The immunophenotype of T-lymphoblastic lymphoma in children and adolescents: a Children's Oncology Group report

Abstract

T-lymphoblastic leukaemia (T-ALL) and T-lymphoblastic lymphoma (T-LBL) are neoplasms derived from immature lymphoid cells of T-cell lineage. These neoplasms are biologically similar, but significant differences may exist between the two given their clinical differences. Although ample data regarding the immunophenotypic characterization T-ALL are available, there is a paucity of such data in children and adolescents with T-LBL. We used flow cytometry and/or immunohistochemistry to characterize the immunophenotypic profile of 180 children and adolescents with newly diagnosed T-LBL enrolled in the Children's Oncology Group 5971 study. Multiple T-cell, B-cell, myeloid, and other markers were evaluated. We identified diagnostically useful immunophenotypic features of T-LBL as well as distinct immunophenotypic subgroups, although none of these was statistically related to event-free or overall survival in this retrospective analysis. Further studies of biologically and immunophenotypically distinct subgroups of T-LBL, such as the early T-cell precursor phenotype, are warranted.

Fig 1

T-lymphoblastic lymphoma: sites of diagnostic biopsy. The majority of patients presented with T-lymphoblastic lymphoma involving mediastinal and/or nodal disease as the primary site. Head and neck lymph nodes showed highest incidence of involvement among lymph node groups, while visceral organs were rarely affected.

Fig 2

Expression of selected immunophenotypic markers in T-lymphoblastic lymphoma patients. All cases demonstrated positivity for cytoplasmic and/or surface CD3 and the pan T-cell antigens CD2, CD5, and CD7 were expressed in the vast majority. Aberrant myeloid antigens were observed in 16% of cases, with CD33 being the most likely antigen to be expressed. TdT was demonstrably positive in 90% of cases. TdT negative cases showed a similar immunoprofile, with notably decreased incidence of CD4/CD8 double positivity and aberrant myeloid antigen expression.

Fig 3

Distribution of T-LBL by postulated stage of T-cell maturation. Six cases (4%) clearly met the criteria, shown above, for early T cell subtype [CD1a⁻, CD8⁻, and CD5^+/weak with positivity for one or more myeloid (e.g., CD13, CD33) or stem cell (e.g., CD34) antigens] while an additional 10 cases (7%) showed phenotypic features in keeping with early T cell but lacked myeloid antigen data. The great majority of cases showed an immunoprofile consistent with that of subcapsular or cortical thymocytes (84%). Thirty-four cases could not be classified due to incomplete immunophenotypic data.

Fig 4

Event-free survival curves for all patients by selected immunophenotypic parameters and bone marrow disseminated disease. Kaplan–Meier plots showing (A) event-free survival (EFS) for all eligible patients, (B) early T cell subtype versus non early T cell, (C) CD33 positive versus negative, (D) TdT positive versus negative, (E) Bone marrow disseminated disease <1% vs. ≥1% bone marrow T-lymphoblasts by flow cytometric analysis. Statistically significant differences in EFS were not observed.