Terminal Deoxynucleotidyl Transferase (TdT)-negative Lymphoblastic Leukemia in Pediatric Patients: Incidence and Clinical Significance

Pediatr Dev Pathol. 2017 Nov-Dec;20(6):463-468. doi: 10.1177/1093526617698610. Epub 2017 Mar 15.

Abstract

Pediatric terminal deoxynucleotidyl tranferase (TdT)-negative precursor B- or T-lymphoblastic leukemia/lymphoma (B-LL and T-LL) cases are rare and their prognostic significance remains controversial. We aimed to determine the frequency of TdT-negative B- and T-LL in the community hospital setting. Between 2005 and 2015, 43 pediatric patients were diagnosed with lymphoblastic leukemia at our institution, of which 6 (14%) were characterized as TdT-negative by flow cytometric analysis. Four of these 6 patients had B-LL and the other 2 had T-LL. Two of the 6 TdT-negative patients also had undetectable CD34 expression by flow cytometry (TdT/CD34 double-negatives). Subsequent paraffin immunohistochemistry confirmed the negative CD34 expression in both cases. By contrast, all the 6 patients had weak TdT-like immunoreactivity in their marrow despite the negative flow cytometric analysis. Furthermore, neither TdT/CD34-negative cases showed myc rearrangement by fluorescent in situ hybridization, ruling out Burkitt leukemia as a differential diagnostic consideration. We conclude that TdT-negative pediatric B- and T-LL cases (especially those that are TdT/CD34 double-negative) may pose diagnostic challenge to hematopathologists, and ancillary studies (paraffin immunohistochemistry to detect TdT and fluorescent in situ hybridization to exclude myc rearrangement) may be instrumental in reaching the correct diagnosis.

Keywords: CD34; TdT; TdT-negative ALL; flow cytometry.

MeSH terms

  • Antigens, CD34 / metabolism
  • Biomarkers, Tumor / metabolism*
  • Child
  • Child, Preschool
  • DNA Nucleotidylexotransferase / metabolism*
  • Female
  • Flow Cytometry
  • Follow-Up Studies
  • Humans
  • Immunohistochemistry
  • Incidence
  • Male
  • New Jersey / epidemiology
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / diagnosis*
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / epidemiology
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / metabolism
  • Retrospective Studies

Substances

  • Antigens, CD34
  • Biomarkers, Tumor
  • DNA Nucleotidylexotransferase