-
Mediastinum (Hong Kong, China) 2019Mediastinal germ cell tumors (GCTs) are a rare and heterogeneous group of neoplasms. Although histologically resembling their gonadal counterparts, they differ... (Review)
Review
Mediastinal germ cell tumors (GCTs) are a rare and heterogeneous group of neoplasms. Although histologically resembling their gonadal counterparts, they differ considerably in their clinical characteristics, biological behavior and prognostic outcome. The rarity of mediastinal GCTs has hindered their meaningful analysis, with most studies and clinical trials including them along with other extragonadal GCTs, which has led to a lack of consensus on optimal treatment strategies, and a lull in improvement in patient outcomes. Diagnosis of mediastinal GCT requires a multipronged approach, and encompasses multidisciplinary treatment including chemotherapy followed by surgery, with or without radiotherapy. In view of sustained response rates to current management protocols, the focus needs to be shifted to identifying patients in whom treatment regimens can be downscaled with the aim of decreasing long term morbidity and improving quality of life in low risk patient groups, while improving survival rates in poor risk patient subsets. In this scenario, better understanding of the molecular pathogenesis of these tumors may lead to identification of novel biomarkers and therapeutic targets, as well as improved disease segmentation and risk stratification, thus helping to avoid the toxicity and morbidity associated with current one-fits-all treatment strategies. Multi-institutional collaborations across continents are necessary to generate meaningful data, and are the face of future developments in this arena.
PubMed: 35118258
DOI: 10.21037/med.2019.07.02 -
Cancers Mar 2022Testicular Germ Cell Tumours (TGCT) are widely considered a "curable cancer" due to their exceptionally high survival rate, even if it is reduced by many years after the... (Review)
Review
Testicular Germ Cell Tumours (TGCT) are widely considered a "curable cancer" due to their exceptionally high survival rate, even if it is reduced by many years after the diagnosis due to metastases and relapses. The most common therapeutic approach to TGCTs has not changed in the last 50 years despite its multiple long-term side effects, and because it is the most common malignancy in young Caucasian men, much research is needed to better the quality of life of the many survivors. Proprotein Convertases (PC) are nine serine proteases responsible for the maturation of inactive proproteins with many diverse functions. Alterations in their expression have been associated with various diseases, including cancer and inflammation. Many of their substrates are adhesion molecules, metalloproteases and proinflammatory molecules, all of which are involved in tumour development. Inhibition of certain convertases has also been shown to slow tumour formation, demonstrating their involvement in this process. Considering the very established link between PCs and inflammation-related malignancies and the recent studies carried out into the immune microenvironment of TGCTs, the study of the involvement of PCs in testicular cancer may open up avenues for being both a biomarker for diagnosis and a therapeutic target.
PubMed: 35406405
DOI: 10.3390/cancers14071633 -
Journal of Ayub Medical College,... 2021Persistent Mullerian Duct Syndrome is extremely rare. Our patient, a 32 years old male, with history of orchidectomy presented with mass abdomen. He was initially...
Persistent Mullerian Duct Syndrome is extremely rare. Our patient, a 32 years old male, with history of orchidectomy presented with mass abdomen. He was initially diagnosed with seminoma and subsequently treated with chemotherapy. Biopsy of the mass showed germ cell tumour and MRI abdomen revealed female rudimentary organs confirmed on per operative and later on histopathology. Karyotype was 46 XY.
Topics: Adult; Disorder of Sex Development, 46,XY; Female; Humans; Male; Mullerian Ducts; Orchiectomy; Seminoma; Testicular Neoplasms
PubMed: 35077632
DOI: No ID Found -
Research in Veterinary Science Sep 2023Cryptorchidism, the failed descent of one or both testes into the scrotum, is a common developmental disorder in male dogs. Cryptorchidism may affect canine fertility,...
Cryptorchidism, the failed descent of one or both testes into the scrotum, is a common developmental disorder in male dogs. Cryptorchidism may affect canine fertility, reducing the quality of the semen, and may promote spermatic cord torsion and onset of neoplasia. MicroRNAs (miRNAs) are epigenetic regulators of gene expression and their dysregulation is associated with disorders of spermatogenesis and testis neoplasia. The present study aimed at investigating the expression of miRNAs in formalin-fixed, paraffin-embedded (FFPE) canine retained testes and testes affected by seminoma, and at integrating miRNAs to their target genes. Forty testicular FFPE specimens from 30 dogs were included - 10 scrotal and 10 contralateral retained from 10 unilateral cryptorchid dogs; 10 tumoral testes affected by seminoma from non-cryptorchid dogs; 10 scrotal normal testes from non-cryptorchid dogs included as the control. The expression level of three miRNAs, namely miR-302c-3p, miR-302a-3p, and miR-371-3p, associated with testicular disorders, were quantified using RT-qPCR. The comparative analysis demonstrated that the level of miR-302a-3p and miR-371a-3p were quantifiable exclusively in control testes. The expression level of miR-302c-3p was higher in the control than in the other groups; its expression decreased in retained testes compared to scrotal testes and testes with seminoma. Gene Ontology analysis pointed out that these miRNAs may be involved in the modulation of estrogen and thyroid hormone signaling pathways. In conclusion, this study demonstrated that miRNAs are dysregulated in canine cryptorchid and seminoma-affected testes compared to control tissues, confirming the pivotal role of miRNAs in cryptorchidism.
