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This article reports on two cases of testicular sclerosing stromal tumors (SSTs) that show GLI1 gene alterations. These tumors have a lobulated microscopic appearance with alternating cellular and fibroedematous zones. The patients, aged 35 and 65, presented with testicular masses. The study suggests that testicular SSTs may have a pathogenesis related to ovarian SSTs, involving GLI protein-mediated up-regulation of the Hedgehog signaling pathway. Further research is needed to determine if GLI1 alterations are consistent in this rare testicular neoplasm. [Extracted from the article]

Introduction: Urologists observed reduced cancer consultations and surgeries during the SARS-CoV-2 pandemic, raising concern about treatment delays. Testicular cancer serves as a particularly sensitive marker of this phenomenon, as the clinical stage of testicular cancer at presentation is predictive of cancerspecific survival. We aimed to investigate whether COVID-related restrictions to primary care access resulted in increased incidence of metastatic germ cell testis cancer. Methods: A retrospective chart review was conducted on all cases of testicular cancer managed surgically at our center from March 1, 2018, to February 28, 2023. Patients were categorized into temporal cohorts, representing before, during, and following the implementation of COVID-19 public health restrictions in the province of Newfoundland and Labrador. Results: Forty-one cases of testicular germ cell tumors were identified during the study period. The mean age at diagnosis was 40.8 years (standard deviation ±13.7). Demographics did not vary across the cohorts. Clinical stage 3 disease remained stable before and during the pandemic at 10.5% and 9.1% of cases, respectively. In the post-pandemic period, there was an increase to 27.3% (p=0.617). Surgical wait times remained stable across the pandemic (p=0.151). Conclusions: There was a 16.8% rise in clinical stage III disease from the pre-pandemic to postpandemic period. Our study failed to identify a statistically significant increase in metastatic testis cancer incidence upon lifting of pandemic restrictions. Further study is necessary to confirm suspicions that pandemic restrictions contributed to increased incidence of metastatic testis cancer. [ABSTRACT FROM AUTHOR]

Chemotherapy-induced peripheral neuropathy (CIPN) is a common and debilitating side effect of numerous anticancer agents. CIPN can persist as chronic pain or sensory symptoms for months to years after discontinuation of the anticancer agent, affecting a patient's quality of life, function, and morbidity. Although treatment recommendations are limited because of insufficient evidence, many pharmacologic and nonpharmacologic therapies are being explored to prevent and treat CIPN. [ABSTRACT FROM AUTHOR]

Summary: This case report describes the diagnosis and surgical treatment of a 12‐year‐old Friesian stallion that presented with colic and was diagnosed with an unilateral abdominal seminoma. The diagnostic work‐up included haematology, blood chemistry, rectal examination and ultrasonography before the tentative diagnosis of a neoplastic intra‐abdominal testicle was made. The mass was removed surgically and diagnosed as a seminoma via histopathology. Regular follow‐up was performed since suspected metastasis was seen on transrectal ultrasonography and laparoscopy. Unfortunately, the patient was subjected to euthanasia 18 months post‐surgery due to clinical deterioration. Post‐mortem examination was performed and confirmed the cause of clinical deterioration was due to metastasis of the previously removed seminoma. Colic is, to the author's knowledge, rarely seen in stallions with an abdominal testicular neoplasm, in contrast to humans and dogs. [ABSTRACT FROM AUTHOR]

Simple Summary: Females prenatally exposed to diethylstilbestrol have an elevated risk of severe cervical dysplasia and some cancers, while testicular cancer is increased in males. We assessed these associations in the prenatally exposed female's offspring (third generation). Based on third-generation females' self-reports, diethylstilbestrol exposure was not associated with risks of overall cancer, breast cancer, or severe cervical dysplasia. Borderline ovarian cancer risk in exposed vs. unexposed was elevated but compatible with chance. Based on mothers' reports, diethylstilbestrol exposure did not increase the risk of overall or other cancers in third-generation females. Overall cancer risk in exposed males appeared elevated but compatible with chance. Testicular cancer risk was not elevated in exposed males, and there were no prostate cancers reported. These data do not provide evidence that diethylstilbestrol is associated with cancer risk in third-generation females or males. The third generation is relatively young and requires follow-up to assess risk as the cohort ages. Background: Females exposed prenatally to diethylstilbestrol (DES) have an elevated risk of cervical dysplasia, breast cancer, and clear cell adenocarcinoma (CCA) of the cervix/vagina. Testicular cancer risk is increased in prenatally exposed males. Epigenetic changes may mediate the transmission of DES effects to the next ("third") generation of offspring. Methods: Using data self-reported by third-generation females, we assessed DES in relation to the risk of cancer and benign breast and reproductive tract conditions. Using data from prenatally DES-exposed and unexposed mothers, we assessed DES in relation to cancer risk in their female and male offspring. Cancer risk was assessed by standardized incidence ratios (SIR) and 95% confidence intervals (CI); the risks of benign and malignant diagnoses were assessed by hazard ratios (HR) and 95% CI. Results: In self-reported data, DES exposure was not associated with an increased risk of overall cancer (HR 0.83; CI 0.36–1.90), breast cancer, or severe cervical dysplasia. No females reported CCA. The risk of borderline ovarian cancer appeared elevated, but the HR was imprecise (3.46; CI 0.37–32.42). Based on mothers' reports, DES exposure did not increase the risk of overall cancer (HR 0.80; CI 0.49–1.32) or of other cancers in third-generation females. Overall cancer risk in exposed males appeared elevated (HR 1.41; CI 0.70–2.86), but the CI was wide. The risk of testicular cancer was not elevated in exposed males; no cases of prostate cancer were reported. Conclusions: To date, there is little evidence that DES is associated with cancer risk in third-generation females or males, but these individuals are relatively young, and further follow-up is needed. [ABSTRACT FROM AUTHOR]

Background: Congenital adrenal hyperplasia (CAH) encompassed a bunch of autosomal recessive disorders characterized by impaired cortisol levels due to an enzymatic deficiency in steroid synthesis. In adult male patients with CAH, a frequent complication related to poor disease control is the development of ectopic adrenocortical tissue in the testes, named testicular adrenal rest tumors (TART). Conversely, ovarian adrenal rest tumors (OART) in females are extremely rare and adrenal rests in sites other than gonads are so uncommon to have been described only few times in literature. Case presentation: We report a case of a male patient with untreated CAH and oncologic history of pleomorphic sarcoma who presented with massive bilateral adrenal enlargement and adrenal rest tumors in peri-lumbar and peri-cecal sites, which mimicked metastasis from sarcoma. Conclusions: The development of massive adrenal enlargement and ectopic adrenal rest tumors in sites other than gonads, even if very uncommon, should be suspected in patients with CAH and prolonged periods of undertreatment. [ABSTRACT FROM AUTHOR]

