Lymphoplasmacytic lymphoma/Waldenstrom macroglobulinemia: An evolving concept

The concept of Waldenstrom macroglobulinemia has evolved from the original description of a clinical syndrome to its more recent designation as a distinct clinicopathologic entity, that is, lymphoplasmacytic lymphoma/Waldenstrom macroglobulinemia (LPL/WM), in the World Health Organization (WHO) classification and by the participants of consensus meetings on WM. The diagnosis of LPL/WM, however, remains a challenge in daily practice. Distinguishing LPL/WM from other B-cell lymphomas, especially marginal zone B-cell lymphomas, which share overlapping morphologic features, is difficult. The traditional practice of separating LPL/WM from other lymphomas by an arbitrary level of serum IgM is no longer considered valid. The characteristic immunophenotype described for LPL/WM by the WHO classification, that is, CD5^-CD10^-CD23^-, is observed in 60-80% of neoplasms, but variations from this pattern of antigen expression are common, with CD23 being detected in up to 40% of cases. Lack of a distinct molecular genetic hallmark complicates the distinction of LPL/WM from other B-cell lymphomas. Although the t(9;14) is stated to be present in 50% of cases in the WHO classification, translocations involving the Ig heavy chain including the t(9;14) are actually rare in LPL/WM. Deletion of 6q21-q23, a nonspecific finding, is the most common aberration reported in 40-70% of patients. At the molecular level, the neoplastic clone in most cases has undergone Ig variable gene mutation, but not isotype switching, and the clone retains the capability of plasmacytic differentiation. Currently, the diagnosis of LPL/WM can only be established by incorporating clinical and pathologic findings and excluding alternative diagnoses. In some cases, in our opinion, distinguishing LPL/WM from marginal zone B-cell lymphomas seems arbitrary using currently recommended criteria.