Clonal Rearrangements of T-Cell Receptor Genes in Mycosis Fungoides and Dermatopathic Lymphadenopathy

Abstract

Histologic diagnosis of mycosis fungoides may be difficult, especially in lymph nodes that show changes frequently associated with chronic skin disease. As an alternative approach to diagnosis, we have analyzed the configuration of DNA for the beta T-cell receptor genes in biopsy tissues from 14 patients with mycosis fungoides. Clonal rearrangements of these genes were found in each specimen tht contained histologically unambiguous mycosis fungoides. Clonal rearrangements were also found in seven of nine lymph nodes removed from patients with mycosis fungoides and considered histologically to contain only benign lymphadenopathy. Matching rearrangements of beta T-cell receptor genes were detected in benign lymph nodes and histologically involved tissues when paired specimens were available from the same cases. Our findings provide molecular evidence for the clonal T-cell origin of mycosis fungoides and indicate the high incidence of extracutaneous disease in patients with palpable lymphadenopathy. In addition, this study demonstrates that the detection of rearranged T-cell receptor genes can be a sensitive and practical method for the diagnosis and characterization of T-cell neoplasms.

Serological detection of cutaneous T-cell lymphoma-associated antigens

“…group of lymphoproliferative disorders with predominantly CD4 T-cells as the malignant cell type (1-3) with a mono-or, at least, oligo-clonal origin (4). Besides various other subtypes, Mycosis fungoides (MF) and the Sézary Syndrome (SS) are the most common forms of CTCL (1,2).…”

Diminished TCR signaling in cutaneous T cell lymphoma is associated with decreased activities of Zap70, Syk and membrane-associated Csk

“…In addition, TCR engagecharacteristic of 'memory' T lymphocytes. [1][2][3][4][5] A high percentment results in Zap70 activation after its binding to the tyrosylage of the malignant cells constitutively express BE2, a late phosphorylated immunoreceptor tyrosine-based activation activation marker of 78 kDa, that appears on cloned normal motifs (ITAMs) of the chains and the CD3 complex 23,24 (for T cells only after stimulation with specific antigen, and on review see Ref. 25) and in rapid tyrosine phosphorylation and freshly isolated normal T cells in response to mitogens, 6,7 sugactivation of Syk.…”

Kutane Maligne Lymphome. Nutzen und Grenzen des Nachweises klonaler T-Zellen

“…Seit Ende der 1980er-Jahre werden die oben geschilderten molekulargenetischen Techniken genutzt, um mittels des Nachweises eines dominanten T-Zell-Klons die Diagnose kutanes T-Zell-Lymphom zu bestätigen [4,5]. Zusammenfassend muss also bemerkt werden, dass mit dem molekulargenetischen Nachweis eines dominanten T-Zell-Klons die Diagnose kutanes T-Zell-Lymphom nicht gestellt werden kann.…”