ORIGINAL ARTICLE
Diagnostically misleading aberrant terminal deoxynucleotidyl transferase expression in germ cell tumors
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Department of Pathomorphology, Medical University of Gdańsk, Gdańsk, Poland
Submission date: 2022-03-19
Acceptance date: 2022-09-05
Publication date: 2022-10-10
Pol J Pathol 2022;73(2):159-165
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ABSTRACT
Terminal deoxynucleotidyl transferase (TdT) is a unique type of DNA polymerase predominantly expressed in precursor lymphoid cells and acute lymphoblastic leukemia. It participates in the junctional diversity of T-cell receptors and immunoglobulins. Recently, aberrant TdT expression was found in seminomas. Here, we evaluated the expression of TdT in our cohort of germ cell tumors (GCTs) with two anti-TdT antibody clones.
We included 173 cases of testicular GCTs, 5 ovarian dysgerminomas, and one gonadoblastoma in the study. Tissue microarrays containing representative tumor samples were constructed and subsequently stained with anti-TdT monoclonal rabbit antibody EP266 (Dako) and TdT rabbit polyclonal antibody (Cell Marque).
Expression was assessed with the H-score. No specific nuclear reaction was observed for the polyclonal anti-TdT antibody. The H-score values varied between the histological subtypes for the EP266 antibody. Positive nuclear staining was consistently seen in germ cell neoplasia in situ, seminoma, dysgerminoma, and embryonal carcinoma. Pure tumors had higher TdT H-scores than the mixed ones. Teratomas, yolk sac tumors, and choriocarcinomas were almost uniformly negative.
Our study confirms that aberrant expression of TdT by testicular and ovarian GCTs exemplifies a potential diagnostic pitfall in histopathological diagnostics.
REFERENCES (17)
1.
Thai TH, Kearney JF. Distinct and opposite activities of human terminal deoxynucleotidyltransferase splice variants. J Immunol 2004; 173: 4009-4019.
2.
Peralta-Zaragoza O, Recillas-Targa F, Madrid-Marina V. Terminal deoxynucleotidyl transferase is down-regulated by AP-1-like regulatory elements in human lymphoid cells. Immunology 2004; 111: 195-203.
3.
Liu L, McGavran L, Lovell MA, et al. Nonpositive terminal deoxynucleotidyl transferase in pediatric precursor b-lymphoblastic leukemia. Am J Clin Pathol 2004; 121: 810-815.
4.
Sidiropoulos M, Hanna W, Raphael SJ, Ghorab Z. Expression of TdT in Merkel cell carcinoma and small cell lung carcinoma. Am J Clin Pathol 2011; 135: 831-838.
5.
Brobeil F, Wagenlehner S. Gattenlöhner expression of terminal deoxynucleotidyl transferase (TdT) in classical seminoma: a potential diagnostic pitfall. Virchows Arch 2018; 472: 433-440.
6.
Henwood AF. Aberrant cytoplasmic terminal deoxynucleotidyl transferase (TdT) immunostaining on previously frozen, formalin-fixed paraffin-embedded tissue: cryotomy-induced antigen diffusion (CIAD). Appl Immunohistochem Mol Morphol AIMM 2021; 29: e17-e19.
7.
Gayhart MG, Richard H, Wiles AB, Smith SC. Aberrant expression of TdT in seminomatous germ cell neoplasia. Virchows Arch 2018; 473: 385-386.
8.
Zhou J, Wang S, Zhu L, et al. Terminal deoxynucleotidyl transferase commonly expresses in germ cell tumors: evaluation on a large series from multiple centers. Int J Gen Med 2021; 14: 119-129.
9.
Jaconi M, Magni F, Raimondo F, et al. TdT expression in germ cell tumours: a possible immunohistochemical cross-reaction and diagnostic pitfall. J Clin Pathol 2019; 72: 536-541.
10.
Bateman MJ, Martin S, Orchard M, et al. Teodoro, UniProt: the universal protein knowledgebase in 2021. Nucleic Acids Res 2021; 49: D480-D489.
11.
Miyai K, Yonekura Y, Ito K, Matsukuma S, Tsuda H. Gene expression microarray analysis of adult testicular germ cell tumor: a comparison between pure-type seminomas and seminoma components in mixed tumors. Virchows Arch 2021; 479: 1177-1186.
12.
Hoang MP, Donizy P, Wu CL, et al. TdT expression is a marker of better survival in Merkel cell carcinoma, and expression of B-cell markers is associated with Merkel cell polyomavirus. Am J Clin Pathol 2020; 154: 38-47.
13.
Zur Hausen A, Rennspiess D, Winnepenninckx V, Speel EJ, Kurz AK. Early B-cell differentiation in Merkel cell carcinomas: clues to cellular ancestry. Cancer Res 2013; 73: 4982-4987.
14.
Sur M, AlArdati H, Ross C, Alowami S. TdT expression in Merkel cell carcinoma: potential diagnostic pitfall with blastic hematological malignancies and expanded immunohistochemical analysis. Mod Pathol 2007; 20: 1113-1120.
15.
Mathewson RC, Kjeldsberg CR, Perkins SL. Detection of terminal deoxynucleotidyl transferase (TdT) in nonhematopoietic small round cell tumors of children. Pediatr Pathol Lab Med 1997; 17: 835-844.
16.
Tzorakoleftheraki SE, Iliadis A, Kostopoulos I, Koletsa T. TdT expression in normal and neoplastic sebaceous cells. Histopathology 2017; 71: 985-988.
17.
Zhou J, Xu H, Zeng H, et al. Expression of TdT in myoepithelial cells: investigation in breasts, sweat glands, and salivary lesions emphasizing the never-documented immunohistochemical findings. Int J Surg Pathol 2020; 28: 711-720.