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Background: Venous thromboembolism (VTE) may jeopardise excellent treatment results of germ cell tumours (GCT). We previously constructed a VTE risk score for GCT patients qualified for first‐line chemotherapy (CTH), including vein compression, clinical stage (CS) and haemoglobin concentration. Aim: Validating our score in a separate cohort and establishing the cut‐off point for the score. Re‐assessing the numerical score in the training cohort. Materials and Methods: We retrospectively analysed a new cohort of GCT patients staged IS–IIIC. Area under the curve of receiver‐operating characteristic (AUC‐ROC) was calculated for the developed score, Khorana Risk Score (KRS) and Padua Prediction Score (PPS). AUC‐ROC of the integer score was calculated for the training cohort. Cut‐off point was established by Youden's and Liu's indices. Results: Among 336 eligible patients in the validation cohort, VTE occurred in 41 (12.2%). AUC‐ROC for our score, KRS and PPS were 0.818 (95% confidence interval (CI): 0.746–0.891), 0.608 (0.529–0.688) and 0.634 (0.547–0.720), respectively, p < 0.001. The optimal cut‐off point for a low/high risk was 6 (≤ 6 vs. ≥ 7). In the training cohort, 369 patients had complete data on vein compression. AUC‐ROC for our score, KRS and PPS were 0.819 (95% CI: 0.758–0.879), 0.710 (0.637–0.782) and 0.725 (0.651–0.800), p ≤ 0.001 and 0.015, respectively. Positive and negative predictive values were 30.8% and 96.5%, respectively. Conclusions: Our VTE risk score is a handy tool for GCT patients before first‐line CTH for metastatic disease. Outperforming KRS and PPS, it has a good discriminatory value, especially for identifying low‐risk patients. [ABSTRACT FROM AUTHOR]

Background: Dysgerminomas constitute around 1–2% of all germ cell tumours. It is very very rare to have dysgerminoma with concurrent pregnancy with an incidence of 0.2–1 per 100,000 pregnancies. It is extremely difficult to conceive with no assisted reproductive interventions and carry it till completion with no complications in a concurrent dysgerminoma. Dysgerminoma has a characteristic specific histomorphology and is easy to diagnose. However, occasionally, syncytiotrophoblastic differentiation can be seen in dysgerminoma although it is a rare histopathological finding. Also, the raised serum B-HCG levels due to the syncytiotrophoblast giant cells seen can lead to a diagnostic dilemma. Clinical presentation: Here we report a case of a 27-year-old 8-week pregnant female who came to the hospital with chief complaints of left-sided abdominal pain and a lump abdomen. Clinical and radiological examination revealed a left ovarian tumour of malignant aetiology with the presence of right ectopic pregnancy. A staging laparotomy with left salpingoophorectomy was performed and sent for histopathological examination. It was reported as dysgerminoma with syncytiotrophoblastic giant cells. The right fallopian tube showed products of conception. Finally, she was planned for adjuvant chemotherapy and serial B-HCG levels. Summary: This case is reported not only just for its rare histopathological finding but also for the diagnostic dilemma it causes both to the surgeon as well as the pathologist. There are various factors which can act as prognosticators such as early suspicion of a tumor, radiological findings, surgery, histopathological examination, and oncology team. [ABSTRACT FROM AUTHOR]

Purpose: Patients with Germ cell tumours (GCT) are at risk of long-term toxicities due to multimodality therapy. It is debatable whether there is an impact on the quality of life(QoL) of GCT survivors. Methods: A case–control study was conducted at a tertiary care centre in India, using the EORTC QLQ C30 questionnaire, to compare the QoL between GCT survivors(disease free > 2 years) and healthy matched controls. A multivariate regression model was used to identify factors affecting QoL. Results: A total of 55 cases and 100 controls were recruited. Cases had a median age of 32 years (interquartile range, IQR 28–40 years), ECOG PS of 0–1(75%), advanced stage III (58%), chemotherapy (94%) and 66% were > 5 years from diagnosis. The median age of controls: 35 years (IQR 28–43 years). A statistically significant difference was seen for emotional (85.8 ± 14.2 vs 91.7 ± 10.4, p 0.005), social(83.0 ± 22.0 vs 95.2 ± 9.6, p < 0.001) and global scales (80.4 ± 21.1 vs 91.3 ± 9.7, p < 0.001). Cases had more nausea and vomiting(3.3 ± 7.4 vs 1.0 ± 3.9, p 0.015), pain(13.9 ± 13.9 vs 4.8 ± 9.8, p < 0.001), dyspnea(7.9 + 14.3 vs 2.7 ± 9.1, p 0.007), and appetite loss(6.7 ± 14.9 vs 1.9 ± 7.9, p 0.016) and greater financial toxicity(31.5 ± 32.3 vs 9.0 ± 16.3, p < 0.001). Adjusting for age, performance status, BMI, stage, chemotherapy, RPLND, recurrent disease, and time since diagnosis, no predictive variables were significant. Conclusion: There is a detrimental impact of history of GCT in long term survivors of GCT. [ABSTRACT FROM AUTHOR]

Background Germ cell tumours (GCT) are the most common malignancy affecting young adult men. The introduction of cisplatin-based chemotherapy in recent decades has significantly changed the prognosis of these malignant tumours into highly curable cancer, even in the setting of advanced disease. However, in the last decade, the success of these chemotherapy regimens in curing GCTs has been slowed by a growing recognition of their important late toxicities, such as cardiovascular disease. Case summary We present the case of a 23-year-old male, recently diagnosed with a mixed non-seminomatous testicular germinal tumour, on stage IIIA (pT3 cN2 cM1a), with retroperitoneal adenopathies and pulmonary metastases. After performing a right inguinal orchiectomy, he started chemotherapy treatment with cisplatin + etoposide. Shortly after starting treatment, the patient presented an ST-elevation acute coronary syndrome. The cardiac catheterization revealed a non-occlusive thrombus in the middle segment of the right coronary artery. Intracoronary imaging techniques were used to study the arterial wall, which revealed the presence of atherosclerotic plaque that could have ruptured, with the consequent response of platelet aggregation and thrombus formation. Barely 7 months after this event, the patient was again admitted to hospital for pulmonary thromboembolism with pulmonary infarction. Discussion To date, there are two hypotheses linking the association between cisplatin-based chemotherapy and cardiovascular disease. The direct hypothesis argues for the presence of direct chemotherapy-induced vascular damage. The indirect hypothesis, on the other hand, is based on the induction and development of cardiovascular risk factors by chemotherapy. This cardiovascular toxicity of chemotherapy is aggravated by a cancer-induced proinflammatory and prothrombotic state. [ABSTRACT FROM AUTHOR]

Background: SIOP-CNS-GCT-II European trial was opened for the treatment of patients of any age with central nervous system germ cell tumour (CNS-GCT). Four courses of pre-irradiation chemotherapy were delivered. The influence of patient age on chemotherapy related acute toxicity (CRAT) was assessed. Methods: CRAT was analysed according to age-groups: children (aged ≤11 years), adolescents (aged 12-17 years), adults (aged ≥18 years) and to chemotherapy type: CarboPEI (alternating etoposide-carboplatin/etoposide- ifosfamide) for non-metastatic germinoma; PEI (cisplatin-etoposide- ifosfamide) for standard-risk non-germinomatous GCT (NGGCT); PEI and high-dose PEI (HD-PEI), for high-risk or poorly responsive NGGCTs. Results: 296 patients were assessable for CRAT: 105 children, 121 adolescents, 70 adults (max age: 41 years). Median cumulative doses/m² of chemotherapy were similar among age-groups. The proportion of germinoma over NGGCT (and accordingly use of CarboPEI chemotherapy) was higher in the adult groups (79%) versus the other two groups (62%). Delay in chemotherapy ≥7 days was noticed in 27%, 38%, and 19% of children, adolescents, and adults, respectively. Grade ≥3 haematological and non-haematological adverse events (AEs) were observed in 94%/31%, 97%/36%, and 77%/21% of children, adolescents, and adults, respectively. No toxic death was reported. Grade ≥3 AEs and delayed chemotherapies were significantly rarer in adults when compared with adolescents, even when adjusted on chemotherapy type: odds ratio: 0.1 [95% CI 0.02-0.4], and 0.2 [95%CI 0.1-0.4] in the group treated with CarboPEI. Conclusion: Adult patients can be treated safely with a chemotherapy intensive protocol, with even less toxicity than that observed in adolescents. Further work is required to understand age-related differences regarding toxicity. [ABSTRACT FROM AUTHOR]

