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Testicular tumors represent the most common malignancy among young men. Nevertheless, the pathogenesis and molecular underpinning of testicular tumors remain largely elusive. We aimed to delineate the intricate intra-tumoral heterogeneity and the network of intercellular communication within the tumor microenvironment. A total of 40,760 single-cell transcriptomes were analyzed, encompassing samples from six individuals with seminomas, two patients with mixed germ cell tumors, one patient with a Leydig cell tumor, and three healthy donors. Five distinct malignant subclusters were identified in the constructed landscape. Among them, malignant 1 and 3 subclusters were associated with a more immunosuppressive state and displayed worse disease-free survival. Further analysis identified that APP-CD74 interactions were significantly strengthened between malignant 1 and 3 subclusters and 14 types of immune subpopulations. In addition, we established an aberrant spermatogenesis trajectory and delineated the global gene alterations of somatic cells in seminoma testes. Sertoli cells were identified as the somatic cell type that differed the most from healthy donors to seminoma testes. Cellular communication between spermatogonial stem cells and Sertoli cells is disturbed in seminoma testes. Our study delineates the intra-tumoral heterogeneity and the tumor immune microenvironment in testicular tumors, offering novel insights for targeted therapy. © 2024 The Author(s). The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.
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Both ovarian and testicular germ cell tumors (GCTs) arise from the primordial germ cell and share many similarities. Both malignancies affect mainly young patients, show remarkable responsiveness to cisplatin-based therapy, and have an excellent prognosis, which also highlights the importance of minimizing long-term side effects. However, certain differences can be noted: The spreading of the disease differs, and the staging system and treatment recommendations are dissimilar. Moreover, the prognosis for ovarian GCTs is significantly inferior to that for testicular cancer, as exemplified in this review comparing the survival in Swedish patients diagnosed with testicular (1995-2022) and ovarian (1990-2018) GCTs. The 5-year overall survival in ovarian GCTs was 85.2%, versus 98.2% for testicular GCTs. How can this be explained? One reason may be the difference in knowledge, experience, and evidence because the incidence rate of testicular cancer is more than 15 times that of ovarian GCTs. Given the rarity of the disease in women and the lack of established guidelines, a comprehensive understanding of the disease and treatment decisions is challenging. The main objective of this review is to derive insights from testicular GCTs (seminoma and non-seminoma) by reviewing etiological, tumor biological, and clinical knowledge, and to thereafter suggest actions for ovarian GCTs based on this. We hypothesize that by adopting specific treatment strategies from testicular GCTs-including de-escalating adjuvant chemotherapy for low-risk patients and implementing more standardized and intensive treatment protocols in cases of relapse-we can improve the prognosis and minimize long-term side effects in ovarian GCT patients.
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Neoplasias Embrionárias de Células Germinativas , Neoplasias Ovarianas , Neoplasias Testiculares , Humanos , Neoplasias Testiculares/terapia , Neoplasias Testiculares/patologia , Neoplasias Testiculares/diagnóstico , Neoplasias Embrionárias de Células Germinativas/terapia , Neoplasias Embrionárias de Células Germinativas/patologia , Neoplasias Ovarianas/terapia , Neoplasias Ovarianas/patologia , Masculino , Prognóstico , FemininoRESUMO
Cryptorchidism, the failure of one or both testes to descend into the scrotum, and testicular cancer show a strong correlation in both dogs and humans. Yet, long-standing medical debates persist about whether the location of undescended testes directly causes testicular cancer in humans or if both conditions stem from a common origin. Although testicular cancer is a prevalent disease in dogs, even less is known about its cause and correlation with testicular descent in this species. This review investigates the relation between these two disorders in dogs, drawing insights from human studies, and examines key biomarkers identified thus far. In addition, it explores potential causal links, including the impact of temperature on maturing testicular cells and a potential shared genetic origin. Notably, this literature review reveals significant differences between men and dogs in reproductive development, histological and molecular features of testicular tumors, and the prevalence of specific tumor types, such as Sertoli cell tumors in cryptorchid dogs and germ cell tumors in humans. These disparities caution against using dogs as models for human testicular cancer research and underscore the limitations when drawing comparisons between species. The paper concludes by suggesting specific research initiatives to enhance our understanding of the complex interplay between cryptorchidism and testicular cancer in dogs.
