To evaluate the oncological outcomes and safety of primary retroperitoneal lymph node dissection (RPLND) in patients with clinical stage (CS) II seminomatous testicular germ cell tumor (TGCT). A literature search using PubMed, Scopus, and Cochrane Library was conducted on July 2023 to identify relevant studies according to the Preferred Reporting Items for Systematic Review and Meta Analysis (PRISMA) guidelines. The pooled recurrence rate and treatment-related complications were calculated using a random effects model. Overall 8 studies published between 1997 and 2023 including a total of 355 patients were selected for systematic review and meta-analysis with the overall median follow-up of 38 months. The overall and infield recurrence rate were 0.14 (95% CI: 0.08-0.22) and 0.04 (95% CI: 0.00-0.11), respectively. The overall pooled rate of ≥ Clavien Dindo grade III complications was 0.04 (95% CI: 0.01-0.10); there was no significant heterogeneity (I^2 = 35.10%, P = 0.19). Antegrade ejaculation was preserved with the overall pooled rate of 0.98 (95% CI: 0.95-1.00); there was no significant heterogeneity on Chi-square and I2 tests (I^2 = 0.00%, P = 0.58). Primary RPLND is a safe and effective treatment option for patients with CS II seminomatous TGCT resulting highly promising cure rates combined with low treatment-associated adverse events, at medium-term follow-up. However, owing to the lack of comparative studies to the current standard of care and the limited follow-up, individual decision must be made with the informed patient in a shared decision process together with a multidisciplinary team.
- MeSH
- germinální a embryonální nádory * chirurgie patologie MeSH
- lidé MeSH
- lymfadenektomie škodlivé účinky metody MeSH
- retroperitoneální prostor patologie MeSH
- retrospektivní studie MeSH
- seminom * patologie MeSH
- staging nádorů MeSH
- testikulární nádory * patologie MeSH
- výsledek terapie MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- metaanalýza MeSH
- přehledy MeSH
- systematický přehled MeSH
In the present study, we investigated protein expression of the transcription factors mammalian doublesex and mab-3 related transcription factor 1 (DMRT1), basic helix-loop-helix transcription factor-like 5 (TCLF5), and octamer-binding transcription factor 4 (OCT4) in normal human spermatogenesis, testicular mixed germ cell-sex cord stromal tumor (MGC-SCST), spermatocytic tumor, and seminoma. In normal human spermatogenesis, DMRT1 is expressed in the nuclei of spermatogonia but not in those of more mature germ cells. By way of contrast, TCLF5 is expressed in the nuclei of some clusters of primary spermatocytes that have entered meiosis 1, in secondary spermatocytes, and in round (early) spermatids in the seminiferous tubules of adults during the reproductive years. OCT4 is expressed in primordial germ cells but not in the seminiferous tubules of the normal adult testis during the reproductive years. DMRT1 is expressed in the germ cells of both testicular MGC-SCST and spermatocytic tumor, whereas TCLF5 is not expressed in either neoplasm. These low-grade neoplasms, however, differ histologically in that all the germ cell nuclei of testicular MGC-SCST resemble spermatogonia, whereas in spermatocytic tumor, the nuclei of the medium-sized and large cells resemble those of primary spermatocytes. Both neoplasms lack expression of OCT4. By way of contrast, in seminoma, a fully malignant testicular germ cell tumor, the germ cell nuclei express OCT4 but do not express either DMRT1 or TCLF5.