Topics: Dogs; Animals; Male; Cryptorchidism; MicroRNAs; Seminoma; Testis; Testicular Neoplasms; Epigenesis, Genetic; Dog Diseases
PubMed: 37487386
DOI: 10.1016/j.rvsc.2023.104961 -
Nature Communications May 2023Germ cell tumors (GCTs) are neoplasms of the testis, ovary and extragonadal sites that occur in infants, children, adolescents and adults. Post-pubertal (type II)...
Germ cell tumors (GCTs) are neoplasms of the testis, ovary and extragonadal sites that occur in infants, children, adolescents and adults. Post-pubertal (type II) malignant GCTs may present as seminoma, non-seminoma or mixed histologies. In contrast, pre-pubertal (type I) GCTs are limited to (benign) teratoma and (malignant) yolk sac tumor (YST). Epidemiologic and molecular data have shown that pre- and post-pubertal GCTs arise by distinct mechanisms. Dedicated studies of the genomic landscape of type I and II GCT in children and adolescents are lacking. Here we present an integrated genomic analysis of extracranial GCTs across the age spectrum from 0-24 years. Activation of the WNT pathway by somatic mutation, copy-number alteration, and differential promoter methylation is a prominent feature of GCTs in children, adolescents and young adults, and is associated with poor clinical outcomes. Significantly, we find that small molecule WNT inhibitors can suppress GCT cells both in vitro and in vivo. These results highlight the importance of WNT pathway signaling in GCTs across all ages and provide a foundation for future efforts to develop targeted therapies for these cancers.
Topics: Male; Child; Infant; Female; Young Adult; Humans; Adolescent; Infant, Newborn; Child, Preschool; Adult; Wnt Signaling Pathway; Neoplasms, Germ Cell and Embryonal; Teratoma; Testicular Neoplasms; Genomics
PubMed: 37149691
DOI: 10.1038/s41467-023-38378-9 -
Briefings in Bioinformatics Jul 2019Testicular germ cell tumors (TGCTs) are classified into two main subtypes, seminoma (SE) and non-seminoma (NSE), but their molecular distinctions remain largely... (Review)
Review
Testicular germ cell tumors (TGCTs) are classified into two main subtypes, seminoma (SE) and non-seminoma (NSE), but their molecular distinctions remain largely unexplored. Here, we used expression data for mRNAs and microRNAs (miRNAs) from The Cancer Genome Atlas (TCGA) to perform a systematic investigation to explain the different telomere length (TL) features between NSE (n = 48) and SE (n = 55). We found that TL elongation was dominant in NSE, whereas TL shortening prevailed in SE. We further showed that both mRNA and miRNA expression profiles could clearly distinguish these two subtypes. Notably, four telomere-related genes (TelGenes) showed significantly higher expression and positively correlated with telomere elongation in NSE than SE: three telomerase activity-related genes (TERT, WRAP53 and MYC) and an independent telomerase activity gene (ZSCAN4). We also found that the expression of genes encoding Yamanaka factors was positively correlated with telomere lengthening in NSE. Among them, SOX2 and MYC were highly expressed in NSE versus SE, while POU5F1 and KLF4 had the opposite patterns. These results suggested that enhanced expression of both TelGenes (TERT, WRAP53, MYC and ZSCAN4) and Yamanaka factors might induce telomere elongation in NSE. Conversely, the relative lack of telomerase activation and low expression of independent telomerase activity pathway during cell division may be contributed to telomere shortening in SE. Taken together, our results revealed the potential molecular profiles and regulatory roles involving the TL difference between NSE and SE, and provided a better molecular understanding of this complex disease.
Topics: Computational Biology; Gene Regulatory Networks; Humans; Kruppel-Like Factor 4; Male; MicroRNAs; Models, Genetic; Neoplasms, Germ Cell and Embryonal; RNA, Messenger; Seminoma; Telomere Homeostasis; Telomere Shortening; Testicular Neoplasms; Transcriptome
PubMed: 29579225
DOI: 10.1093/bib/bby020 -
Autopsy & Case Reports 2021The sacrococcygeal region is the most common site for the extragonadal germ cell tumors comprising seminomatous and non-seminomatous tumors. Seminomatous tumors are... (Review)
Review
The sacrococcygeal region is the most common site for the extragonadal germ cell tumors comprising seminomatous and non-seminomatous tumors. Seminomatous tumors are seminomas, and non-seminomatous tumors comprise mainly teratoma (mature and immature), yolk sac tumor (YST), embryonal carcinoma (EC), and choriocarcinoma. These tumors occur in newborns, infants, and adolescents. Other common sites for extragonadal germ cell tumors are the brain and mediastinum, although they may occur anywhere in the body. These tumors may occur in mixed as well as pure form. So, sectioning from different areas should be done before labeling them as pure germ cell tumors. YST, in its pure form, is rare and therefore should not be missed as it is chemosensitive. The patient should be thoroughly assessed clinically. Imaging also becomes necessary while evaluating swelling in the sacrococcygeal region and can aid in differentials. When the clinical and imaging suspicion of either Sacrococcygeal teratoma or other germ cell tumor is high, serum biomarkers as alfa-fetoprotein should be requested. The serum levels are necessary and should be done preoperatively, postoperatively, and during the course of chemotherapy as follow-up. However, the final diagnosis rests on the histopathological diagnosis. We report one such case of pure YST in the sacrococcygeal region in a 9-month-old female child. The imaging suggested sacrococcygeal teratoma type 4, and high alfa-fetoprotein levels were determined postoperatively.