Leydig cell tumors (LCT) are usually unilateral and can seldom show malignant behavior. Testicular adrenal rest tumors (TART), which typically present bilaterally, are always benign and associated with congenital adrenal hyperplasia (CAH). Herein, along with a literature review, we aim to present a rare case of CAH associated with bilateral testicular masses, which led to difficulty in differential diagnosis between LCT and TART. An 8-year-old boy with 11ß-hydroxylase deficiency was referred to an outpatient clinic because of bilateral testicular masses. From his medical history, it was ascertained that he was under hydrocortisone treatment for 4 years after his first surgical examination, followed by serial ultrasounds with a preliminary diagnosis of TART. However, testicular masses gradually enlarged during follow-up, and magnetic resonance imaging showed characteristic findings for LCT. The patient underwent bilateral testis-sparing surgery, and histopathological examination was reported as benign LCT. The patient has been doing well postoperatively for 6 months. Although emerging bilateral testicular masses in patients with CAH may suggest TART, they may rarely originate from LCT and cause delay in diagnosis or difficulties in differential diagnosis in cases that do not respond to hormonal replacement. [ABSTRACT FROM AUTHOR]

Background: Testicular Leydig cell tumours (LCTs) are the most common type of sex cord–stromal tumour in men, representing 1%–3% of all testicular neoplasms. Among testicular sex cord–stromal tumours, CTNNB1 mutations and nuclear expression of β‐catenin have been typically associated with Sertoli cell tumour. Recent genomic analyses have shown that CTNNB1 variants are also identified in a subset of LCTs; however, the frequency and clinicopathologic associations of β‐catenin alterations remain incompletely understood in this tumour type. Methods: In this study, we evaluated 32 LCTs (five malignant/metastasizing, 27 nonmetastasizing) using β‐catenin immunohistochemistry and DNA sequencing. Results: Immunohistochemistry revealed focal or multifocal nuclear β‐catenin expression in 47% of the tumours. Diffuse nuclear β‐catenin expression (in >50% of the tumour cells) was not detected in any of the cases analysed herein. Comparison of β‐catenin‐positive and β‐catenin‐negative cases did not show significant differences in the frequency of adverse histopathologic findings or malignant clinical behaviour. DNA sequencing performed de novo on a subset of seven cases revealed the presence of exon 3 CTNNB1 variants in four of them (4/7, 57%), with variant allele frequencies (VAF) ranging from 7 to 33%. Two additional β‐catenin‐positive cases that had been sequenced as part of a previous study harboured exon 3 CTNNB1 variants at VAF of 28% and 7%, respectively. Conclusion: These results demonstrate that β‐catenin alterations are relatively common in LCT, most likely occurring as subclonal events that are not enriched in cases with aggressive features. Further studies are needed to clarify the oncogenic role of β‐catenin in this tumour type. [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]

Purpose: Sinonasal nuclear protein in testis carcinoma (SNUTC) is a rare, aggressive malignancy caused by genetic rearrangements in the NUTM1 gene. The prognosis of SNUTC ranks among the most unfavorable within the naso-sinusal district, with an overall survival of 9.7 months. This systematic review aimed to determine the best therapeutic strategy for SNUTC. Methods: We reviewed eligible articles for patient demographics, TNM and stage at presentation, best response after primary treatment, disease-free survival and overall survival (OS) times, other following therapy lines, and final outcomes. Results: Among 472 unique citations, 17 studies were considered eligible, with reported treatment data for 25 patients. Most studies (n = 12) were case reports. The most frequently administered treatment regimen was surgery as primary treatment and combined radiochemotherapy as second-line or adjuvant treatment. Four patients were alive at follow-up. Conclusion: Basing on the existing literature, a standardized line in the treatment of SNUTC is not yet well delineated. A self-personalized strategy of therapy should be drawn on each patient affected by SNUTC. [ABSTRACT FROM AUTHOR]

Key Clinical Message: The importance of urologists and pathologists being knowledgable about primary testicular hemangiomas and other benign adult testicular neoplasms, though rare, is crucial. Ensuring these professionals are well‐versed in these conditions is vital in medicine. Testicular sparing surgery, especially when tumor markers are negative, is a common approach for patients with small or uncertain testicular masses. The cause of the uncommon benign testicular tumor known as testicular capillary hemangioma is currently unclear. Children are shown to have a greater incidence than adults. Histopathological examination reveals a vascular tumor with a well‐formed capillary lumina. The lesions are bordered by flattened endothelium and have lobulated clusters of closely spaced capillaries with an abundance of vascular gaps. These capillaries have anaplastic characteristics and lack mitotic activity. The patient, who was 24‐year‐old, came to the urology department complaining of severe testicular pain. He had no significant medical history. Clinical examination found a mass at the upper pole of the testicle. An ultrasonography Doppler study found a left varicocele that measured 3.5 mm in diameter, as well as a mass at the upper part of the left testicle. Pathologic examination confirmed the presence of a benign hemangioma with. Although rare, it is important for urologists and pathologists to be aware of primary testicular hemangiomas and other benign adult testicular neoplasms. Testicular sparing surgery has always been considered in patients with small or indeterminate testicular masses with negative tumor markers. [ABSTRACT FROM AUTHOR]

Copyright of Canadian Veterinary Journal / Revue Vétérinaire Canadienne is the property of Canadian Veterinary Medical Association and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Germ cell tumor of the testis (GCT) is a curable cancer even when it is widely metastatic; however, outcomes can differ based on tumor histology. Chemo-resistance in certain phenotypes, such as teratoma and yolk sac tumor, contributes to poor clinical outcomes in some patients with GCT. Despite this resistance to S-YSTemic therapy, many of these tumor subtypes remain amenable to surgical resection and possible cure. In this study, we report on a series of seven patients highlighting two chemo-resistant subtypes of nonseminomatous germ cell tumor (NSGCT), sarcomatoid yolk sac tumor (S-YST), and epithelioid trophoblastic tumor (ETT) for which early resection rather than additional salvage chemotherapy or high-dose intense chemotherapy might provide a superior clinical outcome and enhance cure rate. [ABSTRACT FROM AUTHOR]

