Multiple clonal Ig/TCR products: implications for interpretation of clonality findings

Clonality assessment via analysis of immunoglobulin (Ig) and T cell receptor (TCR) gene rearrangements has become an important and valuable adjunct in the diagnostic process of suspect lymphoproliferations. One of the major issues in correct interpretation of clonality testing results appears to be the occurrence of multiple clonal PCR products. The presence of two different PCR products could reflect biclonality but can often more easily be attributed to the occurrence of biallelic rearrangements in a single clone. Furthermore, due to the specific configuration of the IGK and TCRB loci, multiple rearrangements can occur on one allele, resulting in the possibility that up to four PCR products could be compatible with a single clone. Finally, >2 clonal Ig/TCR products (>4 for IGK and TCRB) could reflect biclonality, oligoclonality, or even pseudoclonality. It is not always easy to distinguish between those options, but the use of duplicates will be helpful to determine reproducibility and relevance of the detected clonal PCR products. In conclusion, straightforward interpretation of clonality testing results can be hampered by the occurrence of multiple clonal products. Only careful consideration of immunobiological and technical explanations will prevent incorrect interpretation in such cases.

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