OVERVIEW
High-grade B-cell lymphomas and diffuse large B-cell lyphomas are tumors of B-cells with aggressive appearing histology that encompass a variety of disease entities using current WHO criteria, including diffuse large B-cell lymphoma, Burkitt lymphoma, high-grade B-cell lymphoma, NOS, etc.
INDICATION
Testing is indicated for all patients with a diffuse large B-cell lymphoma or high grade B-cell lymphoma to aid in the diagnosis and treatment decisions.
See High grade B-cell lymphoma for information on FISH testing.
TEST REQUIREMENTS
For LExA testing request, the following are required or the case will be returned without testing:
- Tumour content estimate for the whole section written in the space provided in the Specimen section of the requisition
- Tissue block – which will be returned when the test is completed
- Completed CGL Lymphoid requisition form
A minimum tumour content of 40% is required for LExA in the whole section to proceed with testing.
Tumour content refers to the proportion (%) of tumour cell nuclei relative to non-tumour cell nuclei in a given area.
NOTE: Decalcified specimens are not amenable to FISH or LExA testing.
See sample Specimen Guidelines for additional information.
TURN-AROUND TIME
Results are reported within 14 days from receipt of the necessary specimen, completed requisition form and all relevant documentation.
RESULTS REPORTING
Results will be reported qualitatively for each of the three gene signatures detectable by the assay:
• Cell-of-origin signature – Germinal Centre B-cell-like (GCB) Activated B-cell-like (ABC), Unclassifiable
• Dark Zone signature – Positive, Negative, Unclassifiable
• Signature associated with primary mediastinal large B-cell lymphoma (PMBL) – PMBCL, DLBCL, Unclassifiable
METHOD
Total RNA was extracted from tumour tissue isolated from the submitted specimen (noted above) using a Promega Maxwell nucleic acid isolation system. Isolated RNA was profiled using the Nanostring nCounter platform and Elements chemistry as previously described (references below). Gene expression counts were analyzed in R using the DLBCL90 analysis package to generate linear predictor scores and assign classifications for each of cell-of-origin, dark zone, and PMBL gene expression signatures (software version 1.0.1). The limit of reliable detection for this assay has been validated for specimens with 40% or greater tumour content (with a minimum of 100ng of input RNA). The performance characteristics of this test were determined by the Cancer Genetics & Genomics Laboratory, BC Cancer.
REFERENCES
- Scott et al. Determining cell-of-origin subtypes of diffuse large B-cell lymphoma using gene expression in formalin-fixed paraffin-embedded tissue Blood (2014) PMID:24398326
- Mottok et al. Molecular classification of primary mediastinal large B-cell lymphoma using routinely available tissue specimens Blood (2018) PMID:30257882
- Ennishi et al. Double-Hit Gene Expression Signature Defines a Distinct Subgroup of Germinal Center B-Cell-Like Diffuse Large B-Cell Lymphoma J. Clin. Oncol. (2019) PMID:30523716
- Duns et al. Characterization of DLBCL with a PMBL gene expression signature Blood (2021) PMID:33684939
- Alduaij et al. Molecular determinants of clinical outcomes in a real-world diffuse large B-cell lymphoma population Blood (2023) PMID:36302166