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Criptorquidismo , Doenças do Cão , Neoplasias Testiculares , Criptorquidismo/veterinária , Criptorquidismo/genética , Criptorquidismo/patologia , Cães , Neoplasias Testiculares/veterinária , Neoplasias Testiculares/genética , Neoplasias Testiculares/patologia , Animais , Humanos , Masculino , Doenças do Cão/genética , Doenças do Cão/patologiaRESUMO
PURPOSE: The purpose of this American Urological Association (AUA) guideline amendment is to provide a useful reference on the effective evidence-based treatment strategies for early-stage testicular cancer. METHODOLOGY/METHODS: The original methodology protocol included searches of PubMed®, Embase®, and the Cochrane Central Register of Controlled Trials (CENTRAL) from January 1980 through August 2018. The search strategy used medical subject heading (MeSH) terms and key words relevant to the diagnosis and treatment of early-stage testicular cancer. The searches conducted for the update presented herein utilized the same methodological protocol to capture literature published through March 2023. When sufficient evidence existed, the body of evidence was assigned a strength rating of A (high), B (moderate), or C (low) for support of Strong, Moderate, or Conditional Recommendations. In the absence of sufficient evidence, additional information is provided as Clinical Principles and Expert Opinions. RESULTS: Updates were made to statements on imaging, seminoma management, non-seminoma management, surveillance for stage I testicular cancer, and additional survivorship. Further revisions were made to the methodology and reference sections as appropriate. CONCLUSIONS: This guideline seeks to improve clinicians' ability to evaluate and treat patients with early-stage testicular cancer based on currently available evidence. Future studies will be essential to further support or refine these statements to improve patient care.
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Neoplasias Testiculares , Humanos , Masculino , Neoplasias Testiculares/diagnóstico , Neoplasias Testiculares/terapia , Estados UnidosRESUMO
PURPOSE: The SWENOTECA-MIR prospective multicenter study aims to assess the clinical value of miR-371a-3p as a novel marker in metastatic germ cell tumor patients undergoing retroperitoneal lymph node dissection (RPLND), to predict the presence of viable residual tumor. MATERIALS AND METHODS: A total of 114 patients (86 nonseminomas, 28 seminomas) who underwent surgery for presumed metastatic disease pre chemotherapy (primary RPLND) and post chemotherapy RPLND were included. The expression of miR-371a-3p was evaluated using reverse transcription-digital droplet polymerase chain reaction before and after RPLND. Pre- and postoperative miR-371a-3p levels were statistically compared, and optimism-corrected performance calculations compared with conventional serum tumor markers. Associations were evaluated by logistic regression. Patients who underwent primary RPLND were categorized into seminoma and nonseminoma groups. RESULTS: Among the seminoma patients (n = 24) undergoing primary RPLND, all had normal conventional markers. Six patients received adjuvant treatment before surgery. miR-371a-3p exhibited a sensitivity of 74%, specificity of 100%, positive predictive value of 100%, and negative predictive value of 21% for viable tumor. The levels of miR-371a-3p significantly decreased after surgery. In the nonseminoma group (n = 18) treated with primary RPLND, 22% had elevated conventional markers and 3 had received prior adjuvant treatment. miR-371a-3p showed a sensitivity of 34%, specificity of 88%, positive predictive value of 67%, and negative predictive value of 62% for the primary nonseminoma patients. No association was observed between stage or prior adjuvant treatment and the outcome of the miR test. In the postchemotherapy group (n = 72), the miR-371a-3p sensitivity was 9%, reducing to 0 when excluding patients with seminoma (n = 4). Teratomas and benign histology were essentially negative. CONCLUSIONS: Our study highlights miR-371a-3p as a fairly sensitive and highly specific marker for prechemotherapy seminomas, outperforming conventional markers. However, in prechemotherapy nonseminomas as well as in postchemotherapy patients, we observed low sensitivity and no significant differences in miR-371a-3p levels before and after surgery, suggesting limited utility for miR-371a-3p in this context.
