Background:
B-cell lymphomas account for greater than 90% of non-Hodgkin lymphomas and may pose a diagnostic challenge on the basis of histopathology alone. During normal B-cell maturation, the immunoglobulin heavy chain gene is rearranged such that each mature B-cell and plasma cell has a unique rearranged heavy chain gene profile. This process is vital to proliferation of B-cells in normal immune function, but can be exploited to aid in the distinction between reactive (benign) versus neoplastic processes of B-cell proliferation. A reactive, benign B-cell proliferation is characterized by polyclonal expansion of B-cells whereas a malignant process is often characterized by a clonal expansion of a predominant B-cell population. In conjunction with histopathology study of lymph nodes, bone marrow and other tissue types, the detection of a clonal immunoglobulin heavy chain gene rearrangement by polymerase chain reaction (PCR) is intended as an aid in the diagnosis of malignant B-cell lymphoma.
Clinical Utility:
PCR-based detection of rearranged immunoglobulin heavy chain genes can be used as an aid to establish a diagnosis of a B-cell lymphoma, plasma cell malignancy, monitor treatment response, and/or measure minimal residual disease (MRD).
Methodology:
Genomic DNA is extracted from blood, lymph node, bone marrow, or other tissue types and the rearranged immunoglobulin kappa chain genes are amplified by PCR using a multiplex primer method based on the BIOMED-2 strategy. Precise fragment sizing of the amplicons is accomplished using capillary gel electrophoresis. The presence or absence of a monoclonal population is determined based on the overall analysis of the gel electrophoretic pattern.
Clinical Sensitivity:
> 95% for the detection of clonality in most tissue types. Clinical
Specificity:
As cross-lineage immunoglobulin heavy chain gene rearrangements have been reported in certain T-cell malignancies, interpretation of this test requires clinical, morphologic, and immunophenotypic correlation.
Specimen Requirements:
- 5-10 mL of blood or bone marrow — yellow (ACD) or purple (EDTA) tube. Store and ship refrigerated.
- Formalin-fixed paraffin-embedded (FFPE) tissue blocks or minimum 15 slides (5 microns). Store and ship at room temperature.
- Pathology report MUST accompany sample for interpretation of results.
DNA: 200g at a minimum of 10ng/µL (DNA must be extracted in a CLIA-certified laboratory or a laboratory meeting equivalent requirements as determined by the CAP and/or CMS)
A REQUISITION FORM MUST ACCOMPANY ALL SAMPLES. Please include detailed clinical information.
Test Performed (Days):
Once per week
Turn Around Time:
7-10 days
Shipment Sensitivity Requirements:
- Keep specimen cold during transit, but do not ship on dry ice.
- Please use the cold pack provided in the KDL shipping kit.
- Ship the specimen overnight express, using the FedEx priority overnight label provided.
References:
- Van Dongen JJ, Langerak AW, Bruggemann 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(12):2257-2317.
- Langerak AW, Molina TJ, Lavender FL, et al. Polymerase chain reaction-based clonality testing in tissue samples with reactive lymphoproliferations: usefulness and pitfalls. Report of the BIOMED-2 Concerted Action BMH4-CT98-3936. Leukemia 2007; 21:222-229.
Additional Info: