Detection of terminal deoxynucleotidyl transferase (TdT) in nonhematopoietic small round cell tumors of children

In the differential diagnosis of small round cell tumors (SRCTs), terminal deoxynucleotidyl transferase (TdT) is often used as a marker for lymphoblastic lymphomas and leukemias. However, the specificity of TdT using the avidin-biotin-immunoperoxidase (ABC) method is not well documented. To address this issue, we stained paraffin-embedded biopsy specimens of 64 cases of childhood SRCTs using the ABC method with anti-TdT. For any TdT-positive tumors, an additional antibody panel for lymphoid markers was applied. Two patterns of TdT positivity were observed: (1) tumor specific, consisting of strong to moderate nuclear staining, and (2) scattered positive lymphoid cells, usually in a perivascular location and expressing T-cell markers. Analysis showed that 7 of 10 medulloblastomas stained with TdT in a tumor-specific pattern (4 cases moderately to strongly positive in 75-100% of tumor cells, 3 cases weakly to moderately positive in 25-50% of cells). Also, 1 of 19 rhabdomyosarcomas and 1 of 8 Ewing's sarcomas showed moderate to strong tumor-specific TdT staining in 100 and 10% of cells, respectively. Scattered TdT-positive lymphoid cells were observed in 27% of these 64 SRCTs. These findings emphasize that TdT positivity should not be relied upon exclusively for making a diagnosis of lymphoblastic leukemia or lymphoma or ruling out other SRCTs.