Overview of the role of molecular methods in the diagnosis of malignant lymphomas

OBJECTIVE: To review the role of molecular genetics in the diagnosis of malignant lymphomas. DATA SOURCES AND STUDY SELECTION: Primary research studies and reviews published in the English literature that focus on molecular genetics and malignant lymphoma, in particular, clonality, chromosomal translocations, tumor suppressor genes, and Hodgkin disease. DATA EXTRACTION AND SYNTHESIS: Molecular genetics has an important role in the assessment of malignant lymphomas. Clonality, detected by Southern blot analysis or the polymerase chain reaction, is helpful for establishing the diagnosis of lymphoma in lesions with ambiguous morphologic and immunophenotypic findings. Southern blot analysis is the "gold standard" for clonality assessment, but the process is labor-intensive and time-consuming. Polymerase chain reaction analysis is more convenient, but a potentially significant false-negative rate exists in the analysis of some antigen receptor genes as a result of using consensus primers and the process of somatic hypermutation. Chromosomal translocations, which result in oncogene activation, occur in many types of B- and T-cell lymphomas, and their detection is helpful in classification as well as in establishing a diagnosis of malignancy. Gene rearrangements and chromosomal translocations also can be used to monitor minimal residual disease. Tumor suppressor genes, although their analysis is relatively less useful for diagnosis, are involved in both pathogenesis and tumor progression and will be more important diagnostically as this field continues to expand. Molecular genetic analysis has played a major role in improving our understanding of Hodgkin disease. CONCLUSIONS: Molecular genetic tests are currently important ancillary tools for the diagnosis and classification of malignant lymphomas, and their role is likely to increase in the future.