Assessment of t(2;5)(p23;q35) translocation and variants in pediatric ALK+ anaplastic large cell lymphoma.

To evaluate t(2;5) and its variants, we studied 21 pediatric cases of anaplastic lymphoma kinase (ALK)+ anaplastic large cell lymphoma (ALCL) by using immunohistochemical staining, fluorescence in situ hybridization, cytogenetics, and reverse transcriptase–polymerase chain reaction. Results showed 7 (33%) cases with t(2;5), 6 (29%) with variant gene rearrangements, 7 (33%) with uncharacterized rearrangements, and 1 with ALK protein expression but no ALK rearrangement. Among 6 variant gene rearrangements, 1 had TPM4-ALK/t(2;19)(p23;p13) and 2 had inv(2) with the breakpoint proximate to ATIC-ALK and an unknown partner gene separately. The genetic features of the remaining 3 cases were as follows: ins(8;2) with an unknown partner gene; conversion from ALK– at diagnosis to ALK+ at recurrence with unspecified gene rearrangement; complex karyotype without involvement of 2p23, suggesting a cryptic translocation. Concordance between different laboratory results varied from 47% to 81%. These data suggest that ALK variants are not uncommon and underscore the necessity of integrating immunohistochemical, cytogenetic, and molecular genetic approaches to detect, characterize, and confirm t(2;5) and its variant translocations. Anaplastic large cell lymphoma (ALCL) was first described in 1985 by Stein et al 1 as a large-cell non-Hodgkin lymphoma characterized by a sheet-like growth pattern of bizarre, CD30+ tumor cells with prominent involvement of the intrasinusoidal and paracortical areas of lymph nodes. It has been recognized as a distinct clinicopathologic entity of T-cell or null cell lineage in the Revised European-American Lymphoma classification 2 and the World Health Organization (WHO) classification. 3 ALCL constitutes approximately 10% to 15% of all non-Hodgkin lymphomas 4-9 and 20% to 30% of large cell lymphomas in children. 7,10 A portion of ALCLs was found to be associated with a recurrent cytogenetic abnormality, the t(2;5)(p23;q35). 11-13