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INTRODUCTION: Paraneoplastic hyperthyroidism (PH) has been reported in patients with testicular germ cell tumors (GCTs), sporadically. This disorder is caused by extremely elevated serum levels of beta-human chorionic gonadotropin (bHCG). To date, little is known about the prevalence of PH, and its clinical features are poorly understood. The aim of the present study was to analyze the relative frequency and clinical features of PH in GCTs and evaluate their effects on therapeutic outcomes. METHODS: A cohort of 438 patients treated for testicular GCT from 2017 to 2023 was retrospectively analyzed for histology, age, clinical stage, and presence of PH. The clinical features of the patients with PH were evaluated descriptively. The relative frequency of PH was compared among the subgroups using descriptive statistical methods. RESULTS: Three patients with PH were identified; all had clinical symptoms of hyperthyroidism, suppressed serum levels of thyroid-stimulating hormone (TSH), and increased levels of tri-iodothyronin (fT3). All the patients had advanced, metastasized, and non-seminomatous GCTs. Serum bHCG levels ranged from 225,00 U/L to 1,520,000 U/L. The prevalence of PH was 0.7% in the entire GCT population and 60% in those with very high bHCG serum levels. All the patients received standard cisplatin-based chemotherapy along with thyrostatic treatment. The clinical symptoms of the hyperthyroidism rapidly disappeared. TSH levels normalized with decreasing bHCG levels. The PH treatment did not affect the therapeutic outcomes of the patients. CONCLUSION: PH may occur in 0.7% of all patients with GCT but may be present in up to 60% of patients with very high levels of bHCG. Measuring serum levels of TSH and fT3 should be performed in addition to routine diagnostic measures in all patients with poor prognosis GCTs. Thyrostatic medication is recommended for patients with the clinical symptoms of hyperthyroidism. Early recognition of hyperthyroidism and prompt intervention will reduce comorbidity and help optimize therapeutic outcomes.
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OBJECTIVES: To compare the outcomes and treatment burden of primary retroperitoneal lymph node dissection (pRPLND) alone versus pRPLND + adjuvant chemotherapy (AC) in patients with pathological stage II (PSII) non-seminomatous germ cell tumours (NSGCT). PATIENTS AND METHODS: Retrospective review of the Princess Margaret Cancer Center eTestes cancer database identified patients with PSII NSGCT after pRPLND between 1995 and 2020. The primary outcome was relapse-free survival (RFS). Secondary outcomes included disease-specific survival (DSS), burden of relapse treatment, and factors associated with relapse. RESULTS: A total of 109 PSII patients were included in the study. There were 96 patients treated with pRPLND alone and 13 treated with pRPLND + AC. The median follow-up was 61 months. The 5-year RFS was 72% for the pRPLND-only group vs 92% for the pRPLND + AC group (hazard ratio [HR] 4.372, 95% confidence interval [CI] 0.59-32.36; P = 0.11). Within the pRPLND-only group the 5-year RFS differed by pN stage (pN1 = 94% vs pN2/N3 = 67%, P = 0.03). Despite a higher relapse rate within the pRPLND-only group, the DSS was similar at 5 years (98% pRPLND only vs 100% pRPLND + AC, P = 0.48). Only 24 (25%) of the patients in the pRPLND-only group required any subsequent chemotherapy. Despite achieving similar survival, the cumulative post-RPLND treatment burden was less for the pRPLND-only group than the pRPLND+AC group overall (average 1.23 vs 2.46 cycles of chemotherapy per patient in group). CONCLUSION: The majority of patients with PSII NSGCT treated with pRPLND alone do not experience a recurrence or require chemotherapy. Despite a lower relapse risk when AC is given, no difference in survival was seen but higher chemotherapy burden was entertained. AC may constitute overtreatment for most patients with PSII NSGCT treated with pRPLND.
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OBJECTIVES: To assess whether extended surveillance with repeated computed tomography (CT) scans for patients with clinical stage IIA (CS IIA; <2 cm abdominal node involvement) and negative markers (Mk-) non-seminomatous germ cell tumours (NSGCTs) can identify those with true CS I. To assess the rate of benign lymph nodes, teratoma, and viable cancer in retroperitoneal lymph node dissection (RPLND) histopathology for patients with CS IIA Mk- NSGCT. PATIENTS AND METHODS: Observational prospective population-based study of patients diagnosed 2008-2019 with CS IIA Mk- NSGCT in the Swedish and Norwegian Testicular Cancer Group (SWENOTECA) registry. Patients were managed with surveillance, with CT scans, and tumour markers every sixth week for a maximum of 18 weeks. Patients with radiological regression were treated as CS I, if progression with chemotherapy, and remaining CS IIA Mk- disease with RPLND. The end-point was the number and percentage of patients down-staged to CS I on surveillance and rate of RPLND histopathology presented as benign, teratoma, or viable cancer. RESULTS: Overall, 126 patients with CS IIA Mk- NSGCT were included but 41 received therapy upfront. After surveillance for a median (range) of 6 (6-18) weeks, 23/85 (27%) patients were in true CS I and four (5%) progressed. Of the remaining 58 patients with lasting CS IIA Mk- NSGCT, 16 received chemotherapy and 42 underwent RPLND. The RPLND histopathology revealed benign lymph nodes in 11 (26%), teratoma in two (6%), and viable cancer in 29 (70%) patients. CONCLUSIONS: Surveillance with repeated CT scans can identify patients in true CS I, thus avoiding overtreatment. The RPLND histopathology in patients with CS IIA Mk- NSGCT had a high rate of cancer and a low rate of teratoma.