Objective: Ovarian carcinomas are considered one of the deadliest malignancies, accounting for a significant number of cancer-related deaths than any other gynaecological malignancy. Advanced stage at diagnosis can be attributed to vague presenting symptoms, rarely bizarre, which usually point towards any disease but ovarian tumour. Here, we discuss a similar case, with presentations that compels us to think in favor of disseminated Koch’s, but turns out to be germ cell tumor (GCT) of the ovary; thereby pointing at the wide spectrum of bizarre signs and symptoms which should have ovarian malignancies as a differential during workup. Case report: A 21-year-old unmarried female came to our gynaecology outpatient department with complaints of pain lower abdomen, high-grade fever, shortness of breath and progressively increasing abdominal distension. After routine hematological and imaging workup, she was diagnosed with an ovarian tumour with ascites and bilateral pleural effusion. Fertility-sparing surgery was done after the patient was hemodynamically stable. The histopathology report was suggestive of mixed GCT. The patient was thereby referred to the department of medical oncology for adjuvant chemotherapy. Conclusion: Mixed GCTs are among the rare and inordinately malignant tumours of the ovary. Though they have their usual presentations, we ought to be heedful of their atypical presentations as well because these form grounds for early diagnosis and management. In our patients, the unusual feature was the high-grade fever with associated shortness of breath (due to pleural effusion), but the effusion was non-malignant and non-infectious in origin. In the literature there are not many cases of atypical clinical presentation; hence, this could be an area of further research. Besides, such case reports with bizarre manifestations widen our spectrum of diagnostic probabilities, thereby avoiding any gaps in management. Our workup should be comprehensive enough to diagnose the patient as early as possible because these tumors, though aggressive, have a very good prognosis due to excellent chemosensitivity. [ABSTRACT FROM AUTHOR]

Simple Summary: Gonadal teratomas are tumours that can be benign or malignant and affect the gonads, specifically the ovaries in women and the testicles in men. They are predominantly young tumours that affect children and adolescents; therefore, early diagnosis is essential to apply the most suitable therapy to preserve fertility. In this article, based on articles found in the literature, we analysed the past, present and future of gonadal teratomas, starting from the description of the possible causes, the distinction between benign and malignant, and consequent diversification of the diagnostic and, therefore, therapeutic procedure. Furthermore, we concluded on the importance of a team that involves various specialists, including the pathologist, for the correct diagnosis and therapy to guarantee the best possible quality of life for the patient. Teratomas are neoplasms arising from germ cells and encompass tissues derived from two or more embryonic germ layers, including ectoderm, mesoderm, and endoderm. These tumours typically localize along the midline or in paramedian positions and can manifest as gonadal (20%) or extragonadal (80%) entities. Although gonadal teratomas are uncommon, they represent the predominant type of gonadal tumour in the paediatric population. They comprise approximately 20–25% of all ovarian tumours in females and about 3–5% of all testicular tumours in males. Ovarian teratomas exhibit a higher incidence in early childhood and adolescence, whereas testicular teratomas are more prevalent during the first three months of life and between the ages of 15 and 19. While the majority of paediatric gonadal teratomas are benign, malignant or mixed variants may also arise, necessitating more aggressive therapeutic interventions. [ABSTRACT FROM AUTHOR]

Objectives: To assess whether extended surveillance with repeated computed tomography (CT) scans for patients with clinical stage IIA (CS IIA; <2 cm abdominal node involvement) and negative markers (Mk−) non‐seminomatous germ cell tumours (NSGCTs) can identify those with true CS I. To assess the rate of benign lymph nodes, teratoma, and viable cancer in retroperitoneal lymph node dissection (RPLND) histopathology for patients with CS IIA Mk− NSGCT. Patients and methods: Observational prospective population‐based study of patients diagnosed 2008–2019 with CS IIA Mk− NSGCT in the Swedish and Norwegian Testicular Cancer Group (SWENOTECA) registry. Patients were managed with surveillance, with CT scans, and tumour markers every sixth week for a maximum of 18 weeks. Patients with radiological regression were treated as CS I, if progression with chemotherapy, and remaining CS IIA Mk− disease with RPLND. The end‐point was the number and percentage of patients down‐staged to CS I on surveillance and rate of RPLND histopathology presented as benign, teratoma, or viable cancer. Results: Overall, 126 patients with CS IIA Mk− NSGCT were included but 41 received therapy upfront. After surveillance for a median (range) of 6 (6–18) weeks, 23/85 (27%) patients were in true CS I and four (5%) progressed. Of the remaining 58 patients with lasting CS IIA Mk− NSGCT, 16 received chemotherapy and 42 underwent RPLND. The RPLND histopathology revealed benign lymph nodes in 11 (26%), teratoma in two (6%), and viable cancer in 29 (70%) patients. Conclusions: Surveillance with repeated CT scans can identify patients in true CS I, thus avoiding overtreatment. The RPLND histopathology in patients with CS IIA Mk− NSGCT had a high rate of cancer and a low rate of teratoma. [ABSTRACT FROM AUTHOR]

ABSTRACT Background Venous thromboembolism (VTE) may jeopardise excellent treatment results of germ cell tumours (GCT). We previously constructed a VTE risk score for GCT patients qualified for first‐line chemotherapy (CTH), including vein compression, clinical stage (CS) and haemoglobin concentration. Aim Validating our score in a separate cohort and establishing the cut‐off point for the score. Re‐assessing the numerical score in the training cohort. Materials and Methods We retrospectively analysed a new cohort of GCT patients staged IS–IIIC. Area under the curve of receiver‐operating characteristic (AUC‐ROC) was calculated for the developed score, Khorana Risk Score (KRS) and Padua Prediction Score (PPS). AUC‐ROC of the integer score was calculated for the training cohort. Cut‐off point was established by Youden's and Liu's indices. Results Among 336 eligible patients in the validation cohort, VTE occurred in 41 (12.2%). AUC‐ROC for our score, KRS and PPS were 0.818 (95% confidence interval (CI): 0.746–0.891), 0.608 (0.529–0.688) and 0.634 (0.547–0.720), respectively, p

This article proposes a reappraisal of the current classification of "somatic-type" malignancies that arise in germ cell tumors. These malignancies, which occur in about 7% of germ cell tumors, are currently classified as "teratoma with somatic-type malignancy." However, the authors argue that this classification is suboptimal and does not align with the growing body of evidence that suggests these malignancies are significantly different from true somatic neoplasms. The authors propose an alternative classification that is more in line with current biological concepts and refers to these neoplasms as "sarcoma-like tumor, (adeno)carcinoma-like tumor, leukemia-like tumor, nephroblastoma-like tumor, or embryonic-type neuroectodermal tumor of germ cell origin." They believe that adopting this terminology is important for accuracy and to prevent inappropriate treatments. [Extracted from the article]

This research letter discusses a study on patients with testicular cancer who underwent chemotherapy before having their testes removed. The study found that many patients still had cancerous cells or abnormal tissue in their testes after chemotherapy. The study suggests that certain factors, such as the type of cancer and risk level, may help predict the outcomes of the surgery and potentially avoid unnecessary procedures. However, the study also emphasizes that the removal of the testes should not be skipped for patients with advanced non-seminoma/mixed germ cell tumors. [Extracted from the article]

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. [ABSTRACT FROM AUTHOR]

