Lymphoplasmacytic Lymphoma and Hypogammaglobulinemia
Lymphoplasmacytic lymphoma (LPL) is characteristically associated with hypergammaglobulinemia (elevated IgM), not hypogammaglobulinemia. The defining feature of LPL, particularly when presenting as Waldenström macroglobulinemia (WM), is the presence of a monoclonal IgM protein, which represents an overproduction rather than deficiency of immunoglobulins 1.
Typical Immunoglobulin Pattern in LPL/WM
LPL/WM is defined by the presence of monoclonal IgM protein in the serum, which is detected through serum protein electrophoresis and confirmed by immunofixation or nephelometry 1.
The diagnosis of WM specifically requires demonstration of IgM monoclonal protein along with bone marrow infiltration by lymphoplasmacytic cells 1.
Approximately 95% of LPL cases secrete IgM paraprotein, with rare variants (<5%) secreting IgG, IgA, or being non-secretory 1.
When Hypogammaglobulinemia May Occur
While hypergammaglobulinemia is the hallmark, there are specific clinical scenarios where immunoglobulin deficiency can develop:
Quantitative immunoglobulin testing is recommended in patients with recurrent infections to uncover underlying hypogammaglobulinemia, which can occur as a secondary phenomenon in lymphoproliferative disorders 2.
In rare non-IgM secreting LPL variants, patients may present without a detectable monoclonal protein (non-secretory subtype), though this represents absence of paraprotein rather than true hypogammaglobulinemia 1, 3.
Hypogammaglobulinemia can develop as a treatment-related complication or late in disease course due to immune dysfunction, but this is not a characteristic presenting feature 2.
Clinical Implications
The presence of hypogammaglobulinemia in a patient with suspected lymphoproliferative disorder should prompt consideration of alternative diagnoses such as chronic lymphocytic leukemia (CLL), which more commonly presents with immunoglobulin deficiency 2.
If a patient presents with lymphoplasmacytic infiltration on bone marrow but without IgM monoclonal protein, the diagnosis is LPL but not WM by definition 1.
Serum protein electrophoresis with quantitative immunoglobulins should be performed at diagnosis to establish the baseline immunoglobulin pattern and monitor for changes during disease course 1, 4.