Waldenström macroglobulinemia is a rare B-cell malignancy representing less than 2% of all hematologic malignancies, with an annual incidence of approximately 3-5 cases per million. The disease is characterized by lymphoplasmacytic lymphoma infiltrating bone marrow and lymphoid organs with concurrent IgM monoclonal protein secretion. Many patients are diagnosed asymptomatically through incidental laboratory findings, requiring careful evaluation to distinguish from other B-cell disorders and determine appropriate management strategies.

A 54-year-old female was referred to hematology following discovery of a monoclonal spike on routine serum protein electrophoresis during routine health screening. The patient denied symptoms suggestive of hyperviscosity syndrome including headache, visual disturbances, epistaxis, or neurological complaints. She reported no B-symptoms (fever, night sweats, weight loss) and had no history of recurrent infections or bleeding tendencies.

Physical examination was unremarkable without palpable lymphadenopathy, hepatomegaly, or splenomegaly. The patient appeared well with stable vital signs and no evidence of hyperviscosity syndrome.

Laboratory evaluation revealed significant findings on protein studies. Serum protein electrophoresis showed increased gamma fraction (26.3%; normal: 10.7-20.3%) with relatively decreased albumin (47.9%; normal: 52-65%) and albumin/globulin ratio of 0.92. A sharp M-spike was evident in the gamma region. Immunofixation electrophoresis confirmed IgM-kappa monoclonal protein.

Quantitative immunoglobulins demonstrated markedly elevated IgM at 27.98 g/L with normal IgG (7.6 g/L) and IgA (2.4 g/L). Beta-2 microglobulin was normal (1.91 mg/L), indicating low tumor burden. Urine free light chain analysis showed normal kappa (3.78 mg/L) and lambda (0.73 mg/L) levels with elevated kappa/lambda ratio (5.18), consistent with kappa-predominant monoclonality.

Bone marrow examination revealed 40% cellularity with approximately 25% infiltration by small B-lymphocytes with plasmacytic differentiation organized in 4-5 intertrabecular lymphoid aggregates. Reticulin fibrosis was absent (grade 0/4), and amyloid staining was negative.

Immunohistochemistry demonstrated CD20+, CD38+, CD138+ cells with negative CD5, CD23, cyclin D1, LEF-1, and CD56, excluding chronic lymphocytic leukemia/small lymphocytic lymphoma and mantle cell lymphoma. Flow cytometry confirmed CD19+/CD20+/CD45+ clonal B-cell population with CD138+ plasmacytic subset showing intracytoplasmic kappa restriction and negative CD56, consistent with lymphoplasmacytic lymphoma rather than multiple myeloma.

Based on the constellation of findings including IgM-kappa monoclonal protein, characteristic bone marrow morphology and immunophenotype, the diagnosis of lymphoplasmacytic lymphoma/Waldenström macroglobulinemia was established.

This case illustrates typical presentation of asymptomatic WM discovered through routine screening. The markedly elevated IgM level (27.98 g/L) without hyperviscosity symptoms demonstrates the variable clinical presentation of WM patients. The characteristic immunophenotype (CD20+/CD38+/CD138+/CD5-/CD23-/CD56-) with intracytoplasmic kappa restriction distinguishes WM from other B-cell disorders.

Current management guidelines recommend "watch and wait" approach for asymptomatic WM patients without end-organ damage or symptomatic disease. However, given the markedly elevated IgM level, careful monitoring for hyperviscosity syndrome development is essential.

Molecular testing for MYD88 L265P mutation (present in >90% of WM cases) would provide diagnostic confirmation and prognostic information regarding treatment response, particularly to BTK inhibitors.

Asymptomatic Waldenström macroglobulinemia requires comprehensive diagnostic evaluation to confirm diagnosis and assess disease burden. Despite markedly elevated IgM levels, many patients can be safely observed with regular monitoring, emphasizing the importance of individualized management approaches in this rare but well-characterized lymphoproliferative disorder.