We present a case report of a 54-year-old male with a metastatic testicular sex cord tumor harboring a EWSR1::ATF1 gene fusion. The tumor displayed a solid and nested architecture with sclerotic stroma and variable inflammatory infiltrate, and was positive for SF-1, inhibin, EMA, CD30, and WT1 expression. Further genetic analysis identified a EWSR1::ATF1 gene fusion. Overall findings were consistent with an "inflammatory and nested testicular sex cord tumor," a recently described testicular neoplasm characterized by EWSR1::ATF1 gene fusion and aggressive clinical behavior. Due to the aggressive nature of this entity and the limited response to current treatment options available, identification of potential biomarkers for early diagnosis and targeted therapies are critical. This case report provides important insights into the genomic landscape of testicular sex cord-stromal tumors, especially within the CTNNB1 -negative subset of patients with an aggressive clinical course, and further supports the distinction of "inflammatory and nested testicular sex cord tumor" as a separate entity from Sertoli cell tumors due to its characteristic morphological, immunohistochemical and molecular, features and clinical behavior. [ABSTRACT FROM AUTHOR]

Pure embryonal carcinoma (EC) is a rare malignant tumor that primarily occurs in infants with a sex development disorder and adults aged in their thirties to forties. This tumor behaves more aggressively than other germ cell tumors in the testis, and most of them should undergo surgery or chemotherapy. However, only a few case reports have involved imaging, and most of them are limited. Here, we present a case of pure EC in the testis of a 27-year-old male with multimodal ultrasonography, computed tomography, and magnetic resonance imaging. [ABSTRACT FROM AUTHOR]

Hydroxysteroid (17β) dehydrogenase (HSD17B) enzymes convert 17-ketosteroids to 17beta-hydroxysteroids, an essential step in testosterone biosynthesis. Human XY individuals with inactivating HSD17B3 mutations are born with female-appearing external genitalia due to testosterone deficiency. However, at puberty their testosterone production reactivates, indicating HSD17B3-independent testosterone synthesis. We have recently shown that Hsd17b3 knockout (3-KO) male mice display a similar endocrine imbalance, with high serum androstenedione and testosterone in adulthood, but milder undermasculinization than humans. Here, we studied whether HSD17B1 is responsible for the remaining HSD17B activity in the 3-KO male mice by generating a Ser134Ala point mutation that disrupted the enzymatic activity of HSD17B1 (1-KO) followed by breeding Hsd17b1 / Hsd17b3 double-KO (DKO) mice. In contrast to 3-KO, inactivation of both HSD17B3 and HSD17B1 in mice results in a dramatic drop in testosterone synthesis during the fetal period. This resulted in a female-like anogenital distance at birth, and adult DKO males displayed more severe undermasculinization than 3-KO, including more strongly reduced weight of seminal vesicles, levator ani, epididymis, and testis. However, qualitatively normal spermatogenesis was detected in adult DKO males. Furthermore, similar to 3-KO mice, high serum testosterone was still detected in adult DKO mice, accompanied by upregulation of various steroidogenic enzymes. The data show that HSD17B1 compensates for HSD17B3 deficiency in fetal mouse testis but is not the enzyme responsible for testosterone synthesis in adult mice with inactivated HSD17B3. Therefore, other enzymes are able to convert androstenedione to testosterone in the adult mouse testis and presumably also in the human testis. [ABSTRACT FROM AUTHOR]

An intense period of human population expansion over the past 250 years is about to cease. Total fertility rates are falling dramatically all over the world such that highly industrialized nations, including China and the tiger economies of SE Asia, will see their populations decline significantly in the coming decades. The socioeconomic, geopolitical and environmental ramifications of this change are considerable and invite a multidisciplinary consideration of the underlying mechanisms. In the short-term, socioeconomic factors, particularly urbanization and delayed childbearing are powerful drivers of reduced fertility. In parallel, lifestyle factors such as obesity and the presence of numerous reproductive toxicants in the environment, including air-borne pollutants, nanoplastics and electromagnetic radiation, are seriously compromising reproductive health. In the longer term, it is hypothesized that the reduction in family size that accompanies the demographic transition will decrease selection pressure on high fertility genes leading to a progressive loss of human fecundity. Paradoxically, the uptake of assisted reproductive technologies at scale, may also contribute to such fecundity loss by encouraging the retention of poor fertility genotypes within the population. Since the decline in fertility rate that accompanies the demographic transition appears to be ubiquitous, the public health implications for our species are potentially devastating. [ABSTRACT FROM AUTHOR]

Copyright of Türk Radyoloji Seminerleri is the property of Galenos Yayinevi Tic. LTD. STI and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Background: Adenocarcinoma of the rete testis (AORT) is an extremely rare and aggressive tumor with a poor prognosis. Its etiology and pathological characteristics have not been extensively studied, making accurate diagnosis and appropriate management challenging. AORT, an invasive testicular tumor with a mortality rate of 46%, treatment typically involves radical orchiectomy, retroperitoneal pelvic lymph node dissection (RPLND), adjuvant chemotherapy, and/or ongoing monitoring, but the response to conventional radiation and chemotherapy is limited. At present, no effective targeted therapy for AORT has been found. Case description: In this case report, we present the clinical scenario of a 50-year-old male patient initially diagnosed with a right testicular hydrocele, who subsequently underwent eversion of the parietal tunica vaginalis. Postoperative pathological analysis revealed metastatic clear cell renal cell carcinoma (ccRCC). PET/CT demonstrated findings suggestive of left renal upper pole carcinoma with involvement of the right scrotum, para-aortic region, bilateral iliac vessels, bilateral inguinal region, and multiple metastases. Sunitinib, a tyrosine kinase inhibitor, is commonly employed in the treatment of ccRCC. The patient underwent treatment with sunitinib for a duration of 20 months, resulting in the inactivation of multiple metastases. Following this, a radical orchiectomy was performed, and the postoperative pathology confirmed the presence of AORT. This article provides a comprehensive account of the patient's medical history, diagnostic process, treatment modalities, and subsequent follow-up observations. Conclusions: This case report highlights the successful use of targeted therapy with sunitinib in a patient with AORT. The patient showed a positive response to targeted therapy. This study not only provides a novel foundation for the treatment of AORT, but also offers valuable insights for future treatment strategies in managing this particular form of testicular cancer. [ABSTRACT FROM AUTHOR]

