Tumor espermatocítico variante anaplásica sincrónico bilateral: reporte de una neoplasia infrecuente / Bilateral synchronous anaplastic variant spermatocytic tumor: Report of a rare neoplasm

El tumor espermatocítico es una neoplasia testicular de células germinales, muy infrecuente, que representa menos del 1% de los cánceres testiculares. Afecta generalmente a hombres mayores con una edad media de 53,6 años (rango 19-92 años). El tumor espermatocítico se clasifica dentro del grupo de tumores germinales no relacionados con la neoplasia de células germinales in situ. Muestra características clinicopatológicas diferentes del seminoma clásico y no se considera una variante de este último. Debido a una superposición morfológica con el seminoma clásico, en el pasado se denominó «seminoma espermatocítico». La variante anaplásica del tumor espermatocítico es excepcional, se han descrito pocos casos en la literatura, presenta un inicio más temprano en comparación con el tumor espermatocítico y un buen comportamiento a pesar de mostrar patrones histológicos similares al seminoma clásico. Presentamos el segundo caso de tumor espermatocítico anaplásico sincrónico bilateral, en un paciente joven tratado con orquiectomía y quimioterapia. (AU)

Spermatocytic tumor is a very rare germ cell testicular neoplasm that accounts for less than 1% of testicular cancers. It generally affects older men with a mean age of 53.6 years (range 19-92 years). Spermatocytic tumor is classified within the group of germ cell tumors not related to germ cell neoplasia in situ. It presents clinicopathological characteristics different from classic seminoma and is not considered a variant of the latter. Due to a morphologic overlap with classical seminoma, it was called “sperm cell seminoma” in the past. The anaplastic variant of spermatocytic tumor is exceptional, few cases have been described in the literature, it presents an earlier onset compared to spermatocytic tumor and a benign behavior despite showing histological patterns similar to classic seminoma. We present the second case of bilateral synchronous anaplastic spermatocytic tumor, in a young patient treated with orchiectomy and chemotherapy. (AU)

Primary Retroperitoneal Lymph Node Dissection for Clinical Stage II A/B Seminomas: A Systematic Review and Meta-Analysis.

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.

Expression of CD44 is associated with aggressiveness in seminomas.

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.

[Bilateral synchronous anaplastic variant spermatocytic tumor: Report of a rare neoplasm]. / Tumor espermatocítico variante anaplásica sincrónico bilateral: reporte de una neoplasia infrecuente.

Spermatocytic tumor is a very rare germ cell testicular neoplasm that accounts for less than 1% of testicular cancers. It generally affects older men with a mean age of 53.6 years (range 19-92 years). Spermatocytic tumor is classified within the group of germ cell tumors not related to germ cell neoplasia in situ. It presents clinicopathological characteristics different from classic seminoma and is not considered a variant of the latter. Due to a morphologic overlap with classical seminoma, it was called "sperm cell seminoma" in the past. The anaplastic variant of spermatocytic tumor is exceptional, few cases have been described in the literature, it presents an earlier onset compared to spermatocytic tumor and a benign behavior despite showing histological patterns similar to classic seminoma. We present the second case of bilateral synchronous anaplastic spermatocytic tumor, in a young patient treated with orchiectomy and chemotherapy.

Impact of teratoma on survival probabilities of patients with metastatic non-seminomatous germ cell cancer: Results from the IGCCCG Update Consortium.

AIMS: To resolve the ongoing controversy surrounding the impact of teratoma (TER) in the primary among patients with metastatic testicular non-seminomatous germ-cell tumours (NSGCT). PATIENTS AND METHODS: Using the International Germ Cell Cancer Collaborative Group (IGCCCG) Update Consortium database, we compared the survival probabilities of patients with metastatic testicular GCT with TER (TER) or without TER (NTER) in their primaries corrected for known prognostic factors. Progression-free survival (5y-PFS) and overall survival at 5 years (5y-OS) were estimated by the Kaplan-Meier method. RESULTS: Among 6792 patients with metastatic testicular NSGCT, 3224 (47%) had TER in their primary, and 3568 (53%) did not. In the IGCCCG good prognosis group, the 5y-PFS was 87.8% in TER versus 92.0% in NTER patients (p = 0.0001), the respective 5y-OS were 94.5% versus 96.5% (p = 0.0032). The corresponding figures in the intermediate prognosis group were 5y-PFS 76.9% versus 81.6% (p = 0.0432) in TER and NTER and 5y-OS 90.4% versus 90.9% (p = 0.8514), respectively. In the poor prognosis group, there was no difference, neither in 5y-PFS [54.3% in TER patients versus 55.4% (p = 0.7472) in NTER], nor in 5y-OS [69.4% versus 67.7% (p = 0.3841)]. NSGCT patients with TER had more residual masses (65.3% versus 51.7%, p < 0.0001), and therefore received post-chemotherapy surgery more frequently than NTER patients (46.8% versus 32.0%, p < 0.0001). CONCLUSION: Teratoma in the primary tumour of patients with metastatic NSGCT negatively impacts on survival in the good and intermediate, but not in the poor IGCCCG prognostic groups.

Differentiation of testicular seminomas from nonseminomas based on multiphase CT radiomics combined with machine learning: A multicenter study.

BACKGROUND: Differentiating seminomas from nonseminomas is crucial for formulating optimal treatment strategies for testicular germ cell tumors (TGCTs). Therefore, our study aimed to develop and validate a clinical-radiomics model for this purpose. METHODS: In this study, 221 patients with TGCTs confirmed by pathology from four hospitals were enrolled and classified into training (n = 126), internal validation (n = 55) and external test (n = 40) cohorts. Radiomics features were extracted from the CT images. After feature selection, we constructed a clinical model, radiomics models and clinical-radiomics model with different machine learning algorithms. The top-performing model was chosen utilizing receiver operating characteristic (ROC) curve analysis. Decision curve analysis (DCA) was also conducted to assess its practical utility. RESULTS: Compared with those of the clinical and radiomics models, the clinical-radiomics model demonstrated the highest discriminatory ability, with AUCs of 0.918 (95 % CI: 0.870 - 0.966), 0.909 (95 % CI: 0.829 - 0.988) and 0.839 (95 % CI: 0.709 - 0.968) in the training, validation and test cohorts, respectively. Moreover, DCA confirmed that the combined model had a greater net benefit in predicting seminomas and nonseminomas. CONCLUSION: The clinical-radiomics model serves as a potential tool for noninvasive differentiation between testicular seminomas and nonseminomas, offering valuable guidance for clinical treatment.

Evolution of Testicular Germ Cell Tumors in the Molecular Era With Histogenetic Implications.

The current WHO classification of testicular germ cell tumors is based on the pathogenesis of the tumors driven by different genomic events. The germ cell neoplasia in situ is the precursor lesion for all malignant germ cell tumors. The current understanding of pathogenesis is that the developmental and environmental factors with the erasure of parental genomic imprinting lead to the development of abnormal gonocytes that settle in the "spermatogonial Niche" in seminiferous tubules. The abnormal primordial germ cells in the seminiferous tubules give rise to pre-GCNIS cells under the influence of TPSY and OCT4 genes. The whole genome duplication events give rise to germ cell neoplasia in situ, which further acquires alterations in 12p along with NRAS and KRAS mutations to produce seminoma. A subset of seminomas acquires KIT mutation and does not differentiate further. The remaining KIT-stable seminomas differentiate to nonseminomatous GCTs after obtaining recurrent chromosomal losses, epigenetic modification, and posttranscriptional regulation by multiple genes. Nonseminomatous germ cell tumors also develop directly from differentiated germ cell neoplasia in situ. TP53 pathway with downstream drivers may give rise to somatic-type malignancies of GCT. The GCTs are remarkably sensitive to cisplatin-based combination chemotherapy; however, resistance to cisplatin develops in up to 8% of tumors and appears to be driven by TP53/MDM2 gene mutations. Serum and Plasma miRNAs show promise in diagnosing, managing, and following up on these tumors. The mechanisms underlying the development of most tumors have been elucidated; however, additional studies are required to pinpoint the events directing specific characteristics. Advances in identifying specific molecular markers have been seen recently and may be adopted as gold standards in the future.

Prognostic factors for relapse in patients with clinical stage I testicular non-seminoma: A nationwide, population-based cohort study.

BACKGROUND: Approximately 30% of patients with clinical stage I non-seminoma (CSI-NS) relapse. Current risk stratification is based on lymphovascular invasion (LVI) alone. The extent to which additional tumor characteristics can improve risk prediction remains unclear. OBJECTIVE: To determine the most important prognostic factors for relapse in CSI-NS patients. DESIGN, SETTING, AND PARTICIPANTS: Population-based cohort study including all patients with CSI-NS diagnosed in Denmark between 2013 and 2018 with follow-up until 2022. Patients were identified in the prospective Danish Testicular Cancer database. By linkage to the Danish National Pathology Registry, histological slides from the orchiectomy specimens were retrieved. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Histological slides were reviewed blinded to the clinical outcome. Clinical data were obtained from medical records. The association between prespecified potential prognostic factors and relapse was assessed using Cox regression analysis. Model performance was evaluated by discrimination (Harrell's C-index) and calibration. RESULTS: Of 453 patients included, 139 patients (30.6%) relapsed during a median follow-up of 6.3 years. Tumor invasion into the hilar soft tissue of the testicular hilum, tumor size, LVI and embryonal carcinoma were independent predictors of relapse. The estimated 5-year risk of relapse ranged from < 5% to > 85%, depending on the number of risk factors. After internal model validation, the model had an overall concordance statistic of 0.75. Model calibration was excellent. CONCLUSION AND RELEVANCE: The identified prognostic factors provide a much more accurate risk stratification than current clinical practice, potentially aiding clinical decision-making.

Ex-vivo microscopic oncotesticular sperm extraction: step-by-step surgical technique at time of radical orchiectomy.

OBJECTIVE: To demonstrate the intraoperative surgical techniques required for simultaneous radical orchiectomy and microscopic oncotesticular sperm extraction (m-OncoTESE) in a step-by-step fashion. DESIGN: Video presentation. SETTING: University Hospital (University of Chicago). PATIENTS: A 37-year-old man (status after right orchiectomy at another institution for stage II-C testicular seminoma with positive preoperative tumor markers) was referred for contralateral orchiectomy of multifocal left testis mass and fertility preservation. Semen analysis before, microscopic testicular sperm extraction during, and semen or testicular specimen analysis after the first orchiectomy were unable to identify any sperm. A postoperative analysis of the m-OncoTESE performed on the left testis resulted in the cryopreservation of 200,000 motile sperm for future assisted reproductive technology (i.e., in vitro fertilization or in vitro fertilization-intracytoplasmic sperm injection). INTERVENTIONS: Left radical orchiectomy and left m-OncoTESE. MAIN OUTCOME MEASURES: A comprehensive visual documentation of m-OncoTESE surgical techniques with concurrent commentary detailing the reasons behind each surgical step. A brief discussion on the background of m-OncoTESE and alternative fertility preservation methods accompanies the procedure. RESULTS: This video provides a step-by-step guide to performing an m-OncoTESE (proceeding a radical orchiectomy in a patient with testicular cancer) as a means of fertility preservation in an azoospermic patient. Successful extraction and cryopreservation of testicular spermatozoa were achieved after targeted ex-vivo testicular microdissection. CONCLUSIONS: Sperm extraction via m-OncoTESE is a viable option for azoospermic patients with testicular cancer undergoing radical orchiectomies. The use of preoperative imaging and microsurgical techniques facilitates and optimizes surgical dissection and sperm recovery.

Robot-assisted retroperitoneal lymph node dissection as primary treatment for stage II seminoma germ cell tumor.

INTRODUCTION: Historically, therapeutic avenues for patients with clinical stage II seminoma germ cell tumors (SGCT) were confined to radiotherapy and chemotherapy. While survival rates with these modalities are commendable, both entail substantial long-term morbidities. Furthermore, this youthful patient cohort exhibits elevated rates of secondary malignancies, surfacing decades post-successful primary cancer treatment (1). Recently, retroperitoneal lymph node dissection (RPLND) has emerged as a primary treatment consideration for individuals with low-volume metastatic seminoma (2-4). However, there is a dearth of video documentation illustrating the robotic assisted (RA) bilateral approach (5- 7). METHODS: We present the case of a 24-year-old male who underwent prior left orchiectomy for seminoma (pT1b). Despite negative serum tumor markers, a 1.7 x 1.4cm lymph node enlargement was identified in the aortic bifurcation after 4 months, classifying the patient as stage IIA per the IGCCCG risk classification. Subsequently, a RA bilateral template RPLND was performed due to the patient's refusal of chemotherapy, citing concerns about offspring. RESULTS: The surgery was performed, incorporating nerve sparing techniques, lasting 4h13minutes, an estimated bleeding rate of 400ml, without intraoperative complications. The patient was discharged within 24 hours of the procedure, following a prescribed low-fat diet. CONCLUSION: The patient experienced postoperative well-being, painlessness, and resumed work three weeks post-procedure. Preserved ejaculation was noted, and adjuvant therapy was performed with 2 cycles of EP due to the anatomopathological result. The feasibility of robotic primary RPLND for SGCT was demonstrated, showing reduced postoperative pain and early hospital discharge. Further studies are necessary to validate our findings regarding oncological, safety, and functional outcomes.

Primary retroperitoneal lymph node dissection for clinical stage II seminoma: A systematic review and meta-analysis of safety and oncological effectiveness.

To evaluate the oncological outcomes and safety of primary retroperitoneal lymph node dissection (RPLND) in patients with clinical stage (CS) II seminomatous testicular germ cell tumor (TGCT). A literature search using PubMed, Scopus, and Cochrane Library was conducted on July 2023 to identify relevant studies according to the Preferred Reporting Items for Systematic Review and Meta Analysis (PRISMA) guidelines. The pooled recurrence rate and treatment-related complications were calculated using a random effects model. Overall 8 studies published between 1997 and 2023 including a total of 355 patients were selected for systematic review and meta-analysis with the overall median follow-up of 38 months. The overall and infield recurrence rate were 0.14 (95% CI: 0.08-0.22) and 0.04 (95% CI: 0.00-0.11), respectively. The overall pooled rate of ≥ Clavien Dindo grade III complications was 0.04 (95% CI: 0.01-0.10); there was no significant heterogeneity (I^2 = 35.10%, P = 0.19). Antegrade ejaculation was preserved with the overall pooled rate of 0.98 (95% CI: 0.95-1.00); there was no significant heterogeneity on Chi-square and I2 tests (I^2 = 0.00%, P = 0.58). Primary RPLND is a safe and effective treatment option for patients with CS II seminomatous TGCT resulting highly promising cure rates combined with low treatment-associated adverse events, at medium-term follow-up. However, owing to the lack of comparative studies to the current standard of care and the limited follow-up, individual decision must be made with the informed patient in a shared decision process together with a multidisciplinary team.

Testicular cancer with small metastatic burden: optimal approach in 2024.

PURPOSE OF REVIEW: Recent advancements in the management of clinical stage II (CS II) testicular cancer have transformed it into a predominantly curable condition. This success in treatment advancements has markedly extended patient survival. However, these treatments carry risks and morbidities, which is important to consider given the disease's impact on young men and the emerging understanding of long-term treatment consequences. RECENT FINDINGS: Emerging data support primary retroperitoneal lymph node dissection (RPLND) for select CS II seminoma patients, with similar short-term outcomes to chemotherapy but less treatment intensity. Recent studies have also challenged the reflexive use of adjuvant chemotherapy for pathologic node-positive disease, as growing evidence shows low relapse rates regardless of nodal stage. Furthermore, novel biomarkers like circulating serum microRNA-371a-3p levels can help predict the presence of viable germ cell tumor at time of RPLND. SUMMARY: Advances in risk stratification and therapy enable personalized de-escalation approaches for oligometastatic testicular cancer, optimizing survivorship. Upfront RPLND, reassessing adjuvant systemic therapy for RPLND pN+ disease, and novel biomarkers will shape precision treatment to achieve high cure rates with excellent quality of life. Ongoing trials of reduced-intensity regimens, accurate prognostic models, improved surgical strategy, and emerging biomarkers represent the next frontier in tailored curative therapy.

New analysis of atypical spermatocytic tumours reveals extensive heterogeneity and plasticity of germ cell tumours†.

Testicular germ cell tumours (TGCTs) derived from immature (type I) and pluripotent germ cell neoplasia in situ (GCNIS, type II) are characterised by remarkable phenotypic heterogeneity and plasticity. In contrast, the rare spermatocytic tumour (SpT, type III), derived from mature spermatogonia, is considered a homogenous and benign tumour but may occasionally present as an anaplastic or an aggressive sarcomatoid tumour. While various oncogenic processes had been proposed, the precise mechanism driving malignant progression remained elusive until the molecular characterisation of a series of atypical SpTs described in a recent issue of The Journal of Pathology. The emerging picture suggests the presence of two distinct trajectories for SpTs, involving either RAS/mitogen-activated protein kinase pathway mutations or a ploidy shift with secondary TP53 mutations and/or gain of chromosome 12p, the latter known as pathognomonic for type II GCNIS-derived TGCTs. Here, we discuss the implications of these findings, seen from the perspective of germ cell biology and the unique features of different TGCTs. The evolving phenotype of SpTs, induced by genomic and epigenetic changes, illustrates that the concept of plasticity applies to all germ cell tumours, making them inherently heterogenous and capable of significant transformation during progression. © 2024 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

SMARCB1-Deficient Skull Base Chondrosarcoma with 12p Duplication Presenting as Somatic-Type Malignancy Arising from Metastatic Seminoma.

Somatic-type malignancy (STM) can occur infrequently within a primary or metastatic testicular germ cell tumor (TGCT) and is associated with dismal prognosis and survival. STM with chondrosarcomatous features is exceedingly rare and head and neck involvement has not been previously documented. A 39-year-old white man presented with nasal obstruction and epistaxis. Imaging disclosed a 6.9-cm expansile tumor involving the nasal cavity and skull base with intraorbital and intracranial extension. The histopathologic properties of the tumor were compatible with chondrosarcoma, grade II-III. Immunohistochemically, malignant cells were strongly and diffusely positive for S100 and epithelial markers, and showed loss of SMARCB1 expression. IDH1/2 mutations were not detected. Following whole-body PET scan, a 7.0-cm left testicular mass was discovered and diagnosed as seminoma with syncytiotrophoblastic cells, stage pT3NXM1b. Extensive retroperitoneal, mediastinal, and supraclavicular lymphadenopathy was also noticed. Histopathologic examination of the left supraclavicular lymph node revealed metastatic seminoma. By FISH, most metastatic nodal seminoma cells harbored 1 to 4 copies of isochromosome 12p, while the chondrosarcoma featured duplication of 12p. Presence of a malignant TGCT with disseminated supradiaphragmatic lymphadenopathy, the unique immunophenotypic properties of the skull-based chondrosarcoma and lack of IDH1/2 aberrations with gain of 12p strongly support the diagnosis of STM chondrosarcoma arising from metastatic TGCT. The patient did not respond to chemotherapy and succumbed three months after diagnosis. Although exceedingly uncommon, metastasis to the head and neck may occur in patients with TGCT. This case of STM chondrosarcoma demonstrated divergent immunophenotypic and molecular characteristics compared to "typical" examples of head and neck chondrosarcoma. High index of suspicion is advised regarding the diagnosis of lesions that present with otherwise typical histomorphology but unexpected immunohistochemical or molecular features.

Frequent expression of CD45RO memory T cell marker as well as low to high expression of PD-1 and PD-L1 inhibitory molecules in seminoma and dysgerminoma.

BACKGROUND: Seminoma and dysgerminoma are rare testicular and ovarian germ cell tumors characterized by a significant infiltration of immune cells in the tumor microenvironment. According to the failure of conventional treatments in some patients, it is crucial to identify novel prognostic and therapeutic biomarkers for these patients. The objectives of this study were to evaluate the expression of CD45RO and PD-1/PD-L1 and investigate their association with the clinicopathological characteristics of the patients. METHODS: Immunohistochemistry was performed to assess the expression of CD45RO, PD-1, and PD-L1 in tumor-infiltrated lymphocytes (TILs), and tumor cells in 33 seminoma and 31 dysgerminoma patients. The expression levels were evaluated using a semiquantitative approach, weighted histoscore, which considers both the intensity and extent of staining. RESULTS: All seminoma and dysgerminoma patients exhibited CD45RO expression in TILs, with 66.7 % and 90.3 % displaying high levels of expression, respectively. PD-1 expression in TILs was observed at low levels in 81.8 % and 77.4 % and at high levels in 18.2 % and 19.4 % of seminoma and dysgerminoma patients, respectively. Likewise, low expression of PD-L1 in tumor cells was detected in 63.6 % of seminoma and 61.3 % of dysgerminoma patients, while none of the patients exhibited high expression of PD-L1. In seminoma patients, a positive correlation was observed between PD-1 expression in TILs and CD45RO expression and between PD-L1 expression in tumor cells and TILs score. CONCLUSION: The frequent infiltration of CD45RO, along with variable expression of PD-1 and PD-L1 on TILs and tumor cells, could impact the effectiveness of anti-tumor responses and immunotherapy.

The prognostic impact of treatment centralization in patients with testicular germ cell tumors: analysis of hospital-based cancer registry data in Japan.

BACKGROUND: To identify the prognostic impact of treatment centralization in patients with testicular germ cell tumors (TGCT). METHODS: We used a hospital-based cancer registry data in Japan to extract seminoma and non-seminoma cases that were diagnosed in 2013, histologically confirmed, and received the first course of treatment. To compare the 5-years overall survival (OS) rates of patients stratified by institutional care volume, we performed a Cox proportional hazards regression analysis using inverse probability of treatment weighting (IPTW) method to adjust patient backgrounds. RESULTS: A total of 1767 TGCT patients were identified. The 5-years OS rates for stage II and III TGCT patients treated at low-volume institutions (< 7 cases) were significantly worse than high-volume institutions (≥ 7 cases) (91.2% vs. 83.4%, p = 0.012). Histological stratification revealed that 5-year OS rates for stage II and III seminoma patients in the low-volume group were significantly worse than the high-volume group (93.5% vs. 84.5%, p = 0.041). Multivariate OS analysis using an IPTW-matched cohort showed that institutional care volume was an independent prognostic factor (hazard ratio 2.13 [95% confidence interval: 1.23-3.71], p = 0.0072). CONCLUSION: Our results indicate that stage II and III TGCT patients experience lower survival rates at low-volume institutions and would benefit from treatment centralization.

Predictive tissue markers in testicular germ cell tumors: Immunohistochemical expression of MLH1 and REV-7 proteins.

PURPOSE: Testicular Germ Cell Tumors (TGCTs) are the most frequent solid malignancies in young adult men. Regardless of differences in their cell of origin, all TGCTs are considered highly curable malignancies. However, approximately 3-5% of all TGCTs do not respond to platinum-based chemotherapies. The purpose of our paper is to investigate whether immunohistochemical expression of MLH1 and REV-7 can be used as predictive tissue markers for TGCTs. MATERIAL AND METHODS: The main demographic and clinicopathological characteristics of 64 male patients with TGCTs who underwent orchiectomy from 2007 to 2022 were retrospectively obtained from two large Oncology Clinics in Greece. Both patients with chemosensitive and chemoresistant disease were included. Immunohistochemical staining for MLH1 and REV-7 proteins was applied in specimens of these patients. RESULTS: 31 seminomas and 33 non-seminomas were included. 48 patients had chemosensitive disease, while 16 had chemoresistant disease. 53 specimens showed preserved MLH1 expression, while 11 specimens had lost MLH1 expression. Expression of MLH1 was only significantly associated with patients' age. 16 specimens showed positive REV-7 expression, while 48 specimens were REV-7 negative. Interestingly, 50% of patients with chemoresistant disease and 16,7% of patients with chemosensitive disease were REV-7 positive. This difference was statistically significant. Moreover, REV-7 positivity was significantly associated with chemoresistance, various clinicopathological parameters and patients' prognosis and survival. CONCLUSION: Loss of MLH1 expression was only found to be significantly associated with lower patients' age. Positive immunohistochemical REV-7 expression was significantly associated with various clinicopathological parameters, while it was also associated with significantly lower survival and greater hazard. REV-7 positive percentages were significantly higher in patients with chemoresistant disease. Our findings imply that immunohistochemical staining for REV-7 could potentially be used as a predictive tissue marker for TGCT tumors. Moreover, targeting of REV-7 protein, could represent a potential therapeutic strategy for chemoresistant TGCT cases. The implementation of well-designed studies on a larger scale is of utmost importance, in order to draw safer conclusions. Additional studies are needed so as to draw safer conclusions.

Single-cell mRNA sequencing of giant panda (Ailuropoda melanoleuca) seminoma reveals the cellular and molecular characteristics of tumour cells.

Testicular tumours are zoonoses that can occur in not only human, but other animals, include giant pandas. A middle-aged male giant panda named Fufu was diagnosed with a testicular tumour and underwent surgery to remove the entire left testis. The testis was mainly composed of three substantive parts: normal tissue on the outside, tumour tissue in the middle, and necrosis in the centre. HE stains revealed that the tumour was a seminoma. Single-cell mRNA sequence was applied to characterise cellular states and molecular circuitries of giant panda testicular seminoma. Only germ cell markers expressed in nearly all tumour cells, and the tumour cells appeared to be the same subtype of seminoma cells. We identified four clusters with unique genes expression. They were early apoptosis cells (EAC), inactive cells (IC), active cells subcluster 1 (AC-1) and active cells subcluster 2 (AC-2). We utilised monocle tools and found that IC cells was in the initiation stage, and EAC was one type of terminal stage, suggesting that tumour cells may undergo apoptosis in the future. AC-2 was another type of terminal stage, representing a group of progressive cells. Our study represents the first report to utilise scRNA-seq to characterise the cellular states and molecular circuitries of a giant panda testicular tumour. This investigation proposes CD117 and CD30 as dependable markers for future pathologic diagnosis. Our findings also suggest that CTSV and other genes with unique expression patterns in active and progressive giant panda seminoma cells may act as early prognostic biomarkers.

The increasing burden of testicular seminomas and non-seminomas in adolescents and young adults (AYAs): incidence, treatment, disease-specific survival and mortality trends in the Netherlands between 1989 and 2019.

BACKGROUND: Testicular cancer incidence among adolescents and young adults (AYAs, aged 18-39 years at diagnosis) is increasing worldwide and most patients will survive the initial disease. Still, detailed epidemiological information about testicular cancer among AYAs is scarce. This study aimed to provide a detailed overview of testicular cancer trends in incidence, treatment, long-term relative survival and mortality by histological subtype among AYAs diagnosed in the Netherlands between 1989 and 2019. MATERIALS AND METHODS: Data of all malignant testicular cancers (ICD-code C62) were extracted from the Netherlands Cancer Registry. Mortality data were retrieved from Statistics Netherlands. European age-standardized incidence and mortality rates with average annual percentage change statistics and relative survival estimates up to 20 years of follow-up were calculated. RESULTS: A total of 12 528 testicular cancers were diagnosed between 1989 and 2019. Comparing 1989-1999 to 2010-2019, the incidence increased from 4.4 to 11.4 for seminomas and from 5.7 to 11.1 per 100 000 person-years for non-seminomas. Rising trends were most prominent for localized disease. Radiotherapy use in localized testicular seminomas declined from 78% in 1989-1993 to 5% in 2015-2019. Meanwhile, there was a slight increase in chemotherapy use. Most AYAs with localized seminomas and non-seminomas received active surveillance only (>80%). Overall, relative survival estimates remained well above 90% even at 20 years of follow-up for both seminomas and non-seminomas. Mortality rates declined from 0.5 to 0.4 per 100 000 person-years between 1989-1999 and 2010-2019. CONCLUSIONS: The incidence of seminoma and non-seminoma testicular cancers significantly increased in AYAs in the Netherlands between 1989 and 2019. There was a shift towards less-aggressive treatment regimens without negative survival effects. Relative survival estimates remained well above 90% at 20 years of follow-up in most cases. Testicular cancer mortality was already low, but has improved further over time, which makes survivorship care an important issue for these young adults.