Bone Marrow Pathology in Cold Agglutinin-Mediated Autoimmune Hemolytic Anemia: A Study of 56 Cases

Cold agglutinin disease (CAD) is a rare form of autoimmune hemolytic anemia (AIHA). CAD occurs in the context of a small clonal B-cell lymphoproliferation restricted to blood and/or bone marrow (BM), without overt or extramedullary lymphoma. The WHO-HAEM5 introduced a description of the CAD-associated lymphoproliferative disorder (CAD-LPD) in the BM as a desirable criterium for CAD. Still, data on BM pathology underlying CAD remain scarce. We assessed the clinical and pathologic characteristics of a large patient cohort with cold-type AIHA. A total of 85 BM biopsies of 56 patients were evaluated. In 10 patients (18%), pathology revision revealed other overt B-cell malignancies leading to a diagnosis of cold agglutinin syndrome. In the remaining 46, evidence for B-cell clonality was found in the vast majority (45; 98%), manifesting as a paraproteinemia and/or clonal B-cells or plasma cells in BM. Most of these 45 had an M-protein (89%), evidence of monoclonal B-cells and/or plasma cells in BM tissue (89%), and were MYD88 wild-type (100%). Surprisingly, while ancillary methods detected clonality in the majority (84%), only 5 (11%) of 45 CAD cases strictly fulfilled the WHO-HAEM5 morphological description for CAD-LPD. These data imply that sensitive techniques should be used in BM evaluation in CAD.