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Estadiamento de Neoplasias , Neoplasias Embrionárias de Células Germinativas , Neoplasias Testiculares , Humanos , Masculino , Neoplasias Embrionárias de Células Germinativas/patologia , Neoplasias Embrionárias de Células Germinativas/diagnóstico por imagem , Neoplasias Embrionárias de Células Germinativas/terapia , Neoplasias Testiculares/patologia , Neoplasias Testiculares/diagnóstico por imagem , Neoplasias Testiculares/terapia , Estudos Prospectivos , Adulto , Adulto Jovem , Tomografia Computadorizada por Raios X , Excisão de Linfonodo , Biomarcadores Tumorais , Pessoa de Meia-Idade , Adolescente , Metástase Linfática , Suécia/epidemiologiaRESUMO
BACKGROUND: The transcription factor SALL4 is associated with embryonic pluripotency and has proposed as a novel immunohistochemistry (IHC) marker for diagnosing germ cell tumours. SALL4 comprises three isoforms, and SALL4-A being the full-length isoform. Studying its isoforms could revolutionize testicular cancer prognosis and subtype differentiation. METHODS: The expression and clinical significance of isoform 'A' of SALL4 was evaluated in 124 testicular germ cell tumours (TGCTs) subtypes, adjacent 67 normal tissues and 22 benign tumours, using immunohistochemistry on tissue microarrays (TMA). RESULTS: A statistically significant higher expression of nuclear and cytoplasmic SALL4-A was detected in TGCTs histological subtypes and benign tumours compared to the normal tissues. Seminoma and yolk sac tumours had the highest nuclear and cytoplasmic expression of SALL4-A. A significant correlation was detected between the higher nuclear expression of SALL4-A and increased pT stages (P = 0.026) in seminomas. Whereas in embryonal carcinomas, cytoplasmic expression of SALL4-A was associated with the tumour recurrence (P = 0.04) and invasion of the epididymis (P = 0.011). CONCLUSIONS: SALL4-A isoform expression in the cytoplasm and nucleus of TGCTs may be associated with histological differentiation. In the seminoma subtype of TGCTs, higher expression of SALL4-A may be used as a predictive indicator of poorer outcomes and prognosis.
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Biomarcadores Tumorais , Neoplasias Embrionárias de Células Germinativas , Isoformas de Proteínas , Neoplasias Testiculares , Fatores de Transcrição , Humanos , Neoplasias Testiculares/metabolismo , Neoplasias Testiculares/patologia , Masculino , Neoplasias Embrionárias de Células Germinativas/metabolismo , Neoplasias Embrionárias de Células Germinativas/patologia , Isoformas de Proteínas/metabolismo , Fatores de Transcrição/metabolismo , Biomarcadores Tumorais/metabolismo , Prognóstico , Progressão da Doença , Imuno-Histoquímica , Seminoma/metabolismo , Seminoma/patologia , Adulto , Citoplasma/metabolismo , Núcleo Celular/metabolismo , Análise Serial de TecidosRESUMO
BACKGROUND: Testicular germ cell tumors (TGCTs) exhibit diverse biological and pathological features and are divided in two main types, seminomas and nonseminomatous germ cell tumors (NSGCTs). CD44 is a cell surface receptor, which is highly expressed in malignancies and is implicated in tumorigenesis affecting cell-matrix interactions and cell signaling. METHODS AND RESULTS: Here, we examined the expression of CD44 in tumor cell lines and in patients' material. We found that CD44 is over-expressed in TGCTs compared to normal tissues. Immunohistochemical staining in 71 tissue specimens demonstrated increased expression of CD44 in some patients, whereas CD44 was absent in normal tissue. In seminomas, a high percentage of tumor and stromal cells showed cytoplasmic and/or cell surface staining for CD44 as well as increased staining for CD44 in the tumor stroma was found in some cases. The increased expression of CD44 either in tumor cells or in stromal components was associated with tumor size, nodal metastasis, vascular/lymphatic invasion, and disease stage only in seminomas. The increased stromal expression of CD44 in TGCTs was positively associated with angiogenesis. CONCLUSIONS: CD44 may exhibit diverse biological functions in seminomas and NSGCTs. The expression of CD44 in tumor cells as well as in tumor stroma fosters an aggressive phenotype in seminomas and should be considered in disease treatment.
