Screening Strategy for Detecting Double-Hit Lymphoma in a Resource-Limited Setting

Area of Science:

• Hematology
• Oncology
• Pathology

Background:

• High-grade B-cell lymphomas with MYC and BCL2 rearrangements, known as double-hit lymphomas (DHL), are aggressive and require accurate diagnosis.
• Current diagnostic guidelines recommend fluorescent in-situ hybridization (FISH) for all diffuse large B-cell lymphoma (DLBCL) cases to detect DHL.
• FISH analysis is often not feasible in resource-limited settings, necessitating alternative diagnostic strategies.

Purpose of the Study:

• To develop and evaluate a cost-effective screening strategy for identifying DHL in de novo high-grade B-cell non-Hodgkin lymphoma.
• To determine which histomorphological and immunohistochemical features can reliably predict the need for FISH testing in resource-limited environments.

Main Methods:

• Analysis of 109 cases of de novo high-grade B-cell non-Hodgkin lymphoma, including DLBCL and B-cell lymphoma unclassifiable (BCLU) with intermediate features.
• Utilized histomorphology, Hans algorithm, immunohistochemistry (MYC, BCL2, Ki67), and FISH on selected cases.
• Evaluated the sensitivity and specificity of BCLU/blastoid morphology, CD10 expression, germinal center B-cell phenotype, and MYC/BCL2 co-expression for predicting MYC/BCL2 rearrangement.

Main Results:

• MYC/BCL2 co-expression was observed in 22% of cases, with 11.9% confirmed as DHL via FISH.
• MYC/BCL2 co-expression, BCLU/blastoid morphology, CD10 positivity, and germinal center B-cell phenotype were significantly correlated with single-hit or double-hit lymphoma.
• A screening strategy incorporating these parameters demonstrated 100% sensitivity and 68% specificity for selecting cases requiring FISH testing.

Conclusions:

• A proposed screening strategy combining histomorphology and immunohistochemistry can effectively identify high-grade B-cell lymphomas requiring FISH testing in resource-limited settings.
• This approach enhances diagnostic capabilities for aggressive lymphomas where advanced molecular testing is not readily available.
• Further validation in larger cohorts is recommended to confirm the utility of this screening strategy.