History and exam
Key diagnostic factors
common
age >70 years
More common in those aged >70 years.[7][10]
In one US study using Surveillance Epidemiology and End Results (SEER) data (1980-2016), the annual Waldenström's macroglobulinaemia incidence rate increased with age, from 0.06 per 100,000 in those aged under 50 years to 3.2 per 100,000 in those aged 80 years and over.[6]
In the US, median age at diagnosis is 73 years.[7]
male sex
white ancestry
Other diagnostic factors
common
history of IgM monoclonal gammopathy of undetermined significance (MGUS)
MGUS is a risk factor for Waldenström's macroglobulinaemia (WM).
In one study of 1384 patients with MGUS, the relative risk of progression to WM was increased by a factor of 46 compared with the general population.[14]
family history of B-cell lymphoproliferative disease
Family history of a first-degree relative with B-cell lymphoproliferative disease is associated with Waldenström's macroglobulinaemia (WM).
In one study of 257 WM patients, 48 (18.7%) had a family history of at least one first-degree relative with a B-cell lymphoproliferative disease (including 13 [5.1%] with WM; 9 [3.5%] non-Hodgkin's lymphoma; 8 [3.1%] multiple myeloma; 7 [2.7%] chronic lymphocytic leukaemia; 5 [1.9%] MGUS; 3 [1.2%] acute lymphoblastic leukaemia; and 3 [1.2%] Hodgkin's lymphoma).[12]
family history of WM (or related monoclonal gammopathies)
fatigue, weakness, shortness of breath
Due to anaemia resulting from bone marrow infiltration, or less commonly cold haemolytic anaemia (cold agglutinin disease) caused by autoimmune activity of monoclonal IgM to red blood cells at cooler temperatures.[4][31][47]
Fatigue is the most common presenting symptom in Waldenström's macroglobulinaemia.[4]
anorexia
Anorexia is the second most common presenting symptom in Waldenström's macroglobulinaemia, after fatigue.[47]
infections
Infections, particularly recurrent sinus and bronchial infections, are common due to a weakened immune system.[30]
uncommon
B symptoms (weight loss, fevers, night sweats)
Raynaud's syndrome
May occur due to cryoglobulinaemia caused by circulating IgM undergoing precipitation at cooler temperatures. Cryoglobulins may be detected in 20% of Waldenström's macroglobulinaemia patients, but less than 5% of patients present with symptoms.[33]
May also be associated with cold haemolytic anaemia (cold agglutinin disease) caused by autoantibody activity of IgM to red blood cells at cooler temperatures.[33]
splenomegaly
May be present in 15% of Waldenström's macroglobulinaemia (WM) patients.[4]
Rarely palpable.
Presence of splenomegaly (along with absence of lytic bone lesions) can differentiate WM from multiple myeloma.
lymphadenopathy
May be present in 15% of Waldenström's macroglobulinaemia (WM) patients.[4]
Usually low volume (i.e., not bulky).
Presence of lymphadenopathy (along with absence of lytic bone lesions) can differentiate WM from multiple myeloma.
hepatomegaly
Reported in 20% of Waldenström's macroglobulinaemia patients.[4]
Clinically significant hepatomegaly is rare.
skin and/or mucosal bleeding (purpura, epistaxis)
Purpura is present in approximately 9% of patients.[47] Mucosal bleeding (including epistaxis) is present in approximately 7% of patients.[47]
Bleeding is a sign of hyperviscosity. Observed in a minority of patients at diagnosis, and usually appears when serum IgM level is ≥3 g/dL.[35]
Interaction of IgM with coagulation factors can disturb clotting and bleeding times (e.g., resulting in acquired von Willebrand disease). IgM may also coat platelets, thereby impairing their function. This can give rise to bleeding from mucous membranes.[33]
Purpura may occur due to cryoglobulinaemia.
Cryoglobulins may be detected in 20% of Waldenström's macroglobulinaemia patients, but less than 5% of patients present with symptoms.[33]
ophthalmological symptoms
Includes blurring or loss of vision, and retinal changes caused by hyperviscosity such as dot and blot haemorrhages, tortuous blood vessels, venous 'sausaging', and/or optic disc oedema.[36][37]
Observed in a minority of patients at diagnosis, and usually appears when serum IgM level is ≥3 g/dL.[35]
headache
Potential symptom of hyperviscosity.
Observed in a minority of patients at diagnosis, and usually appears when serum IgM level is ≥3 g/dL.[35]
dizziness and/or vertigo
Potential symptom of hyperviscosity.
Observed in a minority of patients at diagnosis, and usually appears when serum IgM level is ≥3 g/dL.[35]
tinnitus
thrombosis
Potential sign of hyperviscosity and may manifest as stroke, angina, myocardial infarction, pulmonary embolism, or deep vein thrombosis.
Observed in a minority of patients at diagnosis, and usually appears when serum IgM level is ≥3 g/dL.[35]
Risk factors
strong
IgM monoclonal gammopathy of undetermined significance (MGUS)
In one study of 1384 patients with MGUS, the relative risk of progression to Waldenström's macroglobulinaemia was increased by a factor of 46 compared with the general population.[14]
family history of B-cell lymphoproliferative disease
In one study of 257 Waldenström's macroglobulinaemia (WM) patients, 48 (18.7%) had a family history of at least one first-degree relative with a B-cell lymphoproliferative disease (including 13 [5.1%] with WM; 9 [3.5%] non-Hodgkin's lymphoma; 8 [3.1%] multiple myeloma; 7 [2.7%] chronic lymphocytic leukaemia; 5 [1.9%] MGUS; 3 [1.2%] acute lymphoblastic leukaemia; and 3 [1.2%] Hodgkin's lymphoma).[12]
Additional findings in these patients included younger age at diagnosis and more extensive bone marrow infiltration by WM.[12]
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