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Purpose: Serum platinum is measurable for years after completion of cisplatin-based chemotherapy (CBC). We report the largest investigation of serum platinum levels to date of 1,010 testicular cancer survivors (TCS) assessed 1-35 years after CBC and evaluate genetic contributions to these levels., Experimental Design: Eligible TCS given 300 or 400 (±15) mg/m 2 cisplatin underwent extensive audiometric testing, clinical examination, completed questionnaires, and had crude serum platinum levels measured. Associations between serum platinum and various risk factors and toxicities were assessed after fitting a biexponential model adjusted for follow-up time and cumulative cisplatin dose. A genome-wide association study (GWAS) was performed using the serum platinum residuals of the dose and time-adjusted model., Results: Serum platinum levels exceeded the reference range for approximately 31 years, with a strong inverse relationship with creatinine clearance at follow-up (age-adjusted P = 2.13 × 10 -3 ). We observed a significant, positive association between residual platinum values and luteinizing hormone (age-adjusted P = 6.58 × 10 -3 ). Patients with high residual platinum levels experienced greater Raynaud phenomenon than those with medium or low levels (age-adjusted OR high/low = 1.46; P = 0.04), as well as a higher likelihood of developing tinnitus (age-adjusted OR high/low = 1.68, P = 0.07). GWAS identified one single-nucleotide polymorphism (SNP) meeting genome-wide significance, rs1377817 ( P = 4.6 × 10 -8 , a SNP intronic to MYH14 )., Conclusions: This study indicates that residual platinum values are correlated with several cisplatin-related toxicities. One genetic variant is associated with these levels., (©2019 American Association for Cancer Research.)

Two clusters of microRNAs have been discovered highly expressed by seminoma and nonseminoma germ cell tumors. They are secreted in blood of patients with testicular germ cell tumors and can be extracted from the serum or plasma and quantified by real-time-polymerase chain reaction. Results have confirmed the feasibility of the technique and demonstrated that sensitivity and specificity of those microRNAs in detecting viable germ cell tumors are higher than with current methods. If operation characteristics are confirmed in larger studies, those microRNAs will be valuable to manage equivocal clinical scenarios characterized by high uncertainty and high risk of over-treatment or under-treatment., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Study Question: When should 'not so rare' Leydig cell tumors (LCTs) of the testis be suspected, diagnosed, and treated?, Summary Answer: LCTs are more frequent than generally believed, are associated with male infertility, cryptorchidism and gynecomastia, and should be treated conservatively (in compliant patients) with active surveillance, which appears to be a safe alternative to surgical enucleation., What Is Known Already: Increasing referrals for testicular imaging have led to an increase in findings of LCTs. The features and natural history of these tumors remain largely unknown, as the available studies are small and heterogeneous. LCTs were previously treated aggressively and follow-up data are lacking., Study Design, Size, Duration: A case-cohort study of consecutive patients diagnosed with LCTs over a 10-year period was prospectively enrolled from 2009 to 2018 and compared to matched cohorts of patients with seminomas or no testicular lesions screened in the same timeframe., Participants/materials, Setting, Methods: Of the 9949 inpatients and outpatients referred for scrotal ultrasound, a total of 83 men with LCTs were included. Enrolled subjects underwent medical history and clinical examination and were asked to undergo routine blood tests, hormone investigations (FSH, LH, total testosterone, estradiol, inhibin B, sex hormone-binding globulin (SHBG), prolactin), and semen analysis. Patients who consented also underwent contrast-enhanced ultrasound, elastography, gadolinium-enhanced scrotal magnetic resonance imaging, and hCG stimulation test (5000 IU i.m.) with serum total testosterone and estradiol measured at 0, 24, 48, and 72 hours., Main Results and the Role of Chance: In total, 83 patients diagnosed with LCTs were compared against 90 patients diagnosed with seminoma and 2683 patients without testicular lesions (NoL). LCTs were diagnosed by enucleation (48.2%), orchiectomy (13.3%), or clinical surveillance (38.5%). Testicular volume, sperm concentration, and morphology were lower (P = 0.001, P = 0.001, and P < 0.001, respectively) in patients with LCTs than in the NoL group. FSH, LH, and SHBG were higher and the testosterone/LH ratio was lower in LCTs than in the NoL group (P < 0.001). The LCT group showed higher SHBG (P = 0.018), lower sperm concentration (P = 0.029), and lower motility (P = 0.049) than the seminoma group. Risk factors for LCTs were cryptorchidism (χ2 = 28.27, P < 0.001), gynecomastia (χ2 = 54.22, P < 0.001), and low testicular volume (χ2 = 11.13, P = 0.001). Five cases were recurrences or bilateral lesions; none developed metastases during follow-up (median, 66 months)., Limitations, Reasons for Caution: This study has some limitations. First, hCG and second-line diagnostic investigations were not available for all tumor patients. Second, ours is a referral center for infertility, thus a selection bias may have altered the baseline features of the LCT population. However, given that the comparison cohorts were also from the same center and had been managed with a similar protocol, we do not expect a significant effect., Wider Implications of the Findings: LCTs are strongly associated with male infertility, cryptorchidism, and gynecomastia, supporting the hypothesis that testicular dysgenesis syndrome plays a role in their development. Patients with LCTs are at a greater risk of endocrine and spermatogenesis abnormalities even when the tumor is resected, and thus require long-term follow-up and prompt efforts to preserve fertility after diagnosis.LCTs have a good oncological prognosis when recognized early, as tissue-sparing enucleation is curative and should replace orchiectomy. Conservative surgery and, in compliant patients, active surveillance through clinical and radiological follow-up are safe options, but require monitoring of testicular failure and recurrence., Study Funding/competing Interest(s): The project was funded by the Ministry of University and Research Grant MIUR 2015ZTT5KB. There are no conflicts of interest., Trial Registration Number: ALCeP trial (ClinicalTrials.gov Identifier: NCT01206270)., (© The Author(s) 2019. Published by Oxford University Press.)

Objective: Testicular cancers, which are less common than other cancers, are important in terms of being seen in young people. Physical examination, imaging, laboratory and tumor markers are used for diagnosis. There are some studies of some blood parameters that can be involved in inflammation and tumorogenesis. We retrospectively compared hematological values measured in our patients who were diagnosed with testicular tumor in comparison with patients with similar age group who underwent varicocelectomy repair., Materials and Methods: This cross-sectional retrospective study included 120 patients who underwent radical inguinal orchiectomy for testicular tumor between January 2010 and December 2018, and 171 patients who underwent varicocelectomy as a control group. Patients with an active infection and hematological disorders were excluded from the study. We evaulated hematological parameters including neutrophil (NEU), lymphocyte (LYM), platelet (PLT) count, and mean platelet volume. The study was conducted on 291 patients. divided in two groups: tumor (n = 120) and varicocele (n = 171)., Results: There was no statistically significant difference between the groups in terms of PLT / lymphocyte ratio and mean platelet volume (MPV) levels (p > 0.05). The neutrophil /lymphocyte ratio (NLR) of the tumor group was significantly higher than the varicocele group (p = 0.001; p < 0.05). There was a statistically significant difference between the tumor stages in terms of PLT / Lymphocyte ratios (p = 0.006; p < 0.05)., Conclusions: There was only a statistically significant increase in NLR values in the testicular tumor group compared to the varicocele group. Larger, randomized controlled studies are needed at this field.

Introduction: The immune system plays an essential role in the organism's response to cancer. Several haematological markers can influence prognosis and survival of patients. The objective of this study is to determine their prognostic value in testicular germ cell tumours., Material and Methods: Retrospective cohort study on 164 patients with germ cell tumours. Clinical, analytical, histological and evolutionary data were collected. The absolute neutrophil and absolute platelet counts, neutrophil-lymphocyte (NLR), platelet-lymphocyte and lymphocyte-monocyte ratios were estimated at diagnosis. The association that these markers can have with the classic prognostic factors, as well as their effect on prognosis and survival, have been analysed., Results: 17.7% had NLR>4 and 14.6% ANC>8000/μL. These patients presented higher percentages of residual disease and stage II-III tumours. Patients with elevated absolute neutrophil showed also higher percentages of progression and exitus. 7.3% presented absolute platelet >400000/μL. These patients obtained higher rates of residual disease, nonseminomatous and stage III tumours. 28.4% showed platelet-lymphocyte values>150. This data was associated to higher percentages of residual disease, progression, stage II and III tumours and seminomatous tumours. 83.3% had an lymphocyte-monocyte >3. These patients presented: higher tumour markers in normal range, decreased residual disease rates and higher percentages of stage I and II tumours. The mean survival time was shorter in patients with NLR>4 and absolute neutrophil >8,000/μL. The ROC curves showed significance in the prediction of progression and values of lymphocyte-monocyte >3, and prediction of survival and values NLR>4., Conclusion: Our results indicate that the analysed haematological markers are associated with poor prognoses at diagnosis. Therefore, their use in daily clinical practice can be a valuable tool in the diagnosis and prognosis of patients with testicular germ cell tumours., (Copyright © 2019 AEU. Publicado por Elsevier España, S.L.U. All rights reserved.)