BackgroundSIOP-CNS-GCT-II European trial was opened for the treatment of patients of any age with central nervous system germ cell tumour (CNS-GCT). Four courses of pre-irradiation chemotherapy were delivered. The influence of patient age on chemotherapy related acute toxicity (CRAT) was assessed.MethodsCRAT was analysed according to age-groups: children (aged ≤11 years), adolescents (aged 12-17 years), adults (aged ≥18 years) and to chemotherapy type: CarboPEI (alternating etoposide-carboplatin/etoposide-ifosfamide) for non-metastatic germinoma; PEI (cisplatin-etoposide-ifosfamide) for standard-risk non-germinomatous GCT (NGGCT); PEI and high-dose PEI (HD-PEI), for high-risk or poorly responsive NGGCTs.Results296 patients were assessable for CRAT: 105 children, 121 adolescents, 70 adults (max age: 41 years). Median cumulative doses/m² of chemotherapy were similar among age-groups. The proportion of germinoma over NGGCT (and accordingly use of CarboPEI chemotherapy) was higher in the adult groups (79%) versus the other two groups (62%). Delay in chemotherapy ≥7 days was noticed in 27%, 38%, and 19% of children, adolescents, and adults, respectively. Grade ≥3 haematological and non-haematological adverse events (AEs) were observed in 94%/31%, 97%/36%, and 77%/21% of children, adolescents, and adults, respectively. No toxic death was reported. Grade ≥3 AEs and delayed chemotherapies were significantly rarer in adults when compared with adolescents, even when adjusted on chemotherapy type: odds ratio: 0.1 [95%CI 0.02-0.4], and 0.2 [95%CI 0.1-0.4] in the group treated with CarboPEI.ConclusionAdult patients can be treated safely with a chemotherapy intensive protocol, with even less toxicity than that observed in adolescents. Further work is required to understand age-related differences regarding toxicity.

Central nervous system germ cell tumours (CNS GCT) form a diverse group of tumour entities, including germinoma, yolk sac tumour, embryonal carcinoma, choriocarcinoma, teratoma, and mixed tumours. Incidence peaks in the second decade, predominantly in males. Incidence rates vary globally, higher in Asia, suggesting genetic factors are important. CNS GCTs split into pure germinomas and non-germinomatous GCTs (NGGCT), influencing prognosis/treatment. Serum and CSF markers (alpha-fetoprotein, human chorionic gonadotropin) aid diagnosis, potentially avoiding neurosurgical biopsy. Histological features are distinguished by immunohistochemical staining. Studies have identified specific microRNAs in serum/CSF at diagnosis as promising biomarkers. Mutated pathways have been identified, but targeted therapies have shown limited success to date. Diagnosis involves recognising symptoms like raised intracranial pressure, endocrinological, and ophthalmological disturbances. MRI imaging is crucial for diagnosis and guiding treatment decisions. Treatment strategies vary, as pure germinomas respond well to chemotherapy and radiotherapy, or craniospinal radiotherapy alone, with excellent outcomes; in contrast NGGCTs demand aggressive combined chemo-radiotherapy, yielding generally inferior outcomes. Teratomas are typically chemo-/radio-resistant, requiring surgical intervention. Relapses need re-staging and (re-)biopsy consideration. Relapsed germinomas, though rare, may be cured with standard-dose chemotherapy and re-irradiation, or high-dose chemotherapy with stem-cell-transplantation, with/without further radiation. The more commonly observed NGGCT relapses have poor prognosis, even with thiotepa-based high-dose chemotherapy and stem-cell-transplantation delivered with curative intent. In summary, CNS GCT management integrates clinical, radiological, and histological findings, along with serum and CSF markers, for tailored treatment. Ongoing research aims to incorporate microRNA markers and molecular pathology for improved diagnosis, prognostication, and therapeutic intervention.

Abstract Background Extragonadal germ cell tumors originating from the prostate are exceptionally rare. To the best of our knowledge, there have been no reported cases of mixed germ cell tumors in individuals with 46 XX disorder of sex development. In this study, we conducted a comprehensive analysis using whole genome sequencing to investigate the clinicopathological and molecular genetic characteristics of a submitted case, with the objective of elucidating its underlying pathogenesis. Case presentation A 40-year-old male patient was diagnosed with a combination of 46, XX disorder of sex development and a primary prostate mixed germ cell tumor with yolk sac tumor and teratoma components. Whole-genome sequencing revealed that the tumor cells had a high somatic mutational load. Analysis of genomic structural variations and copy number variants confirmed the patient's karyotype as 46, XX (SRY +). Additionally, the patient exhibited short stature, small bilateral testes, slightly enlarged breasts, elevated serum alpha-fetoprotein concentrations, elevated follicle-stimulating hormone and luteinizing hormone levels, and low testosterone levels. Discussion A case of 46, XX disorder of sex development, along with a primary prostatic mixed germ cell tumor, was diagnosed. This diagnosis has contributed to advancing our understanding of the genetic and phenotypic profile of the disease and may provide some insights for its treatment.

Introduction: Mature cystic teratoma is a kind of ovarian germ cell tumour. Malignant transformation in it is uncommon with thyroid cancer being rarely found. Given its rarity and nonspecific symptoms, misdiagnosis and indifference when compared to other ovarian lesions is very common. Case presentation: Herein we report a case of a 58 year old post-menopausal female who presented with a history of abdominal distension and loss of appetite. She was found to have an abdominopelvic mass on examination and a raised CA125 levels for which she underwent an MRI pelvis which was suggestive of an O-RADS 5 lesion for which she underwent a staging laparotomy. The final histopathology and immunohistochemistry were suggestive of papillary thyroid carcinoma arising from a mature ovarian teratoma. After a multidisciplinary tumour board analysis, she was planned to be kept under follow–up with regular serum thyroglobulin monitoring. She has no signs of disease recurrence to date. Discussion: Struma ovarii is one type of monodermal ovarian teratoma in which the tumour contains more than 50 % thyroid tissue. Diagnosis in such cases is difficult due to the lack of typical symptoms. In most of the cases, the diagnosis is incidental. Optimal treatment is still unclear given the rarity of the disease. In a few cases, thyroidectomy was done whereas in a few others it was omitted. Further therapy may include radioiodine treatment if needed. Conclusion: To the best of our knowledge there is very scant information available on the natural history, prognosis and management of papillary thyroid carcinoma arising from mature cystic teratoma ovary. Hence, a multidisciplinary treatment approach may be needed for the same.

Several studies have highlighted the functional indispensability of methyltransferase‐like 3 (METTL3) in the reproductive system. However, a review that comprehensively interprets these studies and elucidates their relationships is lacking. Therefore, the present work aimed to review studies that have investigated the functions of METTL3 in the reproductive system (including spermatogenesis, follicle development, gametogenesis, reproductive cancer, asthenozoospermia and assisted reproduction failure). This review suggests that METTL3 functions not only essential for normal development, but also detrimental in the occurrence of disorders. In addition, promising applications of METTL3 as a diagnostic or prognostic biomarker and therapeutic target for reproductive disorders have been proposed. Collectively, this review provides comprehensive interpretations, novel insights, potential applications and future perspectives on the role of METTL3 in regulating the reproductive system, which may be a valuable reference for researchers and clinicians. [ABSTRACT FROM AUTHOR]

Background: Extragonadal germ cell tumors originating from the prostate are exceptionally rare. To the best of our knowledge, there have been no reported cases of mixed germ cell tumors in individuals with 46 XX disorder of sex development. In this study, we conducted a comprehensive analysis using whole genome sequencing to investigate the clinicopathological and molecular genetic characteristics of a submitted case, with the objective of elucidating its underlying pathogenesis. Case presentation: A 40-year-old male patient was diagnosed with a combination of 46, XX disorder of sex development and a primary prostate mixed germ cell tumor with yolk sac tumor and teratoma components. Whole-genome sequencing revealed that the tumor cells had a high somatic mutational load. Analysis of genomic structural variations and copy number variants confirmed the patient's karyotype as 46, XX (SRY +). Additionally, the patient exhibited short stature, small bilateral testes, slightly enlarged breasts, elevated serum alpha-fetoprotein concentrations, elevated follicle-stimulating hormone and luteinizing hormone levels, and low testosterone levels. Discussion: A case of 46, XX disorder of sex development, along with a primary prostatic mixed germ cell tumor, was diagnosed. This diagnosis has contributed to advancing our understanding of the genetic and phenotypic profile of the disease and may provide some insights for its treatment. [ABSTRACT FROM AUTHOR]

