- No FAQs found
- ABL Kinase Domain Mutation in CML, Cell-based
- ABO Group and Rh Type
- Acid-Fast Bacillus (AFB) Identification, Sequencing and Stain, Paraffin Block
- ADAMTS13 Activity with Reflex to ADAMTS13 Inhibitor
- Alcohol Metabolites, Quantitative, Urine
- Alpha-Globin Common Mutation Analysis
- Alpha-Globin Gene Deletion or Duplication
- Alpha-Globin Gene Sequencing
- Anti-Müllerian Hormone AssessR™
- Anti-PF4 and Serotonin Release Assay (SRA) for Diagnosing Heparin-induced Thrombocytopenia/Thrombosis (HIT/HITT)
- Antiphospholipid Antibodies
- ASCVD Risk Panel with Score
- Autoimmune Epilepsy Evaluation
- Autoimmune Diseases, Tests for
- B-cell and T-cell Clonality Assays by PCR
- B-Type Natriuretic Peptide (BNP)
- BCR-ABL1 Gene Rearrangement, Quantitative PCR
- Beta-Globin Complete
- Biotin: Interference with Laboratory Assays
- BRCAvantage®, Ashkenazi Jewish Screen
- BRCAvantage®, Rearrangements
- BRCAvantage™, Comprehensive
- BRCAvantage™, Single Site
- CDH1 Sequencing and Deletion/Duplication
- Clostridium difficile Diagnostic Testing
- C1 Inhibitor, Protein and Functional Tests
- Calreticulin (CALR) Mutation Analysis
- Carbapenem Resistant Enterobacteriaceae Culture Screen
- Cardio IQ Lipoprotein Fractionation, Ion Mobility
- Cervical Cancer, TERC, FISH
- CFvantage® Cystic Fibrosis Expanded Screen
- Chlamydia trachomatis, TMA
- Chlamydia trachomatis/Neisseria gonorrhoeae RNA, TMA
- Chromosomal Microarray, POC, ClariSure®, Oligo-SNP
- Chromosomal Microarray, Postnatal, ClariSure® Oligo-SNP
- Chromosome Analysis and AFP with Reflex to AChE, Fetal Hgb, Amniotic Fluid
- Chromosome Analysis, Amniotic Fluid
- Chromosome Analysis, Blood
- Chromosome Analysis, Blood with Reflex to Postnatal, ClariSure® Oligo-SNP Array
- Chromosome Analysis, Chorionic Villus Sample
- Chromosome Analysis, High Resolution
- Chromosome Analysis, High Resolution with Reflex to Postnatal, ClariSure® Oligo-SNP Array
- Chromosome Analysis, Mosaicism
- Chromosome Analysis, Neonatal Blood
- Chromosome Analysis, Sister Chromatid Exchange
- Chromosome Analysis, Tissue
- Chromosome DEB Assay for Fanconi anemia
- Chronic Lymphocytic Leukemia (CLL) - Diagnostic and Prognostic Testing
- Culture, Fungus
- Culture, Urine, Routine
- Cystic Fibrosis Screen
- Cytomegalovirus (CMV) and Epstein Barr Virus (EBV) PCR
- D-Dimer, Quantitative
- Dementia, Secondary Causes
- Dengue Virus Testing
- Diabetes Risk Panel with Score and Cardio IQ® Diabetes Risk Panel with Score
- Drug Testing, General Toxicology (Blood, Urine, or Serum)
- Drug Toxicology Alcohol Metab, QN, Oral Fluid
- Drug Toxicology Monitoring, Oral Fluid Testing
- Factor V (Leiden) Mutation Analysis
- Familial Hypercholesterolemia (FH) Panel
- Familial Hypercholesterolemia (FH) Single Site
- Familial Mediterranean Fever Mutation Analysis
- First Trimester Screen, hCG
- First Trimester Screen, Hyperglycosylated hCG (h-hCG)
- FISH, Angelman
- FISH, MET Amplification
- FISH, Myeloma, 17p-, rea 14q32 with Reflexes
- FISH, Prader-Willi
- FISH, Prenatal Screen
- No FAQs found
- HCV Genotyping
- Helicobacter pylori (H pylori) Antibody Discontinuation
- Heparin, Anti-Xa
- Hepatitis B Surface Antibody, Quantitative
- Hepatitis B Surface Antigen, Quantitative, Monitoring
- Hepatitis C Antibody with Reflex to HCV RNA, PCR with Reflex to Genotype
- Hepatitis C Viral RNA Genotype 1 NS5A Drug-resistance
- Hepatitis C Viral RNA Genotype 3 NS5A Drug Resistance
- Hepatitis C Viral RNA NS3 Drug Resistance
- Hepatitis C Virus Antibody and RNA Testing
- Hereditary Cancer Panels: MYvantageTM Hereditary Comprehensive Cancer Panel and GIvantageTM Hereditary Colorectal Cancer Panel
- Hereditary Hemochromatosis DNA Mutation Analysis
- Herpes Simplex Virus (HSV) Type-Specific IgG Antibodies
- Herpes Simplex Virus Type 2 (HSV-2) IgG Inhibition, ELISA
- HIV-1 Coreceptor Tropism, Proviral DNA
- HIV-1 Coreceptor Tropism, Ultradeep Sequencing
- HIV-1 Integrase Genotype
- HIV-1 Resistance, Proviral DNA (RTI, PI, Integrase Inhibitors)
- HIV-1/2 Antigen and Antibodies, Fourth Generation, with Reflexes
- HPV mRNA E6/E7
- Infliximab and Adalimumab Drug and Anti-drug Antibody Testing
- Influenza A and B Antigen, Immunoassay
