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B-cell and T-cell Clonality Assays by PCRTest code(s) 90362, 90363, 90509, 91445, 91446, 91634, 91635
Question 1. What testing does Quest Diagnostics offer for T-cell and B-cell gene rearrangement studies?
Quest Diagnostics offers 7 test codes for lymphoid clonality studies.
For T-cell lymphomas:
90509 T-cell Receptor (TCR) Gamma Gene Rearrangement, PCR
91446 T-cell Receptor (TCR) Beta Gene Rearrangement, PCR
91445 T-cell Clonality Panel (TCRG, TCRB), PCR
For B-cell lymphomas:
- 90362 B-cell Receptor IGH Gene Rearrangement, PCR
- 90363 B-cell Receptor IGK Gene Rearrangement, PCR
- 91635 B-cell Clonality Panel (IGH, IGK), PCR
For mixed B-cell and T-cell infiltrates or for lymphomas of unclear lineage:
- 91634 Lymphocyte Clonality Panel, PCR; includes IGH, IGK, TCRG and TCRB
All 7 test codes include a pathologist’s integrated interpretation.
Question 2. When should the T-cell clonality panel be used rather than a T-cell receptor (TCR) single gene rearrangement assay?
The TCR-gamma gene rearrangement PCR (test code 90509) is the preferred assay for T-cell clonality determination. However, false-positives can occur in samples with many reactive gamma-delta T-cells.
Use of the panel, which includes analysis for TCRG and TCRB gene rearrangements, can help avoid over-diagnosis of T-cell clonality in skin biopsies, spleen, and blood.1 Combining analysis for TCRG and TCRB gene rearrangements can also improve the diagnostic sensitivity compared to either TCRG or TCRB gene rearrangements alone in up to 10% of cases.2 In a multicenter study from the BIOMED-2 group, all definitive cases of T-cell lymphomas and leukemias (including T-PLL, T-LGL, and PTCL) showed clonal TCRB and/or TCRG gene rearrangements.2
The TCR-beta gene rearrangement PCR (test code 91446) should only be ordered as a stand-alone test if a prior TCR-gamma gene rearrangement result is inconclusive or inconsistent morphologically or clinically, and additional testing is desired.
Question 3. When might the B-cell clonality panel be used rather than a B-cell receptor single gene rearrangement assay?
The B-cell receptor IGH gene rearrangement PCR (test code 90362) is the preferred assay for B-cell clonality determination.
However, false-negative results are seen in the IGH PCR assay in 5-20% of B-cell lymphoproliferative neoplasms due to intrinsic biologic mechanisms. These include absent or incomplete IGH rearrangements in immature B-cell neoplasms, such as lymphoblastic leukemia/lymphoma, and the presence of extensive somatic mutation in some mature B-cell lymphoma, particularly follicular lymphoma and plasma cell neoplasms. The combination of IGH and IGK PCR can overcome these limitations and detect a clonal rearrangement in up to 99% of B-cell neoplasms.3 The B-cell clonality panel is thus recommended for lymphoblastic neoplasms and in suspected follicular lymphoma. Dual IGH and IGK testing can also help to distinguish oligoclonal rearrangements patterns from true monoclonal B-cell infiltrates.1
The B-cell receptor IGK gene rearrangement PCR (test code 90363) should only be ordered as a stand-alone test if a prior IGH result is inconclusive or inconsistent morphologically or clinically, and additional testing is desired. The IGK gene rearrangement assay is also useful in determining clonality in lymphoblastic leukemia/l lymphoma.
Question 4. When might the full lymphoid clonality panel be useful?
Immature lymphoid neoplasms such as acute lymphoblastic leukemia/lymphoma (ALL/LBL) often lack complete IGH, IGK, TCRG, and TCRB rearrangements4 or can have a bilineal or mixed immunophenotype. Therefore, clonality determination in ALL/LBL often requires several PCR assays to identify a detectable rearrangement that can be used for diagnosis and follow up.
Mixed B-cell and T-cell infiltrates are also commonly encountered. They are particularly common in skin lesions in which it is not clear whether the lesion represents a B-cell lymphoma, a T-cell lymphoma, or a mixed reactive proliferation. Finally, composite B-cell and T-cell lymphomas can occur, especially when atypical T-cell and EBV+ B-cell infiltrates are identified by immunohistochemistry. In these cases, a full lymphoid clonality PCR panel may be a useful adjunct to diagnosis.
Question 5. What sample types are acceptable for these assays?
The following samples can be submitted for all of these PCR assays:
- Peripheral blood or bone marrow aspirate (do not freeze)
- Fine needle aspirate material, in an alcohol-based fixative
- Formalin-fixed paraffin-embedded (FFPE) sections or tissue blocks
- Fresh-frozen tissues shipped on dry ice
See test description in our online Test Center for minimal sample requirements.
Question 6. Does a positive TCR-gamma gene rearrangement equate with a gamma/delta T-cell lineage in a T-cell lymphoma?
No. TCR-gamma gene rearrangements are present in both TCR-a/b+ and TCR-g/d+ T-cell lymphoproliferative disorders and are not necessarily indicative of gamma/delta lineage.
Question 7. Why does the laboratory require a pathology report for interpretation of these assays?
Pathology reports are critical, especially for FFPE samples, for matching the sample number and for information about the sample source, type of specimen, and, when available, the T-cell and B-cell proportions from immunostain results. Interpretation of PCR-based lymphoid assays is complex and impacted by these factors.
If no final pathology report is available, a preliminary report showing the sample number and specimen source is acceptable.
- Langerak AK, Molina TJ, Lavender FL, et al. Polymerase chain reaction-based clonality testing in tissue samples with reactive lymphoproliferations: usefulness and pitfalls. A report of the BIOMED-2 Concerted Action BMH4-CT98-3936. Leukemia. 2007;21:222–229.
- Brüggemann M, White H, Gaulard P, et al. Powerful strategy for polymerase chain reaction-based clonality assessment in T-cell malignancies: report of the BIOMED-2 Concerted Action BHM4 CT98-3936. Leukemia. 2007;21:215–221.
- van Krieken JH, Langerak AW, Macintyre EA, et al. Improved reliability of lymphoma diagnostics via PCR-based clonality testing: report of the BIOMED-2 Concerted Action BHM4-CT98-3936. Leukemia. 2007;21:201–206.
- van Dongen JJ, Langerak AW, Brüggemann M, et al. Design and standardization of PCR primers and protocols for detection of clonal immunoglobulin and T-cell receptor gene recombinations in suspect lymphoproliferations: report of the BIOMED-2 Concerted Action BMH4-CT98-3936. Leukemia. 2003;17:2257–2317.
- Evans PA, Pott CH, Groenen PJ, et al. Significantly improved PCR-based clonality testing in B-cell malignancies by use of multiple immunoglobulin gene targets. Report of the BIOMED-2 Concerted Action BHM4-CT98-3936. Leukemia. 2007;21:207–214.