Is this patient's presentation more consistent with Waldenström's Macroglobulinemia (WM) or multiple myeloma, given the monoclonal B-cell immunophenotype and elevated Immunoglobulin M (IgM) level?

Waldenström's Macroglobulinemia (WM)

This patient's presentation is consistent with Waldenström's Macroglobulinemia, not multiple myeloma, based on the monoclonal B-cell immunophenotype (CD19+, CD20+, surface kappa+), positive MYD88 mutation, and markedly elevated IgM of 5100 mg/dL. 1

Diagnostic Reasoning

Key Features Supporting WM Diagnosis

• Monoclonal IgM elevation (5100 mg/dL) is the hallmark of WM and distinguishes it from multiple myeloma, which typically presents with IgG or IgA paraproteins 1, 2

• MYD88 L265P mutation positivity is detected in more than 90% of WM patients and serves as a critical diagnostic tool to differentiate WM from multiple myeloma, where this mutation is rare 1, 3, 2

• B-cell immunophenotype (CD19+, CD20+, CD45+, CD200+, surface kappa+) with approximately 4.8% abnormal monoclonal B-cells is characteristic of lymphoplasmacytic lymphoma, the underlying pathology of WM 1

• Absence of plasma cells (0.00%) on flow cytometry argues strongly against multiple myeloma, which requires clonal plasma cell proliferation 1

Critical Distinguishing Features from Multiple Myeloma

• Lytic bone lesions are characteristically absent in WM and serve as a major differentiating feature from multiple myeloma 4

• WM requires bone marrow infiltration with lymphoplasmacytic cells (small lymphocytes and plasmacytoid lymphocytes), not sheets of plasma cells as seen in myeloma 1, 2

• The immunophenotype shows mature B-cell markers (CD19+, CD20+) rather than the plasma cell markers (CD38++, CD138+) that define myeloma 1

Diagnostic Confirmation Required

• Bone marrow biopsy and aspirate must demonstrate ≥10% clonal lymphoplasmacytic cells to confirm WM diagnosis, as peripheral blood findings alone are insufficient 1, 2

• Immunohistochemistry or flow cytometry of bone marrow should confirm CD19, CD20, CD22, and CD79a expression on the clonal population 1

• Serum protein electrophoresis with immunofixation should quantify the IgM monoclonal protein by nephelometry, with sequential measurements performed in the same laboratory 1

Additional Workup Considerations

• Assess for hyperviscosity syndrome given the markedly elevated IgM (5100 mg/dL), including fundoscopic examination for retinal vein "sausaging," as patients may become symptomatic at serum viscosity levels over 4.0 centipoise 1, 5

• Test for cold agglutinins and cryoglobulins at diagnosis, as their presence can affect IgM level determination and occur in up to 10% and 20% of WM patients respectively 1

• Obtain CT chest/abdomen/pelvis to assess for lymphadenopathy, splenomegaly, and extramedullary disease, which are common in WM 1

• Check complete blood count, β2-microglobulin, albumin, and LDH for prognostic stratification using the International Prognostic Scoring System for WM (IPSSWM) 1, 2

Common Pitfalls to Avoid

• Do not diagnose WM based solely on IgM paraprotein and MYD88 positivity without bone marrow confirmation of lymphoplasmacytic infiltration, as IgM MGUS can also have MYD88 mutations 1, 2

• Absence of MYD88 mutation should not exclude WM diagnosis if other criteria are met, as approximately 10% of WM patients are MYD88 wild-type 1, 3

• The peripheral blood lymphocytosis (24.49%) represents circulating clonal B-cells, which is common in WM but requires bone marrow confirmation for diagnosis 2