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TdT expression in germ cell tumours: a possible immunohistochemical cross-reaction and diagnostic pitfall
  1. Marta Jaconi1,
  2. Fulvio Magni1,
  3. Francesca Raimondo1,
  4. Maurilio Ponzoni2,
  5. Clizia Chinello1,
  6. Andrew Smith1,
  7. Isabella Piga1,
  8. Nicola Fusco3,
  9. Camillo Di Bella1,
  10. Fabio Pagni1
  1. 1 Department of Medicine and Surgery, University Milan Bicocca, Milan, Italy
  2. 2 Division of Pathology, University San Raffaele, Milan, Italy
  3. 3 Division of Pathology, Ospedale Maggiore Policlinico, University of Milan, Milan, Italy
  1. Correspondence to Professor Fabio Pagni, Unimib, Department Of Pathology, Monza 20900, Italy; fabio.pagni{at}


Aims Very recent papers proposed a possible role for the expression of terminal deoxynucleotidyl transferase (TdT) in the tumourigenesis of gonadal and extragonadal germ cell-derived tumours (GCTs). Our multicentric study evaluated the magnitude of the immunoreactivity for TdT in GCTs, encompassing seminoma, dysgerminoma, mature teratoma and mixed GCTs.

Methods and results The histological series was stained with both monoclonal and polyclonal antibodies, yielding a positivity of 80% of cases with well-defined nuclear reactivity. A significant difference in staining intensity between monoclonal and polyclonal antibodies was observed (p=0.005). However, exploiting western blot and more innovative proteomic approaches, no clear-cut evidence of the TdT protein was observed in the neoplastic tissues of the series.

Conclusions Alternatively to the pathogenetic link between TdT expression and GCTs tumourigenesis, we hypothesised the occurrence of a spurious immunohistochemical nuclear cross-reaction, a well-known phenomenon with important implications and a possible source of diagnostic pitfalls in routine practice for pathologists.

  • tdt
  • seminoma
  • terminal deoxynucleotidyl transferase
  • germinal cell tumor
  • differential diagnosis
  • haematopoietic
  • genital system

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  • Handling editor Dhirendra Govender.

  • Contributors All the authors gave substantial contributions to the conception or design of the work, or the acquisition, analysis or interpretation of data.

  • Funding This work was funded thanks to AIRC (Associazione Italiana per la Ricerca sul Cancro) MFAG GRANT 2016- Id. 18445.

  • Competing interests None declared.

  • Patient consent for publication Not required.

  • Ethics approval The study followed the Italian general rules for research for scientific purposes (official regulations n.72–26/03/2012); specific ethical board approval for biological specimens by the ASST Monza, under the approval #N.1311, dated 17 July 2018.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data availability statement Data are available on reasonable request. All data relevant to the study are included in the article or uploaded as online supplementary information.