Background: Primary hypogonadism (low testosterone and high luteinizing hormone, LH) is present in approximately 20% of testicular cancer (TC) survivors after orchidectomy with or without chemotherapy., Objectives: We investigated insulin-like factor 3 (INSL3), a novel marker of Leydig cell function, in TC patients., Materials and Methods: We analyzed: (I) a cross-sectional cohort of TC patients after orchidectomy with or without chemotherapy (1988-1999) at long-term follow-up (median 36 and 35 years of age at follow-up, respectively) and healthy men of similar age; (II) a longitudinal cohort of chemotherapy-treated TC patients (2000-2008), analyzed before and 1 year after chemotherapy (median 29 years of age at chemotherapy). INSL3, testosterone, and LH were compared between groups and over time and related to pre-chemotherapy β-hCG levels., Results: In the cross-sectional cohort, TC patients at median 7 years after orchidectomy and chemotherapy (n = 79) had higher LH (p < 0.001), lower testosterone (p = 0.001), but similar INSL3 as controls (n = 40). After orchidectomy only (n = 25), higher LH (p = 0.02), but no differences in testosterone or INSL3 were observed compared to controls. In the longitudinal cohort, patients with normal pre-chemotherapy β-hCG (≤5 mU/L, n = 35) had increased LH 1 year after chemotherapy compared to pre-chemotherapy (p = 0.001), and no change in testosterone or INSL3. In contrast, patients with high β-hCG pre-chemotherapy (n = 42) had suppressed LH, markedly elevated testosterone, and low INSL3 at start of chemotherapy, with increased LH, decreased testosterone, and increased INSL3 1 year later (all p < 0.001)., Discussion: Changes in LH show that gonadal endocrine function is disturbed before chemotherapy, 1 year later, and at long-term follow-up in chemotherapy-treated TC patients., Conclusion: Pre-chemotherapy, β-hCG-producing tumors affect the gonadal endocrine axis, demonstrated by increased testosterone and decreased LH. INSL3 did not uniformly follow the pattern of testosterone., (© 2019 American Society of Andrology and European Academy of Andrology.)

Inhibin B is a gonadal hormone that downregulates the pituitary production of follicle-stimulating hormone (FSH). In recent years, inhibin B has proved to be an excellent marker of spermatogenesis and even a predictive factor for the recovery of fertility in patients undergoing orchiectomy and antineoplastic treatments. We propose to study inhibin B levels in orchiectomised testicular cancer patients, in order to identify a minimum value representative of normal semen quality. This retrospective study evaluates hormonal and semen parameters of 290 normozoospermic patients attending the Laboratory of Seminology - Sperm Bank "Loredana Gandini" (Rome, Italy) for cryopreservation of seminal fluid following a diagnosis of testicular cancer (TC group) and 117 healthy, normozoospermic men as a control group (CTR group). The percentile distribution of gonadotropin and inhibin B values in the TC and CTR groups was analyzed. There was a statistically significant difference between the two groups in the levels of all hormones (P ≤ 0.001) and in all semen parameters (P < 0.05). About 20% of TC patients revealed inhibin B levels below the 5 th percentile of CTR group, despite normozoospermia, and 31.4% had normal spermatogenesis in the presence of FSH values >95 th percentile of CTR group. Orchiectomised patients for testicular cancer presented inhibin B levels lower than healthy patients, despite normozoospermia. Our study revealed the poor sensitivity of the current inhibin B reference range when applied to monorchidic patients, suggesting the need to establish more representative ranges to enable more appropriate counseling in relation to the patient's new endocrine condition.

Purpose: Previous studies suggested that serum levels of microRNA (miR)-371a-3p (so-called M371 test) have a much higher sensitivity and specificity than the classic markers of testicular germ cell tumors (GCTs) and are applicable toward both seminoma and nonseminoma. We sought to confirm the usefulness of this test as a novel biomarker for GCT., Patients and Methods: In a prospective, multicentric study, serum samples of 616 patients with testicular GCTs and 258 male controls were examined for serum levels of miRNA-371a-3p (miR levels) by quantitative polymerase chain reaction. The GCT population encompassed 359 patients with seminoma and 257 with nonseminoma; 371 had clinical stage I disease, 201 had systemic disease, and 46 had relapses. Paired measurements before and after orchiectomy were performed in 424 patients; 118 with systemic disease had serial measurements during treatment. miR levels were compared with those of β-human chorionic gonadotropin, α-fetoprotein, and lactate dehydrogenase., Results: For the primary diagnosis of GCT, the M371 test showed a sensitivity of 90.1%, a specificity of 94.0%, an area under the curve of 0.966 upon receiver operating characteristic analysis, and a positive predictive value of 97.2%. α-Fetoprotein, β-human chorionic gonadotropin, and lactate dehydrogenase had sensitivities of less than 50% in seminoma and slightly higher sensitivities in nonseminomas. miR levels were significantly associated with clinical stage, primary tumor size, and response to treatment. Relapses had elevated miR levels that subsequently dropped to normal upon remission. Teratoma did not express miR-371a-3p., Conclusion: The M371 test outperforms the classic markers of GCT with both a sensitivity and a specificity greater than 90%. All histologic subgroups, except teratoma, express this marker. The test could be considered for clinical implementation after further validation.

Introduction: Although serum tumor markers beta human chorionic gonadotropin (bHCG), alpha-fetoprotein (AFP), and lactate dehydrogenase (LDH) are well-established tools for the management of testicular germ cell tumours (GCTs), there are only few data from contemporary cohorts of primary GCT patients regarding these biomarkers. Our aim was to evaluate marker elevations in testicular GCTs and to document their associations with various clinical characteristics., Patients and Methods: A total of 422 consecutive patients with GCTs were retrospectively analysed regarding serum levels of bHCG, AFP, and LDH during the course of treatment. Additionally, the following characteristics were recorded: histology, age, laterality, clinical stage (CS), pT-stage, and tumour size. Marker elevations were first tabulated in dichotomized way (elevated: yes/no) in various subgroups and second as continuous measured serum values. Descriptive statistical methods were employed to look for differences among subgroups and for associations of elevations with clinical parameters., Results: In all GCT patients, the frequencies of elevated levels of bHCG, AFP, LDH, and bHCG or AFP were 37.9%, 25.6%, 32.9%, and 47.6%; in pure seminomas 28%, 2.8%, 29.1%, and 30.3%; and in nonseminoma 53.0%, 60.1%, 38.7%, and 73.8%. Significant associations were noted with pT-stages >pT1, clinical stages >CS1, tumour size, and younger age. Frequencies of marker elevations dropped significantly after treatment, but LDH levels remained elevated in 30.5%-34.1%. Relapsing patients (n=27) had elevated levels of bHCG, AFP, and LDH in 25.9%, 22.2%, and 29.6%, respectively, thirteen of whom with a changed marker pattern., Conclusions: The classical GCT-biomarkers correlate with treatment success. Clinical utility is limited due to proportions of < 50% of patients with elevated levels and the low specificity of LDH. The elevation rates are significantly associated with histology, clinical and pT-stages, tumour size, and younger age. Individual marker patterns may change upon relapse. Clinically, ideal biomarkers are yet to be found.

Purpose: Imaging studies can show metastasis in testicular cancer (TCa); however, a test for risk of metastasis in TCa has not been described. The ratio of aspartate aminotransferase to alanine aminotransferase, also called the De Ritis ratio (DRR), is used for many other malignancies. We aimed to evaluate the association between preoperatively assessed DRR and prognosis in patients with TCa., Materials and Methods: One hundred twenty-eight patients with TCa were enrolled in a retrospective study between March 2007 and January 2017. Clinical, biochemical, and pathological data were recorded. Univariate and multivariate logistic regression analyses were used. The prognostic value of DRR and the threshold value were assessed by use of receiver operating characteristic curves. Significance was defined as p<0.05., Results: Mean follow-up was 37±9.7 months. There were 45 and 73 TCa patients with and without lymph node metastasis, respectively. Lung metastases and other solid organ metastases occurred in 14 and 4 patients, respectively. The optimal DRR threshold was 1.30 for both retroperitoneal lymph node involvement and metastasis. DRR was determined as an independent prognostic factor for retroperitoneal lymph node involvement and organ metastasis in univariate and multivariate analyses (p<0.001, p=0.006 and p=0.002, p=0.047, respectively)., Conclusions: A preoperative DRR greater than 1.30 may be an independent risk factor for retroperitoneal lymph node involvement and organ metastases in patients with TCa., Competing Interests: CONFLICTS OF INTEREST: The authors have nothing to disclose.

Purpose: An elevated neutrophil-to-lymphocyte ratio (NLR) has been associated with adverse outcomes in various malignancies. However, its role in prognosticating testicular cancer (TC) has not been validated. We aim to study the relationship between NLR and TC., Materials and Methods: We retrospectively reviewed 160 patients with histological proven TC from January 2005 to June 2016. Youden's index was used to analyse NLR and a cut-off point of 3.0 was obtained, with statistical receiver operating characteristics of 0.755. Chi-square test, Kaplan-Meier (log rank test) and logistics regression models were used to predict NLR association with survival outcomes., Results: Median age was 34 years old (range, 17-68 years old). There were 102 pure seminomas and 58 non-seminomatous germ cell tumours. Median follow-up period was 8 years (range, 2.5-17 years). NLR ≥3.0 was independently associated with lymph node involvement (p=0.031; odds ratio [OR], 2.91; 95% confidence interval [CI], 1.67-5.83; p=0.038; OR, 4.12; 95% CI, 1.26-6.51) and metastatic disease (p=0.041; OR, 2.48; 95% CI, 1.22-3.98; p=0.043; OR, 2.21; 95% CI, 1.17-3.65) in both seminomatous and non-seminomatous germ cell tumours, translating to a more advanced disease. Moreover, NLR ≥3.0 also predicts poorer cancer specific survival in these patients., Conclusions: NLR can be an inexpensive haematological marker in predicting advanced TC staging and poorer survival outcome. NLR complements the traditional cancer staging by identifying a group of high risk patients who may benefit from multimodal treatment and closer surveillance to achieve long term survival., Competing Interests: CONFLICTS OF INTEREST: The authors have nothing to disclose.

