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Leo I. Gordon, MD, FACP


Can the Malignancy of B-Cell Lymphoid Aggregates Be Determined Via IGH/IGK Analysis?

By: Emily Rhode
Posted: Thursday, December 15, 2022

In a study published in the journal Human Pathology, Mark G. Evans, MD, of Caris Life Sciences; Sherif A. Rezk, MD, of the University of California, Irvine Medical Center; and colleagues aimed to explore the utility of testing for immunoglobulin heavy chain (IGH) and kappa light chain (IGK) gene rearrangements to help distinguish between benign and malignant B cell-predominant lymphoid aggregates. The study authors found that IGH/IGK rearrangement analysis does produce helpful diagnostic information; however, false-negative results as well as the presence of autoimmune disorders or infectious diseases that could cause false-positive results make this diagnostic tool most useful when combined with careful interpretation of morphologic examinations, immunohistochemical staining, and accurate flow-cytometric analysis.

“The results obtained from IGH/IGK rearrangement studies or flow cytometry should be considered as supplemental to the information provided by other histologic methodologies,” the study authors concluded.

The retrospective evaluation looked at 120 bone marrow aspirate and biopsy specimens collected at the University of California, Irvine Medical Center, from patients with lymphoid aggregates. Based on the specimens studied, 79 patients received nonmalignant diagnoses, and 41 had a diagnosis of a malignant B-cell lymphoid neoplasm. Associated flow-cytometric results were available for 98% of the samples. Immunohistochemical staining and polymerase chain reaction (PCR) analysis were performed on all samples. PCR amplification provided IGH/IGK rearrangement analysis results from 109 specimens.

IGH/IGK clonal analysis found structural alterations in samples from 15% of patients with nonmalignant diagnoses, whereas flow cytometry detected clonal B cells in 1.5% of those patients. No IGH/IGK structural alterations were found in 40% of bone marrow biopsies with malignant diagnoses, whereas flow cytometry found no clonal B cells in 13% of those patients. Two patients with nonmalignant diagnoses developed a B-cell lymphoma within 5 years of biopsy and aspiration. Overall sensitivity for identifying malignant lymphoid aggregates was 88% for flow cytometry compared with 80% for PCR testing.

Disclosure: The study authors reported no conflicts of interest.

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