- MeSH
- biopsie MeSH
- buněčné jádro chemie patologie MeSH
- germinální a embryonální nádory chemie patologie MeSH
- imunohistochemie MeSH
- lidé MeSH
- nádorové biomarkery analýza MeSH
- oktamerní transkripční faktor 3 analýza MeSH
- semenotvorné kanálky chemie patologie MeSH
- seminom chemie patologie MeSH
- spermatocyty chemie patologie MeSH
- spermatogeneze MeSH
- testikulární nádory chemie patologie MeSH
- transkripční faktory bHLH analýza MeSH
- transkripční faktory analýza MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- srovnávací studie MeSH
Germ cell tumors and particularly seminomas reflect the epigenomic features of their parental primordial germ cells (PGCs), including genomic DNA hypomethylation and expression of pluripotent cell markers. Because the DNA hypomethylation might be a result of TET dioxygenase activity, we examined expression of TET1-3 enzymes and the level of their product, 5-hydroxymethylcytosine (5hmC), in a panel of histologically characterized seminomas and non-seminomatous germ cell tumors. Expression of TET dioxygenase mRNAs was quantified by real-time PCR. TET1 expression and the level of 5hmC were examined immunohistochemically. Quantitative assessment of 5-methylcytosine (5mC) and 5hmC levels was done by the liquid chromatography-mass spectroscopy technique. We found highly increased expression of TET1 dioxygenase in most seminomas and strong TET1 staining in seminoma cells. Isocitrate dehydrogenase 1 and 2 mutations were not detected, suggesting the enzymatic activity of TET1. The levels of 5mC and 5hmC in seminomas were found decreased in comparison to non-seminomatous germ cell tumors and healthy testicular tissue. We propose that TET1 expression should be studied as a potential marker of seminomas and mixed germ cell tumors and we suggest that elevated expression of TET dioxygenase enzymes is associated with the maintenance of low DNA methylation levels in seminomas. This "anti-methylator" phenotype of seminomas is in contrast to the CpG island methylator phenotype (CIMP) observed in a fraction of tumors of various types.
- MeSH
- 5-methylcytosin analogy a deriváty analýza MeSH
- dioxygenasy analýza genetika MeSH
- DNA vazebné proteiny analýza genetika MeSH
- dospělí MeSH
- lidé MeSH
- metylace DNA * MeSH
- oxygenasy se smíšenou funkcí analýza genetika MeSH
- protoonkogenní proteiny analýza genetika MeSH
- regulace genové exprese u nádorů MeSH
- seminom genetika patologie MeSH
- testikulární nádory genetika patologie MeSH
- testis metabolismus patologie MeSH
- upregulace MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- mužské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
BACKGROUND: Syncytin-1 and 2, human fusogenic glycoproteins encoded by the env genes of the endogenous retroviral loci ERVWE1 and ERVFRDE1, respectively, contribute to the differentiation of multinucleated syncytiotrophoblast in chorionic villi. In non-trophoblastic cells, however, the expression of syncytins has to be suppressed to avoid potential pathogenic effects. Previously, we have shown that the transcriptional suppression of ERVWE1 promoter is controlled epigenetically by DNA methylation and chromatin modifications. In this study, we describe the aberrant expression of syncytin-1 in biopsies of testicular germ cell tumors. RESULTS: We found efficient expression and splicing of syncytin-1 in seminomas and mixed germ cell tumors with seminoma component. Although another fusogenic gene, syncytin-2 was also derepressed in seminomas, its expression was significantly lower than that of syncytin-1. Neither the transcription factor GCM1 nor the increased copy number of ERVWE1 were sufficient for this aberrant expression of syncytin-1 in seminomas. In accordance with our recent finding of the highly increased expression of TET1 dioxygenase in most seminomas, the ERVWE1 promoter was significantly hypomethylated in comparison with the matched controls. In contrast, 5-hydroxymethylcytosine levels were not detectable at the ERVWE1 promoter. We further describe that another endogenous retroviral element adjacent to ERVWE1 remains transcriptionally suppressed and two additional HERV-W family members are only slightly upregulated in seminomas. CONCLUSIONS: We conclude that DNA demethylation of the ERVWE1 promoter in seminomas is a prerequisite for syncytin-1 derepression. We propose the spliced syncytin-1 expression as a marker of seminoma and suggest that aberrant expression of endogenous retroviruses might be a correlate of the hypomethylated genome of seminomas.
- MeSH
- DNA virů metabolismus MeSH
- endogenní retroviry genetika MeSH
- epigeneze genetická MeSH
- genové produkty env biosyntéza MeSH
- lidé MeSH
- metylace DNA MeSH
- regulace genové exprese * MeSH
- seminom patologie virologie MeSH
- těhotenské proteiny biosyntéza MeSH
- testikulární nádory patologie virologie MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
Nádory varlat jsou nejčastějším nádorovým onemocněním mužů ve věku 20–40 let. Jedním z rizikových faktorů je rodinný výskyt nádoru varlete. U bratrů je riziko vzniku nádoru 8–10krát vyšší. Nádory jsou stejného histologického typu nejčastěji u identických dvojčat, ale u většiny nedvojčecích sourozenců jsou histologické nálezy různé. Toto sdělení prezentuje případy 2 bratrů ve věku 25 a 23 let s tumorem varlete, kteří byli v krátkém časovém odstupu 6 měsíců vyšetřeni a léčeni na našem pracovišti. U obou pacientů byla časně provedena radikální orchiektomie z inguinálního přístupu. V případě staršího bratra byl histologický nález smíšeného germinálního tumoru – 70 % embryonální karcinom a 30 % nádor ze žloutkového váčku. U mladšího z obou bratrů histologické vyšetření prokázalo klasický seminom varlete. Oba mladé muže jsme po dokončení stagingu odeslali k další léčbě na onkologii.
