Molecular genetic approaches for the diagnosis of clonality in lymphoid neoplasms

Rearrangements of immunoglobulin (Ig) and T cell receptor (TCR) genes provide a highly sensitive molecular marker for the detection of clonality in lymphoid lesions and allow the pathologist to (1) distinguish polyclonal from monoclonal lymphoid proliferations, (2) provide corroborative evidence for lineage when used in conjunction with immunophenotypic techniques, (3) differentiate clonal lymphoid lesions from poorly differentiated nonlymphoid neoplasms, and (4) assess residual disease at the molecular level. The use of these probes in conjunction with morphology and immunohistochemistry or flow cytometry allows the pathologist to assign virtually all lymphoid neoplasms to the B or T cell lineage. The cloning of Ig and TCR genes also has led to the identification of new protooncogenes that reside at the breakpoints of chromosomal translocations frequently observed in lymphoid neoplasms. Molecular probes for these new genes involved in the pathogenesis of lymphoid neoplasms may be used as additional molecular markers for the determination of clonality, lineage, and even histologic subtype of lymphoid neoplasms. Finally, the development of new molecular technologies such as polymerase chain reaction and pulsed-field gel electrophoresis has provided new tools for the highly sensitive detection of genetic rearrangements in human tumors and will greatly enhance the ability of the pathologist to monitor minimal residual disease and detect early relapse.