Waldenström's macroglobulinemia differential diagnosis

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Sara Mohsin, M.D.[2]Grammar Reviewer: Natalie Harpenau, B.S.[3]

Overview

Waldenstrom's macroglobulinemia must be differentiated from multiple myeloma, chronic lymphocytic leukemia/small lymphocytic lymphoma, b-cell prolymphocytic leukemia, follicular lymphoma, mantle cell lymphoma, and marginal zone lymphoma.

Differentiating Lymphoplasmacytic lymphoma from other Diseases

Waldenstrom's macroglobulinemia must be differentiated from following other B cell lymphoid neoplasms:

Disease Etiology (Genetic or other) Clinical manifestations Paraclinical findings Associated findings
Lab findings
Symptoms Signs Immunochemistry Histopathology
Constitutional symptoms Rash Abdominal pain Diarrhea Mass Other
Waldenström's macroglobulinemia
[1][2][3][4][5]
+ Expresses pan B-cell antigens:

Variable expression of:

Majority express:

Fewer express:

Lack expression of:

B cell chronic lymphocytic leukemia/small lymphocytic lymphoma
[6]

33% of patients present with:

Always expresses:

Usually expresses:

Dim expression of:

Follicular lymphoma
[7][8][9][10][11]
20% of patients present with: + + ± Expresses:

Expresses Surface:

Mantle cell lymphoma
[12][13][14][15][16]
Abdominal distention + Positive for:

Co-express surface:

Negative for:

_
Marginal zone lymphoma Extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue (MALT) type
[17][18][19][20][21][22][23][24][25][26]
± + + Symptoms depend on the location of the tumor and may include: B-cell associated antigens that co-express:

Negative for:

Splenic marginal zone lymphoma
[27][28][29][30][31][32][33]
+ +
Nodal marginal zone B-cell lymphoma
[34][35]
+ _
Multiple Myeloma[36][37][38][39][40][41] Expresses: Relevant history includes:
B-cell prolymphocytic leukemia[42][43][44][45][46][47] Expresses:

Doesn't express:

GC-associated lymphoid clones infiltrating the BM osteoblastic niche exhibit mesenchymal features in common with SLO germinal centers.(A–D) Histological examination of B-cell non-Hodgkin lymphoma (B-NHL) patient specimens. (A) The frequency of para-trabecular/osteoblastic localization of lymphoid malignant clones in 197 cases of B-NHL with bone marrow (BM) infiltration. Lymphoid clones of germinal center (GC)-derivation exhibiting preferential tropism for the BM osteoblastic niche include: follicular lymphoma (FL), T-cell rich histiocyte rich diffuse large B-cell lymphoma (TCRBCL), and diffuse large B-cell lymphoma of GC type (DLBCL-GC). Non-GC-related lymphoid clones include: DLBCL- activated B-cell type (ABC); mantle-cell lymmphoma, (MCL); marginal-zone lymphoma, (MZL); lymphoplasmacytic lymphoma, (LPL). (B) Para-trabecular (left panel) and inter-trabecular (right panel) localization of two representative cases of FL with BM infiltration. The distribution of the lymphomatous infiltrates around bone trabeculae or in the inter-trabecular lacunae is highlighted by CD20 immunostaining (inserts). (C–D) FL lymphoid infiltrates localizing within the osteoblastic niche area (left panels) and inter-trabecular BM (right panels) display a stromal architecture reminiscent of that of secondary lymphoid organ (SLO) GCs and are characterized by the expression of BM-MSC markers SPARC (C) and CD146 (right D).Source: Sangaletti S. et al, Molecular Immunology Unit; Department of Experimental Oncology and Molecular Medicine; Fondazione IRCCS Istituto Nazionale Tumori; Milan, Italy.
Expression of CD19 and CD20 in B-cell lineage.Notes: Illustrative representation of B-cell differentiation, maturation, antigen expression and B-cell neoplasm associated with different stages of B-cell development. Cell lines used in the research study.47–51Abbreviations: GC, germinal center; ALL, acute lymphoblastic leukemia; MCL, Mantle cell lymphoma; FL, follicular lymphoma; BL, Burkitt lymphoma; DLBCL, Diffuse Large B-Cell Lymphoma; MZL, Marginal Zone Lymphoma; CLL/SLL, Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma; MALT, Mucosa-Associated lymphoid tissue; WM, Waldenstrom macroglobulinemia; MM, plasma cell myeloma; WSU-BL, Wayne State University-Burkitt lymphoma cell line; WSU-FSCCL, Wayne State University-follicular small cleaved cell lymphoma Cell line; WSU-NHL, Wayne State University-FL grade 3 Cell line; WSU-DLCL and WSU-DLCL2, Wayne State University-Diffuse large B-Cell lymphoma cell line; WSU-WM, Wayne State University-Waldenstrom macroglobulinemia Cell line.Source: Raufi A. et al, Lymphoma Research Laboratory, Wayne State University School of Medicine (WSU-SOM), Gordon Scott Hall for Basic Medical Sciences, Detroit, MI, USA.

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