%0 Journal Article
%T The Role of Molecular Pathology in the Diagnosis of Cutaneous Lymphomas
%A Philipp W. Raess
%A Adam Bagg
%J Pathology Research International
%D 2012
%I Hindawi Publishing Corporation
%R 10.1155/2012/913523
%X Primary cutaneous lymphomas can be difficult to be distinguished from reactive mimics, even when integrating histologic, immunophenotypic, and clinical findings. Molecular studies, especially PCR-based antigen receptor gene rearrangement (ARGR) analysis, are frequently useful ancillary studies in the evaluation of cutaneous lymphoproliferations. The biologic basis of ARGR studies is discussed, as well as a comparison of various current protocols. The pitfalls and limitations of ARGR analysis are also highlighted. Recent advances in the understanding of the molecular pathogenesis of various cutaneous lymphomas are discussed. Some of these nascent discoveries may lead to the development of diagnostically useful molecular assays. 1. Introduction Cutaneous lymphoproliferations remain a challenging area to both dermatopathologists and hematopathologists despite concerted research efforts and recent diagnostic advances. The molecular pathogenesis of systemic lymphomas has been rigorously studied for some time, whereas cutaneous lymphomas were initially not given the same focus. However, over the last 5¨C10 years, cutaneous lymphomas have been the subject of intensive investigation at the genetic level [1]. Together with the standardization of diagnostic approaches and clinical classification, molecular analysis is likely to assume an increasing role in the evaluation of cutaneous lymphomas and their mimics. Indeed, molecular testing is already incorporated into recommendations for diagnosis and staging of cutaneous T-cell lymphoma (CTCL) [1¨C3]. The purpose of this paper is twofold: (1) to discuss the role and limitations of antigen receptor gene rearrangement studies and (2) to summarize recent developments in our understanding of the molecular pathogenesis of cutaneous lymphomas. 2. Antigen Receptor Gene Rearrangements 2.1. Generation of Immunological Diversity An understanding of the diagnostic utility of evaluating immunoglobulin and T-cell receptor gene (collectively referred to hereafter as antigen receptor genes (ARGs)) rearrangements is predicated upon an understanding of their normal biology. ARG structure and the processes through which they are rearranged are responsible for the ability of the adaptive immune system to identify a vast array of antigens. ARGs are composed of multiple variable (V), diversity (D), and joining (J) regions, followed by a constant (C) region. Several antigen receptor genes (IGK@, IGL@, TRG@, and TRD@) do not contain D regions. In the IGH@ gene, for example, the process of recombination begins with the alteration of
%U http://www.hindawi.com/journals/pri/2012/913523/