PubMed: 34249791
DOI: 10.4322/acr.2021.287 -
International Journal of Particle... 2020To determine the clinical outcomes and toxicities of proton beam therapy (PBT) versus 3D-conformal photon radiation therapy (XRT) in patients with testicular seminoma.
PURPOSE
To determine the clinical outcomes and toxicities of proton beam therapy (PBT) versus 3D-conformal photon radiation therapy (XRT) in patients with testicular seminoma.
MATERIALS AND METHODS
This observational study evaluated consecutive patients with testicular seminoma who were treated with inguinal orchiectomy and radiation therapy at a single, tertiary, high-volume center in 2008-19. Acute toxicity was scored with the Common Terminology Criteria for Adverse Events V 4.0. Organs at risk were contoured retrospectively by 2 investigators. Recurrences and secondary malignancies were based on routine follow-up imaging, either computed tomography or magnetic resonance imaging.
RESULTS
Fifty-five patients were treated with radiation therapy, 11 in the PBT-arm and 44 in the XRT-arm, with a median follow-up interval of 61 months (interquartile range [IQR]: 32-79 months). Acute treatment-related diarrhea, grade 1 to 2, was more common among XRT-treated patients (0% vs 29.5%, = .039), and dermatitis, grade 1, was more likely among PBT-treated patients (27.3% vs 2.3%, = .004). Dosimetrically, PBT-treated patients, relative to XRT-treated patients, had lower dose to organs at risk including the kidney, bladder, femoral head, spinal cord, bowel, pancreas, and stomach. The 5-year overall survival rate was 100% and disease-free survival rate was 96.4% for all patients. Two patients, all in the XRT-arm, had disease recurrence: 1 in the pelvis and 1 in the lung. Three patients, all in the XRT-arm, were diagnosed with a secondary malignancy: 1 in-field pancreaticoblastoma, 1 in-field colon adenocarcinoma, and a stage IV T-cell lymphoma.
CONCLUSION
Proton beam therapy for testicular seminoma resulted in excellent clinical outcomes and was associated with lower rates of acute diarrhea but higher rates of acute dermatitis. Proton beam therapy resulted in no in-field secondary malignancies and a more favorable dosimetric profile for organs at risk relative to XRT. Reduced dose to organs at risk, such as the kidneys, may result in long-term improvement in function.
PubMed: 33274253
DOI: 10.14338/IJPT-20-00018.1 -
International Braz J Urol : Official... 2021Testicular cancer is considered a rare disease affecting approximately 1% to 2% of the male population. This neoplasm has a cure rate of over 95%; as a result, a major... (Review)
Review
Testicular cancer is considered a rare disease affecting approximately 1% to 2% of the male population. This neoplasm has a cure rate of over 95%; as a result, a major concern is the future of fertility of carriers from this disease. There are several histological subtypes of testicular tumors; however, the Testicular Germ Cell Tumors (TGCTs), comprising both seminoma and non-seminoma tumors, are considered the main subtypes of testicular neoplasms. TGCT are characterized by being a solid tumor that mostly affects young men aged between 15 and 40 years old. While TGCT subtypes may have an invasive potential, seminoma subtype does not affect other cells rather than germ cells, while non-seminomas have more invasive properties and can achieve somatic cells; thus, having a more aggressive nature. This research intends to review the literature regarding information about sperm parameters, correlating the data found in those studies to the subfertility and infertility of patients with TCGTs. Furthermore, it will also correlate the data to the non-seminoma and seminoma histological subtypes from pre- and post-cancer therapy. PubMed databases were used. Searched keywords included: seminoma AND non-seminoma; male infertility; germ cell tumor; chemotherapy AND radiotherapy. Only articles published in English were considered. Current studies demonstrate that both TGCT subtypes promote deleterious effects on semen quality resulting in decreased sperm concentration, declined sperm total motility and an increase in the morphology alterations. However, findings suggest that the non-seminoma subtype effects are more pronounced and deleterious. More studies will be necessary to clarify the behavior of seminoma and non-seminoma tumors implicating the reproductive health of male patients.
Topics: Adolescent; Adult; Humans; Male; Neoplasms, Germ Cell and Embryonal; Semen Analysis; Seminoma; Spermatozoa; Testicular Neoplasms; Young Adult
PubMed: 32459453
DOI: 10.1590/S1677-5538.IBJU.2021.99.01