Persistent Anemia Revealing Underlying B-cell Malignancies: A Report of Two Cases Highlighting a Diagnostic Gap in Primary Care

Persistent anemia in older adults is commonly attributed to nutritional deficiency, chronic disease, or age-related change, particularly when routine laboratory investigations are unrevealing. However, plasma cell and lymphoplasmacytic disorders may present subtly, with anemia as the only consistent abnormality. We report two cases in which extended laboratory evaluation led to early identification of clinically significant B-cell malignancies. The first case involved a man in his early 70s with stable, asymptomatic normocytic anemia despite normal iron studies, vitamin B12 and folate levels, renal function, thyroid studies, and liver enzymes. Serum protein electrophoresis revealed a monoclonal immunoglobulin G kappa paraprotein with an abnormal serum free light-chain ratio. Bone marrow biopsy confirmed clonal plasma cell infiltration consistent with smoldering multiple myeloma, and imaging demonstrated no myeloma-defining bone disease. The patient remains under active surveillance. The second case involved a man in his late 70s with a several-year history of progressive macrocytic anemia and repeatedly normal first-line investigations. Extended testing revealed a marked immunoglobulin M lambda monoclonal gammopathy, and bone marrow biopsy confirmed Waldenström macroglobulinemia. He required treatment due to severe anemia and responded to bendamustine-rituximab therapy. These cases highlight the diagnostic value of serum protein electrophoresis, quantitative immunoglobulins, and serum free light-chain testing in patients with persistent unexplained anemia. Early use of extended investigations can facilitate timely diagnosis before end-organ damage occurs and details the critical role of primary care clinicians in recognizing patterns that warrant escalation beyond routine anemia algorithms.