Leukemia with L3 morphology: cytogenetic characterization and diagnostic challenges
Year: 2025
Type: article
Study design: Observational Study
Abstract: Burkitt lymphoma/leukemia (BL) is a highly aggressive B-cell non-Hodgkin lymphoma with a strong predilection for extranodal involvement and frequent multi-organ dissemination. When the bone marrow is affected, BL is typically characterized by three key signs: L3 morphology as defined by the French-American-British classification, a MYC gene rearrangement, and a mature immunophenotype with surface immunoglobulin expression as confirmed by flow cytometry. However, in some BL cases, some of these features may be absent. Here, we studied a correlation between L3 morphology and the presence of MYC gene rearrangements in the bone marrow. The study was approved by the Independent Ethics Committee and the Scientific Council of the Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology of Ministry of Healthcare of the Russian Federation. Out of the 127 patients with L3 morphology, 89.8% (n = 114) harbored MYC rearrangements, while in the patients with L1/L2 morphology such rearrangements were extremely rare (0.1%; 2 out of 2049). We identified the following MYC rearrangements: t(8;14)(q24;q32)/IGH::MYC (91.2%; n = 104), t(8;22)(q24;q11)/IGK::MYC (7.0%; n = 8), t(2;8)(p12;q24)/IGL::MYC (1%; n = 1), and t(8;14)(q24;q32)/IGH::MYC combined with t(14;18)(q32;q21)/IGH::BCL2 (n = 1). At the same time, 13 patients with L3 morphology did not have MYC rearrangements. Among these cases, 69.2% (n = 9) of patients harbored other chromosomal aberrations commonly associated with B-lineage acute lymphoblastic leukemia, including rearrangements involving the KMT2A and ETV6 genes and IGH locus, as well as hyperdiploidy and hypodiploidy. According to the findings of the initial analysis of cytogenetic samples using the fluorescence in situ hybridization (FISH) method, 23.6% (n = 25) of the MYC-positive cases either did not have abnormal cells or had a minimal amount. In such cases, MYC positivity was reliably confirmed by FISH performed on morphological samples with established blastosis. Notably, the percentage of blast cells varied significantly among the MYC-positive samples depending on the puncture site, which can potentially lead to false negative cytogenetic results. However, this variation was much lower in other genetic alterations such as hyperdiploidy, KMT2A rearrangements, and t(12;21)(p13;q22)/ETV6::RUNX1. Therefore, if there are any discrepancies between the results of morphological and cytogenetic analyses, it is recommended to perform additional testing using morphological smears with previously confirmed blastosis with L3 morphology.
Language: English
Subfield: Pathology and Forensic Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
OpenAlex ID: W4412099908