Malignant germ‐cell‐tumours (GCTs) are characterised by microRNA (miRNA/miR‐) dysregulation, with universal over‐expression of miR‐371~373 and miR‐302/367 clusters regardless of patient age, tumour site, or subtype (seminoma/yolk‐sac‐tumour/embryonal carcinoma). These miRNAs are released into the bloodstream, presumed within extracellular‐vesicles (EVs) and represent promising biomarkers. Here, we comprehensively examined the role of EVs, and their miRNA cargo, on (fibroblast/endothelial/macrophage) cells representative of the testicular GCT (TGCT) tumour microenvironment (TME). Small RNA next‐generation‐sequencing was performed on 34 samples, comprising representative malignant GCT cell lines/EVs and controls (testis fibroblast [Hs1.Tes] cell‐line/EVs and testis/ovary samples). TME cells received TGCT co‐culture, TGCT‐derived EVs, and a miRNA overexpression system (miR‐371a‐OE) to assess functional relevance. TGCT cells secreted EVs into culture media. MiR‐371~373 and miR‐302/367 cluster miRNAs were overexpressed in all TGCT cells/subtypes compared with control cells and were highly abundant in TGCT‐derived EVs, with miR‐371a‐3p/miR‐371a‐5p the most abundant. TGCT co‐culture resulted in increased levels of miRNAs from the miR‐371~373 and miR‐302/367 clusters in TME (fibroblast) cells. Next, fluorescent labelling demonstrated TGCT‐derived EVs were internalised by all TME (fibroblast/endothelial/macrophage) cells. TME (fibroblast/endothelial) cell treatment with EVs derived from different TGCT subtypes resulted in increased miR‐371~373 and miR‐302/367 miRNA levels, and other generic (eg, miR‐205‐5p/miR‐148‐3p) and subtype‐specific (seminoma, eg, miR‐203a‐3p; yolk‐sac‐tumour, eg, miR‐375‐3p) miRNAs. MiR‐371a‐OE in TME cells resulted in increased collagen contraction (fibroblasts) and angiogenesis (endothelial cells), via direct mRNA downregulation and alteration of relevant pathways. TGCT cells communicate with nontumour stromal TME cells through release of EVs enriched in oncogenic miRNAs, potentially contributing to tumour progression. [ABSTRACT FROM AUTHOR]

This article will review current aspects of the histopathological, immunohistochemical and molecular analysis of primary mediastinal germ cell tumours (PMGCTs) as well as their aetiological, epidemiological, clinical and therapeutic features. PMGCTs represent an important differential diagnosis in the spectrum of mediastinal tumours, and their diagnosis is usually made on small tissue samples from core needle biopsies in combination with diagnostic imaging and serum tumour markers. As in lymphomas, a small biopsy is often the only viable tumour sample available from these patients, as they receive chemotherapy prior to eventual surgical resection. Pathologists therefore need to apply an efficient combination of immunohistochemical markers to confirm the diagnosis of a PMGCT and to exclude morphological mimics. [ABSTRACT FROM AUTHOR]

Background: Testicular malignancies, though less common neoplasms typically present in middle aged men. Some established risk factors such as cryptorchidism, in utero exposure to oestrogens and occupational risks are associated with them and often pose diagnostic challenges. Aims and Objectives: To study the incidence and histo-morphology of nonneoplastic and neoplastic lesions of scrotum (includes testis, epididymis, spermatic cord and tunica vaginalis) and to assess the trend and pattern of scrotal masses over 20 years. Materials and Methods: This is a single centre 20 years retrospective study on the incidence and distribution of scrotal masses between 15 to 80 years of age conducted in pathology department of a tertiary centre. Gross and histomorphological features of all specimens related to scrotal pathology were evaluated as per institutional protocol. Results: Around 433 scrotal masses were studied over a period of 20 years. Of which 289 were paratesticular masses, 82 cases (19%) were testicular masses and 62 cases (14%) were lesions of scrotal skin. Among 39 neoplastic testicular masses, 16 (41%) were classical seminoma and 14 (36%) were mixed germ cell tumors. Thus the incidence of neoplastic scrotal masses ranged from 0.01% to 0.1% per year and the incidence of non-neoplastic masses ranged from 0.2% to 0.4% per year. Conclusion: Majority of scrotal masses were non-neoplastic and seen between 16 to 35 years of age. Most of testicular neoplasms were germ cell tumour. Hydrocele, infective lesions and varicocele were the commonest lesions observed in tunica vaginalis, epididymis and cord structures respectively. [ABSTRACT FROM AUTHOR]

Abstract Background Non-gestational choriocarcinoma (NGC) is a rare subtype of malignant germ cell tumour and there is no consensus on its treatment. The lack of suitable preclinical models for NGC is a challenge in drug discovery research. Patient-derived xenograft (PDX) models recapitulate the tumour microenvironment of the original cancer tissue. Therefore, they have received considerable attention for studies on rare cancer. Here, we aimed to establish a PDX model from a patient with recurrent NGC. Methods Fresh NGC tumour tissue was immediately transplanted into a severely immune-deficient mouse (NOD.Cg-Prkdc scid 1l2rg tm1Wjl/SzJ) and maintained for more than three in vivo passages. Subsequently, we evaluated the molecular characteristics of the PDX model using immunohistochemistry, polymerase chain reaction, and RNA sequencing. Moreover, the PDX tumours were transplanted into BALB/c nude mice, and we evaluated their sensitivity for cisplatin and methotrexate. Results The PDX tumour maintained the morphological features of NGC. Moreover, Immunohistochemistry revealed that the human chorionic gonadotropin, cytokeratin 7, and EpCAM expression levels were similar to those in the primary tumour. Furthermore, serum human chorionic gonadotropin levels were elevated in both the primary tumour and the PDX models. Additionally, using PCR analysis with species-specific primers, we confirmed that the PDX tumour contained human genes and was derived from human tissue. Moreover, the gene expression profile of the NGC was compared with that of epithelial ovarian cancer samples and cell lines, and 568 dysregulated genes in the NGC were extracted. The expression of the dysregulated genes in PDX was significantly correlated with that in the primary tumour (R2 = 0.873, P

Background: Non-gestational choriocarcinoma (NGC) is a rare subtype of malignant germ cell tumour and there is no consensus on its treatment. The lack of suitable preclinical models for NGC is a challenge in drug discovery research. Patient-derived xenograft (PDX) models recapitulate the tumour microenvironment of the original cancer tissue. Therefore, they have received considerable attention for studies on rare cancer. Here, we aimed to establish a PDX model from a patient with recurrent NGC. Methods: Fresh NGC tumour tissue was immediately transplanted into a severely immune-deficient mouse (NOD.Cg-Prkdcscid1l2rgtm1Wjl/SzJ) and maintained for more than three in vivo passages. Subsequently, we evaluated the molecular characteristics of the PDX model using immunohistochemistry, polymerase chain reaction, and RNA sequencing. Moreover, the PDX tumours were transplanted into BALB/c nude mice, and we evaluated their sensitivity for cisplatin and methotrexate. Results: The PDX tumour maintained the morphological features of NGC. Moreover, Immunohistochemistry revealed that the human chorionic gonadotropin, cytokeratin 7, and EpCAM expression levels were similar to those in the primary tumour. Furthermore, serum human chorionic gonadotropin levels were elevated in both the primary tumour and the PDX models. Additionally, using PCR analysis with species-specific primers, we confirmed that the PDX tumour contained human genes and was derived from human tissue. Moreover, the gene expression profile of the NGC was compared with that of epithelial ovarian cancer samples and cell lines, and 568 dysregulated genes in the NGC were extracted. The expression of the dysregulated genes in PDX was significantly correlated with that in the primary tumour (R2 = 0.873, P < 0.001). Finally, we demonstrated that the PDX tumour was sensitive to cisplatin and methotrexate; therefore, its clinical response to the agents was similar to that of the primary tumour. Conclusions: We successfully established a PDX model of NGC, to the best of our knowledge, for the first time. The established PDX retained the molecular and transcriptome characteristics of the primary tumour and can be used to predict drug effects. It may facilitate further research and the development of novel therapeutic agents for NGC. [ABSTRACT FROM AUTHOR]