Simple Summary: Novel therapeutics are urgently needed for high-risk and refractory solid tumors. Clinical studies have demonstrated the safety and efficacy of PV-10 (10% rose bengal sodium) by intralesional injection in skin cancer. However, this agent has not yet been evaluated for the treatment of various adult solid tumors. The aim of our study was to test PV-10 in breast, colorectal, head and neck, and testicular cancers. Using a combination of in vitro and in vivo experiments, we found that PV-10 exhibits anti-cancer activity against a panel of human cell lines derived from these tumors. Our results support further clinical development of PV-10 for the treatment of solid tumors in adults. PV-10 is a 10% formulation of rose bengal sodium that has potent immunotherapeutic and anti-cancer activity against various tumors, including metastatic melanoma and refractory neuroblastoma. Currently, PV-10 is undergoing clinical testing for refractory metastatic neuroendocrine cancer and melanomas. However, preclinical investigation of PV-10 activity and its mechanisms against phenotypically and molecularly diverse adult solid tumors had not been conducted. In a panel of human cell lines derived from breast, colorectal, head and neck, and testicular cancers, we demonstrated that PV-10 induces cytotoxicity by apoptotic and autophagic pathways involving caspase-mediated PARP cleavage, downregulation of SQSTM1/p62, and upregulation of beclin-1. Treatment with PV-10 also consistently reduced phosphorylation of WNK1, which has been implicated in cancer cell migration and autophagy inhibition. By wound healing assay, PV-10 treatment inhibited the migration of cancer cells. Finally, significant inhibition of tumor growth was also noted in tumor-bearing mice treated with PV-10 by intralesional or systemic administration. In addition to known PV-10-mediated tumor-specific cytotoxic effects, we identified the mechanisms of PV-10 and provide new insights into its effect on autophagy and metastasis. Our data provide essential mechanism-based evidence and biomarkers of activity to formulate clinical studies of PV-10 in the future. [ABSTRACT FROM AUTHOR]

Colorectal cancer, with the liver being themost common site of distant metastasis, followed by the lungs and bones. Although reports of metastasis to the testis exist, paratesticular metastasis is extremely rare. A 37-year-old male presented with scrotal swelling. Ultrasound revealed hydrocele of the tunica vaginalis. The patient underwent routine surgical treatment, and postoperative pathology of the tunica vaginalis indicated adenocarcinoma of gastrointestinal origin. Colonoscopic biopsy confirmed adenocarcinoma of the sigmoid colon. After six months of systemic therapy, tumor reduction surgery was performed in conjunction with tunica vaginalis excision. Postoperative pathology suggested histological similarity in both sites, with immunohistochemistry results supporting the diagnosis of sigmoid colon adenocarcinoma metastasizing to the tunica vaginalis. We conducted a literature review, summarizing and discussing clinical presentations, metastatic pathways, and diagnostic approaches. [ABSTRACT FROM AUTHOR]

Simple Summary: The diagnosis and management of testicular germ cell tumors (TGCTs) currently relies on the use of unreliable biomarkers—conventional serum tumor markers (STMs). Variable levels of elevation in serum samples among patients and cancer types make the use of conventional STMs unfavorable for dependable diagnosis and clinical management of TGCTs. This review of recent studies suggests germ cell tumor associated miRNAs, such as miR-371a-3p, can be utilized as not only a reliable but cost-effective and convenient blood-based biomarker. However, before widespread clinical implementation, the development of a protocol for sample collection, analysis, and interpretation is necessary to prevent overtreatment and guide the management of patients. MicroRNAs, short non-protein coding RNAs, are overexpressed in GCTs. Circulating levels of germ cell tumor (GCT)-associated miRNAs, such as miR-371a-3p, can be utilized as efficient and cost-effective alternatives in diagnosing and managing patients presenting with GCTs. This quality of miRNAs has demonstrated favorable performance characteristics as a reliable blood-based biomarker with high diagnostic accuracy compared to current serum tumor markers (STMs), including α-fetoprotein (AFP), beta human chorionic gonadotropin (β-hCG), and lactate dehydrogenase (LDH). The conventional STMs exhibit limited specificity and sensitivity. Potential clinical implications of miRNAs include impact on de-escalating or intensifying treatment, detecting recurrence at earlier stages, and lessening the necessity of cross-sectional imaging or invasive tissue biopsy for non-teratomatous GCTs. Here, we also highlight the outstanding issues that must be addressed prior to clinical implementation. Standards for measuring circulating miRNAs and determining ideal cutoff values are essential for integration into current clinical guidelines. [ABSTRACT FROM AUTHOR]

This thesis focuses on the perception and experience of dying and the moment of death of an oncologically ill child from the parental perspective. The main intention is to point out the existence and meaning of this moment. The secondary aim is to discover what parents are experiencing during these moments. The interviews were conducted with eight women and five men. Children were diagnosed with osteosarcoma, testicular sarcoma, non-Hodgkin lymphoma, leukemia, and liver cancer. We used qualitative methodology. The results show that this moment can be perceived as sacred. It has been shown that the dignity of this moment is essential for the parents, as also the need to be with the child in the situation of dying, of the death itself, and also in the hours following death. There is present pain, fear, mutual closeness and peace of mind, and a friendly and respectful attitude of the staff. [ABSTRACT FROM AUTHOR]

Key Clinical Message: Testicular epidermoid cysts have characteristic findings. Testicular tumor markers are negative in patients with epidermoid cysts. Clear margins and sole and small testicular tumors (20 mm or less) suggest the possibility of epidermoid cyst. Testicular‐sparing surgery with intraoperative frozen section examination should be performed when suspecting epidermoid cysts. Testicular epidermoid cysts are rare tumors that account for 1% of all testicular tumors and are often clinically misdiagnosed as malignant lesions. We report three cases of epidermoid cysts. The chief manifestations were scrotal induration in two patients and pruritus scrotum in one. The median age of the patients was 23 years (18–30). All tumors were determined to be sole lesions (<20 mm in diameter). Testing for tumor markers in all patients revealed negative results. We could not rule out malignancy; hence, we performed high inguinal orchiectomy in all cases. Histologically, the inner walls of the cysts were lined with stratified squamous epithelium; their contents were keratinized. All patients were diagnosed with epidermoid cysts. [ABSTRACT FROM AUTHOR]

