Indolent hematodermic CD4+ T-cell lymphoma lacking surface CD3 expression: Structural and functional deficiency of T-cell receptor/CD3 complex

Abstract

The expression of surface CD3 (sCD3) is often missing in T-cell neoplasms. We present two patients with indolent cutaneous T-cell lymphoma (CTCL) who had a clonal leukemic fraction of sCD3-, cCD3+, sCD4+ T-cell cells with less cell atypia. The cutaneous lesion of case 1 (60s, female) showed epidermotropic and perivascular infiltration of cCD3+, CD4+ T-cells, the features of which were consistent with those of mycosis fungoides, while in case 2 (50s, male), the diagnosis of CTCL was not confirmed histologically. In both cases, clonality analysis with T-cell receptor (TCR) gene rearrangement detected the same T-cell clones in the cutaneous lesions and leukemic cells. We further examined subclones of the neoplastic T cells infiltrating in the skin and blood, and the expression of TCR/ CD3 complex. Flow cytometric analysis revealed that the leukemic T-cells lost TCR/CD3 complex on the cell surface. Of the same T-cell clones, the CD62L+ subclone was mainly present in the blood, while the CD62L- one was infiltrating in the skin. Induction of activation markers such as CD69 and CD25 following CD3/CD28-stimulation was markedly diminished in the neoplastic T-cells, whereas PMA/ionomycin-mediated activation was normal. In conclusions, our observations indicate that TCR/CD3 complex is missing in the neoplastic cells, and the presence of CD62L+ and CD62L- subclones may account for the hematodermic involvement. We attribute our patients’ indolent clinical course partly to the deficiency of cell activation via TCR/CD3 complex. Based on our results, we propose a diagnosis of ‘indolent hematodermic TCR/CD3 complex-deficient lymphoma’ to our patients.