Testicular tumors are the most common malignacy in men between the ages of 20 and 40 years. One of the risk factors is thefamilial incidence of testicular cancer. For brothers the risk of developing of the tumor is 8–10 times higher. The tumors are ofthe same histological type mainly in identical twins, but for most non-twin siblings there are different histological findings. Thisreport presents cases of two brothers aged 25 and 23 with testicular tumor who were examined and treated at our departmentin short time of 6 months. In both patiens was early performed radical inguinal orchiectomy. In the case of an older brother, therewas a histological finding of a mixed germinal tumor – 70 % of embryonal carcinoma and 30 % of yolk sac tumor. In younger ofboth brothers there was histologically confirmed classic seminoma of testis. After finishing of staging we sent both young mento oncology department for further management of the disease.
- MeSH
- dospělí MeSH
- germinální a embryonální nádory patologie MeSH
- lidé MeSH
- mladý dospělý MeSH
- nádor z entodermálního sinusu patologie MeSH
- orchiektomie MeSH
- seminom patologie MeSH
- sourozenci * MeSH
- testikulární nádory * diagnóza chirurgie patologie MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- MeSH
- analýza přežití MeSH
- antigen CTLA-4 antagonisté a inhibitory MeSH
- antigeny CD279 antagonisté a inhibitory MeSH
- everolimus terapeutické užití MeSH
- karcinom z přechodných buněk farmakoterapie MeSH
- karcinom z renálních buněk farmakoterapie patologie MeSH
- lidé MeSH
- nádory močového měchýře farmakoterapie patologie MeSH
- nádory prostaty rezistentní na kastraci farmakoterapie klasifikace MeSH
- prognóza MeSH
- seminom patologie terapie MeSH
- uchování spermatu MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
Cíl práce: Prezentujeme kazuistiku pacienta, u kterého došlo k rozvoji oboustranného seminomu na podkladě intratubulární germinální neoplazie – neklasifikovatelný typ (IGCNU – intratubular germ cell neoplasia unclassified type). Kazuistika: Pacient s anamnézou seminomu levého varlete klinického stadia I a IGCNU po radikální orchiektomii a adjuvantní radioterapii byl odeslán k urologickému vyšetření pro suspektní tumor solitárního pravého varlete dle sonografického vyšetření. Indikovali jsme 3biopsii varlete, která prokázala přítomnost IGCNU. Následovala radikální orchiektomie, kde byl histologicky verifikován klasický seminom. Závěr: Intratubulární germinální neoplazie představuje vysoké riziko rozvoje invazivního germinálního tumoru varlete. Léčba zahrnuje radioterapii či chemoterapii cisplatinou. Alternativou je pečlivá dispenzarizace a pravidelné sonografické kontroly, zejména u pacientů se solitárním varletem, kteří chtějí zachovat fertilitu a endokrinní funkci. Biopsie kontralaterálního varlete u pacientů s germinálním tumorem k vyloučení IGCNU by měla být provedena v případě kryptorchizmu, poruchy spermiogeneze a atrofií varlete s objemem pod 12 ml, vhodná je rovněž u pacientů s mikrolitiázou varlete a předchozím výskytem IGCNU.
Objective: We are presenting a case report of young man who developed an asynchronous bilateral seminoma based on an intratubular germ cell neoplasia of unclassified type (IGCNU). Case report: A patient, with history of a stage I seminoma of the left testis, based on an IGCNU of the left testis, after a radical orchidectomy and adjuvant radiotherapy, was referred to the urology clinic with a suspected tumor of the right testis. A testicular biopsy was made and the histological examination showed an IGCNU. A radical orchidectomy was performed and a seminoma was found. Conclusion: IGCNU is a precursor lesion of germ cell testicular tumors. Treatment of the IGCNU includes radiotherapy or chemotherapy with cisplatin. Surveillance remains an option for those with a solitary testicle who wish to preserve fertility and endocrine function. A contralateral testicular biopsy, in patients with a history of germ cell tumors, should be made in cases of cryptorchidism, poor spermatogenesis, and testicular atrophy with a testicular volume of less than 12 ml. Biopsy is also recommended in patients with testicular microlithiasis and history of ITGCNU.
