Molecular methods to distinguish reactive and neoplastic lymphocyte expansions and their importance in transitional neoplastic states

: Although lymphoma and leukemia usually can be diagnosed by routine cytology and histology, some cases present a diagnostic challenge for pathologists and clinicians. Often the dilemma lies in determining whether a population of lymphocytes is reactive or neoplastic. We review currently available methods for analyzing lymphocyte populations by immunophenotyping and by identifying clonally rearranged immunoglobulin and T‐cell receptor genes and discuss how these tests can be used to clarify such diagnostic dilemmas. We also describe the detection of chromosomal abnormalities and methods on the horizon, such as gene expression profiling, to identify diagnostically useful oncogenes. Finally, we review the emerging concept of transitional neoplastic states, in which reactive lymphocytes transform to neoplastic lymphocytes in the presence of continued antigenic stimulation, such as that caused by infection with Helicobacter pylori. The existence of transitional neoplastic states underscores the need for an array of molecular diagnostic tools that would improve our ability to characterize lymphocyte populations in human and animal patients and enhance early detection of neoplastic lymphocytes such that eradication of the infectious or inflammatory stimulus could lead to cure. (Vet Clin Pathol 2004;33:196–207)