In this diagnostic test accuracy systematic review we summarise the evidence on the diagnostic accuracy of blood α-fetoprotein (AFP), human chorionic gonadotropin (HCG) and lactate dehydrogenase (LDH) in surveillance for testicular cancer recurrence in adults. We searched four electronic databases for studies that reported the diagnostic accuracy of HCG, AFP, and/or LDH in sufficient detail for sensitivity and specificity to be calculated by extracting a 2 × 2 table comparing biomarker positivity with testicular cancer recurrence. Screening, data extraction and QUADAS-2 quality assessment were completed by two independent reviewers. From 2406 studies, nine met our inclusion criteria. Eight reported data at the per-patient level. Sample sizes were small (range 5 to 449 patients) and clinical heterogeneity precluded meta-analysis. In most studies the specificity for recurrence with AFP and HCG was high (90-100%) but sensitivity was often relatively low, suggesting that many recurrences would not be detected by tumour markers alone. The diagnostic performance of LDH appears poorer. Studies were methodologically weak, with probable selection, incorporation and partial verification bias, and many studies were excluded for not reporting on recurrence-free patients. Limitations including small sample sizes, high heterogeneity, and inconsistent and incomplete reporting mean these results must be interpreted with caution. Despite inclusion of biomarkers in international surveillance guidance, there remains a lack of high quality evidence about their accuracy, optimal thresholds, and the most effective surveillance strategy in relation to contemporary investigative modalities. Higher quality research using data from modern-day follow-up cohorts is necessary to identify opportunities to reduce unnecessary testing., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Study Question: Which Y genes mapped to the 'Gonadoblastoma Y (GBY)' locus on human Y chromosome are expressed in germ cells of individuals with some Differences of Sexual Development (DSD) and a Y chromosome in their karyotype (DSD-XY groups)?, Summary Answer: The GBY candidate genes DDX3Y and TSPY are expressed in the germ cells of DSD-XY patients from distinct etiologies: patients with mixed gonadal dysgenesis (MGD) and sex chromosome mosaics (45,X0/46,XY; 46,XX/46,XY); patients with complete androgen insensitivity (CAIS), patients with complete gonadal dysgenesis (CGD; e.g. Swyer syndrome)., What Is Known Already: A GBY locus was proposed to be present on the human Y chromosome because only DSD patients with a Y chromosome in their karyotype have a high-although variable-risk (up to 55%) for germ cell tumour development. GBY was mapped to the proximal part of the short and long Y arm. TSPY located in the proximal part of the short Y arm (Yp11.1) was found to be a strong GBY candidate gene. It is expressed in the germ cells of DSD-XY patients with distinct etiologies but also in foetal and pre-meiotic male spermatogonia. However, the GBY region extends to proximal Yq11 and therefore includes probably more than one candidate gene., Study Design, Size, Duration: Protein expression of the putative GBY candidate gene in proximal Yq11, DDX3Y, is compared with that of TSPY in serial gonadal tissue sections of 40 DSD-XY individuals from the three DSD patient groups (MGD, Complete Androgen Insensitivity Syndrome [CAIS], CGD) with and without displaying malignancy. Expression of OCT3/4 in the same tissue samples marks the rate of pluripotent germ cells., Participants/materials, Setting, Method: A total of 145 DSD individuals were analysed for the Y chromosome to select the DSD-XY subgroup. PCR multiplex assays with Y gene specific marker set score for putative microdeletions in GBY Locus. Immunohistochemical experiments with specific antisera mark expression of the GBY candidate proteins, DDX3Y, TSPY, in serial sections of the gonadal tissue samples; OCT3/4 expression analyses in parallel reveal the pluripotent germ cell fraction., Main Results and the Role of Chance: Similar DDX3Y and TSPY protein expression patterns were found in the germ cells of DSD-XY patients from each subgroup, independent of age. In CAIS patients OCT3/4 expression was often found only in a fraction of these germ cells. This suggest that GBY candidate proteins are also expressed in the non-malignant germ cells of DSD-XY individuals like in male spermatogonia., Limitations, Reasons for Caution: Variation of the expression profiles of GBY candidate genes in the germ cells of some DSD-XY individuals suggests distinct transcriptional and translational control mechanisms which are functioning during expression of these Y genes in the DSD-XY germ cells. Their proposed GBY tumour susceptibility function to transform these germ cells to pre-malignant GB/Germ Cell Neoplasia in Situ (GB/GCNIS) cells seems therefore to be limited and depending on their state of pluripotency., Wider Implications of the Findings: These experimental findings are of general importance for each individual identified in the clinic with DSD and a Y chromosome in the karyotype. To judge their risk of germ cell tumour development, OCT3/4 expression analyses on their gonadal tissue section is mandatory to reveal the fraction of germ cells still being pluripotent. Comparative expression analysis of the GBY candidate genes can be helpful to reveal the fraction of germ cells with genetically still activated Y chromosomes contributing to further development of malignancy if at high expression level., Study Funding/competing Interest(s): This research project was supported by a grant (01GM0627) from the BMBF (Bundesministerium für Bildung und Forschung), Germany to P.H.V. and B.B. The authors have no competing interests., (© The Author(s) 2019. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

A novel sampling concept for mass spectrometric bottom-up targeted protein analysis is here demonstrated with polymeric sampling spots integrated with instant immunocapture for analysis of dried matrix spots. The polymers 2-hydroxyethyl methacrylate-co-2-vinyl-4,4-dimethyl azlactone (pHEMA-VDM) and pHEMA-Tosyl for covalent attachment of antibodies where investigated alongside with adsorption on non-treated filter paper. From performance characterization, the pHEMA-VDM had the best performance. The sampling spots demonstrated fast and easy sampling and preparation of human serum spiked with the biomarker human chorionic gonadotropin. The sampling spots enabled a detection limit of 1 ng/mL (26.4 pM) within a five point concentration curve from 1 ng/mL to 20 ng/mL (R 2 = 0.97). The detection limit was demonstrated to be two times lower than previously demonstrated with standard DMPK-C sampling cards. A five point concentration curve from 100 ng/mL to 2000 ng/mL was also investigated (R 2 = 0.998). Intra day precision was within 16% and 23% for concentration range 1 ng/mL to 20 ng/mL and 100 ng/mL to 2000 ng/mL, respectively. Inter day precision was within 20%. Accuracy was determined to 10% and 11% for 2.5 ng/mL and 20 ng/mL, respectively. The sampling spots were also demonstrated in a realistic setting where serum samples from two confirmed patients with testicular germ cell cancer were analyzed. These analyses confirmed an elevated hCG content in the sera of 418.5 ± 4.2 ng/mL and 21 ± 0.02 ng/mL hCG for patient one and two respectively., (Copyright © 2018 Elsevier B.V. All rights reserved.)

The clinical predictive factors for malignant testicular histology remain unclear because of the low prevalence. Therefore, the aim of this study was to investigate predictors of malignant histology for testicular masses and decide more testis-sparing surgeries before surgery. This retrospective study enrolled 325 consecutive testicular mass patients who underwent radical orchiectomy (310/325) or testicular preserving surgery (15/325) from January 2001 to June 2016. The clinicopathological factors, including tumor diameter, cryptorchidism history, ultrasound findings, serum alpha-fetoprotein, and human chorionic gonadotropin (HCG) levels, were collected retrospectively for statistical analysis. A predictive nomogram was also generated to evaluate the quantitative probability. Among all patients, 247 (76.0%) were diagnosed with a malignant testicular tumor and 78 (24.0%) with benign histology. Larger tumor diameter (per cm increased, hazard ratio [HR] = 1.284, P = 0.036), lower ultrasound echo (HR = 3.191, P = 0.001), higher ultrasound blood flow (HR = 3.320, P < 0.001), and abnormal blood HCG (HR = 10.550, P < 0.001) were significant predictive factors for malignant disease in all testicular mass patients. The nomogram generated was well calibrated for all predictions of malignant probability, and the accuracy of the model nomogram measured by Harrell's C statistic (C-index) was 0.92. According to our data, the proportion of patients who underwent radical orchiectomy for benign tumors (24.0%) was much larger than generally believed (10.0%). Our results indicated that the diameter, ultrasonic echo, ultrasonic blood flow, and serum HCG levels could predict the malignancy in testicular mass patients., Competing Interests: None

Serum tumor markers (STMs) play a critical role in the diagnosis, staging and follow-up of both seminomatous and nonseminomatous testicular germ cell neoplasms. Levels of alpha-fetoprotein (AFP), human chorionic gonadotropin (HCG), and lactate dehydrogenase (LDH), especially those measured after orchiectomy, also have implications for patient prognosis. Given that testicular germ cell tumors represent the most common solid tumor in men aged 20-34, radiologists must have familiarity with the clinical utilization and implications of these STMs. This article will review the classical patterns of STM elevation most commonly seen in pure seminomatous and nonseminomatous germ cell tumors while also providing case-based examples highlighting the importance of STM correlation with imaging. The role of STMs in clinical staging and disease surveillance will also be discussed.

Background: Primary malignant mediastinal germ cell tumors (PMMGCTs) including seminomas and nonseminomatous germ cell tumors (NSGCTs) are rare, and sometimes the diagnosis is very difficult., Purpose: The purpose of this study is to compare the clinical characteristics, biomarkers, and imaging findings of seminomas and NSGCTs and to determine whether these features could help distinguish these two types of PMMGCT., Material and Methods: A retrospective study of 24 male patients with histopathologically proven PMMGCT was performed. We collected the information of computed tomography (CT) (the scan area ranged from the apex of lung to the costophrenic angles) and magnetic resonance imaging blood test and histology characteristics of these patients., Results: Twelve of 24 cases were confirmed to be seminomas, whereas the other 12 cases were NSGCTs. Alfa-fetoprotein (AFP) was found to be elevated in all patients with NSGCT, whereas none of the patients with seminomas had elevated AFP level. Beta-human chorionic gonadotropin (β-HCG) level was elevated in all the patients with seminomas (seven/seven), whereas in NSGCT only two of seven patients had elevated β-HCG. Lactate dehydrogenase level was increased in five of the nine patients with seminomas, as well as in the eight patients with NSGCT. CT imaging revealed that 12 masses from the seminoma group were homogeneous, soft tissue opacity and showed minimal contrast enhancement. On the contrary, all 12 NSGCT cases showed cystic and solid masses; on contrast-enhanced CT, heterogeneous enhancement was found on the capsule of the tumor, septum, and solid masses., Conclusion: Seminomas and NSGCT showed different profiles of tumor biomarkers and radiographic features. Evidence from serum test, histopathological analysis, and imaging should be combined to ensure the accurate diagnosis of these two types of PMMGCT., Competing Interests: None

Purpose: To investigate relapse detection methods among children and adolescents with nongerminomatous malignant germ cell tumors (MGCTs) and to determine whether tumor markers alone might be sufficient for surveillance., Methods: We retrospectively reviewed all patients enrolled in a phase III, single-arm trial for low-risk and intermediate-risk MGCTs. The method used to detect relapse was assessed based on case report forms, tumor markers, imaging, and pathology reports. Relapses were classified into one of two categories on the basis of whether they were (1) detectable by tumor marker elevation or (2) not detectable by tumor markers., Results: A total of 302 patients were enrolled, and 284 patients had complete data for review. Seven patients had normal tumor markers at initial diagnosis, and none experienced a relapse. At a median follow-up of 5.3 years, 48 patients (16.9%) had experienced a relapse. After central review, 47 of 48 relapses (98%) were detected by tumor marker elevation. Of the 47 patients, 16 (33.3%) had abnormal tumor markers with normal/unknown imaging, 31 patients (64.6%) had abnormal tumor markers with abnormal imaging, and one patient (2.1%) had abnormal imaging with unknown marker levels at relapse., Conclusion: Tumor marker elevation is a highly sensitive method of relapse surveillance, at least among children and adolescents with tumor marker elevation at initial diagnosis. Eliminating exposure to imaging with ionizing radiation may enhance the safety of relapse surveillance in patients treated for MGCT.

Background: Growing teratoma syndrome is a rare phenomenon seen in nonseminomatous germ cell tumors after chemotherapy, where the tumor grows paradoxically despite normalization of tumor markers. It has been found in various locations, most commonly, the retroperitoneum in association with metastatic disease. The occurrence of growing teratoma syndrome in a mediastinal primary is very rare and there are only a few reports in the literature., Methods: In a retrospective review, out of 12 patients with mediastinal involvement by a germ cell tumor, 5 had a primary from the mediastinum. We present a series of 3 cases of primary germ cell tumor of the mediastinum, which after chemotherapy, fulfilled the criteria for growing teratoma syndrome and were managed with surgical excision., Conclusion: Development of growing teratoma syndrome in a primary mediastinal germ cell tumor is extremely rare. Its awareness and early detection can lead to successful surgical excision and long-term cure.

Germ cell tumours predominantly of the testis ((T)GCTs) are remarkably chemotherapy sensitive. However, a small proportion of patients fail to be cured with cisplatin-based combination chemotherapy. miR-371a-3p is a new liquid biopsy biomarker for (T)GCTs. The aim of this study was to evaluate clinical utility of plasma miR-371a-3p level in patients starting systemic chemotherapy. Patients were included before the first cycle (N = 180) and second cycle (N = 101) of systemic first line chemotherapy, treated between July 2010 and May 2017. Plasma miR-371a-3p levels were measured with the ampTSmiR test and compared to disease characteristics and outcome. Pretreatment plasma miR-371a-3p levels were increased in 51.7% of cases and associated with number of metastatic sites, presence of lung, retroperitoneal, and mediastinal lymph node metastases, S - stage, IGCCCG risk group, and response to therapy. Patients with a negative pretreatment plasma level had better progression-free survival (PFS) and overall survival (OS) compared to patients being positive for miR-371a-3p (hazard ratio [HR] = 0.26, 95% confidence interval [CI] 0.09-0.71, P = 0.02 for PFS and HR = 0.21, 95% CI 0.07-0.67, P = 0.03 for OS, respectively). Patients negative for miR-371a-3p in both samples had a superior PFS (HR = 0.10, 95% CI 0.01-21.49, P = 0.02) and OS (HR = 0.08, 95% CI 0.01-27.81, P = 0.008) compared to patients with miR-371a-3p positive in both samples (multivariate analyses were non-significant). In total 68% of the patients were S0. This study demonstrates clinical value of plasma miR-371a-3p level in chemotherapy naïve (T)GCT patients starting first line of chemotherapy to predict prognosis., (© 2018 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.)

Testicular choriocarcinoma needs to be considered in the differential diagnosis of cutaneous metastases in young adult men because of its propensity for early hematogenous dissemination. Furthermore, the diagnosis may not be suspected in many cases in which there is clinically no testicular enlargement. This highly aggressive germ cell tumor typically metastasizes to the liver, lungs, and brain. Skin metastasis is exceedingly rare with only 22 cases previously reported in the world literature. We herein report 2 additional cases: a 25-year-old man and a 32-year-old man, both of whom were treated for mixed germ cell tumors and developed multiple cutaneous metastases to the head.

Introduction: Due to variety of treatment alternatives for testicular tumours, parameters other than existing staging criteria are also needed. Most studies have revealed the correlation between cancer and inflammation. In this study, we aimed to investigate the value of preoperative inflammatory markers between early-stage testicular tumours and patients with advanced-stage, their relationship with tumour pathology and their importance in predicting stage. To calculate the differences between inflammatory markers, stage 1 tumours localized to the testis and advanced-stage tumours spread beyond the testis were classified into 2 groups according to tumour pathology., Materials and Methods: The data of 112 patients undergoing inguinal orchiectomy in between 2008 and 2018 were recorded retrospectively. Neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), lymphocyte-to-monocyte ratio (LMR) and systemic immune-inflammation index (SII) were calculated by using the numbers of blood cell counts based systemic markers of inflammation. The differences between markers of inflammation were calculated by dividing tumours into 2 groups including early-stage and advanced- stage testicle tumours., Results: According to the results of preoperative inflammatory markers in predicting the stage; in the seminoma group, the difference between the median NLR (2.37 vs. 4.39, p = 0.012), LMR (3.80 vs. 2.40, p = 0.018) and SII (612 vs. 1,127, p = 0.009) of stage 1 and advanced stage were statistically significant, while in the non-seminoma group, only the difference between median PLR (99 vs. 154, p = 0.002) of stage 1 and advanced stage was statistically significant. Sensitivity and specificity of predicting advanced stage according to cut-off values of markers were 69 and 75% in NLR (3.21), 83 and 75% in LMR, and 59 and 75% in SII in the seminoma group; on the other hand, in the non-seminoma group, the sensitivity, and specificity of predicting the advanced stage of PLR cut-off (104) were 71 and 88% respectively., Conclusions: The clinical use of inflammatory biomarkers in testicular tumours may represent an important step in understanding germ cell tumours biology and in supporting staging criteria and prognostic criteria., (© 2019 S. Karger AG, Basel.)

Background: The significance of hilar soft tissue invasion of rete testis in malign germ cell tumors is still controversial on current guidelines., Objectives: We aimed to investigate the importance of hilar soft tissue involvement in germ cell tumors and evaluated the possibility of a risk factor such as rete testis., Method: Totally, 59 radical orchiectomy specimens operated between 2007 and 2015 at our clinics. All records were retrospectively researched. Patients' age, level of tumor markers, tumor size, histological subtype, clinical stage, presence or absence of carcinoma in situ, vascular/lymphatic and/or hilar soft tissue invasion, tumoral necrosis, number, site and diameter of metastasis, type of further treatment (radiotherapy or chemotheraphy) and follow-up period were recorded and evaluated for all patients., Results: Twenty-six of totally 59 malign germ cell tumors were seminomatous and 33 were nonseminomatous (NS). Mean patients age was 38.54 years (range 17-89 years). Mean follow-up duration was 39.84 months (range 3-96). Serum tumor marker levels were found associated with rete testis invasion (p = 0.035). Hilar soft tissue invasion was significantly associated with vascular invasion (p = 0.001). As it was expected, vascular invasion was significantly associated with metastasis (p = 0.024)., Conclusions: We concluded that there is a strong association between hilar soft tissue invasion and vascular invasion. Especially in NS germ cell tumors, hilar soft tissue involvement a risk factor for prognosis and to determine the need for additional treatment. According to our study, hilar soft tissue status should be reported on routine pathology report., (© 2019 S. Karger AG, Basel.)

Metastatic testicular germ cell tumors (TGCTs) are a potentially curable disease by administration of risk-adapted cytotoxic chemotherapy. Nevertheless, a disease-relapse after curative chemotherapy needs more intensive salvage chemotherapy and significantly worsens the prognosis of TGCT patients. Circulating tumor markers (β-subunit of human chorionic gonadotropin (β-HCG), alpha-Fetoprotein (AFP), and Lactate Dehydrogenase (LDH)) are frequently used for monitoring disease recurrence in TGCT patients, though they lack diagnostic sensitivity and specificity. Increasing evidence suggests that serum levels of stem cell-associated microRNAs (miR-371a-3p and miR-302/367 cluster) are outperforming the traditional tumor markers in terms of sensitivity to detect newly diagnosed TGCT patients. The aim of this study was to investigate whether these miRNAs are also informative in detection of disease recurrence in TGCT patients after curative first line therapy. For this purpose, we measured the serum levels of miR-371a-3p and miR-367 in 52 samples of ten TGCT patients at different time points during disease relapse and during salvage chemotherapy. In our study, miR-371a-3p levels in serum samples with proven disease recurrence were 13.65 fold higher than levels from the same patients without evidence of disease ( p = 0.014). In contrast, miR-367 levels were not different in these patient groups ( p = 0.985). In conclusion, miR-371a-3p is a sensitive and potentially novel biomarker for detecting disease relapse in TGCT patients. This promising biomarker should be investigated in further large prospective trials.

The clinical significance of limited choriocarcinoma in a malignant mixed germ cell tumor (MGCT) is unknown. Men with a MGCT with ≤5% choriocarcinoma at radical orchiectomy (RO) between 2000 and 2016 from our consult service were studied. Of 50 men in our cohort, we had clinical information for 30 men. Median follow-up was 41 months (1 to 168 mo). Median tumor size was 4.5 cm (1.1 to 8.0 cm). In total, 22/30 (73%) cases were pT1, 6/30(20%) cases were pT2, and 2/30 (7%) cases were pT3. In total, 4/30(13%) cases had lymph node metastases and 2/30 (7%) cases had distant metastases at the time of RO. In 30 cases with RO we had information on immediate postorchiectomy treatment: 14/30 (46.7%) active surveillance, 4/30 (13.3%) retroperitoneal lymph node dissection, 10/30 (33.3%) chemotherapy (chemotherapy), 1/30 (3.3%) retroperitoneal lymph node dissection followed by chemotherapy, and 1/30 (3.3%) resection of a distant metastasis. Preoperative serum human chorionic gonadotropin (hCG) levels ranged between 0.1 and 60,715 mIU/mL (mean, 4796; median, 485). One patient had an hCG level of 6367 mIU/mL and another 60,715 mIU/mL with the remaining cases <5000 mIU/mL. In total, 4/30 (13%) patients had elevated serum markers after surgery, 3 of them normalized following chemotherapy while the fourth one continued to have elevated serum alpha fetoprotein levels after chemotherapy. All patients were alive at last follow-up. In total, 7/30 (23.3%) patients subsequently developed metastatic disease to lymph nodes or distal organs, the histology of the metastasis consisted mainly of teratoma and yolk sac tumor. Embryonal carcinoma was present in 2 metastatic sites. One lung metastasis was suggestive for choriocarcinoma. Definitive choriocarcinoma was not present in any of the metastasis. A small component of choriocarcinoma in a MGCT is typically associated with relatively low-level elevations of serum hCG levels, and is not associated with aggressive disease. The presence of limited choriocarcinoma (≤5%) does not add to the prognostic information provided by standard TNM staging, which uses levels of serum markers (hCG, alpha fetoprotein, lactate dehydrogenase) as surrogates for extent of disease.

Purpose: Small benign testicular masses are often misinterpreted as germ cell tumors and immediate inguinal orchiectomy is performed. We analyzed the diagnostic and therapeutic workup of testicular masses to improve preoperative stratification algorithms., Materials and Methods: We performed a retrospective, single center analysis of the records of 522 patients diagnosed with primary testicular masses of unknown malignant potential., Results: A total of 28 patients (5%) showed a primary benign tumor after resection, including Leydig cell tumors in 9 (32%), epidermoid cysts in 9 (32%), adenomatoid tumors in 8 (29%) and Sertoli cell tumors in 2 (7%). The median volume of benign tumors was significantly less than that of malignant tumors (0.75 cm 3 , range 0.1 to 2.1 vs 15, range 4.5-39.9, p ≤0.001). At a cutoff of 2.8 cm 3 tumor volume most accurately differentiated between benign and malignant disease, and it was a predictor of malignancy with 83% sensitivity and 89% specificity (OR 1.389, 95% CI 1.035-1.864, p = 0.029). Symptom duration in patients with benign tumors was significantly longer (365 days, range 25.5 to 365 vs 20, range 7 to 42, p ≤0.001). Also, tumor markers were unaltered in benign lesions. In patients with benign tumors significantly more fertility disorders or cryptorchidism were found (p ≤0.001) as well as a tendency toward lower testosterone (3.9 μg/l, range 0.9 to 4.9 vs 5.3, range 3.5 to 6.8, p = 0.084). Testis sparing surgery was performed in 22 of all patients (79%) with benign tumors. There was no case of relapse during followup., Conclusions: Nongerm cell tumors should be considered when small testicular masses have a volume of less than 2.8 cm 3 and there are hormone disorders or normal tumor markers. Immediate orchiectomy should be avoided, favoring testis sparing surgery., (Copyright © 2018 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Purpose: Retroperitoneal lymph node dissection is recommended for residual masses greater than 1 cm after chemotherapy of nonseminomatous germ cell tumors. Currently there is no reliable predictor of post-chemotherapy retroperitoneal lymph node dissection histology. Up to 50% of patients harbor necrosis/fibrosis only so that a potentially morbid surgery has limited therapeutic value. In this study we evaluated the ability of defined serum miRNAs to predict residual viable nonseminomatous germ cell tumors after chemotherapy., Materials and Methods: Levels of serum miRNA, including miR-371a-3p, miR-373-3p and miR-367-3p, were measured using the ampTSmiR (amplification targeted serum miRNA) test in 82 patients, including 39 in cohort 1 and 43 in cohort 2, who were treated with orchiectomy, chemotherapy and post-chemotherapy retroperitoneal lymph node dissection. miRNA levels were compared to clinical characteristics and serum tumor markers, and correlated with the presence of viable germ cell tumor vs fibrosis/necrosis and teratoma. ROC analysis was done to determine miRNA discriminative capacity., Results: miRNA levels were significantly associated with disease extent at chemotherapy and they decreased significantly after chemotherapy. Conventional serum tumor marker levels were uninformative after chemotherapy. However, after chemotherapy miRNA levels remained elevated in patients harboring viable germ cell tumor in post-chemotherapy retroperitoneal lymph node dissection specimens. miR-371a-3p demonstrated the highest discriminative capacity for viable germ cell tumors (AUC 0.874, 95% CI 0.774-0.974, p <0.0001). Using an adapted hypothetical cutoff of 3 cm or less for surgical intervention miR-371a-3p correctly stratified all patients with viable residual retroperitoneal germ cell tumors with 100% sensitivity (p = 0.02)., Conclusions: Our study demonstrates for the first time the potential value of miR-371a-3p to predict viable germ cell tumors in residual masses after chemotherapy. Prospective studies are required to confirm clinical usefulness., (Copyright © 2018 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Tumor cells shed exosomes, which are released to the blood. Detecting tumor-derived exosomes containing RNA in plasma (liquid biopsy) is currently being investigated for early identification of occult metastases or relapses. Isolation of exosomes is laborious, resulting in low RNA yields. As a more robust (but less sensitive) alternative, the authors examined whether whole blood can be used as well. Tumor samples from nonmetastasized seminoma (n = 5) and colon cancer patients (n = 6) were taken during surgery. Whole-blood samples were taken before and 5-7 d after surgery. A whole genome mRNA microarray screening was performed. Candidate genes were selected based on two criteria: (1) gene expression in the presurgical whole-blood sample/tumor biopsy; and (2) a two-fold decrease in the copy number of candidate genes was expected in the postsurgical whole-blood sample 5-7 d after intervention, relative to the presurgical blood sample. The rationale behind this is the loss of tumor material in the body and the decline in the release of tumor-derived RNA in exosomes. For both tumor entities and for each patient, several hundred candidate genes could be identified. In a group-wise comparison, 20 candidate genes could be identified in the seminoma and 32 in the colon cancer group. These findings indicate that whole blood might be suitable for a liquid biopsy. However, this study identified the short period after surgery (5-7 d) as a possible confounder. The authors plan to add an additional time point several weeks after the operation to discriminate tumor candidate genes from genes induced by the surgery.

Background: Controversy exists whether Leydig cells recover after testicular cancer (TC) treatment or whether premature hormonal aging will occur., Objective: Evaluate serial changes in total testosterone (TT) and luteinizing hormone (LH) in patients treated with orchiectomy alone (Stage I) or combination chemotherapy with bleomycin, etoposide, and cisplatin (BEP)., Design, Settings, and Participants: Changes in TT and LH were investigated during 5-yr follow-up (Stage I: n=75, BEP: n=81). A selected group of TC patients with mild Leydig cell dysfunction (LH ≥ 8 IU/l) were followed for a longer period (Stage I: n=20, BEP: n=23). An age-matched control group of 839 healthy men served as controls for TT and LH levels., Outcome Measurements and Statistical Analysis: Changes in age-adjusted TT and LH were evaluated separately in each treatment group with univariate linear regression analysis. The proportion of patients initiating testosterone substitution during follow-up was calculated., Results and Limitations: In the 75 Stage I patients there were no significant changes in LH and TT, while in the 81 BEP treated patients there was a significant decline in LH during follow-up (-24.2 percentage point/yr, 95% confidence interval: -38.5 to -9.9, p=0.001). In total, 11% of Stage I patients and 15% of BEP-treated patients initiated testosterone substitution. In the 23 BEP-treated patients with mild Leydig cell dysfunction there was a significant decline in age-adjusted TT (-0.9 percentage point/yr, 95% confidence interval: -1.8 to -0.04, p=0.04), while in the 20 Stage I patients there were no significant changes in age-adjusted LH and TT. Limitations include the retrospective study design., Conclusions: TT remained stable during 5-yr follow-up in TC patients treated with orchiectomy alone or BEP. BEP-treated patients with mild Leydig cell dysfunction during follow-up were at risk of long-term testicular failure and evaluation of Leydig cell function beyond follow-up should be considered in this group of patients., Patient Summary: This study shows that the majority of testicular cancer survivors had stable testosterone levels after treatment for testicular cancer. However, 11-15% of patients needed testosterone substitution after treatment., (Copyright © 2016 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Objective: Hypogonadism is a major complication in testicular cancer survivors, but its prevalence varies among studies. In Japan, free testosterone has been used for diagnosis of late-onset hypogonadism syndrome. In the present study, we evaluated the hormone level of testicular cancer survivors and its impact on their quality of life., Methods: Overall, 50 testicular cancer survivors treated from 1990 to 2013 were enrolled. The median age was 44 years. The serum levels of free testosterone, total testosterone and luteinizing hormone were measured. All patients completed the Aging Males' Symptom scale and International Index of Erectile Function-15. The hormone levels of 337 healthy volunteers were used as the control., Results: A total of 32 (64%) patients showed free testosterone levels <8.5 pg/mL. In contrast, just 26% of 50 patients showed total testosterone levels <3.5 ng/mL. Testicular cancer survivors had significantly lower free testosterone and higher luteinizing hormone compared with healthy controls. In contrast, there was no difference in total testosterone between patients and controls. The prevalence of late-onset hypogonadism symptoms of any grade (Aging Males' Symptom total score ≥27) was 60%. Overall, 64% were defined as having moderate erectile dysfunction (International Index of Erectile Function-Erectile Function domain score <17). However, Aging Males' Symptom, International Index of Erectile Function-15 and Erectile Function domain scores did not differ by free testosterone or total testosterone level., Conclusions: This is the first report on the prevalence of hypogonadism determined by free testosterone level in Japanese testicular cancer survivors. Because Aging Males' Symptom and International Index of Erectile Function-15 scores do not necessarily reflect the hormone level, measuring free testosterone is also important in the follow up of these patients., (© 2018 The Japanese Urological Association.)

Background: We evaluated systemic immune-inflammation index (SII) and its association with patient outcome in germ-cell tumours (GCTs)., Methods: Two independent cohorts of patients were analysed; the discovery set (n=171) from a single institution and the validation set (n=181) previously included in a study evaluating PD-L1 in GCTs. The SII was calculated using platelet (P), neutrophil (N) and lymphocyte (L) counts before chemotherapy and correlated with survival using regression analyses and Kaplan-Meier method., Results: In the discovery cohort, the SII was associated with poor risk clinical features. Patients with low SII had significantly longer progression-free survival (HR=0.22, 95% CI 0.12-0.41, P<0.001) and overall survival (OS) (HR=0.16, 95% CI 0.08-0.32, P<0.001) compared to high SII. This index was independent of International Germ Cell Cancer Collaborative Group criteria in multivariable Cox regression analysis for OS and was validated in an independent cohort. When combining PD-L1 expression on tumour infiltrating lymphocytes (TILs) and SII, we identified three distinctive prognostic groups., Conclusions: High SII was associated with poor outcome in GCTs. Combination of PD-L1 positive TILs and SII could further refine prognosis in GCTs.

Background: The prognostic utility of systemic inflammatory markers has so far not been investigated in patients with metastatic testicular germ cell tumours (GCTs)., Methods: International Germ Cell Cancer Cooperative Group (IGCCCG) risk groups and blood-based systemic inflammatory markers (haemoglobin, leukocytes, platelets (P), neutrophils (N), lymphocytes (L), C-reactive protein (CRP) and albumin) of 146 patients undergoing first-line chemotherapy for GCT were retrieved. In addition, N to L ratio (NLR), P to L ratio and the systemic immune-inflammation index (SII=N × P/L) were calculated. The prognostic ability of these markers for overall survival (OS) were assessed using regression analyses and Kaplan-Meier curves with log-rank tests., Results: In univariate Cox regression, low haemoglobin and albumin as well as high leukocytes, N, NLR, SII and CRP were associated with a shorter OS. In multivariable Cox regression analyses, high leukocyte (hazard ratio (HR) 1.274 (95% confidence interval (CI) 1.057-1.535); P=0.011) and N count (1.470 (1.092-1.980); P=0.011), higher NLR (84.5 (2.2-3193.4); P=0.017) and SII (12.15 (1.17-126.26); P=0.037) remained independent prognostic predictors for OS besides the IGCCCG risk groups., Conclusions: Systemic inflammatory markers might have prognostic utility for patients with metastatic GCT. The planned IGCCCG update could be an opportunity to test these markers in a larger data set.

Context: Current knowledge on gonadal function in congenital adrenal hyperplasia (CAH) is mostly limited to single-center/country studies enrolling small patient numbers. Overall data indicate that gonadal function can be compromised in men with CAH., Objective: To determine gonadal function in men with CAH within the European 'dsd-LIFE' cohort., Design: Cross-sectional clinical outcome study, including retrospective data from medical records., Methods: Fourteen academic hospitals included 121 men with CAH aged 16-68 years. Main outcome measures were serum hormone concentrations, semen parameters and imaging data of the testes., Results: At the time of assessment, 14/69 patients had a serum testosterone concentration below the reference range; 7 of those were hypogonadotropic, 6 normogonadotropic and 1 hypergonadotropic. In contrast, among the patients with normal serum testosterone (55/69), 4 were hypogonadotropic, 44 normogonadotropic and 7 hypergonadotropic. The association of decreased testosterone with reduced gonadotropin concentrations (odds ratio (OR) = 12.8 (2.9-57.3)) was weaker than the association between serum androstenedione/testosterone ratio ≥1 and reduced gonadotropin concentrations (OR = 39.3 (2.1-732.4)). Evaluation of sperm quality revealed decreased sperm concentrations (15/39), motility (13/37) and abnormal morphology (4/28). Testicular adrenal rest tumor (TART)s were present in 39/80 patients, with a higher prevalence in patients with the most severe genotype (14/18) and in patients with increased current 17-hydroxyprogesterone 20/35) or androstenedione (12/18) serum concentrations. Forty-three children were fathered by 26/113 patients., Conclusions: Men with CAH have a high risk of developing hypothalamic-pituitary-gonadal disturbances and spermatogenic abnormalities. Regular assessment of endocrine gonadal function and imaging for TART development are recommended, in addition to measures for fertility protection., (© 2018 European Society of Endocrinology.)

Background: Human Chorionic Gonadotropin (hCG) is produced by germ cell tumors, but can also be elevated in benign conditions such as primary hypogonadism, where hCG is produced by the pituitary gland. In our experience, the reference limits for hCG (Elecsys hCG+β-assay, Roche Diagnostics), were unnecessarily high and did not reflect levels encountered in clinical practice. We wanted to establish new reference limits to increase the clinical utility of the hCG-assay., Methods: We analysed hCG in serum samples from a healthy adult population and in a cohort of testicular cancer survivors. The gonadotropins LH and FSH were measured in the cohort and in a selection of the reference population to assess gonadal function., Results: We found low hCG levels for all men and women <45years (97.5 percentiles 0.1 and 0.2IU/L, respectively) from the healthy population (n=795) having normal FSH and LH. Due to assay limitations, we suggest a common reference limit of <0.3IU/L. For the age group ≥45, the 97.5 percentiles in the healthy population were 0.5IU/L for men and 6.0IU/L for women. In all subjects from both the reference population and the cohort (n=732), hCG levels exceeding the reference limit could be fully explained by reduced gonadal function indicated by elevated LH and FSH levels., Conclusion: The Elecsys hCG+β-assay should have lower reference limits than recommended by the manufacturer, with important implications for tumor follow-up. Elevated hCG is rare with intact gonadal function, both in a normal population and among survivors of testicular cancer, and should lead to further investigations when encountered in clinical practice., (Copyright © 2017 Oslo University Hospital. Published by Elsevier Inc. All rights reserved.)