Background: A 26-year old male testicular cancer survivor presented for Chiropractic care with a primary complaint of intermittent thigh pain. Intervention: The patient underwent a course of subluxation-based Chiropractic care during which he was checked and adjusted using Advanced Bio-Structural Correction Technique. Outcome: Despite a singular presenting concern of intermittent thigh pain from an four-year-old injury, he returned numerous other positive outcomes he attributed to Chiropractic. This presents numerous questions as to the body's state of adaptability even years after cancer, and the role Chiropractic may play in building up this adaptability again over time. [ABSTRACT FROM AUTHOR]

Adult-type Granulosa cell tumor of the testis is a rare subtype of sex cord-stromal tumors, with fewer than 100 cases reported. The typical clinical presentation is an asymptomatic, painless testicular mass. We report a case of a 16-year-old male with adult-type testicular Granulosa cell tumor who presented with a palpable, painless right testicular mass, and subsequently underwent right inguinal radical orchiectomy. This report contributes to the growing body of literature regarding this rare diagnosis, furthering our understanding of clinical, imaging, and histological findings of its presentation. [ABSTRACT FROM AUTHOR]

Background: We report an unusual testicular mass with small bowel and retroperitoneal lymph node deposit proven to be myeloid sarcoma after complete histopathological and hematological workup. Myeloid sarcoma (MS) usually involves lymph nodes and head and neck regions. Uncommon sites like testis and ovary are rarely involved and pose a diagnostic challenge. Extramedullary myeloid sarcoma is most commonly associated with hematological malignancies like acute myeloid leukemia and myelodysplastic syndromes. It can precede or co-occur with AML. Considering it as a differential diagnosis in atypical presentation of testicular tumor helps in early treatment. Case presentation: We present a case of TMS with small bowel and retroperitoneal deposits presenting initially as intussusception and a vague scrotal pain. The patient underwent unilateral left radical inguinal orchidectomy. Surgical pathology revealed myeloid sarcoma of the testicle. And later jejunojejunostomy was done for small bowel deposit causing obstruction with retroperitoneal lymph node biopsy taken which revealed granulocytic sarcoma deposit. He developed peripheral blood involvement 4 weeks postoperatively, and bone marrow biopsy showed acute myeloid leukemia. Conclusions: With very short median survival period of 7.5 months, high index of suspicion is required where multifocal lesions are observed in various sites as in our case. [ABSTRACT FROM AUTHOR]

Objectives: To perform a retrospective cohort analysis for metastatic tumours in the testes to explore the timing, presentation and prognosis of this particular type of metastases and the factors that influence outcome. Patients and methods: A nationwide retrospective review of pathology reports of patients with pathologically confirmed metastases to the testis between 1991 and 2021 was performed. Data were collected from the Dutch nationwide pathology databank (PALGA) and the Netherlands Cancer Registry. Log‐rank testing and Kaplan–Meier analyses were used to assess overall survival (OS), and Cox proportional hazard models were used for multivariate survival analysis. Results: A total of 175 patients with a testicular metastasis were included. The median (range) age at diagnosis of testicular metastasis was 67 (3–88) years. Testicular metastases originated from a variety of primary tumours, although most frequently from the prostate (40.6%), kidney (13.7%), colon (10.3%), bladder (7.4%) and skin (5.7%). Synchronous testicular metastasis was detected in 53 cases, while 114 metachronous lesions were found after a median (interquartile range) interval of 22 (1–53) months after the original cancer diagnosis. OS after the diagnosis of a testicular metastasis was poor, with a median survival of 14.2 months (95% confidence interval 10.2–18.3). Primary tumour origin was an independent factor for survival, with worst survival for patients with primary skin, bladder and colon cancer. Conclusion: Testicular metastases are very uncommon and arise mainly from primary tumours anatomically close to the testes. Most patients develop metachronous testicular metastasis at an oligometastatic disease stage. These metastases are invariably associated with poor survival. [ABSTRACT FROM AUTHOR]

The article focuses on exploring genetic polymorphisms as potential contributors to severe postoperative pain. Topics include the use of pharmacogenetics in pain therapy to predict individual analgesic response, the impact of genetic variants on opioid metabolism, and the influence of genetic polymorphisms on the effectiveness of analgesics in specific patient populations, such as those with red hair.

Testicular mixed germ cell tumor is common in the post-pubertal age, less so in prepuberty. There are only 3 reports of prepubertal mixed teratoma and yolk sac tumor. Two of these cases had immature teratoma component and were in the neonatal age group. The third case in a toddler had a mature teratoma component. An 18-month-old boy presented with a testicular mass. Serum AFP was elevated (2200 ng/ml). The orchidectomy specimen contained a yolk-sac tumor and a small epidermoid cyst, indicating a mature teratomatous component. We report a testicular mixed teratoma and yolk sac tumor, prepubertal type along with summary of prior published cases. There is only one report describing this combination of mature teratoma with yolk sac tumor in the prepubertal testis. [ABSTRACT FROM AUTHOR]

INTRODUCTION: High-dose chemotherapy with autologous stem-cell transplantation (HDC-ASCT) is standard therapy for metastatic germ cell tumors (mGCTs) in patients whose disease progresses during or after conventional chemotherapy. We conducted a retrospective review of HDC-ASCT in relapsed mGCT patients in the province of Alberta, Canada, over the past two decades. METHODS: Patients with mGCTs who received HDC-ASCT at two provincial cancer referral centers from 2000-2018 were identified from institutional databases. Baseline clinical and treatment characteristics were collected, as well as overall survival (OS) and disease-free survival (DFS). Relevant prognostic variables were analyzed. RESULTS: Forty-three patients were identified. The median age was 28 years (range 19-56). A majority (95%) had non-seminoma histology and testis/retroperitoneal primary (84%). Twenty patients (47%) had poor-risk disease, as per The International Germ Cell Consensus Classification (IGCCC), at start of first-line chemotherapy. HDC-ASCT was used as secondline therapy in 65% of patients, and 58% of ASCT patients received tandem transplants. Median followup after ASCT was 22 months (range 2-181). At last followup, 42% of patients were alive without disease, including 3/7 (43%) of patients with primary mediastinal disease. Two-year and five-year DFS/OS ratios were 44%/65% and 38%/45%, respectively. Median OS and DFS for all patients were 30.0 months (13.3-46.6) and 8.0 months (0.9-15.1), respectively. CONCLUSIONS: We found that HDC-ASCT is an effective salvage therapy in mGCT, consistent with existing literature. Patients appeared to benefit regardless of primary site. Although limited by small sample size, we found a numerical difference in DFS and OS between second- and third-line HDC-ASCT and single vs. tandem ASCT. [ABSTRACT FROM AUTHOR]