- Influenza Type A and B Antibodies
- Insulin, Intact, LC/MS/MS
- Integrated Screen, Part 1
- Integrated Screen, Part 2
- Intrinsic Factor Blocking Antibody
- No FAQs found
- No FAQs found
- Maternal Serum AFP
- Melanoma, BRAF V600E and V600K Mutation Analysis, THxID®
- Metanephrines, Fractionated, Free, LC/MS/MS, Plasma
- Methylenetetrahydrofolate Reductase (MTHFR), DNA Analysis
- Microalbumin (Urinary Albumin Excretion)
- Pain Management and CYP2D6/CYP2C19
- Pain Management Antidepressants, With Confirmation, Urine
- Pain Management Antipsychotics, With Confirmation, Serum and Urine
- Pain Management, Naltrexone, Quantitative, Urine
- Partial Thromboplastin Time, Activated (aPTT)
- Penta Screen
- PIK3CA Mutation Analysis
- Platelet Antibody Screen (Indirect)
- PNH with FLAER (High Sensitivity)
- Prothrombin Time with INR
- PTH, Intact and Calcium
- Streptococcus pneumoniae (Pneumococcal) Antibody Tests
- Saccharomyces cerevisiae Antibodies (ASCA) (IgG, IgA)
- Sequential Integrated Screen, Part 1
- Sequential Integrated Screen, Part 2
- Serum Integrated Screen, Part 1
- Serum Integrated Screen, Part 2
- Serum Pregnancy Tests
- Sickle Cell Screen
- Stepwise, Part 1
- Stepwise, Part 2
- SureSwab® Trichomonas vaginalis RNA, Qualitative TMA
- SureSwab®, Candidiasis, PCR
- TP53 Sequencing and Deletion/Duplication
- T4, Free
- Tamoxifen and Metabolites, LC-MS/MS
- Testosterone Testing
- Total Testosterone, LC/MS/MS
- Triple Screen
- No FAQs found
- No FAQs found
- No FAQs found
B-cell and T-cell Clonality Assays by PCRTest code(s) 90362, 90363, 90509, 91445, 91446, 91634, 91635
This is an outdated version of this FAQ. It was effective 09/23/2013 to 10/29/2014.
The current version is available here.
Question 1. What testing does Quest Diagnostics offer for T-cell and B-cell gene rearrangement studies?
Effective September 22, 2013, 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. Are the older T-cell and B-cell PCR test codes still available?
No. Effective September 22, 2013, the following test codes have been discontinued: The recommended alternative for 15930X and 17862X (T-cell receptor gene rearrangement) is 90509. The recommended alternative for 14868X and 16119X (B-cell receptor gene rearrangement) is 90362.
Question 3. How are these new codes different from the old T-cell and B-cell codes? Why did the change occur?
Tcuhe European BIOMED-2 multicenter collaboration designed and validated standardized T-cell and B-cell clonality multiplex PCR assays that demonstrated improved performance.1 Subsequently, this group and others have confirmed the superior performance of these assays when used alone and in combination to definitively identify T-cell and B-cell clonality.2-5 The methodology used in Quest Diagnostics current B-cell and T-cell PCR test offerings is based on these studies and thus provides a standardized approach to lymphoid clonality detection.
Our current assays also provide a pathologist’s interpretation of the PCR amplification patterns. Particularly for fixed tissues, this interpretation integrates the molecular results with the pattern and density of the lymphoid infiltrate.
Question 4. 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.5 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.3 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.3
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 5. 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.2 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.5
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 6. 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 rearrangements1 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 7. 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 8. 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 9. 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.
- 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.
- 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.
- 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.
- 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.
- LangerakAK, 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.
Document FAQS.124 Revision: 0