- Klíčová slova
- mikrolitiáza varlete, intratubulární germinální neoplazie – neklasifikovatelný typ (IGCNU),
- MeSH
- adjuvantní chemoterapie MeSH
- adjuvantní radioterapie MeSH
- biopsie MeSH
- dospělí MeSH
- germinální a embryonální nádory diagnóza komplikace MeSH
- lidé MeSH
- litiáza * diagnóza komplikace MeSH
- mnohočetné primární nádory diagnóza patologie terapie MeSH
- nemoci varlat diagnóza komplikace MeSH
- orchiektomie MeSH
- prekancerózy * diagnóza komplikace MeSH
- seminom diagnóza patologie terapie MeSH
- testikulární nádory * diagnóza patologie terapie MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- mužské pohlaví MeSH
- Publikační typ
- kazuistiky MeSH
The presence of human chorionic gonadotropin (hCG) positive syncytiotrophoblastic cells (STC) in classic seminoma (CS) is well documented. CS with extensive hCG positive, non-syncytiotrophoblastic tumour cells (without STC) is exceptionally rare. In this study, we present 15 such cases. 168 CSs were retrieved from the Plzen Tumor registry. Cases of mixed germ cell tumors (with CS) and CSs with typical STC were excluded. Cases with completely embedded tumor mass were selected for further study and immunohistochemically examined with anti-hCG. Positive cases were further analyzed by reverse transcriptase polymerase chain reaction. Two groups of hCG-positive CSs were identified. Group 1 comprised 10 patients with a mean patient age of 37.7 years and mean tumor size of 4.96 cm. Eight cases were pT1 (TMN 2009) and 2 cases pT3a. Blood levels of hCG were elevated in 6 of the 10 patients preoperatively. In 2 patients the blood level of hCG was not tested. Mean follow-up period was 6.1 years. No metastatic behavior was noted. All tumors were extensively immunoreactive for hCG in more than 60% of tumor cells. The expression of hCG beta subunit (CGB)-mRNA in tumor tissue was documented. Group 2: Comprised 5 patients with a mean age was 34 years. Mean tumor size was 4.7 cm. Four cases were stage pT1 and 1 case was pT2. The mean follow-up period was 3.1 years. No metastatic behavior was noted. Preoperative blood levels of hCG were elevated in 1/5 of the patient. Strong hCG positivity was limited to scattered single tumor cells distributed throughout the entire tumor. Only weak expression of CGB mRNA was detected. We can conclude that immunohistochemical detection of expression of hCG in CS is not limited to syncytiotrophoblastic cells. In this study, we report two immunohistochemical patterns of hCG expression in classic seminomas: diffuse hCG staining in the majority of tumor cells and scattered hCG-positive cells within the tumor.
- MeSH
- choriogonadotropin krev MeSH
- dospělí MeSH
- germinální a embryonální nádory genetika patologie MeSH
- imunohistochemie MeSH
- lidé středního věku MeSH
- lidé MeSH
- lidský choriogonadotropin, beta podjednotka krev MeSH
- messenger RNA genetika MeSH
- mladý dospělý MeSH
- nádorové biomarkery krev MeSH
- následné studie MeSH
- RNA nádorová genetika MeSH
- seminom genetika patologie MeSH
- testikulární nádory genetika patologie MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- MeSH
- fluorodeoxyglukosa F18 aplikace a dávkování MeSH
- germinální a embryonální nádory * diagnóza farmakoterapie MeSH
- germinom diagnostické zobrazování MeSH
- lidé MeSH
- nádorové biomarkery analýza MeSH
- PET/CT statistika a číselné údaje MeSH
- prognóza MeSH
- radiofarmaka aplikace a dávkování MeSH
- seminom diagnostické zobrazování farmakoterapie patologie MeSH
- testikulární nádory diagnostické zobrazování MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH