TCR gene rearrangement tests are helpful for lineage determination but are not always definitive due to "lineage infidelity," rearrangement of the TCR gene in non-T cells. In difficult cases of ambiguous lineage, both B- and T-cell clonality studies should be performed to ensure comprehensive assessment. TCRG rearrangements may occur in up to 55% of precursor B-ALL, although they are absent in most mature B-cell malignancies. Approximately 10% of patients with acute myelogenous leukemia (AML) demonstrate positivity in TCRG rearrangement studies. In these settings, the detection of a gene rearrangement should be viewed as evidence of clonality rather than of lineage, and correlation with immunophenotyping data is used to assign lineage. Overall, more than 90% of T lymphoblastic lymphoma/leukemia cases have TCR gene rearrangements, with nearly 20% also having IGH gene rearrangements.
TCR gene rearrangement studies are typically performed to distinguish polyclonal from monoclonal lym-phoproliferations, but the detection of a monoclonal TCR gene rearrangement in isolation is not always indicative of malignancy. There are several scenarios in which TCR gene rearrangements may be detected in nonneoplastic conditions. The most common examples of this phenomenon are in autoimmune disorders, infectious diseases, and cutaneous lesions.22 Lymphomatoid papulosis is a CD30-positive cutaneous lymphoproliferative disorder that may progress to cutaneous anaplastic large cell lymphoma. A subset of cases of lymphomatoid papulosis has TCR gene rearrangements, but this finding is not predictive of progression to lymphoma. Therefore, in this setting, TCR gene rearrangement studies are of little value. Autoimmune disorders and some infectious diseases, including EBV infection, are associated with oligoclonal B- and T-cell proliferations. Such oligoclonal processes may result in selective amplification of one of the clones, mimicking a clonal gene rearrangement. In a similar fashion, small numbers of T cells, particularly in small skin biopsy specimens, may result in monoclonal or oligoclonal amplification patterns by PCR. Duplicate testing of these sample types will frequently reveal different-sized gene rearrangements, indicating "pseudoclonality."
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