A 23‐year‐old man with a history of a testicular germ cell tumor (GCT) that was incompletely treated, is presented with dyspnea. Significant bilateral pulmonary masses were seen on computed tomography (CT). A large, hypermobile mass in the left atrium (LA) as well as mitral valve dysfunction and moderate pulmonary hypertension was detected by transthoracic echocardiography (TTE). Urgent cardiac surgery was performed to prevent the tumor embolism in addition to restore mitral valve function and reduce pulmonary hypertension. Pathologic reports confirmed testicular GCT. GCT metastasis to the heart and lungs is an incredibly rare phenomenon. To our knowledge, this is the first case of simultaneous GCT metastasis to both lungs and LA. This article highlights the importance of cardiac examinations and imaging in germ cell tumor patients. If there is a functional complication for vital organs such as the heart or lungs, surgical interventions are given priority before starting chemotherapy. [ABSTRACT FROM AUTHOR]

We present a case of a 17‐year‐old male with a testicular tumour diagnosed after trauma. A 17‐year‐old male patient came to our clinic with swelling in the right hemiscrotum. The patient had a history of right scrotal blunt trauma 3 weeks before the admission and had no history of urological surgery or chronic disease. The patient doesn't use tobacco, alcohol, or illicit drugs. Genitourinary system examination revealed swelling and tenderness on palpation in the right hemiscrotum. The right testicle was not palpable. The left hemiscrotum was normal. The left testicle had a normal size and shape. Testicular tumour markers were high (AFP:196 μg/L (N: 0–8 μg/L), b‐HCG: 916 mIU/mL (N: <10 mIU/mL), LDH: 364 U/L (N: 0–265 U/L). Scrotal ultrasonography and magnetic resonance imaging revealed that there were areas of 9 × 9 × 11 cm in size of the right scrotal region without viable testis tissue, hematoma area, and areas compatible with necrosis. These findings were related to intratesticular rupture due to trauma. Abdominal tomography revealed lymphadenopathies of approximately 6 × 3 cm in the anterior paracaval area and approximately 4 × 3 cm in the anterior aspect of the psoas muscle. We performed right radical inguinal orchiectomy on the patient. Testicular tumour markers were still high on the 8th postoperative day (AFP:120 μg/L (N: 0–8 μg/L), bHCG: 680 mIU/mL (N: <10 mIU/mL), LDH: 200 U/L (N: 0–265 U/L)). The testicular tumour was diagnosed as mixed germ cell tumour (50% Yolk Sac, 30% Embryonal Carcinoma, 20% Teratoma). The tumour diameter was 9 cm, surgical margins were intact, there was rete testis invasion, and no tumour was detected in the tunica vaginalis. No tumour invasion was seen in the soft tissue around the spermatic cord (pT2). The patient received 3 cycles of chemotherapy with bleomycin, etoposide, and cisplatin. We suggest that patients presenting with scrotal trauma should be carefully evaluated for testicular malignancy, and if malignancy is suspected, radical inguinal orchiectomy should be preferred for the operation. [ABSTRACT FROM AUTHOR]

Testicular germ cell tumor (GCT) is the most common solid tumor in adolescent and young adult men. Progress in the management of GCT has been made in the last 50 years, with a substantial improvement in cure rates for advanced disease, from 25% in the 1970s to nearly 80%. However, relapsed or platinum-refractory disease occurs in a proportion, 20% of whom will die from disease progression. This article reviews the current evidence-based treatments for extracranial GCT, the acute and chronic toxic effects that may result, and highlights contemporary advances and progress in the field. [ABSTRACT FROM AUTHOR]

Oncofertility, an interdisciplinary field, aims at improving the quality of life of cancer patients prone to iatrogenic infertility by offering fertility preservation options for a potentially fertile future. Semen cryopreservation (SC) is a well-established and effective way of preserving fertility in adolescent and young adult cancer-diagnosed males as they face potential fertility loss due to cancer and its treatments. The pathophysiology of certain cancers, such as testicular cancer or Hodgkin's lymphoma, has been shown to have an adverse effect on semen quality. Ablative therapies like chemotherapy and radiotherapy can result in compromised sperm parameters depending on the dose and the type of the drug or radiation. Hence, it is recommended to encourage cancer-diagnosed males to store sperm prior to gonadotoxic therapy to restore potential fertility in the future. Despite the feasibility of SC, this option remains underutilised due to several limitations. [ABSTRACT FROM AUTHOR]

SOX9 is a key transcription factor for testis determination and development. Mutations in and around the SOX9 gene contribute to Differences/Disorders of Sex Development (DSD). However, a substantial proportion of DSD patients lack a definitive genetic diagnosis. SOX9 target genes are potentially DSD-causative genes, yet only a limited subset of these genes has been investigated during testis development. We hypothesize that SOX9 target genes play an integral role in testis development and could potentially be causative genes in DSD. In this study, we describe a novel testicular target gene of SOX9, Trpc3. Trpc3 exhibits high expression levels in the SOX9-expressing male Sertoli cells compared to female granulosa cells in mouse fetal gonads between embryonic day 11.5 (E11.5) and E13.5. In XY Sox9 knockout gonads, Trpc3 expression is markedly downregulated. Moreover, culture of E11.5 XY mouse gonads with TRPC3 inhibitor Pyr3 resulted in decreased germ cell numbers caused by reduced germ cell proliferation. Trpc3 is also expressed in endothelial cells and Pyr3-treated E11.5 XY mouse gonads showed a loss of the coelomic blood vessel due to increased apoptosis of endothelial cells. In the human testicular cell line NT2/D1, TRPC3 promotes cell proliferation and controls cell morphology, as observed by xCELLigence and HoloMonitor real-time analysis. In summary, our study suggests that SOX9 positively regulates Trpc3 in mouse testes and TRPC3 may mediate SOX9 function during Sertoli, germ and endothelial cell development. [ABSTRACT FROM AUTHOR]

The most critical step in the clinical diagnosis workflow is the pathological evaluation of each tumor sample. Deep learning is a powerful approach that is widely used to enhance diagnostic accuracy and streamline the diagnosis process. In our previous study using omics data, we identified 2 distinct subtypes of pure seminoma. Seminoma is the most common histological type of testicular germ cell tumors (TGCTs). Here we developed a deep learning decision making tool for the identification of seminoma subtypes using histopathological slides. We used all available slides for pure seminoma samples from The Cancer Genome Atlas (TCGA). The developed model showed an area under the ROC curve of 0.896. Our model not only confirms the presence of 2 distinct subtypes within pure seminoma but also unveils the presence of morphological differences between them that are imperceptible to the human eye. [ABSTRACT FROM AUTHOR]

