The Histopathology of Cold Agglutinin Disease–Associated B-Cell Lymphoproliferative Disease

Abstract Objectives Primary cold agglutinin disease is a type of autoimmune hemolytic anemia caused by circulating antibodies against I antigen, a carbohydrate expressed on most cells, including red blood cells. The underlying disease has been characterized in recent years as a distinct B-cell lymphoproliferative disease of the bone marrow, occurring mostly in the elderly. The disease has been now been included as a separate entity in the most recent classifications of mature B-cell neoplasms. Methods A review of the characteristics of cold agglutinin disease is provided, with an emphasis on the pathology features. Results A detailed description of the histopathology, immunophenotype, and genetics of cold agglutinin disease is provided and compared to other B-cell lymphoproliferative diseases in the bone marrow with similar features. Conclusions Recognition of the pathology features of cold agglutinin disease allows to distinguish it from other diseases, especially lymphoplasmacytic lymphoma and marginal zone lymphoma.