Diffuse Large B-cell Lymphoma (DLBCL) accounts for approximately 30% of all lymphoid malignancies. It can be difficult to separate DLBCL from Burkitt lymphoma and plasmablastic myeloma by morphology and flow cytometric immunophenotyping alone. Fluorescent in situ hybridization (FISH) targetgene analysis can assist the differential diagnosis by detection of genetic abnormalities associated with DLBCL.

Though no consistent numeric chromosomal abnormalities or translocations are observed as a hallmark for DLBCL, most cases have rearranged immunoglobulin heavy chain (IgH), BCL2 and MYC genes. Standard interphase FISH analysis is widely utilized to detect these genetic rearrangements. However, standard interphase FISH analysis could be falsely negative if the neoplastic cells are limited or if abundant benign cells are present in the background. Thus, the sensitivity to detect genetic abnormalities is low among the cases with a low number of neoplastic cells.

Herein we present three DLBCL cases in which interphase FISH analysis was applied on selective cells that are morphologically consistent with neoplastic large lymphocytes. All three cases showed genetic changes in a high percentage of the selected cells. These three cases were originally analyzed for IgH gene rearrangement, IgH/BCL2 and IgH/MYC translocation by using standard non-selected interphase study and showed false negative results. However, by review of the H&E slide and the flow cytometry results prompted a re-evaluation of the FISH studies using selective analysis of neoplastic cells only.

Our observations indicate that selective interphase FISH analysis improves the sensitivity of detecting genetic abnormalities in DLBCL. This analysis does require a corporation between hematopathologists and technologists performing interphase FISH studies.

Disclosures: No relevant conflicts of interest to declare.

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