Background and Objectives: Despite advancements in the diagnosis and treatment of testicular germ cell tumours (TGTCs), challenges persist in identifying reliable biomarkers for early detection and precise disease management. This narrative review addresses the role of microRNAs (miRNAs) as potential diagnostic tools and therapeutic targets in the treatment of TGCTs. Materials and Methods: Three databases (PubMed®, Web of Science™, and Scopus®) were queried for studies investigating the utility of miRNA as diagnostic tools, assessing their prognostic significance, and evaluating their potential to guide TGCT treatment. Different combinations of the following keywords were used, according to a free-text protocol: "miRNA", "non-coding RNA", "small RNA", "Testicular Cancer", "seminomatous testicular germ cell", "non-seminomatous testicular germ cell". Results: The potential of miRNAs as possible biomarkers for a non-invasive diagnosis of TGCT is appealing. Their integration into the diagnostic pathway for TGCT patients holds the potential to enhance the discriminative power of conventional serum tumour markers (STMs) and could expedite early diagnosis, given that miRNA overexpression was observed in 50% of GCNIS cases. Among miRNAs, miR-371a-3p stands out with the most promising evidence, suggesting its relevance in the primary diagnosis of TGCT, particularly when conventional STMs offer limited value. Indeed, it demonstrated high specificity (90–99%) and sensitivity (84–89%), with good positive predictive value (97.2%) and negative predictive value (82.7%). Furthermore, a direct relationship between miRNA concentration, disease burden, and treatment response exists, regardless of disease stages. The initial evidence of miRNA decrease in response to surgical treatment and systemic chemotherapy has been further supported by more recent results suggesting the potential utility of this tool not only in evaluating treatment response but also in monitoring residual disease and predicting disease relapse. Conclusions: MiRNAs could represent a reliable tool for accurate diagnosis and disease monitoring in the treatment of TGCT, providing more precise tools for early detection and treatment stratification. Nevertheless, well-designed clinical trials and comprehensive long-term data are needed to ensure their translation into effective clinical tools. [ABSTRACT FROM AUTHOR]

Each year the European Association of Urology (EAU) produce a document based on the most recent evidence on the diagnosis, therapy, and follow-up of testicular cancer (TC). To represent a summarised version of the EAU guidelines on TC for 2023 with a focus on key changes in the 2023 update. A multidisciplinary panel of TC experts, comprising urologists, medical and radiation oncologists, and pathologists, reviewed the results from a structured literature search to compile the guidelines document. Each recommendation in the guidelines was assigned a strength rating. For the 2023 EAU guidelines on TC, a review and restructure were undertaken. The key changes incorporated in the 2023 update include: new supporting text regarding venous thromboembolism prophylaxis in males with metastatic germ cell tumours receiving chemotherapy; quality of life after treatment; an update of the histological classifications and inclusion of the World Health Organization 2022 pathological classification; inclusion of the revalidation of the 1997 International Germ Cell Cancer Collaborative Group prognostic risk factors; and a new section covering oncology treatment protocols. The 2023 version of the EAU guidelines on TC include the highest available scientific evidence to standardise the management of TC. Better stratification and optimisation of treatment modalities will continue to improve the high survival rates for patients with TC. This article presents a summary of the European Association of Urology guidelines on testicular cancer published in 2023 and includes the latest recommendations for management of this disease. The guidelines are a valuable resource that may help patients in understanding treatment recommendations. [ABSTRACT FROM AUTHOR]

Malignancy of the testes constitutes only one percent of all male cancers. Most testicular malignancies are Germ Cell Tumours (GCTs), which are broadly categorised into seminomatous and non-seminomatous types. Non seminomatous GCTs are further classified into several subtypes based on their histopathological features. This case report presents a case of Pure Embryonal Cell Carcinoma (PECC) of the testes in a 32-year-old male. The diagnostic work-up involved a detailed medical history, physical examination, and imaging tests, including a scrotal ultrasound and Positron Emission Tomography-Computed Tomography (PET/CT) scan. These tests helped identify a testicular mass without metastasis. Additionally, serum tumour markers such as Alpha Fetoprotein (AFP), human chorionic gonadotropin, and lactate dehydrogenase were elevated, further confirming the presence of testicular malignancy. The management of the patient included surgery and chemotherapy. Histopathology and immunohistochemistry were performed, resulting in a diagnosis of pure embryonal carcinoma. This case highlights the significance of timely diagnosis and prompt management in improving the prognosis of patients with PECC.

Testicular germ cell tumours are the most common malignancies in young men. Germ cell tumours can be classified as seminomas or non-seminomas, each with different clinical features and treatment approaches. Germ cell tumours are occasionally associated with somatic-type malignancy, particularly in metastatic lymph nodes after adjuvant chemotherapy. Adenocarcinomas and rhabdomyosarcoma are the most common malignancies in this setting. In this report, we present a unique case of a 37-year-old patient who presented with a testicular teratoma containing a nephroblastoma component. The tumour exhibited characteristic morphology that resembled foetal kidney and expressed nuclear WT-1 and PAX-8 on immunohistochemistry. Following surgery, the patient opted for active surveillance and remains disease-free. To date, only 7 cases of nephroblastoma in primary testicular teratoma have been reported. This case highlights the importance of considering this rare entity in the differential diagnosis of testicular teratomas and the need for careful pathological examination.

Mediastinal germ cell tumours are a rare group of extragonadal germ cell tumours with less than 5% prevalence of all germ cell tumours. Primary mediastinal germ cell tumours themselves account for 16-36% of the extragonadal germ cell tumours. Along the spectrum of osteosarcoma, parosteal osteosarcoma is a well- differentiated surface osteosarcoma with a prevalence of 4% of all osteosarcoma. As such synchronous primary parosteal osteosarcoma and primary mediastinal germ cell tumour are exceedingly rare. This leads to complexity in determining the most appropriate chemotherapy for two different types of tumours and its potential side effects of reduced immunity leading to potential secondary infection. Here we report a case of a 16-year-old boy who presented with synchronous primary osteosarcoma and primary mediastinal germ cell tumour, complicated with atypical mycobacterial infection post-operatively. Additionally, we discuss our choice of chemotherapy and the management of the atypical mycobacterial infection.

Objective: Primary objective: To study patients' clinical profile and outcomes with germ cell tumours developing in undescended testes. Materials and methods: Case records of patients enlisted in the prospectively maintained 'testicular cancer database' at our tertiary cancer care hospital from 2014 to 2019 were retrospectively reviewed. Any patient who presented with testicular germ cell tumour with a documented history/diagnosis of undescended testes, whether surgically corrected or not, was considered for this study. The patients were managed along the standard lines of treatment for testicular cancer. We evaluated clinical features, difficulties and delays in diagnosis and complexities in management. We evaluated event-free survival (EFS) and overall survival (OS) using the Kaplan-Meier Method. Results: Fifty-four patients were identified from our database. The mean age was 32.4 years (median age 32, range: 15-56 years). Seventeen (31.4%) had developed cancer in orchidopexy testes, and 37 (68.6%) presented with testicular cancer in uncorrected cryptorchid testes. The median age at orchidopexy was 13.5 years (range: 2-32 years). The median time from symptom onset to diagnosis was 2 months (1-36 months). There was a delay in the initiation of treatment of more than 1 month in 13 patients, with the longest delay being 4 months. Two patients were initially misdiagnosed as gastrointestinal tumours. Thirty-two (59.25%) patients had seminoma, and 22 (40.7%) patients had non-seminomatous germ cell tumours (NSGCT). Nineteen patients had metastatic disease at presentation. Thirty (55.5%) patients underwent orchidectomy upfront while in 22 (40.7%) patients, orchidectomy was done after chemotherapy. The surgical approach included high inguinal orchidectomy, exploratory laparotomy or laparoscopic surgery per the clinical situation. Post-operative chemotherapy was offered as clinically indicated. At a median follow-up of 66 months (95% CI: 51-76), there were four relapses (all NSGCT) and one death. The 5-year EFS was 90.7% (95% CI: 82.9-98.7). The 5-year OS was 96.3% (95% CI: 91.2-100) Conclusions: The tumours in undescended testes, particularly those without prior orchiopexy, often presented late and with bulky masses, requiring complex multidisciplinary management. Despite the complexity and challenges, our patient's OS and EFS matched that of patients with tumours in normally descended testes. Orchiopexy may help in earlier detection. In the first such series from India, we show that testicular tumours in the cryptorchid are also as curable as the germ cell tumours developing in the descended testis. A multidisciplinary disease management group with expertise in managing complex cases is crucial for a favourable outcome in these groups of patients. We also found that orchiopexy done even later in life confers an advantage in terms of early detection in a subsequently developing testicular tumour. [ABSTRACT FROM AUTHOR]