Simple Summary: Sexuality remains an unspoken topic in the consulting room regarding testicular germ cell tumor (TGCT) patients in the adolescent and young adult (AYA) age. Little is known about the perspectives and concerns of these patients regarding sexuality. The PRICELESS-study explored these perspectives and concerns through individual interviews with 13 AYA patients treated for TGCT. Interviews revealed seven interacting and interconnected themes: desire to have children, rediscovering sexuality, insecurity about sexual performance, acceptance of physical change, loss of masculinity, burden on relationship, and openness in discussing sexuality. TGCT patients face multiple changes (physical, emotional, relational, and sexual), followed by a difficult period of acceptance, after which a new phase of rediscovering sexuality appears. Insights from this study can help healthcare professionals understand the underlying mechanisms and help to define topics for instrument development to support discussing sexuality. This study aimed to explore perspectives and concerns regarding sexuality among adolescents and young adults (AYAs) possibly experiencing late effects after testicular germ cell tumor (TGCT) treatment. A qualitative study was performed in which semi-structured interviews were held with thirteen AYAs from a center of expertise for TGCT in the Netherlands. Data were analyzed using Braun and Clark's thematic analysis method. Seven interacting and interconnected themes were found: desire to have children, rediscovering sexuality, insecurity about sexual performance, acceptance of physical change, loss of masculinity, burden on relationship, and openness in discussing sexuality. Concerns about the desire to have children seem to play a significant role. In conclusion, TGCT patients face multiple changes (physical, emotional, relational, and sexual), followed by a difficult period of acceptance, after which a new phase of rediscovering sexuality appeared. These findings can help to make healthcare professionals aware of the underlying mechanisms and concerns about sexuality. Furthermore, insights can help to develop sexuality-themed items for a broader monitoring tool to structurally assess the late effects to support discussing sexuality. [ABSTRACT FROM AUTHOR]

Testicular tumors are relatively rare in children and those in prepubertal children tend to present with different histological types and behaviors than their postpubertal counterparts. The majority of these pre- and peripubertal testicular tumors tend to be benign and those that are malignant, tend to present at low stages, not generally requiring systemic treatment. Here we present a rare case of a peri-pubertal, mixed nonseminomatous germ cell tumor of the testes which was found to be widely metastatic at presentation, classifying as poor risk disease. [ABSTRACT FROM AUTHOR]

Polyorchidism, the presence of more than two testes, usually presents as a painless scrotal mass or is diagnosed incidentally during the management of another condition.1 It is a rare congenital abnormality with approximately 200 reported cases in the literature. Most cases are found on the left side within the scrotum. We report a case of right-sided polyorchidism in a 9-year-old patient found incidentally during inguinal orchiopexy. As there is debate on the management of polyorchidism, a careful approach is required as the surgeon must decide between either scrotal fixation or the removal of the supernumerary testis. This case report will discuss the anatomical and clinical considerations when making this decision. [ABSTRACT FROM AUTHOR]

Patients with Down syndrome (DS) are at risk of multiorgan dysfunction; kidney and urological impairment are common. This is due to a likely increased risk of congenital kidney and urological malformations (odds ratio of 4.5 compared to the general population in one study), more frequent associated comorbidities at risk of kidney dysfunction (such as prematurity in 9–24% of children, intrauterine growth retardation or low birth weight in 20%, and congenital heart disease in 44%), and more frequent lower urinary tract dysfunction (reported in 27–77% of children with DS). If present, malformations and comorbidities at risk of kidney dysfunction warrant regular kidney monitoring in addition to their treatment. Serum creatinine in children with DS has been shown to be higher than in the general population and asymptomatic hyperuricemia is reported in 12–33% of children or young adults with DS. Moreover cryptorchidism and testicular cancer are also more common and should be detected by clinical examination. Thus, persons with DS at risk of presenting kidney and urological impairment should be identified by prenatal ultrasonography, comorbidities at risk of kidney sequelae considered, and during regular medical follow-up, clinically examined and questioned to diagnose testicular anomalies and lower urinary tract dysfunction. This is of importance as such kidney and urological impairments are associated with impaired quality of life and mental health, and risk of kidney failure. [ABSTRACT FROM AUTHOR]

The prognosis and optimal treatment approach for stage I mixed germ cell cancers of the testis are not well-established. This study aimed to assess contemporary treatment rates and their correlation with the cancer-specific mortality (CSM) and other-cause mortality (OCM) in patients with stage I testicular mixed germ cell tumors (TMGCT) who underwent orchiectomy, comparing surveillance with active treatment, including chemotherapy (CHT) and retroperitoneal lymph node dissection (RPLND). Retrospective analysis of clinical data from stage I TMGCT patients who underwent orchiectomy was conducted using the Surveillance, Epidemiology, and End Results database from 2004 to 2019. The annual percentage change (APC) in the use of surveillance, postoperative CHT, and RPLND was examined. Propensity score matching (PSM) and cumulative incidence, analyses were employed to compare differences in CSM and OCM between surveillance and active treatment, as well as between CHT and RPLND. Multivariate competing-risks regression models were utilized to investigate independent factors affecting CSM and OCM among stage I TMGCT patients. The study included 5743 individuals with stage I TMGCT that underwent surveillance (61.6%), CHT(27.2%), or RPLND (11.2%). Among them, 82 deaths were attributed to TMGCT, and 82 deaths resulted from other causes. Surveillance rates increased over time (APC: 0.635%, P = 0.008), as did CHT rates (APC: 0.863%, P < 0.001), while RPLND rates declined (APC: −0.96%, P < 0.001). After PSM, multivariate competing-risks regression analysis showed that, active treatment, compared to surveillance, was not an independent factor for CSM and OCM. In contrast, when compared to CHT, RPLND was an independent factor associated with lower CSM (hazard ratio = 0.247, 95% confidence interval: 0.08-0.761; P = 0.015), but not OCM (hazard ratio = 0.946, 95% confidence interval: 0.377-2.37; P = 0.91). Surveillance and CHT rates have increased over time for patients with stage I TMGCT following initial orchiectomy, while RPLND utilization has decreased. There was no significant difference in CSM between surveillance and active treatment groups, but RPLND demonstrated significantly lower CSM than CHT in active treatment. Our findings suggest that the usage of RPLND in patients with stage I TMGCT should be reconsidered. [ABSTRACT FROM AUTHOR]

