Jaconi M, et al. - Via a multicentric study, the researchers sought to assess the magnitude of the immunoreactivity for terminal deoxynucleotidyl transferase (TdT) in germ cell-derived tumors (GCTs), encompassing seminoma, dysgerminoma, mature teratoma, and mixed GCTs. The histological series was stained with both monoclonal and polyclonal antibodies, giving a positivity of 80% of subjects with well-defined nuclear reactivity. A notable variation in staining intensity between monoclonal and polyclonal antibodies was perceived. Nevertheless, in the neoplastic tissues of the series, exploiting western blot and more innovative proteomic approaches, no clear-cut evidence of the TdT protein was recognized. Hence, the occurrence of a spurious immunohistochemical nuclear cross-reaction, a well-known phenomenon with significant indications and a possible source of diagnostic pitfalls in routine practice for pathologists was hypothesized alternatively to the pathogenetic link between TdT expression and GCTs tumourigenesis.