Aberrant expression of TdT in seminomatous germ cell neoplasia

Gayhart, Matthew; Richard, Hope; Wiles, Austin; Smith, Steven C.

doi:10.1007/s00428-018-2402-5

Cited by 3 publications

(2 citation statements)

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“…In contrast, aberrant cytoplasmic TdT staining may occur in previously frozen, formalin-fixed paraffin-embedded samples of lymphoblastic lymphoma [6]. A subsequent study by Gayhart et al utilizing the same clone revealed TdT expression in 4/25 seminomas (16%), 6/12 germinomas (50%), and 1/3 dysgerminomas (33%) [7]. Another study on a larger population (n = 192) reported frequency of TdT expression very similar to our cohort [8].…”

Section: Discussionsupporting

confidence: 80%

Diagnostically misleading aberrant terminal deoxynucleotidyl transferase expression in germ cell tumors

Pęksa

Kunc

Bieńkowski

et al. 2022

pjp

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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.

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Section: Discussionsupporting

confidence: 80%

Diagnostically misleading aberrant terminal deoxynucleotidyl transferase expression in germ cell tumors

Pęksa

Kunc

Bieńkowski

et al. 2022

pjp

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“…16,17 Recently, Gayhart et al also found aberrant expression of TdT in germ cell tumors. 18 However, no clear genetic link between TdT expression and germ cell tumor tumorigenesis has been indicated by western blot analysis; thus, it was hypothesized that the occurrence of immunohistochemical nuclear cross-reactivity may explain the reason for the TdT expression. 19 Accordingly, a similar scenario occurring in MECs could be a plausible explanation.…”

Section: Discussionmentioning

confidence: 99%

Expression of TdT in Myoepithelial Cells: Investigation in Breasts, Sweat Glands, and Salivary Lesions Emphasizing the Never-Documented Immunohistochemical Findings

Zhou

Zeng

et al. 2020

Int J Surg Pathol

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Background. The expression of terminal deoxynucleotidyl transferase (TdT) in myoepithelial cells (MECs) within the breast was recently incidentally observed in our routine practice. This study aimed to elucidate the expression of TdT in MECs. Methods. TdT immunostaining was performed on 180 mammary, 89 cutaneous, and 94 salivary tissues or lesions. Other myoepithelial markers, including P63, calponin, and SMA as well as double staining for TdT and calponin, were also evaluated in some cases. Selected lesions with basal or myoid differentiation were also included in the investigation. Results. MECs were positive for TdT in mammary lesions that contained MECs (132/135) but negative when they did not contain MECs (45/45). MECs in sweat glands (24/30) and their neoplastic counterparts, including those in hidradenoma papilliferum (2/9), spiradenoma (6/6), and cutaneous mixed tumor (9/9), showed weak to moderate TdT positivity. MECs were variably immunolabeled for TdT in salivary or salivary gland–type tumors with myoepithelial differentiation (pleomorphic adenoma, 24/25; basal cell adenoma, 6/7; adenoid cystic carcinoma, 7/7; Warthin tumor, 0/6; mucoepidermoid carcinoma, 0/8; acinic cell carcinoma, 0/4), but MECs in normal salivary gland barely stained for TdT (30/32). Conclusions. Our findings indicate that TdT may be eligible as an additional auxiliary immunohistochemical marker as P63, but not a surrogate, to identify the MECs in the breast with limited cross-reactivity, particularly in lesions with a prominent proportion of MECs. Positivity for TdT, along with other relevant markers, in a subset of sweat gland lesions and salivary tumors may contribute to their diagnosis.

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TdT expression in germ cell tumours: a possible immunohistochemical cross-reaction and diagnostic pitfall

et al. 2019

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AimsVery 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 resultsThe 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.ConclusionsAlternatively 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.

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Aberrant expression of TdT in seminomatous germ cell neoplasia

Cited by 3 publications

References 1 publication

Diagnostically misleading aberrant terminal deoxynucleotidyl transferase expression in germ cell tumors

Diagnostically misleading aberrant terminal deoxynucleotidyl transferase expression in germ cell tumors

Expression of TdT in Myoepithelial Cells: Investigation in Breasts, Sweat Glands, and Salivary Lesions Emphasizing the Never-Documented Immunohistochemical Findings

TdT expression in germ cell tumours: a possible immunohistochemical cross-reaction and diagnostic pitfall

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