Ulla Randen
Oslo University Hospital, Norway
Title: Primary cold agglutinin disease (CAD) associated lymphoproliferative disease: a new entity
Biography
Biography: Ulla Randen
Abstract
Primary chronic cold agglutinin disease (CAD) is a rare hemolytic disease (1:1.000.000) mediated by monoclonal IGHV4-34-encoded cold agglutinins with a predominant specificity for the blood group antigen I. These patients have previously been given a variety of diagnoses on bone marrow biopsies, from ‘no signs of lymphoid infiltration’ to an overt lymphoma, most often lymphoplasmacytic lymphoma (Mb. Waldenström). However, studies including flow cytometry have shown that >90% of them, if not all, have a monoclonal B-cell proliferation. We have therefore performed studies on a larger group of CAD patients and examined bone marrow aspirates and biopsies to better type the underlying lymphoproliferative disorder. Bone marrow biopsies typically showed small infiltrates (median infiltration: 10% of marrow cells) with a mature B- cell immunophenotype. Morphologically, the infiltration did not fit with lymphoplasmacytic lymphoma, as neither mast cells or plasmacytoid cells were present, nor did the small B cells express plasma cell differentiation-associated markers. A limited number of mature monoclonal IgM+ plasma cells were present outside the lymphoid nodules and were diffusely scattered throughout the marrow and regarded as part of the lymphoproliferative disease, as these produce the monoclonal anti-I antibodies. Of interest, the MYD88 L265P mutation, typical of lymphoplasmacytic lymphoma, was not detected. We conclude that cold agglutinin-associated lymphoproliferative disease displays homogeneous histological and immunophenotypic features that distinguishes this entity from lymphoplasmacytic lymphoma, and thereby distinguishes chronic cold agglutinin disease from Mb. Waldenström.