Background: Quantifying circulating nucleic acids is an important new approach to cancer diagnosis/monitoring. Methods: We compared the suitability of serum versus plasma for measuring miRNAs using qRT-PCR and assessed how preanalytic variables that can affect circulating tumor DNA (ctDNA) quantification in plasma also influence miRNA levels. Results: Across 62 blood-derived specimens, plasma samples in EDTA, Streck-DNA, and Streck-RNA tubes showed significantly higher C t values for multiple housekeeping miRNAs, compared with serum samples. For the EDTA-plasma tubes, this difference was only seen when including the high-speed centrifugation protocol used to optimize ctDNA extraction. In plasma samples derived from blood stored at room temperature for up to 14 days (conditions that typically apply to samples processed for biobanking), levels of endogenous housekeeping miRNAs gradually increased, in parallel with the hemolysis marker hsa-miR-451a, consistent with release from blood cells/platelets. It was necessary to normalize levels of the housekeeping miRNAs to those of hsa-miR-451a, to obtain the stable values needed for referencing test miRNA levels. Conclusions: Our data indicate that plasma samples prepared for ctDNA extraction are suboptimal for miRNA quantification and require the incorporation of multiple data normalization steps. For prospective studies designed to measure both miRNAs and ctDNA, the most suitable approach would be to obtain both serum (for miRNAs) and plasma (for ctDNA). If only plasma can be collected, we recommend an initial low-speed centrifugation step, followed by aliquoting the supernatant into parallel samples, one for direct miRNA quantification, and the other for a further high-speed centrifugation step to optimize ctDNA retrieval. Impact: These recommendations will help "future-proof" clinical studies in which quantification of circulating miRNAs is a component. Cancer Epidemiol Biomarkers Prev; 27(2); 208-18. ©2017 AACR ., (©2017 American Association for Cancer Research.)

Background: Clinical practice guidelines recommend the measurement of human chorionic gonadotropin (hCG) and/or hCGβ in serum for management of testicular germ cell tumors (GCTs). These guidelines, however, disregard relevant biochemical information on hCG variants to be detected for oncological application. We set out to provide a critical review of the clinical evidence together with a characterization of the selectivity of currently marketed hCG immunoassays, identifying assays suitable for management of GCTs., Content: Evidence sources in the available literature were critically appraised. Most instances of misdiagnosis and mismanagement of testicular GCTs have been associated with hCG results. According to the clinical evidence, 36% of patients with seminoma show an exclusive hCGβ increase, and 71% of patients with nonseminomatous GCTs (NSGCTs) show an increase of intact hCG and/or hCG + hCGβ, whereas the hCGβ increase in NSGCTs is variable according to the tumor stage and histology., Summary: hCG + hCGβ assays that display an equimolar recognition of hCG and hCGβ, or at least do not overtly underestimate hCGβ, may be employed for management of testicular GCTs. Assays that underestimate hCGβ are not recommended for oncological application. In addition to the hCG + hCGβ assay in service, an additional assay with broader selectivity for other hCG variants should be considered when false-negative or false-positive results are suspected on the basis of clinical data., (© 2017 American Association for Clinical Chemistry.)

Objective: The pituitary production of human chorionic gonadotropin (hCG) can cause false-positive results during or after germ cell tumor (GCT) treatment. Because hypogonadism leads to pituitary hCG production, testosterone administration test (TAT) has been recommended for pituitary hCG diagnosis. However, little is known about its efficacy for the discrimination of pituitary hCG as detected by currently used hCG assays in treatment of GCT. We conducted a retrospective multicenter study to determine the usefulness of TAT., Materials and Methods: The study included 60 patients who underwent TAT for the discrimination of pituitary hCG. In principle, serum hCG levels were measured 1 week after testosterone enanthate administration (250 mg). When the serum hCG levels decreased below the normal upper range, the results of TAT were determined positive. In this case, the elevated hCG was considered to be derived from pituitary and not from GCT., Results: Serum hCG levels were normalized after TAT in 36 of 60 patients (60%). Before TAT, the hCG levels were below 1.0 IU/L in 13 patients (36%), 1.0-1.9 IU/L in 11 (31%), 2.0-2.9 IU/L in 7 (19%), and >3.0 IU/L in 5 (14%) of TAT-positive patients. Of them, 28 (78%) patients were successfully managed without further treatment with chemotherapy after TAT. Pituitary hCG was associated with higher levels of LH and not necessarily associated with low levels of testosterone., Conclusion: Determining the TAT status of patients was effective in discriminating pituitary hCG production.

Cryptorchidism and testicular tumours are very common disorders in dogs genitalia. The aim of the present study was o obtain an overview of serum 17β-oestradiol, anti-Muellerian hormone (AMH) and testosterone levels in intact dogs compared to dogs with different testicular tumours and dogs with cryptorchidism. Testosterone, AMH and 17β-oestradiol concentrations were measured in peripheral and local spermatic venous blood in dogs with unilateral cryptorchidism (n=8), dogs with neoplastic testicular diseases (n=8) and in a control group of mature intact dogs (n=8). Results confirmed significantly higher concentrations of testosterone in local venous blood (control group: right testicle (RT) 46.23 ± 40.88 ng/ml and left testicle (LT) 50.76 ± 43.76 ng/ml; cryptorchid group: RT 23.91 ± 22.79 ng/ml and LT 10.52 ± 7.37 ng/ml; tumour group: RT 37.26 ± 25.26 ng/ml and LT 44.86 ± 19.03 ng/ml) (p<0.05) compared to their concentrations in peripheral blood (PB) in a control (4.92 ± 3.3 ng/ml) and in a cryptorchid group (0.89 ± 0.78 ng/ml), but not in the tumour group (11.37 ± 10.86 ng/ml). However, we have found increased level of testosterone in PB in the tumour group compared to its PB concentrations in the control or the cryptorchid group. Concentrations of AMH in PB observed in the cryptorchid group was 54.98 ± 30.07 μg/ml and in the control group was 6.49 ± 3.24 μg/ml (p<0.05). The same was observed in the case of local blood concentrations, which were significantly higher in the cryptorchid group (RT 51.92 ± 30.59 μg/ml; LT 46.33 ± 34.86 μg/ml) (p<0.05). We also observed high oestradiol concentrations in the cryptorchid group in both peripheral and local blood (PB: 30.86 ± 20.28 pg/ml; RT: 55.71 ± 34.7 pg/ml; LT: 78.99 ± 47.72 pg/ml), and even higher in the tumour group (PB: 52.46 ± 34.02 pg/ml; RT: 188.16 ± 132.67 pg/ml; LT: 297.14 ± 245.56 pg/ml). AMH has been shown to be a specific biomarker of gonadal tumours originated in Sertoli cells. It is also useful marker for confirmation of the existence of a functional cryptorchid testis. According to us, the scientific work dealing with a disorder of testicular descent in dogs, regarding the evaluation of sex hormones levels and the formation of the testes using modern diagnostic methods, significantly contribute to the clarification of some processes, leading to pathophysiological disturbances during this process., (Copyright© by the Polish Academy of Sciences.)

Purpose: Diagnosing germ cell neoplasia in situ (GCNis) can detect germ cell tumours (GCTs) at the pre-invasive stage. To date, testicular biopsy with the potential of surgical complications is the only way of safely diagnosing GCNis. Recently, microRNAs (miRs) 371-3, and miR 367 were shown to be valuable serum biomarkers of GCTs. We explored the usefulness of these candidate miRs as a marker for GCNis., Methods: 27 patients with GCNis and no concomitant GCT were enrolled. All patients underwent measuring serum levels of miR-371a-3p and miR-367-3p before treatment, 11 had repeat measurement after treatment, 2 also had testicular vein blood examinations. Serum levels were measured by quantitative PCR. In addition, four orchiectomy specimens of patients with GCT were examined immunohistochemically and by in situ hybridization (ISH) with a probe specific for miR-371a-3p to look for the presence of this miR in GCNis cells., Results: The median serum level of miR-371a-3p was significantly higher in patients with GCNis than in controls, miR-367 levels were not elevated. Overall, 14 patients (51.9%) had elevated serum levels of miR-371a-3p. The highest levels were found in patients with bilateral GCNis. Levels in testicular vein serum were elevated in both of the cases. After treatment, all elevated levels dropped to normal. In two orchiectomy specimens, miR-371a-3p was detected by ISH in GCNis cells., Conclusions: Measuring miR-371a-3p serum levels can replace control biopsies after treatment of GCNis. In addition, the test can guide clinical decision making regarding the need of testicular biopsy in cases suspicious of GCNis.

Various microRNAs from the miR-371-3 and miR-302a-d clusters have recently been proposed as markers for testicular germ cell tumours. Upregulation of these miRNAs has been found in both the tissue and serum of testicular cancer patients, but they have never been studied in human seminal plasma. The aim of this study was, therefore, to assess the differences in the expression of miR-371-3 and miR-302a-d between the seminal plasma and serum of testicular cancer patients, and to identify new potential testicular cancer markers in seminal plasma. We investigated the serum and seminal plasma of 28 pre-orchiectomy patients subsequently diagnosed with testicular cancer, the seminal plasma of another 20 patients 30 days post-orchiectomy and a control group consisting of 28 cancer-free subjects attending our centre for an andrological check-up. Serum microRNA expression was analysed using RT-qPCR. TaqMan Array Card 3.0 platform was used for microRNA profiling in the seminal plasma of cancer patients. Results for both miR-371-3 and the miR-302 cluster in the serum of testicular cancer patients were in line with literature reports, while miR-371and miR-372 expression in seminal plasma showed the opposite trend to serum. On array analysis, 37 miRNAs were differentially expressed in the seminal plasma of cancer patients, and the upregulated miR-142 and the downregulated miR-34b were validated using RT-qPCR. Our study investigated the expression of miRNAs in the seminal plasma of patients with testicular cancer for the first time. Unlike in serum, miR-371-3 cannot be considered as markers in seminal plasma, whereas miR-142 levels in seminal plasma may be a potential marker for testicular cancer.

Purpose: α-fetoprotein (AFP) and human chorionic gonadotropin subunit beta (B-HCG) are informative serum biomarkers for the primary diagnosis and follow-up of testicular germ cell cancer (TGCC) patients. About 20% of TGCC patients with a non-seminoma (NS) and about 80% with a seminoma (SE) are, however, negative for these biomarkers. Embryonic stem cell microRNAs (miRs) may serve as promising alternative serum biomarkers. Here we investigated a retrospective series of serum samples from selected TGCC patients who developed a relapse in time to test the possible additional value of the serum-based ampTSmiR test compared to the conventional serum-based protein biomarkers for follow-up., Methods: We investigated 261 retrospective serum samples of six selected fully evaluated TGCC patients with a proven relapse using the ampTSmiR test for miR-371a-3p, miR-373-3p, and miR-367-3p and compared the results to those of the conventional protein biomarkers., Results: At primary diagnosis, elevated serum B-HCG, AFP and LDH levels were found to be informative in 4/6, 3/6 and 3/6 patients, respectively. At primary diagnosis the levels of miR-371a-3p and miR-373-3p were elevated in 4/4, and miR-367-3p in 3/4 patients. For two cases no starting serum sample was available for retrospective miR analysis. Residual disease (overlooked by histopathological examination) was detected in one case by miR-371a-3p only. The miR-371a-3p level was increased in one patient two months before detection of an intracranial metastasis. B-HCG was informative in 3/4 and the ampTSmiR test in 4/4 patients with a relapse or residual disease. None of the biomarkers were informative for the detection of residual mature teratoma., Conclusions: The ampTSmiR test is more sensitive than the conventional TGCC protein biomarkers for the detection of residual disease and relapse, excluding mature teratoma.

Background: Elevated serum levels of luteinizing hormone and slightly decreased serum levels of testosterone (mild Leydig cell insufficiency) is a common hormonal disturbance in testicular cancer (TC) survivors. A number of studies have shown that low serum levels of testosterone is associated with low grade inflammation and increased risk of metabolic syndrome. However, so far, no studies have evaluated whether testosterone substitution improves metabolic dysfunction in TC survivors with mild Leydig cell insufficiency., Methods/design: This is a single-center, randomized, double-blind, placebo-controlled study, designed to evaluate the effect of testosterone replacement therapy in TC survivors with mild Leydig cell insufficiency. Seventy subjects will be randomized to receive either testosterone replacement therapy or placebo. The subjects will be invited for an information meeting where informed consent will be obtained. Afterwards, a 52-weeks treatment period begins in which study participants will receive a daily dose of transdermal testosterone or placebo. Dose adjustment will be made three times during the initial 8 weeks of the study to a maximal daily dose of 40 mg of testosterone in the intervention arm. Evaluation of primary and secondary endpoints will be performed at baseline, 26 weeks post-randomization, at the end of treatment (52 weeks) and 3 months after completion of treatment (week 64)., Discussion: This study is the first to investigate the effect of testosterone substitution in testicular cancer survivors with mild Leydig cell insufficiency. If positive, it may change the clinical handling of testicular cancer survivors with borderline low levels of testosterone., Trial Registration: ClinicalTrials.gov : NCT02991209 (November 25, 2016).

More than 95% of testicular cancer are cured but they are at increased long-term risk of cardiovascular disease. The risk of cardiovascular disease and treatment intensity was reported, but it is unknown whether this effect of cancer therapy is direct or indirect, mediated through androgen deficiency. Our aim was, therefore, to evaluate whether testicular cancer patients have increased the prevalence of risk factors of cardiovascular disease and if these risk factors are associated with hypogonadism and/or the cancer treatment given. In 92 testicular cancer patients (mean 9.2 years follow-up) and age-matched controls, blood samples were analysed for lipids, total testosterone, luteinizing hormone (LH), glucose and insulin. An estimate of insulin resistance, HOMAir was calculated. Hypogonadism was defined as total testosterone < 10 nmol/L and/or LH > 10 IU/L and/or androgen replacement. In testicular cancer men with hypogonadism, compared with eugonadal patients, higher insulin (mean difference: 3.10 mIU/L; p = 0.002) and HOMAir (mean difference: 0.792; p = 0.007) were detected. Hypogonadism group presented with increased risk (OR = 4.4; p = 0.01) of metabolic syndrome. Most associations between the treatment given and the metabolic parameters became statistically non-significant after adjustment for hypogonadism. In conclusion, testicular cancer patients with signs of hypogonadism presented with significantly increased risk of metabolic syndrome and investigation of endocrine and metabolic parameters is warranted in these patients., (© 2017 American Society of Andrology and European Academy of Andrology.)

Cancer/testis antigen (CTAg) expression is restricted to spermatogenic cells in an immune-privileged site within the testis. However, these proteins are expressed aberrantly by malignant cells and T-cell responses against CTAgs develop in many cancer patients. We investigated the prevalence, magnitude and phenotype of CTAg-specific T cells in the blood of patients with testicular germ cell tumors (TGCTs). CD8 + and CD4 + T-cell responses against MAGE-A family antigens were present in 44% (20/45) of patients' samples assayed by ex vivo IFN-γ ELISPOT. The presence of MAGE-specific CD8 + T cells was further determined following short-term in vitro expansion through the use of pMHC-I multimers containing known immunogenic peptides. Longitudinal analysis revealed that the frequency of MAGE-specific T cells decreased by 89% following orchidectomy suggesting that persistence of tumor antigen is required to sustain CTAg-specific T-cell immunity. Notably, this decrease correlated with a decline in the global effector/memory T-cell pool following treatment. Spontaneous T-cell immunity against CTAg proteins therefore develops in many patients with testicular cancer and may play an important role in the excellent clinical outcome of patients with this tumor subtype., (© 2017 The Authors. European Journal of Immunology published by WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Background: Cytokines are the communicators of immune system and are involved in all immune responses. The aim of this study was to assess the correlation among plasma cytokines, patient and tumor characteristics, and clinical outcome in chemonaive testicular germ-cell tumor (TGCT) patients., Patients and Methods: This study included 92 metastatic chemotherapy-naive TGCT patients treated with platinum-based chemotherapy from July 2010 to March 2014. Plasma was isolated before first administration of chemotherapy, and the concentration of 51 plasma cytokines were analyzed using multiplex bead arrays., Results: At a median follow-up of 33.2 months (range, 0.1-54.8 months), 10.9% of patients experienced disease progression, and 7.6% died. Several cytokines were associated with different baseline clinicopathologic features. Elevated plasma levels of interferon (IFN)-α2, interleukin (IL)-2Rα, IL-16, hepatocyte growth factor (HGF), and monocyte chemotactic protein (MCP)-3 were significantly associated with worse progression-free survival and overall survival (OS). Moreover, elevated levels of stem-cell growth factor (SCGF)-β were also associated with worse OS. Patients with elevated levels of all 6 cytokines experienced significantly worse outcomes compared to patients who had fewer than 6 cytokines elevated (hazard ratio = 12.06; 95% confidence interval, 7.39-19.49; P = .002 for progression-free survival, and hazard ratio = 39.65; 95% confidence interval, 25.03-62.18; P < .00001 for OS, respectively). Results were independent of International Germ Cell Cancer Collaborative Group criteria., Conclusion: We found a correlation among progression free-survival, OS, and circulating cytokines in TGCT. This suggests the existence an association between plasma cytokines and baseline clinicopathologic features in TGCT. Plasma cytokines could be used for identification of high-risk patients who are candidates for new therapeutic approaches., (Copyright © 2017 Elsevier Inc. All rights reserved.)

A correlation between disturbances in hormone levels and the onset of metabolic disorders has been reported in long-term survivors of testicular cancer (TC).We evaluated serum vitamin D levels and other biological parameters in a consecutive series of 61 long-term (≥3 years) unilateral TC survivors with a median a follow-up of 4 years and in a cohort of healthy males. Deficient vitamin D levels were observed in 10 (17%) of the 58 long-term unilateral TC survivors but were not reported in healthy males (p=.019, Fisher test). Median vitamin D levels were 18.6 ug/L in 58 assessable TC survivors and 23.6 ug/L in 40 healthy males (p=.031). In univariate logistic regression analysis, TC diagnosis was associated with inadequate levels of vitamin D (p=.047). Vitamin D levels were lower when follow-up was > 10 years, albeit this difference was not statistically significant (p=.074). Long-term (especially > 10 years) TC survivors may have difficulty maintaining optimal vitamin D levels. Larger studies are needed to better characterize vitamin D status and possible correlations with premature hormonal aging reported in long-term TC survivors.

Background: Androgen insensitivity syndrome is an X-linked disorder, and is characterised by a female phenotype in a chromosomally male individual. It usually occurs in puberty with primary amenorrhoea or as an inguinal tumour in a female infant. In recent years, it is often also diagnosed in fertility clinics in adulthood., Objective: The case is presented of a pure seminoma in a woman with the reference diagnosis of inguinal hernia., Clinical Case: A 53 year old woman, who was operated on in 2014 due to a nodule in left groin. Androgen insensitivity syndrome was corroborated, and histopathology reported it as a right testicular seminoma., Discussion: The importance of early diagnosis is discussed, highlighting the consequences of misdiagnosis, and question whether these patients have been adequately treated in the past. The risk of malignant transformation of an undescended testicle increases with age, thus gonadectomy should be performed after puberty, and in some cases hormone replacement therapy., (Copyright © 2016 Academia Mexicana de Cirugía A.C. Publicado por Masson Doyma México S.A. All rights reserved.)