Differentials

Multiple myeloma (MM)

SIGNS / SYMPTOMS
INVESTIGATIONS
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 WM.

Flow cytometry and immunohistochemistry reveals tumor 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.

Low-grade B-cell lymphomas (e.g., follicular lymphoma)

SIGNS / SYMPTOMS
INVESTIGATIONS
SIGNS / SYMPTOMS

No specific signs or symptoms differentiate low-grade B-cell lymphomas from WM.

INVESTIGATIONS

Lymph node excisional biopsy reveals morphologic 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 tumor cell surface markers specific for low-grade B-cell lymphoma (e.g., CD5-, CD10+).

Chronic lymphocytic leukemia (CLL)

SIGNS / SYMPTOMS
INVESTIGATIONS
SIGNS / SYMPTOMS

No specific signs or symptoms differentiate this condition from WM.

INVESTIGATIONS

Serum protein electrophoresis with immunofixation may or may not reveal IgM monoclonal protein.

Flow cytometry and immunohistochemistry reveals tumor cell surface markers specific for CLL (e.g., CD5+, CD20 dim, CD23+).

Marginal zone lymphoma (MZL)

SIGNS / SYMPTOMS
INVESTIGATIONS
SIGNS / SYMPTOMS

No specific signs or symptoms differentiate this condition from WM.

INVESTIGATIONS

Serum protein electrophoresis with immunofixation may or may not reveal IgM monoclonal protein.

Flow cytometry and immunohistochemistry reveals tumor cell surface markers specific for MZL (e.g., CD5-, CD10-).

Monoclonal gammopathy of undetermined significance (MGUS)

SIGNS / SYMPTOMS
INVESTIGATIONS
SIGNS / SYMPTOMS

Absence of symptoms. MGUS is an asymptomatic condition.

INVESTIGATIONS

Blood test shows normal CBC.

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
INVESTIGATIONS
SIGNS / SYMPTOMS

No symptoms and signs related to lymphoma, such as lymphadenopathy and splenomegaly.

INVESTIGATIONS

Imaging shows no radiologic evidence of lymphoma such as lymphadenopathy or splenomegaly.

Blood testing shows evidence of hemolysis. In addition, direct antiglobulin test (DAT) is positive for anti-C3d; cold agglutinin titer is 1:64 or larger.

Bone marrow biopsy: no evidence of lymphoma.[51]

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