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Receptores de Hialuronatos , Seminoma , Neoplasias Testiculares , Humanos , Receptores de Hialuronatos/metabolismo , Seminoma/metabolismo , Seminoma/patologia , Seminoma/genética , Masculino , Neoplasias Testiculares/metabolismo , Neoplasias Testiculares/patologia , Adulto , Linhagem Celular Tumoral , Pessoa de Meia-Idade , Neoplasias Embrionárias de Células Germinativas/metabolismo , Neoplasias Embrionárias de Células Germinativas/patologia , Neoplasias Embrionárias de Células Germinativas/genética , Biomarcadores Tumorais/metabolismo , Regulação Neoplásica da Expressão Gênica , Imuno-Histoquímica/métodosRESUMO
BACKGROUND: In 2021, the International Germ Cell Cancer Collaborative Group (IGCCCG) Update Consortium reported improved overall survival (OS) rates in a modern cohort of metastatic non-seminoma testis cancer patients within each of the IGCCCG prognosis groups (96% in good vs. 89% in intermediate vs. 67% in poor), compared to the previous IGCCCG publication (92% in good vs. 80% in intermediate vs. 48% in poor). We hypothesized that a similar survival improvement may apply to a contemporary North-American population-based cohort of non-seminoma testis cancer patients. PATIENTS AND METHODS: The Surveillance, Epidemiology, and End Results (SEER) database (2010-2018) was used. Kaplan-Meier plots and multivariable Cox regression models tested the effect of IGCCCG prognosis groups on overall mortality (OM). RESULTS: Of 1672 surgically treated metastatic non-seminoma patients, 778 (47%) exhibited good vs. 251 (15%) intermediate vs. 643 (38%) poor prognosis. In the overall cohort, five-year OS rate was 94% for good prognosis vs. 87% for intermediate prognosis vs. 65% for poor prognosis. In multivariable Cox regression models predicting OM, intermediate (Hazard ratio [HR] 2.4, 95% confidence interval [CI] 1.4-3.9, P < 0.001) and poor prognosis group (HR 6.6, 95% CI 1.0-1.0, P < 0.001) were independent predictors of higher OM, relative to good prognosis group. CONCLUSIONS: The survival improvement reported by the IGCCCG Update Consortium is also operational in non-seminoma testis cancer patients within the most contemporary SEER database. This observation indicates that the survival improvement is not only applicable to centres of excellence, but also applies to other institutions at large.
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Programa de SEER , Neoplasias Testiculares , Humanos , Masculino , Neoplasias Testiculares/mortalidade , Neoplasias Testiculares/patologia , Adulto , Prognóstico , Pessoa de Meia-Idade , Neoplasias Embrionárias de Células Germinativas/mortalidade , Neoplasias Embrionárias de Células Germinativas/patologia , Neoplasias Embrionárias de Células Germinativas/terapia , Taxa de Sobrevida , Adulto Jovem , Metástase NeoplásicaRESUMO
Tumors in boars are uncommon, and testicular tumors even rarer. This study describes the pathological and immunohistochemical characteristics of a case series of testicular tumors in commercial boars with fertility problems. Tumors were detected in 19 of 333 animals (19/333, 5.9%). Macroscopically, tumors were observed in 13 (13/19, 68%) boars, while 6 cases (6/19, 32%) were only detected by microscopic examination. Testicular enlargement was observed in 1 boar, while in the others, tumors were only observed after removal of the scrotal skin or after sectioning of the testis. Histologically, tumors were classified as seminomas (16/19, 84%), mixed germ cell-stromal tumors (2/19, 11%), and B-cell lymphoma (1/19, 5%). Seminomas had 3 different growth patterns: intratubular (6/16, 38%), diffuse (4/16, 25%), and intratubular/diffuse (6/16, 38%). All tumors that were not evident on macroscopic examination were intratubular seminomas. Intratesticular metastases were observed in 2 cases and extratesticular metastases, located in the pampiniform plexus, were observed in 1 case. In 1 seminoma, the rete testis was also involved. By immunohistochemistry, all intratubular seminomas were negative for c-kit, cytokeratin, and vimentin. In diffuse seminomas, c-kit and cytokeratin were also negative, while vimentin showed granular or perinuclear cytoplasmic labeling in some areas. PAX-5 and CD-3 antibodies classified the lymphoma as a B-cell lymphoma. This study suggests that testicular tumors in boars may be more common than previously reported, especially when microscopic examination is performed. It also shows that testicular tumors in pigs are predominantly seminomas.
