Beyond Negative Electrophoresis and Immunofixation: A Three-Case Series of Non-secretory Multiple Myeloma

Non-secretory multiple myeloma is an uncommon plasma cell neoplasm in which serum and urine electrophoresis and immunofixation fail to identify a measurable monoclonal component. This phenotype may delay diagnosis and make conventional biochemical monitoring difficult. We report three cases of clinically non-secretory multiple myeloma presenting with anemia and multifocal skeletal involvement despite negative monoclonal protein studies. Case 1 was a 33-year-old man with progressive fatigue, normocytic anemia, normal renal function and calcium levels, negative serum and urine monoclonal studies, and a normal serum free light chain ratio. Bone marrow aspiration showed 19% plasma cells, whereas bone marrow biopsy demonstrated extensive CD138-positive plasma cell infiltration; 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) revealed multifocal medullary lesions. Case 2 was a 63-year-old woman with low back pain and anemia, negative serum and urine immunofixation, and a normal serum free light chain ratio. Bone marrow aspiration showed 94% plasma cells, and 18F-FDG PET/CT demonstrated hypermetabolic skeletal lesions. She achieved partial remission after eight cycles of bortezomib, lenalidomide, and dexamethasone. Case 3 was a 68-year-old woman with fatigue, diffuse bone pain, anemia, negative serum and urine immunofixation, a normal serum free light chain ratio, 18% marrow plasma cells, and extensive PET/CT-positive skeletal disease. These cases emphasize that negative electrophoresis and immunofixation should not exclude multiple myeloma when the clinical, marrow, and imaging findings are suggestive. Bone marrow evaluation and whole-body imaging are central to diagnosis and follow-up in this rare entity.