Abstract
T lymphoblastic lymphomas (T-LBL) are rare disorders of immature T cells which predominantly involve the mediastinum. Their oncogenic pathways and prognostic variables are not clear. We undertook a retrospective study of 41 cytoplasmic CD3+ T-LBL (nine cases aged <16 years) by assessing stage of maturation arrest based on T cell receptor (TCR) immunogenotyping, immunohistochemistry, and quantification of the oncogenes thought to be important in immature T cell malignancies. Application of a TCR-based immunogenetic classification allowed the identification of three subcategories: 11 immature IM0/D-LBL showed no TCR or only incomplete TCRD DJ rearrangement and corresponded to cytoplasmic CD3+ precursors of uncertain lineage. Sixteen mature TCRD(del)-LBL showed biallelic TCRD deletion and both TCRG and TCRB rearrangement, consistent with TCRalphabeta lineage restriction. Fourteen intermediate LBL (Int-LBL) showed complete TCRD VDJ and TCRG VJ rearrangement, with TCRB VDJ rearrangement in the majority. All Int-LBL expressed HOX11/TLX1 or HOXA9 transcripts and a proportion of the latter were associated with CALM-AF10 or NUP214-ABL fusion transcripts. IM0/D-LBL were restricted to adults with extrathymic disease and bone marrow involvement, whereas Int-LBL and TCRD(del)-LBL were found in children and adults with predominantly thymic disease. In adults, the Int-LBL subgroup was associated with a significantly superior clinical outcome. This subgroup can be identified either by TCR immunogenotyping or HOXA9/TLX1 transcript quantification. Application of this molecular classification will allow the prospective evaluation of prognostic effects within pediatric and adult protocols.
Highlights
Immunogenotyping, immunohistochemistry, and quantification of the oncogenes thought to be important in immatureTcell malignancies
DNA-based TCRg, y, and h genotyping by multiplex PCR, with additional specific PCR typing when necessary [5], was possible for all 41 cases, whereas Southern blot TCRD analysis was done for 38 cases (Table 2)
The TCRD locus was in a germ line configuration by PCR and Southern blotting in 7 cases, negative by PCR, and deleted on both alleles in cases, whereas it was rearranged on at least one allele by PCR and/or Southern blotting in cases
Summary
Immunogenotyping, immunohistochemistry, and quantification of the oncogenes thought to be important in immatureTcell malignancies. Sixteen mature TCRDdel-LBL showed biallelic TCRD deletion and both TCRG and TCRB rearrangement, consistent withTCRah lineage restriction. The Int-LBL subgroup was associated with a significantly superior clinical outcome. This subgroup can be identified either byTCR immunogenotyping or HOXA9/TLX1 transcript quantification. T lymphoblastic lymphomas (T-LBL) are rare non – Hodgkin lymphomas defined by the expansion of immature cytoplasmic CD3 (cCD3) expressing lymphoblasts, frequent mediastinal involvement, and absent or
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