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Diagnostic Validation of Capillary Electrophoresis Analysis of T-Cell Receptor -Chain Gene Rearrangements: Prediction of Malignant Transformation of Cutaneous T-Cell Lymphoproliferative Disorders

¹ Molecular Diagnosis Centre, Department of Laboratory Medicine, National University Hospital, Singapore 119074

² Department of Pathology, National University of Singapore, 10 Kent Ridge Crescent, Singapore 119260

^aaddress correspondence to this author at: Department of Pathology, National University of Singapore, 10 Kent Ridge Crescent, Singapore 119260; fax 65-67751757, e-mail patkoaye@nus.edu.sg

The first 20% of the full text of this article appears below.

T-Cell lymphoproliferative disorders of the skin constitute in themselves a unique area of diagnostic difficulty for the clinician and the pathologist. Hence, although T-cell clonality analysis by PCR and capillary electrophoresis (CE) has been used extensively in lymphoproliferative disorders in general, there are very few reports describing their application to the differential diagnosis of cutaneous T-cell lymphoma (1)(2) or to cases of cutaneous lymphoproliferative disorders with less conclusive histology, where their superior resolution properties have provided strong confirmatory evidence of evolving lymphoma development (3).

We present here our validation data of the use of CE in the analysis of T-cell receptor -chain (TCR) gene rearrangements for clinical use. We also present a report of a case that was judged to be benign based on clinical and pathologic grounds but was found to have the clonal molecular fingerprint that could have predicted malignant transformation at an early stage. This predictive value, in our opinion, enhances the diagnostic value of this test in the clinical setting.

Pathologists are aware that distinction between benign and malignant T-cell lymphoproliferative disease by use of morphologic criteria can often be difficult, even with the aid of immunotyping. The best marker of T-cell malignancy is T-lymphocyte monoclonality, which is rarely encountered in nonneoplastic disease. Rearrangements of TCR genes in a rapidly proliferating neoplastic lymphoid cell population derived from a single progenitor cell are identical, involving unique combinations of specific variable (V), joining (J), diversity (D), and constant (C) gene segments, and thus serve as unique clonal markers (3)(4). In contrast, nonneoplastic and reactively proliferating T-cells yield different, . . . [Full Text of this Article]

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