Proving Bone Marrow Plasma Cell Clonality by Flow Cytometry: An Important Tool in the Diagnosis of Immunoglobulin Light-Chain Amyloidosis.

Background/Objectives: Light-chain amyloidosis (AL Amyloidosis) is a rare systemic plasma cell disorder in which misfolded light chains form amyloid fibrils that damage vital organs. Diagnosis is often delayed because of variable presentation and overlap with other plasma cell diseases. Methods: We retrospectively analyzed 23 patients diagnosed between 2022 and 2025 at the Fundeni Clinical Institute. All cases underwent free light-chain testing, serum immunofixation, immunohistochemistry, and bone marrow analysis. Since 2022, next-generation flow cytometry (NGF) has been applied to detect clonal plasma cells and characterize their immunophenotype. Results: NGF confirmed clonality in 21 of 23 patients (91.3%), including two cases undetected by conventional assays. Serum immunofixation was positive in 69.6% and immunohistochemistry in 78.3%. Among clonal cases, λ restriction predominated (71.4%). Detection was highest when NGF was combined with standard methods, especially in patients with dFLC < 100, where negative immunofixation was more frequent (p = 0.027). Conclusions: Multiparameter flow cytometry (MFC) provides highly sensitive detection of small clonal plasma cell populations often missed by standard assays, offering a valuable tool for early and accurate diagnosis of low-burden plasma cells in AL amyloidosis. Integrating MFC into routine evaluation improves diagnostic accuracy, identifies overlooked clonal populations, and supports earlier, more informed clinical decisions.