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BACKGROUND: It is unknown whether 5-year overall survival (OS) differs and to what extent between the American Joint Committee on Cancer stage III non-seminoma testicular germ cell tumor (NS-TGCT) patients and simulated age-matched male population-based controls, according to race/ethnicity groups. METHODS: We identified newly diagnosed (2004-2014) stage III NS-TGCT patients within the Surveillance Epidemiology and End Results database 2004-2019. For each case, we simulated an age-matched male control (Monte Carlo simulation), relying on Social Security Administration (SSA) Life Tables with 5 years of follow-up. We compared OS rates between stage III NS-TGCT patients and simulated age-matched male population-based controls, according to race/ethnicity groups (Caucasian, Hispanic, Asian/Pacific Islander and African American). Both, cancer-specific mortality (CSM) and other-cause mortality (OCM) were computed. RESULTS: Of 2054 stage III NS-TGCT patients, 60% were Caucasians versus 33% Hispanics versus 4% Asians/Pacific Islanders versus 3% African Americans. The 5-year OS difference between stage III NS-TGCT patients versus simulated age-matched male population-based controls was highest in Asians/Pacific Islanders (64 vs. 99%, Δ = 35%), followed by African Americans (66 vs. 97%, Δ = 31%), Hispanics (72 vs. 99%, Δ = 27%), and Caucasians (76 vs. 98%, Δ = 22%). The 5-year CSM rate was highest in Asians/Pacific Islanders (32%), followed by African Americans (26%), Hispanics (25%), and Caucasians (20%). The 5-year OCM rate was highest in African Americans (8%), followed by Caucasians (4%), Asians/Pacific Islanders (4%), and Hispanics (2%). CONCLUSION: Relative to SSA Life Tables, the highest 5-year OS disadvantage applied to stage III NS-TGCT Asian/Pacific Islander race/ethnicity group, followed by African American, Hispanic and Caucasian, in that order.
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INTRODUCTION: Chemotherapy and radiation therapy are considered standard treatments for stage II seminoma patients; however, these therapies are associated with long-term toxicities. Recently, retroperitoneal lymph node dissection has emerged as an alternative strategy, and the first three phase II trials were published in 2023 with promising results. The present study conducted a systematic review and meta-analysis to evaluate this surgery as an alternative treatment for stage IIA/B seminoma patients. PURPOSE: Seminomas are the most common testicular tumors, often affecting young adult males. Standard treatments for stage II seminomas include chemotherapy and radiation therapy, but these therapies are associated with long-term toxicities. Thus, identifying alternative strategies is paramount. Herein, we conducted a systematic review and meta-analysis to appraise the efficacy and safety of retroperitoneal lymph node dissection (RPLND) for treating this condition. METHODS: We systematically searched the PubMed, Embase, and Cochrane databases for studies evaluating RPLND as a primary treatment for stage II A/B seminomas. Using a random-effects model, single proportion and means and pooled 2-year recurrence-free survival rates with hazard rates and 95% CI were calculated. RESULTS: Seven studies were included, comprising 331 males with stage II seminomas. In the pooled analysis, the recurrence rate was 17.69% (95% CI 12.31-24.75), and the 2-year RFS rate was 81% (95% CI 0.77-0.86). The complication rate was 9.16% (95% CI 6.16-13.42), the Clavien-Dindo > 2 complication rate was 8.83% (95% CI 5.76-13.31), and the retrograde ejaculation rate was 7.01% (95% CI 3.54-13.40). The median operative time was 174.68 min (95% CI 122.17-249.76 min), median blood loss was 105.91 mL (95% CI 46.89-239.22 mL), and patients with no evidence of lymph node involvement ranged from 0-16%. CONCLUSIONS: Primary RPLNDs for treating stage IIA/B seminomas have favorable RFS rates, with low complication and recurrence rates. These findings provide evidence that this surgery is a viable alternative therapy for these patients.
