Monotypic versus monoclonal: Conceptual distinction in B-cell lymphoproliferative disorders

The pattern of immunoglobulin light chain (IgL) expression has traditionally been important in the diagnosis of B-cell lymphoproliferative disorders (B-LPDs).Identification of selective expression of a single IgL type, also referred to as IgL restriction, in the proliferating fraction confirms its B-cell nature and indicates monoclonality in many instances.However, it should be noted that IgL restriction, which is characterized as monotypic, is not always monoclonal, although the terms 'monotypic' and 'monoclonal', and also 'polytypic' and 'polyclonal', have been synonymously used by some hematologists and hematopathologists for many years.In this note, the difference of the terms is explained by giving several examples and importance of the correct use of the corresponding terms is stressed.Examination for B-cell proliferation based on the pattern of IgL expression is routinely performed by flow cytometry (FCM), immunohistochemistry, or mRNA in situ hybridization, but their results are binary (either monotypic or polytypic).Accordingly, these examinations cannot detect clonal populations in one or both polytypic fractions and more than one clone in a monotypic fraction.Oligoclonality is one of the major conditions which is involved in the dissociation between the two proliferative processes, i.e., monotypic and monoclonal.The condition is unusual in immunocompetent individuals, but is frequently encountered in immunocompromised patients, irrespective of genetically determined or iatrogenic in nature, and we have experimentally reproduced it in a human-mouse chimera model. 1 Furthermore, there are at least two other examples regarding the above dissociation.Firstly, only Ig-positive plasma cells proliferate in human herpes virus 6-positive multicentric Castleman disease, but they are polyclonal. 2This condition is hence characterized as monotypic but polyclonal.The second example is the presence of two different light chains, either two (rarely two ) chains 3 or and chains, 4 in a single B cell.This condition has been studied mostly in the field of autoimmunity and can be explained by some mechanisms, especially by receptor editing. 3 In human B-LPDs, monoclonal proliferation with polytypic IgL expression was initially reported in patients with chronic lymphocytic leukemia, 4,5 but is recently reported in a patient with mantle-cell lymphoma as well. 6t is, therefore, stressed that IgL restriction itself should be characterized as monotypic, but never as monoclonal, in order not to overlook oligoclonal B-cell proliferation.Similarly, polytypic staining of IgL should not be characterized as polyclonal because possibilities of such a process to be oligoclonal or monoclonal exist.