Objectives: To present our intermediate to long-term oncological and functional outcomes of robot-assisted retroperitoneal lymph node dissection (RA-RPLND) in post-chemotherapy (PC) residual mass in testicular cancers. To the best of our knowledge, this is the largest single-centre experience of RA-RPLND for in such setting. Methods: Prospectively maintained database of carcinoma testis patients undergoing RA-RPLND from February 2012 to September 2021 was reviewed. Patient demographics, tumour stage and risk groups and chemotherapy details were recorded. Intraoperative details and post-operative complications were also noted. Pathological outcomes included were lymph node yield and histopathology report. Further, follow-up was done for recurrence and antegrade ejaculation status. Results: Total of 37 cases were done for PC residual masses. International germ cell cancer collaborative group good, intermediate and poor risk proportion was 18 (48.6%), 14 (37.8%) and 5 (13.5%), respectively. Bilateral full template dissection, unilateral modified template dissection and residual mass excision was performed in 59.5% (22/37), 35.1% (13/37) and 5.4% (2/37) patients, respectively. The median size of the excised residual mass was 3.45 cm interquartile range (IQR 2–6 cm), with the largest being 9 cm. The median lymph nodal yield was 19. The most common histology was necrosis (n = 24, 65%), followed by teratoma (n = 11, 30%) and viable malignancy (n = 2, 5%). Antegrade ejaculation was reported in 32 patients (86.4%). After a median follow-up of 41 (IQR 14–64) months, only one patient had a recurrence. Conclusions: RA-PC-RPLND is thus a safe, feasible and oncologically effective option for selected patients. With increasing experience, larger masses can also be dealt with efficiently.

Context: The aim of this review is to describe the proportion of testicular germ cell tumours (tGCTs) with recurrence, and the timing and anatomical sites of relapse across different disease stages and after different treatment options. We summarise published follow-up protocols and discuss current and future developments to personalise follow-up for patients with tGCT. Evidence acquisition: A systematic literature search was conducted and current guidelines and selected institutional follow-up protocols were reviewed. Evidence synthesis: Of 302 publications, we screened 68 full texts and included 29 studies; 22 of these were retrospective and seven were prospective in nature, contributing data for 20 570 patients. The number of patients included per study ranged from 119 to 2483. We compared the guideline follow-up protocols of the European Society for Medical Oncology, European Association of Urology, National Comprehensive Cancer Network, and American Urological Association, as well as institutional follow-up protocols. The protocols differed in terms of the number, time points, and type of follow-up investigations. Conclusions: Future research should assess how tGCT can be followed to ensure high adherence, define the role of miR-371a-3p microRNA during follow-up, and develop follow-up protocols after curative treatment in the metastatic setting. Patient summary: In this review of follow-up protocols for men with testis cancer, we observed different recommendations and discuss future research areas to improve follow-up for these patients.

Abstract Objectives We aim to determine if robot‐assisted retroperitoneal lymph node dissection (R‐RPLND) can be performed as a safe option to open RPLND in selected patients with metastatic germ cell cancer. Patients and methods This population‐based prospective study was performed at a one of two national referral centres for RPLND in Sweden. All patients referred during January 2017–March 2021 were screened for possible inclusion. R‐RPLND was performed using the Da Vinci Xi surgical system. Perioperative parameters, postoperative complications (Clavien–Dindo), final pathology, preservation of antegrade ejaculation and relapse rates were evaluated. Classifiers for selecting patients to open versus robotic RPLND were analysed by logistic regression modelling. The median follow‐up was 23 months. Results Of 87 patients referred, 29 were selected for R‐RPLND, 19 in a post‐chemotherapy setting. In median, retroperitoneal tumour diameter was 18 mm, BMI 24 kg/m2, operative time 433 min, estimated blood loss 50 ml and length of stay 3 days. One patient underwent open conversion due to failure to progress. Four patients had Clavien–Dindo grade 3 complications, of which three were chylous‐related. No in‐field recurrences occurred during follow‐up. Conclusion This population‐based study suggests that R‐RPLND can be safely performed in at least one third of patients referred for an RPLND. A relatively high rate of lymph‐leakage may represent a potential drawback. Tumour size may be the most important discriminator when deciding on robotic versus open RPLND. Further studies with longer follow‐up are needed to validate the results.

Simple Summary: Intracranial germinoma is a rare tumour of the nervous system, primarily affecting children and young adults, causing neurological and endocrinological symptoms. In this study, we found that a delayed diagnosis (>6 months after initial symptoms) leads to worse overall survival rate despite smaller sizes of the primary tumours. The time to diagnosis was shorter in patients who exhibited neurological symptoms, and bifocal lesions were associated with a significantly worse prognosis. This study emphasizes the need for timely diagnosis of intracranial germinoma, and suggests the necessity of thorough differential diagnosis in patients presenting atypical neurological and endocrinological symptoms. Background: Intracranial germinoma is a rare malignant neoplasm of the central nervous system (CNS) that occurs in children and young adults. The aim of our study was to assess the initial manifestation of the disease, and to find differences in outcomes dependent on time of diagnosis. Methods: The study group consisted of 35 consecutive patients (adults and children) who were treated for intracranial germinoma with radiotherapy at a tertiary centre, and their data were retrospectively collected. We evaluated time from the first symptoms to diagnosis and divided patients into early and delayed diagnosis groups. Delayed diagnosis has been defined as the time from initial presentation to final diagnosis longer than six months. Results: A total of 17 (48.6%) of the patients had delayed diagnoses. Patient survival data spanned a median of six (interquartile range 3–12) years. At the time of the diagnosis, patients presented exclusively neurological symptoms in 16 (45.7%) cases, exclusively endocrinological symptoms in five (14.3%) cases, and mixed symptoms in the remaining cases (n = 14; 40.0%). Patients with neurological symptoms had shorter time (p < 0.001) from first symptoms to the final diagnosis (5.91 months) than in patients without them (19.44 months). The delayed diagnosis group presented significantly smaller tumour size (mean maximal dimension 2.35 cm) compared to early diagnosis group (3.1 cm). The 5-year and 10-year survival rates of our patients were 94.3% and 83.4%, respectively. Patients with a delayed diagnosis (n = 17) had a significantly worse (p = 0.02) 10-year OS (63%) compared to the early diagnosis group (n = 18; OS = 100%). Importantly, in five patients (14.29%), initial manifestation occurred before radiological signs of the disease. Conclusion: Our study stresses the need for timely diagnosis in intracranial germinoma, as a delay has a significant impact on the prognosis. In particular, if the tumour is small or causes exclusively endocrinological symptoms, the diagnosis may be difficult and delayed. [ABSTRACT FROM AUTHOR]

