||T-Cell Clonality TCR gamma gene (TCRG) rearrangements occur early in T-cell ontogeny and are unique to each T-cell. TCR- beta (TCRB) rearrangements occur later in ontogeny and also serve as a marker for clonality. The Stanford Molecular Genetic Pathology Laboratory has 2 algorithms integrating TCRG and TCRB testing depending on the pre-test probability of disease – see Figure and explanation below (Zhang et al, J Molec Diag, in press 2010). This test is useful for determining whether a clonal population of T-cells is present in a specimen (blood, tissue, fluid or paraffin block). The T-cell clonality assay by PCR establishes whether a clonal population of T-cells is present in a diagnostic specimen. Clonality studies should be interpreted in light of available clinical and pathologic information. It is important to note that identification of a clonal cell population is not by itself diagnostic of malignancy. This test is useful for diagnosis and monitoring of T-cell malignancies.
The laboratory offers two algorithms for T-cell clonality testing. The TCR-LR algorithm is designed for cases in which the clinician’s pre-test estimate of the probability of lymphoma is low-to-moderate (approx. 0.15 – 0.5). Following this algorithm, if the initial TCRG test is negative the TCRB testing is not performed and the result is interpreted as no clonal support for Mycosis fungicides (MF) (algorithm above). If the TCRG test is positive in a low-to-moderate risk patient, the TCRB testing is performed. If both the TCRG and TCRB testing are positive in the low-to-moderate risk patient, the result is interpreted as clonal support for lymphoma. If the TCRG is positive but the TCRB is negative in a low-to-moderate risk patient, the result is interpreted as non-diagnostic and repeat testing is recommended.
The second algorithm (TCR-HR) is designed for cases in which the clinician’s pre-test estimate of lymphoma is moderate-to-high (approx. 0.5 – 0.75). Following the TCR-HR algorithm, if the initial TCRG testing is positive, the TCRB testing is not performed and the result is interpreted as clonal support for MF. If the initial TCRG testing is negative in a moderate-to-high risk patient, TCRB testing is performed. If the TCRB test is positive in a moderate-to-high risk patient, it is interpreted as clonal support for MF. If both the TCRG and TCRB tests are negative in a moderate-to-high risk patient, the result is interpreted as no clonal support for lymphoma. These two diagnostic algorithms are designed to utilize clinical information to improve the overall accuracy of clonality testing. In choosing the TCR testing algorithm for a patient of moderate risk of lymphoma, clinicians should consider that the TCR-LR algorithm will result in higher specificity (with some loss of sensitivity), while the TCR-HR test will result in higher sensitivity with some loss of specificity.