Terminal Deoxynucleotidyl Transferase Commonly Expresses in Germ Cell Tumors: Evaluation on a Large Series from Multiple Centers

Abstract

The concrete features of expression of terminal deoxynucleotidyl transferase (TdT) are needed to be revealed in male and female germ cell tumors (GCTs). Methods: TdT immunostaining was performed in 195 GCTs, and the tumor and/or tumorous components included seminomas, germ cell neoplasias in situ (GCNISs), dysgerminomas, embryonal carcinomas (ECs), extragonadal germinomas, yolk sac tumors (YSTs), teratomas, and spermatocytic tumors. Twenty-one sex cord-stromal tumors were also added. Expression of the classical germ cell tumor markers (PLAP, OCT4, SALL4, CD117, and D2-40) was compared to that of TDT. Results: Nearly all (tumors or tumorous components) seminomas (99%, 107/108), GCNISs (98%, 51/52), dysgerminomas (94%, 17/18), ECs (100%, 15/15), and extragonadal germinomas (100%, 11/11) were positive for TdT. None of the cells in YSTs (0/38), teratomas (0/ 19), spermatocytic tumors (0/1), or sex cord-stromal tumors (0/21) were immunoreactive for TdT staining. The normal testicular and ovarian gonadal tissues were also negative for TdT. However, TdT presented with significant loss of antigen immunoreactivity in the paraffinembedded tissues older than 3 years, giving rise to weak or moderate staining in a subset of cases. The expressions of TdT showed no significances with PLAP, OCT4, SALL4, CD117, and D2-40 during the diagnosis of the most GCTs (P>0.05), except for with PLAP, SALL4, or CD117 in YST (P=0.000 each), and D117 (P=0.000) or D2-40 (P=0.006) in ECs. Conclusion: Our findings further verify that TdT can serve as a new GCT marker for seminomas, GCNISs, dysgerminomas, ECs, and extragonadal germinomas, with a highly positive rate. Awareness of TdT positivity in GCTs contributes to the prevention of erroneous diagnoses, particularly in the setting of core needle biopsies. To determine the properties where TdT staining may not be apparent in some old archived paraffin-embedded tissues, one could circumvent the potential misinterpretations of false-negative immunohistochemistry results.

Diagnostically misleading aberrant terminal deoxynucleotidyl transferase expression in germ cell tumors

“…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]. None of the aforementioned studies analyzed the association between the level of immunohistochemical expression of TdT and clinicopathological characteristics.…”

“…One study postulated that long-term storage of paraffin-embedded GCT tissues may lead to losing their TdT detectability [8]. In contrast, we observed that deeper parts of the tumor show lower (if any) reactions than superficial areas, where the formalin penetration is more efficient.…”

Spontaneous rupture‑induced life‑threatening mediastinal mixed germ cell tumor: A case report and therapeutic considerations

“…Although AFP and β-hCG levels were not available for the patient of the current report upon admission, postoperative examination revealed elevated levels of both markers. Zhou et al ( 16 ) discovered that terminal deoxynucleotidyl transferase can serve as a novel tumor marker for diagnosing seminoma, germ cell tumor in situ , anaplastic cell tumor, embryonal carcinoma and mixed germ cell tumor with a markedly high positive rate. Furthermore, research has demonstrated that plasma levels of microRNA-371a-3p can be used as an indicator for prognostic assessment of germ cell tumors ( 17 ).…”

Immune-related mechanisms and immunotherapy in extragonadal germ cell tumors

“…At present, markers for these tumors are still being tested and discovered. For example, one study reported that terminal deoxynucleotide transferase (TdT) can be used as a new IHC marker for the diagnosis of various extragonadal GCTs with a high positive rate in seminomas (99%, 107/108), ECs (100%, 15/15), and extragonadal germinomas (100%, 11/11) and absence in YSTs (0/38) and teratomas (0/19) ( 60 ). More clinical trials targeting various types of EGCTs are expected in the future.…”