Background: Analyses of small non‐coding RNA (ncRNA) expression in malignant germ cell tumours (GCTs) have focused on microRNAs (miRNAs). As GCTs all arise from primordial germ cells, and piwi‐interacting RNAs (piRNAs) have important roles in maintaining germline integrity via transposon silencing, we hypothesised that malignant GCTs are characterised by fundamental piRNA dysregulation. Aims: We undertook global small ncRNA sequencing in malignant GCTs, in order to describe small ncRNA expression changes for both miRNAs and piRNAs. Materials and methods: We performed small ncRNA next generation sequencing on a representative panel of 47 samples, comprising malignant GCT (n = 31) and control (n = 16) tissues/cell lines. Following quality control and normalisation, filtered count reads were used for differential miRNA and piRNA expression analyses via DESeq2. Predicted mRNA targets for piRNAs were identified and utilised for pathway enrichment analyses. Results: Overall, miRNAs and piRNAs comprised 21.9% and 43.0% of small ncRNA species, respectively. There were 749 differentially expressed miRNAs in malignant GCTs, of which 536 (72%) were over‐expressed and 213 (28%) under‐expressed. The top‐ranking over‐expressed miRNAs were exclusively from the miR‐371∼373 and miR‐302/367 clusters. The most significantly under‐expressed miRNAs were miR‐100‐5p, miR‐214‐3p, miR‐125b‐5p and let‐7 family members, including miR‐202‐3p. There were 1,121 differentially expressed piRNAs in malignant GCTs, of which 167 (15%) were over‐expressed and 954 (85%) under‐expressed. Of note, of the top‐20 differentially expressed piRNAs, 16 were over‐expressed, of which piR‐hsa‐2506793 was both top‐ranking and most abundant. Mobile element (ME; i.e., transposon)‐associated piRNAs comprised 166 (15%) of the 1,121 differentially expressed piRNAs, of which 165 (>99%) were down‐regulated. The remaining 955 (85%) non‐ME‐associated piRNAs may have wider cellular roles. To explore this, predicted mRNA targets of differentially expressed piRNAs identified putative involvement in cancer‐associated pathways. Conclusion: This study confirms previous miRNA observations, giving credence to our novel demonstration of global piRNA dysregulation in gonadal malignant GCTs, through both ME and non‐ME‐associated pathways, which likely contributes to GCT pathogenesis. [ABSTRACT FROM AUTHOR]

Germ cell tumour (GCT) is the most common testicular tumour that commonly presents as a painless mass. Bone marrow metastasis in cases of testicular GCT is rare; only few case reports are available till date in the literature. Here an adult male presented with an intra-abdominal mass in right iliac fossa with inguinal lymphadenopathy with a deranged kidney function test. Bone marrow (BM) aspirate smear revealed metastatic tumour cells, but BM-biopsy was unremarkable. High serum Beta - HCG (38286 mIU/L) pointed towards germ cell lesion. Lymph node biopsy along with immunomarkers confirmed metastatic foci from germ cell tumor and managed as per standard protocol. Rarely BM aspirate is seen positive for malignancy, while biopsy turns out to be negative. Secondly, BM metastasis of GCT should be considered while dealing with cases like this. Informed consent: This is certified that the informed consent has been obtained from the patient.

Malignancy of the testes constitutes only one percent of all male cancers. Most testicular malignancies are Germ Cell Tumours (GCTs), which are broadly categorised into seminomatous and non-seminomatous types. Non-seminomatous GCTs are further classified into several subtypes based on their histopathological features. This case report presents a case of Pure Embryonal Cell Carcinoma (PECC) of the testes in a 32-year-old male. The diagnostic work-up involved a detailed medical history, physical examination, and imaging tests, including a scrotal ultrasound and Positron Emission Tomography-Computed Tomography (PET/CT) scan. These tests helped identify a testicular mass without metastasis. Additionally, serum tumour markers such as Alpha Fetoprotein (AFP), human chorionic gonadotropin, and lactate dehydrogenase were elevated, further confirming the presence of testicular malignancy. The management of the patient included surgery and chemotherapy. Histopathology and immunohistochemistry were performed, resulting in a diagnosis of pure embryonal carcinoma. This case highlights the significance of timely diagnosis and prompt management in improving the prognosis of patients with PECC. [ABSTRACT FROM AUTHOR]

ObjectivesOnly a small number of studies have reported on the association of parental occupational exposure to benzene and risk of childhood and adolescent leukaemias. We examined associations with acute lymphoblastic leukaemia (ALL) in this population-based study in Denmark.MethodsBenzene was largely banned from Danish workplaces after 1975, thus this case-control study focused on the immediately prior years. Paediatric cancer cases (ResultsWe identified 217 employed case fathers and 169 employed case mothers, of which 22 (10.1%) and 11 (6.5%), respectively, were exposed to benzene (vs 6.7% and 2.9% of control fathers and mothers). Most exposed parents worked as machine or engine mechanics, or in the shoe industry. Maternal occupational exposure to benzene in pregnancy was related to increased risk of ALL in offspring (adjusted OR=2.28, 95% CI 1.17 to 4.41), while paternal preconceptional benzene exposure was not as strongly associated (adjusted OR=1.40, 95% CI 0.88 to 2.22).ConclusionsOur study supports an increased risk for ALL with parental occupational benzene exposure.

Testicular germ cell tumours are the most common malignancies in young men. Germ cell tumours can be classified as seminomas or non-seminomas, each with different clinical features and treatment approaches. Germ cell tumours are occasionally associated with somatic-type malignancy, particularly in metastatic lymph nodes after adjuvant chemotherapy. Adenocarcinomas and rhabdomyosarcoma are the most common malignancies in this setting. In this report, we present a unique case of a 37-year-old patient who presented with a testicular teratoma containing a nephroblastoma component. The tumour exhibited characteristic morphology that resembled foetal kidney and expressed nuclear WT-1 and PAX-8 on immunohistochemistry. Following surgery, the patient opted for active surveillance and remains disease-free. To date, only 7 cases of nephroblastoma in primary testicular teratoma have been reported. This case highlights the importance of considering this rare entity in the differential diagnosis of testicular teratomas and the need for careful pathological examination. [ABSTRACT FROM AUTHOR]

Purpose: Testicular germ cell tumours (GCTs) represent the most common malignancy in young adult males with two thirds of all cases presenting with clinical stage I (CSI). Active surveillance is the management modality mostly favoured by current guidelines. This systematic review assesses the treatment results in CSI patients concerning recurrence rate and overall survival in non-seminoma (NS) and pure seminoma (SE) resulting from surveillance in comparison to adjuvant strategies. Methods/systematic review: We performed a systematic literature review confining the search to most recent studies published 2010–2021 that reported direct comparisons of surveillance to adjuvant management. We searched Medline and the Cochrane Library with additional hand-searching of reference lists to identify relevant studies. Data extraction and quality assessment of included studies were performed with stratification for histology (NS vs. SE) and treatment modalities. The results were tabulated and evaluated with descriptive statistical methods. Results: Thirty-four studies met the inclusion criteria. In NS patients relapse rates were 12 to 37%, 0 to 10%, and 0 to 11.8% for surveillance, chemotherapy and for retroperitoneal lymph node dissection (RPLND) while overall survival rates were 90.7−100%, 91.7−100%, and 97−99.1%, respectively. In SE CSI, relapse rates were 0−22.3%, 0−5%, and 0−12.5% for surveillance, radiotherapy, chemotherapy, while overall survival rates were 84.1−98.7%, 83.5−100%, and 92.3−100%, respectively. Conclusion: In both histologic subgroups, active surveillance offers almost identical overall survival as adjuvant management strategies, however, at the expense of higher relapse rates. Each of the management strategies in CSI GCT patients have specific merits and shared-decision-making is advised to tailor treatment. [ABSTRACT FROM AUTHOR]

A genetic hallmark of malignant germ cell tumours (GCTs) is isochromosome 12p, but oncogenes located in 12p that are specifically expressed in GCT have not yet been identified. SIN3‐HDAC complex‐associated factor (SINHCAF) is a subunit of the Sin3/histone deacetylase (HDAC) complex, and it defines a Sin3a‐Hdac complex variant that is required for the self‐renewal of mouse embryonic stem cells. This study demonstrated that SINHCAF is expressed in a vast majority of malignant GCTs and is rarely expressed in somatic malignancy. Fluorescence in situ hybridisation revealed SINHCAF amplification in malignant GCTs. SINHCAF silencing using shRNA reduced anchorage‐dependent cell proliferation and tumoursphere formation and inhibited tumour cell migration and invasion in GCT cell lines. Moreover, in the GCT cell line NTERA2/D1, SINHCAF silencing inhibited the expression of genes associated with embryonic stem cells and induced the expression of genes associated with neuronal and white fat cell differentiation. Compared with somatic cell lines, GCT cell lines were more susceptible to HDAC inhibitor treatment. Thus, we identified SINHCAF to be a potential oncogene located in the amplicon of chromosome 12p and showed that SINHCAF was specifically expressed in malignant GCTs. HDAC inhibitor treatment may counteract the oncogenic activity of SINHCAF and is a promising therapeutic approach for GCTs. © 2022 The Pathological Society of Great Britain and Ireland. [ABSTRACT FROM AUTHOR]

To explore clinical and pathological characteristics of testicular cancer and also identify factors associated with its oncological outcomes. Testicular cancer has a very good prognosis. Actually, we aim to report on 10 years of experience in the real-world practice of treating testicular cancer in a university-based hospital.

