IGL::CCND1 detected by optical genome mapping revises diagnosis of a B-cell lymphoma.

Objective: Differentiating between the repertoire of immunoglobulin rearrangements is important in guiding diagnoses and management of B-cell lymphoma processes. A subset of these disease entities, such as chronic lymphocytic leukemia (CLL) and mantle cell lymphoma (MCL), can show distinct genomic profiles with a shared cell of origin. In this report, we describe a rare case in which differentiating between the immunoglobulin family of rearrangements (IGH, IGK, IGL) with optical genome mapping (OGM) helped revise the clinical suspicion of CLL.

Methods: We present a 50-year-old woman with a lymphoproliferative disorder. Her clinical laboratory genetics workup included chromosomal banding analysis, fluorescence in situ hybridization, next-generation sequencing, and OGM. Optical genome mapping was performed on the bone marrow specimen, starting with the ultra-high molecular weight DNA mapped on the Saphyr system. Structural variants with OGM were detected using rare variant analysis set to default parameters.

Results: In 2021, flow cytometry performed on the peripheral blood detected a monotypic CD5+/CD23+ B-cell population. A subsequent bone marrow in 2024 detected similar findings by flow with κ light chain restriction. Chromosomal banding analysis found a translocation between the long arms of chromosomes 11 and 22. Optical genome mapping demonstrated that this translocation involved the CCND1 locus juxtaposed to the regulatory immunoglobulin λ (IGL) gene cluster.

Conclusions: We present a case of CD5+/CD10- small B-cell lymphoma that immunophenotypically resembled CLL but showed positive immunostaining for cyclin D1. The combination of the clinicopathologic findings and the CCND1 translocation involving IGL, detected by OGM, supported a revised diagnosis of MCL.