Lymphoplasmacytic lymphoma/waldenstrom macroglobulinemia: an evolving concept

Area of Science:

• Hematology
• Oncology
• Pathology

Background:

• Waldenstrom macroglobulinemia (WM) is now classified as lymphoplasmacytic lymphoma/Waldenstrom macroglobulinemia (LPL/WM).
• Distinguishing LPL/WM from other B-cell lymphomas, particularly marginal zone B-cell lymphomas, presents diagnostic challenges in clinical practice.
• Traditional diagnostic methods, such as arbitrary serum IgM levels, are no longer considered reliable.

Purpose of the Study:

• To review the evolving diagnostic criteria for LPL/WM.
• To highlight the difficulties in differentiating LPL/WM from other B-cell lymphomas.
• To discuss the limitations of current immunophenotypic and molecular markers in LPL/WM diagnosis.

Main Methods:

• Review of World Health Organization (WHO) classification and consensus meeting findings on WM.
• Analysis of characteristic immunophenotypic markers (CD5, CD10, CD23) and their variations in LPL/WM.
• Evaluation of molecular genetic hallmarks, including translocations and chromosomal aberrations like 6q21-q23 deletion.
• Assessment of Ig variable gene mutation and isotype switching in the neoplastic clone.

Main Results:

• The characteristic immunophenotype (CD5(-)CD10(-)CD23-) is not consistently observed in LPL/WM, with CD23 detected in up to 40% of cases.
• A distinct molecular genetic hallmark for LPL/WM is lacking, complicating differential diagnosis.
• Translocations like t(9;14) are rare in LPL/WM, despite WHO classification statements.
• Deletion of 6q21-q23 is the most common chromosomal aberration, found in 40-70% of patients but is nonspecific.
• Neoplastic clones in LPL/WM typically show Ig variable gene mutation without isotype switching, retaining plasmacytic differentiation potential.

Conclusions:

• The diagnosis of LPL/WM requires integration of clinical, pathological findings, and exclusion of alternative diagnoses.
• Current diagnostic criteria, including immunophenotype and molecular markers, can be insufficient for definitive distinction between LPL/WM and other B-cell lymphomas.
• Distinguishing LPL/WM from marginal zone B-cell lymphomas may be arbitrary based on existing criteria.