Anaplastic large cell lymphomas lack the expression of T-cell receptor molecules or molecules of proximal T-cell receptor signaling

Anaplastic large cell lymphoma (ALCL) designates a heterogeneous group of CD30(+) (systemic or primary cutaneous) peripheral T-cell lymphomas (PTCLs). A subgroup of systemic ALCL is transformed by anaplastic lymphoma kinase (ALK). We compared 24 ALK(+), 15 ALK(-) systemic, and 7 cutaneous ALCLs with 29 nonanaplastic PTCLs in terms of T-cell receptor (TCR) rearrangements, expression of TCRs and TCR-associated molecules (CD3, ZAP-70 zeta-associated protein 70). Despite their frequent clonal rearrangement for TCRbeta, only 2 (4%) of 47 ALCLs expressed TCRbeta protein, whereas TCRs were detected on 27 of 29 nonanaplastic PTCLs. Moreover, both TCRbeta(+) ALCLs lacked CD3 and ZAP-70 (ie, molecules indispensable for the transduction of cognate TCR signals). Defective expression of TCRs is a common characteristic of all types of ALCL, which may contribute to the dysregulation of intracellular signaling pathways controlling T-cell activation and survival. This molecular hallmark of ALCL is analogous to defective immunoglobulin expression distinguishing Hodgkin lymphoma from other B-cell lymphomas.