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The role of molecular analysis of immunoglobulin and T cell receptor gene rearrangements in the diagnosis of lymphoproliferative disorders

A W Langerak¹, J H J M van Krieken³, I L M Wolvers-Tettero¹, E Kerkhof³, A H Mulder⁴, L W M A Vrints⁵, J W Coebergh², E Schuuring³, Ph M Kluin³ and J J M van Dongen¹

¹ Department of Immunology, University Hospital Rotterdam/Erasmus University Rotterdam, Dr. Molewaterplein 50, 3015 GE Rotterdam, The Netherlands
² Department of Epidemiology University Hospital Rotterdam/Erasmus University Rotterdam
³ Department of Pathology, Leiden University Medical Centre, Leiden, 2300 RC The Netherlands
⁴ Department of Pathology, Drechtsteden Hospital, Dordrecht, 3317 NL The Netherlands
⁵ Department of Pathology, Catharina Hospital, Eindhoven, 5602 ZA The Netherlands

Correspondence to:
Dr Langerak langerak{at}immu.fgg.eur.nl

Aims—To investigate whether the analysis of immunoglobulin (Ig)/T cell receptor (TCR) rearrangements is useful in the diagnosis of lymphoproliferative disorders.

Methods—In a series of 107 consecutive cases with initial suspicion of non-Hodgkin's lymphoma (NHL), Southern blot (SB) analysis of Ig/TCR rearrangements was performed.

Results—In 98 of 100 histopathologically conclusive cases, Ig/TCR gene results were concordant. In one presumed diffuse large B cell lymphoma (DLCL) and one follicular lymphoma (FL) case no clonality could be detected by SB analysis, or by polymerase chain reaction (PCR) at second stage. In the DLCL, sampling error might have occurred; the FL was revised after an initial diagnosis of reactivity. In many of the histopathologically inconclusive cases Ig/TCR gene SB analysis was helpful, giving support for the histopathological suspicion. However, because of a lack of (clinical) follow up data this could not be confirmed in a few cases.

Conclusions—Experienced haematopathologists or a pathologist panel can diagnose malignant versus reactive lesions in most cases without the need for Ig/TCR gene analysis and can select the 5–10% of cases that might benefit from molecular clonality studies.

Key Words: B cell lymphoma • immunoglobulin and T cell receptor genes • clonality analysis • Southern blotting

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