Differentials
Multiple myeloma (MM)
SIGNS / SYMPTOMS
Bone pain related to lytic bone lesions is frequent in MM though hyperviscosity syndrome is uncommon.
Splenomegaly and hepatomegaly are not a feature in MM.
INVESTIGATIONS
Serum protein electrophoresis with immunofixation typically reveals IgG or IgA monoclonal protein. IgM MM is very rare.
Bone marrow biopsy reveals an infiltrate of clonal plasma cells that are morphologically different to lymphoplasmacytic cells of Waldenström's macroglobulinaemia (WM).
Flow cytometry and immunohistochemistry reveals tumour cell surface markers specific for MM (e.g., CD5-, CD10-, CD20-, CD138+, sIg-).
CT scan frequently reveals lytic bone lesions, which are usually absent in WM.
MYD88 L265P mutation is usually absent in MM.
Low-grade B-cell lymphomas (e.g., follicular lymphoma)
SIGNS / SYMPTOMS
No specific signs or symptoms differentiate low-grade B-cell lymphomas from Waldenström's macroglobulinaemia (WM).
INVESTIGATIONS
Lymph node excisional biopsy reveals morphological appearance suggestive of follicular lymphoma (i.e., follicles, small lymphocytes: centrocytes and centroblasts).
Bone marrow biopsy reveals infiltrate of small lymphocytes that are morphologically different to lymphoplasmacytic cells of WM.
Flow cytometry and immunohistochemistry reveals tumour cell surface markers specific for low-grade B-cell lymphoma (e.g., CD10+, BCL2+, CD23+/-, CD43-, CD5-, CD20+, and BCL6+ for follicular lymphoma).
Chronic lymphocytic leukaemia (CLL)
SIGNS / SYMPTOMS
No specific signs or symptoms differentiate this condition from Waldenström's macroglobulinaemia.
INVESTIGATIONS
Serum protein electrophoresis with immunofixation may or may not reveal IgM monoclonal protein.
Flow cytometry and immunohistochemistry reveals tumour cell surface markers specific for CLL (e.g., CD5+, CD20 dim, CD23+).
Marginal zone lymphoma (MZL)
SIGNS / SYMPTOMS
No specific signs or symptoms differentiate this condition from Waldenström's macroglobulinaemia.
INVESTIGATIONS
Serum protein electrophoresis with immunofixation may or may not reveal IgM monoclonal protein.
Flow cytometry and immunohistochemistry reveals tumour cell surface markers specific for MZL (e.g., CD5-, CD10-).
Monoclonal gammopathy of undetermined significance (MGUS)
SIGNS / SYMPTOMS
Absence of symptoms. MGUS is an asymptomatic condition.
INVESTIGATIONS
Blood test shows normal FBC.
Serum protein electrophoresis with immunofixation reveals monoclonal protein <30 g/L.
Bone marrow biopsy reveals infiltrate of clonal plasma cells <10%.
Primary cold agglutinin disease
SIGNS / SYMPTOMS
No symptoms and signs related to lymphoma, such as lymphadenopathy and splenomegaly.
INVESTIGATIONS
Blood test shows evidence of haemolysis. Direct antiglobulin test (DAT) is positive for anti-C3d; cold agglutinin titre is 1:64 or larger.
Imaging shows no radiological evidence of lymphoma such as lymphadenopathy or splenomegaly.
Bone marrow biopsy reveals no evidence of lymphoma.[54]
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