Testicular Seminoma

Alterations associated with the formation of a somatic-type malignancy and/or the development of cisplatin resistance include TP53 mutations or MDM2 gene amplifications as well as epigenetic alterations...Additionally, we will provide guidance on how to examine a testicular tumour specimen histopathologically to reach an accurate diagnosis. Finally, we will outline the importance of the content of a histopathological report for the urologists and oncologists.

In the third edition of this Special Issue, the participating researchers focused their studies on bispecific antibodies against solid tumors [contribution 1], teratoma development [contribution 2], the seminoma microenvironment [contribution 3], neuroblastoma and peptidergic systems [contribution 4], hepatocellular carcinoma [contribution 5], the synthesis of novel podophyllotoxin-benzothiazole congeners for use as anticancer agents [contribution 6], the effects of podophyllotoxin derivatives on non-cancerous diseases [contribution 7], and the involvement of the aryl hydrocarbon receptor and the signal transducer and activator of transcription 3 in chemical carcinogenesis [contribution 8] [...].

The results showed the absence of expression of POSTN and PDPN in normal canine testes and their expression in neoplastic ones, suggesting a role for these proteins in the carcinogenesis of the testis and encouraging further studies, in particular, on seminomas and Sertoli cell tumours.

Definitive diagnosis of seminoma was established through expanded immunohistochemistry (OCT4+/SALL4+/PLAP+/D2-40+) and molecular confirmation of the characteristic KIT p.D816Y mutation, which concurrently explains the observed imatinib resistance. In conclusion, the findings of the present study highlighted the imperative of integrating morphology, immunohistochemistry and context-specific molecular profiling to avoid diagnostic in CD117-positive tumors.

Based on these findings, we further developed a molecular panel to aid in the identification of seminomas with a higher risk of metastasis. In conclusion, our study identifies unique molecular signatures that facilitate risk stratification based on metastatic potential, providing valuable insights for improving precision medicine.

We present a case of spermatocytic tumor, which is a distinct entity among testicular germ cell tumors, with a generally favorable prognosis following orchiectomy. However, long-term follow-up is recommended due to the potential for late metastasis.

This rare case of synchronous bilateral spermatocytic tumor highlights the importance of considering this diagnosis in older men with bilateral testicular masses. Immunohistochemistry is essential for accurate identification.

BPs may impair male fertility through shared BCL2-mediated apoptosis, with computational evidence suggesting compound-specific pathways involving CYP19A1 (steroidogenesis), AR (androgen signaling), and PTGS2 (inflammation). These findings underscore the need for compound-specific toxicological assessments integrating mechanistic and computational evidence to guide precise prevention and regulatory strategies.

This study provided a comprehensive molecular and genetic profiling of seminoma including key genetic alterations, affected pathways, and potential therapeutic strategies. Moreover, overlap between pathways and gene mutations provides the potential for alternative treatment options for seminoma via multiple pathways.

Immunophenotypic distribution of secretome granules indicates a decrease in the number of Tryptase-, Chymase- and CPA3-mast cells, which is inversely proportional to the pTNM stage of non-metastatic seminoma.

These findings highlight the relevance of TME in TGCT biology and prognosis. The observed associations suggest TME may influence tumor plasticity, metastatization and relapse risk, warranting validation in larger studies.

Our preclinical work on CDX and PDX together with proof-of-concept clinical case provide rationale for further studies. Refractory relapsing TGCTs represent another clinical entity for treatment with ADC-SG.