Pseudo-spikes are common in histologically benign lymphoid tissues

T cell receptor gene rearrangement is a classic marker of T cell clonality and is a useful adjunct in the diagnosis of T cell lymphomas and leukemias. Rearranged V-J gene segments amplified by polymerase chain reaction (PCR) are traditionally analyzed by polyacrylamide gel electrophoresis, We and ot hers have analyzed TCR-gamma PCR products using capillary gel electrophores is, which produces single nucleotide resolution and provides improved diagn ostic sensitivity over conventional methods. However, with this marked incr ease in resolution and sensitivity, it is necessary to re-define normal var iation of TCR-gamma gene rearrangement in control tissues to allow appropri ate interpretation of monoclonality if present. Using DNA capillary gel ele ctrophoresis, we examined the spectrum of normal patterns for TCR-gamma in a variety of T-cell-rich, histologically benign tissue types, including spl een, lymph node, tonsil, and blood, and compared this with the patterns in T cell lymphoma samples. We defined relative peak heights as h(1)/h(2), whe re h(1) represents the peak height of the largest peak above the normally d istributed population, and h(2) represents the peak height of the normally distributed curve. We found spikes in almost 20% of histologically benign s amples with relative peak heights that were more than 0.5 and up to 1.5, We designated these as pseudo-spikes, because they may be mistaken for monocl onal spikes. In contrast, the relative peak height of the T cell lymphoma s amples that showed clonal rearrangement was much higher than that of the ps eudo-spikes, being at least 2 in 11/11 and at least 3 in 10/11 cases. Our d ata suggest that peaks with relative height of at least 3 represent a true clonal population in diagnostic samples. Peaks with relative heights of les s than 1.5 may be insignificant, while peaks with relative heights between 1.5 to 3 may warrant further evaluation. Although capillary gel electrophor esis is superior in assessing T cell clonality, caution must be exercised w hen interpreting results, because pseudo-spikes appear to be common in beni gn tissues with lymphoid populations and are not necessarily indicative of clonal malignant T cell-population.