Testicular Seminoma

Despite considerable heterogeneity between patients, T cell subtypes form a key part of the TGCT microenvironment. The novel finding of rare Treg and Tfh cells in human testis suggests their involvement in TGCT pathobiology, with implications for understanding tumor progression, to assess patients' prognosis, and as putative targets for personalized immunotherapy.

Gonadoblastoma is a rare germ cell-sex cord stromal tumor, which is usually accompanied by gonadal hypoplasia. As a special subtype, dissecting gonadoblastoma will be easily confused with dysgerminoma/seminoma, but the prognosis is better. So we should improve the understanding of this subtype and avoid overdiagnosis.

Additionally, an association between testicular sex cord stromal tumors and paratesticular sarcomas with Familial adenomatous polyposis syndrome and DICER1 syndrome, respectively, has been proposed as well. This review provides a comprehensive overview of the intricate relationship between familial syndromes and associated testicular and paratesticular tumors, shedding light on their clinicopathological and molecular characteristics.

However, histone acetylation may be one of the epigenetic mechanisms involved in PRAME regulation. Thus, the therapeutic combination of histone deacetylase inhibitors and PRAME immunotherapy merits further investigation.

P=N/A, N=55, Active, not recruiting, University of Southern California | Phase classification: P2 --> P=N/A

A comparison with preexisting Melan-A (a melanocyte antigen) data revealed that StAR was more often positive in adrenocortical neoplasms and in Leydig cell tumors while StAR (but not Melan-A) was negative in Sertoli cell tumors. Our data provide a comprehensive overview on the patterns of StAR immunostaining in human tumors and suggest a diagnostic utility of StAR immunohistochemistry for supporting a diagnosis of Leydig cell tumors or of normal or neoplastic adrenocortical tissue.

ctDNA status was found to be correlated with the different stages of testicular cancer. ctDNA may be used for tailoring treatment protocols to patients with negative/mildly elevated serum tumor markers and for treatment escalation/deescalation. Prospective studies with larger cohorts are necessary to validate these initial results.

More ordered conformation and compact structure was observed at this pH (pH 8.0) as compared to other pH values through molecular dynamics simulation studies (MDS). As AURK-B localizes itself in the intracellular compartment, this study may provide a clue about the role of different pH environments in enhancing cancer growth, proliferation, and invasion.

Our patient is the first published case of Cowden syndrome, associated with multifocal pulmonary carcinoids. Besides multiple endocrine neoplasia type 1, we propose Cowden syndrome as another hereditary condition predisposing to multiple pulmonary tumorlets and carcinoid tumours.

Postoperatively, hypertension and norepinephrine blood levels were normalized. The histological report surprisingly showed a Seminoma (positivity for PLAP, OCT ¾, c-kit, MDM2) and the surgical margins were free.

Loss of MLH1 expression was only found to be significantly associated with lower patients' age. Positive immunohistochemical REV-7 expression was significantly associated with various clinicopathological parameters, while it was also associated with significantly lower survival and greater hazard. REV-7 positive percentages were significantly higher in patients with chemoresistant disease. Our findings imply that immunohistochemical staining for REV-7 could potentially be used as a predictive tissue marker for TGCT tumors. Moreover, targeting of REV-7 protein, could represent a potential therapeutic strategy for chemoresistant TGCT cases. The implementation of well-designed studies on a larger scale is of utmost importance, in order to draw safer conclusions. Additional studies are needed so as to draw safer conclusions.

This case of STM chondrosarcoma demonstrated divergent immunophenotypic and molecular characteristics compared to "typical" examples of head and neck chondrosarcoma. High index of suspicion is advised regarding the diagnosis of lesions that present with otherwise typical histomorphology but unexpected immunohistochemical or molecular features.

The frequent infiltration of CD45RO, along with variable expression of PD-1 and PD-L1 on TILs and tumor cells, could impact the effectiveness of anti-tumor responses and immunotherapy.

The expression of the Lgals3 gene encoding galectin-3 in seminomas was slightl higher in relation to the tissue unchanged by the carcinogenetic process. The results of the study suggest a significant role of β-catenin, E-cadherin and galectin-3 in the carcinogenesis of seminomas and may indicate new aspects of the patomechanism of seminomas formation, and thus time lead to better understand the biology of these tumors.

Furthermore, we identify key pathways and genes that may facilitate seminoma disseminating beyond the seminiferous tubules. These findings advance our knowledge of seminoma tumorigenesis and produce a multi-omics atlas of in situ human seminoma microenvironment, which could help discover potential therapy targets for seminoma.

P=N/A, N=956, Recruiting, SWOG Cancer Research Network | Trial completion date: Oct 2025 --> Oct 2026 | Trial primary completion date: Jun 2025 --> Jun 2026

P2, N=818, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Oct 2024 --> May 2026 | Trial primary completion date: Oct 2024 --> May 2026

In conclusion, excessively increased hCG serum levels can appear in patients with pure SEM. To explain detectable hCG serum levels, it is important to diagnose the subtype of a SEM with syncytiotrophoblasts.

Our analysis reveals some differences in survival trends with better survival in seminoma compared to non-seminoma, though Blacks and Hispanics have worse outcomes compared to Whites and Non-Hispanic Whites. This highlights the need for targeted efforts to bridge gaps in care.

This is the first study that utilizes longitudinal tumor-informed ctDNA testing to assess patient outcomes and disease status. Our results suggest that tumor-informed ctDNA analysis may hold promise as a biomarker for EFS in patients with testicular cancer. As such, we developed the first-ever clinical nomogram that includes ctDNA status and other clinicopathological factors to stratify patient outcomes.

