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Positive Lymphocyte Gene Rearrangement Evaluated for Hematologic Malignancies

By LabMedica International staff writers
Posted on 08 Sep 2020
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Image: Bone marrow smear in T-cell acute lymphoblastic leukemia shows pleomorphic blasts cells and smear cells. Two of the blasts have a hand-mirror conformation (arrows) (Photo courtesy of Ke Xu, MD).
Image: Bone marrow smear in T-cell acute lymphoblastic leukemia shows pleomorphic blasts cells and smear cells. Two of the blasts have a hand-mirror conformation (arrows) (Photo courtesy of Ke Xu, MD).
The diagnosis of a lymphoid malignancy requires the establishment of monoclonality of a lymphocyte population through morphologic assessment and laboratory testing, such as flow cytometry, immunohistochemistry, and cytogenetic analysis.

These methods can yield conflicting results, however, and in up to 15% of cases of suspected lymphoid malignancies, molecular assessment of immunoglobulin (IG) and/or T-cell receptor (TCR) gene rearrangements is necessary to confirm a diagnosis. the presence of a population of B or T cells with the same gene rearrangement pattern is highly supportive of lymphoid malignancy.

Medical scientists at the Yale School of Medicine (New Haven, CT, USA) extracted data from medical records of patients who underwent IG or TCR gene rearrangement testing at an affiliated hospital from January 1, 2013 to July 6, 2018. Date of testing, specimen source, and morphologic, flow cytometric, immunohistochemical, and cytogenetic characterization of the tissue source were recorded. Gene rearrangement results were categorized as test positive/phenotype positive (T+/P+), test positive/phenotype negative (T+/P−), test negative/phenotype negative (T−/P−), or test negative/phenotype positive (T−/P+) based on comparison to other studies and/or final diagnosis. Patient records were reviewed for subsequent diagnosis of hematologic malignancy for patients with positive gene rearrangements, but no other evidence for a disease process.

The authors reported that a total of 136 patients with 203 gene rearrangement studies were analyzed. For TCR studies, there were two T+/P− and one T−/P+ results in 47 peripheral blood (PB) assays, as well as seven T+/P− and one T−/P+ results in 54 bone marrow assays. Regarding IG studies, three T+/P− and 12 T−/P+ results in 99 bone marrow (BM) studies were identified. None of the 12 patients with T+/P− TCR or IG gene rearrangement studies later developed a lymphoproliferative disorder.

The 12 T/Pþ IG studies included four cases of multiple myeloma (MM), three cases of monoclonal gammopathy of undetermined significance, one case of low-grade B-cell non-Hodgkin’s lymphoma, one case of monoclonal B-cell lymphocytosis, one case of low-grade B–non-Hodgkin’s lymphoma plus MM, one case of low-grade B–non-Hodgkin’s lymphoma plus myelodysplastic syndrome, and one case of monoclonal gammopathy of undetermined significance plus adult T-cell leukemia/lymphoma. The two T/Pþ TCR studied corresponded to one diagnosis of T-cell acute lymphoblastic leukemia and one diagnosis of T-cell large granular lymphocytic leukemia.

The authors concluded that the results from the present study suggest positive IG/TCR gene rearrangement studies are not predictive of lymphoproliferative disorders in the context of otherwise negative BM or PB findings. As such, when faced with equivocal pathology reports, clinicians can be practically advised that isolated positive IG/TCR gene rearrangement studies do not indicate a need for closer surveillance. The study was published on July 31, 2020 in the journal Archives of Pathology & Laboratory Medicine.

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Yale School of Medicine

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