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Excisão de Linfonodo , Estadiamento de Neoplasias , Seminoma , Neoplasias Testiculares , Humanos , Excisão de Linfonodo/métodos , Seminoma/cirurgia , Seminoma/patologia , Neoplasias Testiculares/cirurgia , Neoplasias Testiculares/patologia , Masculino , Espaço Retroperitoneal , Resultado do Tratamento , Intervalo Livre de DoençaRESUMO
Serpinb9 is an inhibitor of granzyme B and is potentially involved in the immune escape of tumor cells. In the present study, bioinformatics analysis using open databases suggested that SerpinB9 is overexpressed in testicular embryonal carcinoma. Immunohistological analysis was performed on 28 cases of testicular germ cell tumors to investigate the relationship between SerpinB9 expression in testicular germ cell tumors and the tumor immune environment. SerpinB9 was significantly upregulated in the non-seminoma group and inversely correlated with the number of tumor-infiltrating CD8-positive cells. In addition, yolk sac tumors were characterized by the loss of human leukocyte antigen-class I expression. 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.
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Carcinoma Embrionário , Neoplasias Embrionárias de Células Germinativas , Neoplasias Testiculares , Humanos , Masculino , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/análise , Carcinoma Embrionário/metabolismo , Carcinoma Embrionário/patologia , Neoplasias Embrionárias de Células Germinativas/genética , Neoplasias Testiculares/genética , Neoplasias Testiculares/metabolismoRESUMO
The authors describe a case of bilateral diffuse paraneoplastic orbital myositis induced by a stage IA left testicular pure seminoma. The patient presented with findings typical of thyroid-associated orbitopathy (TAO) and was thought to have TAO until discovery of the malignancy. Treatment included an urgent orchiectomy, as well as 7 weeks of therapeutic plasma exchange. This is the fifth reported case of seminoma-associated orbitopathy, and the second to occur while cancer was in the occult phase. Although seminoma-associated orbitopathy is exceedingly rare, it can masquerade as TAO and should be considered in the differential diagnosis of any young male with atypical TAO findings.
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Oftalmopatia de Graves , Orquiectomia , Seminoma , Neoplasias Testiculares , Humanos , Masculino , Seminoma/diagnóstico , Seminoma/cirurgia , Diagnóstico Diferencial , Neoplasias Testiculares/diagnóstico , Oftalmopatia de Graves/diagnóstico , Tomografia Computadorizada por Raios X , Adulto , Imageamento por Ressonância Magnética , Miosite Orbital/diagnóstico , Miosite Orbital/tratamento farmacológico , Síndromes Paraneoplásicas Oculares/diagnósticoRESUMO
The incidence of testicular cancer (TC) has been rapidly increasing over the past years. Diagnosis and early treatment have shown good oncological control, guaranteeing the patient different treatment approaches according to histology and tumor stage. Currently, physicians usually prioritize oncological outcomes over sexual outcomes and quality of life, considering as a first aim the overall survival of the patients; however, differently from other neoplasms, quality of life is still strongly affected among TC patients, and sexual outcomes are frequently compromised after each TC treatment. Several studies have suggested that each treatment approach may be associated with sexual dysfunctions, including erectile dysfunction, ejaculatory disorders, fertility issues, and hormonal changes. Since testicular cancer patients are more frequently young men, the subject of this work is substantial and should be analyzed in detail to help specialists in the management of this disease. The aim of the current narrative review is to generally describe every treatment for TC, including surgery, chemotherapy, radiotherapy, and retroperitoneal lymph node dissection, and to establish which sexual dysfunction may be specifically associated with each therapy.
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Qualidade de Vida , Disfunções Sexuais Fisiológicas , Neoplasias Testiculares , Humanos , Neoplasias Testiculares/terapia , Neoplasias Testiculares/complicações , Masculino , Disfunções Sexuais Fisiológicas/terapia , Disfunções Sexuais Fisiológicas/etiologia , Sexualidade/fisiologia , Disfunção Erétil/etiologia , Disfunção Erétil/terapia , Disfunção Erétil/psicologiaRESUMO
AIMS: Testicular germ cell tumours are the most common solid malignancies in young men of age 14-44 years. It is generally accepted that both seminomas and non-seminomas arise from a common precursor, the germ cell neoplasia in-situ, which itself is the result of a defective (primordial) germ cell development. The stem cell-like population of the non-seminomas, the embryonal carcinoma, is capable of the differentiation of all three germ layers (teratomas) and extra-embryonic tissues (yolk-sac tumours, choriocarcioma) into cells. In contrast, seminomas are thought to have a limited differentiation potential. Nevertheless, several studies have highlighted their ability to undergo reprogramming to an embryonal carcinoma or differentiation into other non-seminomatous entities. Here, we demonstrate that in approximately 5% of seminomas, the yolk-sac tumour driver gene FOXA2 is detectable at the protein level, indicative of an occult yolk-sac tumour subpopulation that putatively arose from seminoma cells, as the presence of other GCT entities could be excluded. The presence of these subpopulations might render the tumour more aggressive and argue for an adjustment of the therapeutic concept. We used our data to update the model of germ cell tumour pathogenesis, especially regarding the developmental potential of seminomas. Additionally, we suggest to include detection of FOXA2 into standard routine diagnosis of seminomas.
