Introduction

The non-Hodgkin lymphomas (NHLs) encompass a wide spectrum of disorders with varying clinical and biologic features. The appropriate diagnosis and classification forms the basis of clinical patient management and the choice of treatment protocol. The diagnosis of lymphoma begins by a thorough evaluation of the histologic and cytologic features. However, this is often inadequate for accurate classification as there is often significant overlap between these entities. Immunophenotyping studies, either by flow cytometry or immunohistochemical staining, are often initially done to determine lineage and possibly clonality. Molecular techniques are of increasing practical importance as they provide an additional level of testing. This is particularly useful in cases where the histologic features or the immunophenotypic findings are not conclusive, or the biopsy is small, hampering an accurate assessment. As well, molecular testing can detect specific lymphomas that have distinctive molecular abnormalities. Figure 14.1 describes an algorithm, outlining how ancillary testing can be utilized in the diagnosis of lymphoma.

This chapter attempts to summarize the basic molecular biology, principles of the molecular techniques, common molecular aberrations, and the application of molecular diagnostics as a key ancillary tool in the diagnosis and classification of lymphoma.

IG and TCR gene rearrangements

Human lymphocytes have the ability to specifically recognize millions of different antigens and antigenic epitopes. This is based on the enormous diversity of their antigen-specific receptors, known as immunoglobulin (IG) and T-cell receptor (TCR) molecules. Each single B or T lymphocyte has a distinct IG or TCR and expresses approximately 105 molecules with identical antigen specificity.