Highlights: • Neutrophil to lymphocyte ratio (NLR) has been reported by several studies for its role as a biomarker in various diseases, however, the role of NLR in testicular GCT is still unclear. • The characteristics and responses of testicular GCT patients among Indonesian men show similarity to other reports worldwide. • As a parameter, NLR shows promise to be used as a potential biomarker for prognosis in testicular GCT. Abstract: The global incidence of testicular cancer is 1-2% from all cancers. The attempts to maintain high therapeutic rates while decreasing the treatment-related side effects and toxicity have become the current concern. However, the reports regarding testicular germ cell tumors (GCT) in Indonesia are limited. Thus, we aimed to evaluate the clinical characteristics of testicular GCT patients undergoing bleomycin, etoposide, and cisplatin (BEP) chemotherapy, as well as their chemotherapy response and side effects. We reported the data of patients with Testicular Germ Cell Tumor from January 2015 to December 2019. Several data were retrieved, including patient demographics, tumor characteristics, treatment, and prognosis outcome. A total of 67 patients with testicular germ cell tumors were included in this study. The mean age was 28.9 years old. The chemotherapy regimens used were four cycles of (BEP) in 36 patients (53.7%), followed by three cycles of BEP in 22 patients (32.8%). Patients with seminoma GCT mostly had a complete response (54.1%), whereas most patients with non-seminoma GCT had progressive disease (47.8%). The multiple logistic regression analysis showed that NLR and S staging were independently associated with the patient’s response to chemotherapy (OR 2.14, 95% CI 1.22, 3.78, p

Background and Objectives: Despite advancements in the diagnosis and treatment of testicular germ cell tumours (TGTCs), challenges persist in identifying reliable biomarkers for early detection and precise disease management. This narrative review addresses the role of microRNAs (miRNAs) as potential diagnostic tools and therapeutic targets in the treatment of TGCTs. Materials and Methods: Three databases (PubMed®, Web of Science™, and Scopus®) were queried for studies investigating the utility of miRNA as diagnostic tools, assessing their prognostic significance, and evaluating their potential to guide TGCT treatment. Different combinations of the following keywords were used, according to a free-text protocol: “miRNA”, “non-coding RNA”, “small RNA”, “Testicular Cancer”, “seminomatous testicular germ cell”, “non-seminomatous testicular germ cell”. Results: The potential of miRNAs as possible biomarkers for a non-invasive diagnosis of TGCT is appealing. Their integration into the diagnostic pathway for TGCT patients holds the potential to enhance the discriminative power of conventional serum tumour markers (STMs) and could expedite early diagnosis, given that miRNA overexpression was observed in 50% of GCNIS cases. Among miRNAs, miR-371a-3p stands out with the most promising evidence, suggesting its relevance in the primary diagnosis of TGCT, particularly when conventional STMs offer limited value. Indeed, it demonstrated high specificity (90–99%) and sensitivity (84–89%), with good positive predictive value (97.2%) and negative predictive value (82.7%). Furthermore, a direct relationship between miRNA concentration, disease burden, and treatment response exists, regardless of disease stages. The initial evidence of miRNA decrease in response to surgical treatment and systemic chemotherapy has been further supported by more recent results suggesting the potential utility of this tool not only in evaluating treatment response but also in monitoring residual disease and predicting disease relapse. Conclusions: MiRNAs could represent a reliable tool for accurate diagnosis and disease monitoring in the treatment of TGCT, providing more precise tools for early detection and treatment stratification. Nevertheless, well-designed clinical trials and comprehensive long-term data are needed to ensure their translation into effective clinical tools.

Abstract Background Testicular cancer (TC) is the most frequent type of cancer among young men aged between 15 and 34 years. TC is treated using cisplatin, but 3%–5% of TC patients fail to respond to cisplatin, with a very bad to fatal prognosis. Accordingly, it is most important to quickly and readily identify those TC patients who are resistant to cisplatin treatment. Methods This study seeks to investigate changes in the glycosylation associated with cisplatin resistance to TC cell lines. Results A specific glycoprofiling of human chorionic gonadotropin (hCG) was analysed in three TC cell lines and one cell line of female origin. A typical calibration curve for hCG glycoprofiling showed a dynamic range up to 50 ng/ml, with a limit of detection of 0.3 ng/ml and assay reproducibility represented by relative standard deviation of 3.0%. Changes in the glycan signatures on hCG were analysed in cisplatin‐sensitive cell lines and in their cisplatin‐resistant sub‐lines using an enzyme‐linked lectin assay (ELLA) protocol. An immobilised antibody was applied to a selective capture of hCG from a cytoplasmic fraction of cell lysates with final incubation using a lectin from a panel of 17 lectins. Conclusion The results suggest that one particular lectin Dolichos biflorus agglutinin (DBA) can selectively discriminate sensitive TC cell lines from resistant TC cell lines. Moreover, there are additional lectins which can provide useful information about the strength of cisplatin resistance.

Objective: To report a single-center experience in non-epithelial malignant ovarian tumours (NEMOT), by presenting different clinical and pathological characteristics, management and outcomes. Methods: We retrospectively reviewed electronic files of all female patients who underwent surgery for NEMOT at the Gynecology Department of King Abdulaziz University Hospital, Jeddah, Saudi Arabia, from July 2003 to July 2019. We collected baseline demographic, anthropomorphic and clinical data; pathological characteristics; management and follow-up data; and outcomes including residual disease, recurrence and last follow-up status (deceased or alive). Results: Thirty-three women were included; mean (standard deviation) age = 33.24 (17.72) years, range = 4, 86 years. Granulosa cell tumor was the most frequent subtype diagnosed in 17 (51.5%) patients, followed by germ cell tumours 13 (39.4%). The majority of patients were diagnosed at FIGO Stage I (22, 66.7%) and with tumor Grade 1 (23, 69.7%), while 8 (24.2%) were diagnosed with Grade 3 tumors. Granulosa cell and Sertoli-Leydig cell tumours were diagnosed at an older age (mean age = 39.30 vs. 23.92 years) compared to germ cell tumours, respectively (P = 0.012). Two-third of the patients benefited from conservative surgery including oophorectomy + staging, and 16 (48.5%) benefited from chemotherapy with bleomycin, etoposide and platinum being the most common protocol (13, 39.4%) for germ cell tumours. Postoperatively, only 2 (6.1%) patients had residual disease. Recurrence and mortality were reported in one and four patients, respectively, resulting in recurrence rate = 3.0% (95% confidence interval [CI] = 0.01%, 15.8%) and mortality rate = 12.1% (95% CI = 3.4%, 28.2%). Conclusions: The present series of NEMOT was predominated by sex cord-stromal cell tumors, which were diagnosed in patients with older age, while germ cell tumours were underrepresented. Although survival rates were comparable to those reported internationally, more consideration should be given to following up patients regarding fertility outcomes to provide a more comprehensive evaluation of treatment success and quality of care.