In human seminoma specimens, we found a strong PTTG1/SPTBN1 colocalization that decreases in areas with nuclear PTTG1 distribution. Overall, these results suggest that SPTBN1, along with PTTG1, is a potential prognostic factor useful in the clinical management of seminoma.

© 2023 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland

This study identified a nanobody-drug-conjugate targeting CXCR4 as a putative therapeutic option for GCT, i.e. seminoma and yolk-sac tumors. Furthermore, this study shed light on the functional role of the CXCR4 / CXCR7 / CXCL12-signaling cascade in GCT, demonstrating an important influence on proliferation and migration.

These findings suggest that SerpinB9 contributes to the immune escape of testicular germ cell tumors. Targeting therapy for SerpinB9 might therefore be useful in immunotherapy for testicular germ cell tumors resistant to immune checkpoint inhibitors.

P2, N=60, Recruiting, Heinrich-Heine University, Duesseldorf

In conclusion, we demonstrated that an oncogenic Gα mutant enables the PDZ-RhoGEF DH-PH module to recognize RhoJ, suggesting an allosteric mechanism by which this constitutively active GTPase stimulates RhoJ via PDZ-RhoGEF. These findings highlight PDZ-RhoGEF and RhoJ as potential targets in tumors driven by mutant Gαq.

Non-pulmonary visceral metastases, high levels of the serum tumor markers alpha-fetoprotein (AFP) and human chorionic gonadotropin (HCG), and primary mediastinal non-seminoma are currently identified as determinants of poor prognosis. In addition, the presence of distinct microRNA profiles between seminomas and non-seminoma GCTs has opened up important perspectives in terms of noninvasive biomarkers that can be used in diagnosis and treatment monitoring.

Both histologies are exquisitely sensitive to platinum chemotherapy, and the combination of bleomycin, etoposide, and cisplatin (BEP) yields survival rates greater than 90%...We present available clinical trial data supporting de-escalation of chemotherapy treatment. Finally, we propose that future trials should enrol men, women, and children to benefit all patients regardless of age or sex.

P2, N=818, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Oct 2023 --> Oct 2024 | Trial primary completion date: Oct 2023 --> Oct 2024

Taking into consideration the high sensitivity and specificity, serum microRNAs 367,371,372,373,302d are of great interest for clinical use in malignant GCT. Significant expression of miR 375-3p was not detected either in malignant GCT or in teratomas.

For patients with a history of cryptorchidism and tumors located in the central axis, special attention should be paid to physical examination of the testes, testicular ultrasonography, and determination of AFP and other indicators to identify gonadal tumor metastasis. And if so, radiotherapy and chemotherapy can be considered first to reduce surgical complications and achieve accurate management.

HKTG improves the function of spermatogenic cells and increases sperm production in the testis tissue of mice by promoting meiosis.

In addition, dysgerminoma/Seminoma have high PDL-1 expressions are associated with high genetic alterations and better prognosis compared to PDL-1 negative yolk Sac. Conclusions Our findings are likely to help improve knowledge about the potential benefits of ovarian cancer immunotherapy in specific subsets of germ cell tumour patients and risk factors for resistance that are mediated by the tumour microenvironment cells.

P2, N=50, Recruiting, Jennifer King | Suspended --> Recruiting

After one cycle of a bleomycin, etoposide and cisplatinum (BEP) regimen, he was referred to our hospital...Denosumab was also administered monthly...Because extirpation of the remaining mass would require resection of the left part of the pelvic bone with significant functional loss of the left limb, we performed close follow-up after an additional 2 courses of the etoposide and cisplatin regimen. The patient is currently alive without recurrence at 45 months after the last systemic chemotherapy.

Using RNA-seq, a network of over 50 genes potentially regulated by the ESX1 gene was determined. Finally, 6 genes, NANOG, CXCR4, RPS6KA5, CCND1, PDE1C, and LINC00662, participating in cell proliferation and differentiation were verified in azoospermic patients with and without a mutation in the ESX1 gene as well as in men with normal spermatogenesis, where inverse correlations in the expression levels of the observed genes were noted.

In this case series, PBT for retroperitoneal and pelvic metastases in Stage IIA/IIB testicular seminoma was associated with oncologic efficacy with minimal toxicity. PBT reduces unnecessary dose to abdominal/pelvic organs compared to x-ray techniques, which is advantageous in young patients who have anticipated long-term survival. This is one of the few series reporting clinical outcomes of PBT in the management of seminoma. Randomized comparisons with x-ray approaches are impractical given the relatively low volume of patients receiving RT in modern seminoma management, so it is essential to report and track longitudinal outcomes across institutions to validate this approach.

The percentages of R-10G-positive cells in these three groups varied with high statistical significance (p<0.001 for all combinations). These findings indicate that the R-10G-reactive antigen is preferentially expressed in human testicular EC tissues and, thus, could be used as a diagnostic marker for this malignancy.

Cytology can provide a reliable, accurate method for diagnosing EGGCTs. The practice of preoperative (neoadjuvant) chemotherapy places an extreme importance on the initial cytopathologic diagnosis because the majority of patients with follow-up resection in this series showed no residual tumor.

This case report points out that there may be a poor correlation between clinical findings and pathophysiologic processes affecting scrotal structures. Additional radiological investigations, such as CT scan, could clarify and confirm the clinical scenario, improving the preoperative planning and surgical outcomes.

GCC patients who relapse after initial CSI can be detected early by active surveillance and have an excellent survival.

In patients with CS-II seminoma treated with modern RT, there were no in-field recurrences. Presentation with de novo CS-II is associated with out-of-field recurrence. Subject to further larger-scale validation, our results suggest that compared to CS-II at time of relapse, de novo CS-II may portend more aggressive or micrometastatic disease beyond the retroperitoneum, raising the possibility of benefit from chemotherapy after radiation.