are a lot of other disease entities that overlap with Waldenström. The MYD88 mutation is seen in about 95% of patients with Waldenström. So it helps you right off the bat to be able to separate out the Waldenström diagnosis from other IgM-secreting entities. And of course, if you can get the CXCR4 mutation status, that’s important because, as we mentioned earlier, it can help you understand the disease presentation as well as help you in your therapeutic decision making.

Meletios A. Dimopoulos, MD: In Waldenström macroglobulinemia, oftentimes the disease is spreading outside the bone marrow. So it is advised to perform CT scans of the chest, abdomen, and pelvis in order to detect enlarged lymph nodes, hepatomegaly, or splenomegaly. Also, the physical exam is necessary in order to see if there are any palpable lymph nodes or a palpable spleen or liver. So this should be part of the initial work-up of a patient with this disease.


Transcript Edited for Clarity
 
View Conference Coverage
Online CME Activities
TitleExpiration DateCME Credits
Medical Crossfire®: How Can We Optimize Outcomes in Head and Neck Cancers with Immunotherapeutic Strategies?Oct 31, 20191.5
The Patient and Provider Connection™: Effective Communication to Optimize the Diagnosis and Management of Irritable Bowel Syndrome and Chronic Idiopathic ConstipationOct 31, 20191.0
Publication Bottom Border
Border Publication
x