Assuntos
Carcinoma Embrionário , Neoplasias Embrionárias de Células Germinativas , Seminoma , Neoplasias Testiculares , Masculino , Humanos , Adolescente , Adulto Jovem , Adulto , Seminoma/patologia , Neoplasias Testiculares/patologia , Diferenciação Celular , Fator 3-beta Nuclear de Hepatócito/genéticaRESUMO
BACKGROUND: Primary mediastinal GCT (PMGCT) is a rare entity and comprises 10-15% of all mediastinal tumors. We present our institutional experience of MGCT treated with multimodality management. MATERIALS AND METHODS: We conducted a retrospective analysis between 2010 to 2020 of all mediastinal germ cell tumors registered at our center. Data on patient demographics, treatments received, treatment toxicities and response were recorded. Overall survival and relapse free survival were estimated using Kaplan-Meier methods. RESULTS: A total of 30 patients were identified. The median age was 25.5 (range, 18-45) years. Common presenting features included cough (70%) and shortness of breath (70%). Histology wise, 60% patients were non seminomatous histology, whereas 33.3% patients were Seminoma. Twenty-seven (90%) patients received chemotherapy as the first-line treatment, of whom five patients (16.6%) underwent surgery and radiation therapy subsequently. Median follow-up was 26.9 months. Thirteen patients (43.3%) had complete response (43.3%) and eight patients had partial response (26.7%), while three patients (5.5%) had progressive disease. Three-year relapse-free survival rate was 69.6% (95% confidence interval [CI], 42.8-85.6%). Overall survival (OS) at 3 years was 73.4% (95% CI, 49.4-87.3%). Patients with seminoma had a 3 year OS of 90.0% (95% CI, 47.3-98.5%) compared to those with non-seminoma (63.53% [95% CI, 32.3-83.3%]). CONCLUSIONS: Multiagent chemotherapy is the backbone of treatment in PMGCT. Seminomatous PMGCT have excellent prognosis, while further improvement is needed in those with nonseminomatous tumor.
Assuntos
Neoplasias do Mediastino , Neoplasias Embrionárias de Células Germinativas , Seminoma , Neoplasias Testiculares , Masculino , Humanos , Adulto , Neoplasias do Mediastino/terapia , Estudos Retrospectivos , Recidiva Local de Neoplasia , Neoplasias Embrionárias de Células Germinativas/terapia , Seminoma/terapiaRESUMO
PURPOSE: Germ cell neoplasia in situ (GCNis), the precursor of adult testicular germ cell tumours (GCTs), is found in 5-6% of contralateral testicles in patients with testicular GCT and in the tumour-surrounding tissue of >â¯90% of testes undergoing testis-sparing surgery (TSS) for GCT. Local radiotherapy to the testis with 18-20â¯Gy eradicates GCNis while preserving Leydig cells. The frequency of treatment failures is so far unknown. METHODS: A 22-year-old patient with right-sided seminoma clinical stage I and contralateral GCNis received radiotherapy with 18â¯Gy to his left testicle. Fifteen years later he underwent orchiectomy of the irradiated testis for seminoma with adjacent GCNis. The patient is well 1 year postoperatively while on testosterone-replacement therapy. The literature was searched for further cases with GCTs arising despite local radiotherapy. RESULTS: Six failures of radiotherapy have been reported previously. An estimated total number of 200 and 100 radiotherapeutic regimens with 18-20â¯Gy applied to cases with contralateral GCNis and with TSS, respectively, are documented in the literature. CONCLUSION: Cumulative experience suggests that radiotherapy with 18-20â¯Gy to the testis may fail with an estimated frequency of around 1%. Reasons for failure are elusive. A primary radioresistant subfraction of GCNis is hypothesized as well as technical failures regarding application of the radiotherapeutic dose volume in small and mobile testes. Caregivers of patients with TSS and contralateral GCNis should be aware of local relapses occurring after intervals of >â¯10 years.