Precision analysis to identify and diagnose

Mature aggressive B-cell neoplasms include several specific disease entities such as diffuse large B-cell lymphoma (DLBCL) and primary mediastinal (thymic) large B-cell lymphoma (PMBL). PMBL occurs primarily in the mediastinum and is one of the few B-cell lymphomas with a slightly higher incidence in young women. Due to differences in treatment options, laboratory testing to establish a specific diagnosis is important to selecting the best therapy.

Among our test offerings to detect, diagnose, and differentiate B-cell lymphomas is a first-in-class molecular evaluation to distinguish PMBL from DLBCL that overcomes the challenges of traditional testing approaches. We also offer comprehensive fluorescence in situ hybridization (FISH) test options that enable detection of abnormal genes associated with various chromosome translocations and inversions in DLBCL.

Molecular testing

Laboratory testing to establish PMBL diagnosis is important to selecting the best treatment. However, accurate identification using traditional tissue immunohistochemistry (IHC) can be difficult due to the challenge of obtaining adequate tissue from difficult biopsy locations, such as the mediastinal area, and the lack of specific immunophenotype. Histologic features are often ambiguous due to cell distortion from crushed biopsies and subtle differences between PMBL and DLBCL samples. To further confound diagnosis, although PMBL occurs primarily in the mediastinum, it has been reported to occur outside the mediastinum while occurrences of DLBCL have been reported within the mediastinum.

The Lymph3Cx test (Mayo ID: PM3CX) is a qualitative gene expression assay performed on RNA extracted from a biopsied tissue sample with a tumor cell content deemed adequate by pathological evaluation. The assay then measures the expression levels of a panel of genes related to lymphoma biology. Finally, the expression levels are analyzed using a mathematical algorithm to determine the likelihood that the tumor is PMBL or DLBCL with a high degree of confidence when the remaining clinical and pathological factors are considered.

PM3CX | Lymph3CX Assay, Primary Mediastinal Large B-cell Lymphoma and Diffuse Large B-cell Lymphoma, mRNA Gene Expression, NanoString, Tissue*(coming soon)

• First-in-class molecular evaluation to differentiate PMBL from DLBCL.
• Aids in determining a final PMBL diagnosis versus a DLBCL diagnosis and cell-of-origin (COO) for DLBCL cases.
• Provides increased sensitivity for distinction of lymphoma subtype compared to IHC alone.
• Analyzes gene expression without an enzymatic cDNA synthesis step, resulting in increased tolerance of degraded RNA and inhibitors associated with the formalin fixation process, which can adversely affect enzymatic reactions.
• Differentiates between PMBL and DLBCL with high confidence.
  • Cases with at least 90% probability of being PMBL are called PMBL.
  • Cases with less than 10% probability of being PMBL are reported as DLBCL.
  • Cases that do not reach 90% probability of either PMBL or DLBCL are reported as unclear (UNC).
  • When determined to be DLBCL, the COO is also reported with equally high confidence: Germinal Center B-cell like (GCB), Activated B-cell like (ABC), and a third, Unclassifiable (UNC) category.
    • Cases with at least 90% probability of being ABC are called ABC.
    • Cases with less than 10% probability of being ABC are reported as GCB.
    • Cases that do not reach 90% probability of being either ABC or GCB are reported as UNC.

Comprehensive FISH testing, simplified

Genetic abnormalities have emerged as one of the most important prognostic markers in B-cell lymphomas and can aid in diagnosis. Several chromosome abnormalities and variants of these abnormalities have been associated with various lymphoma subtypes.

Our approach to fluorescence in situ hybridization (FISH) testing is designed to simplify the ordering process by providing diagnostic panels that include all appropriate genes.

BLPMF | B-Cell Lymphoma, Specified FISH, Varies

• Probe set(s) performed are based on concurrent flow cytometry results (if available), reason for referral, or what is specified upon ordering.

BLYM | B-Cell Lymphoma, FISH, Tissue

• Detecting a neoplastic clone associated with the common chromosome abnormalities seen in patients with various B-cell lymphomas.

CD273 | CD273 (PD-L2) Immunostain, Technical Component Only

MALI | MAL Immunostain, Technical Component Only

• Can help facilitate diagnosis of PMBL.

PATHC | Pathology Consultation

• In addition to an extensive IHC and thoughtfully crafted FISH testing, Mayo Clinic’s hematopathology team has extensive experience with B-cell neoplasms and frequently provides consultations for clients around the globe.