Introduction: Testicular cancer is the most common cancer in men aged 15–44 years in many countries. Most men with testicular cancer present with a lump. Testicular symptoms are more likely to occur secondary to benign diseases like epididymo‐orchitis, a common sexually transmitted infection. Gender and sexual minorities are at an increased risk of testicular diseases and health disparities. The aim of this study was to co‐design an inclusive community‐based campaign to promote testicular awareness. Methods: This study uses the World Café methodology. Participation was sought from Lesbian, Gay, Bisexual, Transgender and Queer+ friendly organisations, testicular cancer survivors, health policy makers, media and marketing experts and graphic designers. Participants engaged in three rounds of conversations to co‐design the campaign. Data were collected using drawing sheets, artefact cards, sticky notes, coloured markers and a voice recorder. Deductive thematic analysis was conducted. Results: Seventeen individuals participated in the study. Six themes emerged from the analysis as follows: (i) online communication; (ii) offline communication; (iii) behavioural targeting and education; (iv) campaign frequency and reach; (v) demographic segmentation; and (vi) campaign identity. The use of social media for campaign delivery featured strongly in all conversations. Participants also recommended offline communication using posters and radio/television advertisements to scale up the campaign and achieve wider reach. Advertisements to overcome embarrassment surrounding testicular health were particularly recommended. Participants emphasised that campaign delivery must be dynamic whilst ensuring that the health‐promoting messages are not diluted or lost. They stressed the importance of being inclusive and tailoring the campaign to different age groups, gender identities and sexual orientations. Conclusions: Study recommendations will be used to design and deliver the campaign. Future research will be needed to evaluate the feasibility, acceptability, cost and effect of the campaign on promoting testicular awareness and early detection of testicular diseases. Patient or Public Contribution: A participatory research approach was used to co‐design the campaign with members of Lesbian, Gay, Bisexual, Transgender and Queer+ (LGBTQ+) friendly organisations, LGBTQ+ student bodies, LGBTQ+ staff networks, LGBTQ+ sports clubs, men's health organisations, testicular cancer survivors, health policy makers, media and marketing experts and graphic designers. [ABSTRACT FROM AUTHOR]

Testicular adrenal rest tumors (TART) are common in males suffering from congenital adrenal hyperplasia (CAH). Correct and timely diagnosis is important for differential diagnosis with malignant testis tumors, related infertility and as TART may worsen in time, especially in the absence of adequate and continuous hormonal control. The rarity of the disease, predominance of small cohorts and case reports and research heterogeneity (concerning type of CAH, patients' age and specific focus of the paper) complicate the understanding of this condition. To review epidemiological and clinical aspects of TART, including treatment and prognosis. Non-systematic review of CAH-related TART research. TART's prevalence grows progressively over time, predominating after puberty, affecting a mean of 20–40 % of CAH males. There is no proof of more frequent proportional affection of specific CAH phenotypes or types of enzyme deficiency, but cases of TART among non-classic CAH patients have been rarely reported. Chronic undertreated are more frequently affected and present larger tumors. Systematic ultrasound screening of CAH males is the state-of–the art for diagnosis, but TART are still often diagnosed in CAH adults seeking infertility treatment. TART are usually asymptomatic and present normal testicular volume. Biopsies are not recommended, except when the differential diagnosis between TART and testicular tumors cannot be guaranteed. Abnormal semen analysis is common. Leydig cell tumors are the main differential diagnosis, due to histological similarities to TART. Misdiagnosis may lead to unnecessary orchiectomies. Preservation of gonadal functions is inversely proportional to the total tumor volume. Tumors tend to regress under adequate adrenal suppression with steroids. Surgery in not indicated to treat TART. The reported prevalence of TART depends on age, usage of systematic follow-up ultrasound, and adequate CAH control. Timely detection of the disease is important to avoid irreversible gonadal dysfunction (not clinically apparent, due to high serum levels of androgen) and infertility. The relationship between TART and specific CAH phenotypes/genotypes has not been proved, and some cases do not present abnormal serum ACTH levels. Knowledge about TART should be disseminated among non-experts, to avoid unnecessary orchiectomies and false diagnosis of malignant testis tumors. Infertility is frequent, but has not been not satisfactorily addressed by physicians, even among experts. Sperm cryopreservation should be early offered to CAH adult males, but there are offer problems related to high cost. [Display omitted] [ABSTRACT FROM AUTHOR]

Nuclear protein of the testis (NUT) midline carcinoma (NMC) is a rare tumor, with particularly low incidence in the lungs, and a correspondingly poor prognosis. To determine the clinicopathological characteristics, outcomes, and prognostic factors of primary pulmonary NMC, a case was reported and a systematic review was performed. Twenty-nine records, including ours, involving 62 cases, were finally included. The median age at diagnosis was 29.5 years. At presentation, the most common symptoms at presentation were cough (47.50%) and chest/back pain (37.50%). In terms of diagnosis, 32.14% of NMC cases were identified through immunohistochemistry (IHC); However, a greater number of cases may be misdiagnosed initially, and ultimately, the diagnosis of NMC was confirmed through a combination of IHC and fluorescence in situ hybridization (FISH). Despite the clinical application of various chemotherapy-based treatments, the actual effectiveness remains unsatisfactory. Furthermore, Cox regression analysis of multiple factors identified male gender and concurrent presence of pleural effusion as indicators of shorter survival time in patients. These results emphasize the importance of increased diagnostic awareness among clinical and pathology practitioners concerning NMC. While there is currently no established standard for treating NMC, a treatment approach combining multiple methods shows promise for future research. Concurrently, clinical and foundational investigations addressing variables such as gender and the presence of pleural effusion may yield valuable insights into the diagnosis and treatment of NMC. [ABSTRACT FROM AUTHOR]

Simple Summary: One-fifth of patients with advanced testicular germ cell tumors (TGCTs) develop platinum-refractory disease. Recent advances in the use of immunotherapy in solid tumors might have a potential impact on the treatment of these patients. The aim of this review is to elucidate the immune contexture of TGCTs, describe various immunotherapeutic biomarkers, and summarize the most recent studies of immunotherapeutic agents targeting this malignancy. In general, due to the rarity of this disease entity, a deeper understanding of its molecular landscape, combined with carefully designed biomarker-driven clinical trials, is needed in order to obtain a clearer view of the efficacy of different immunotherapeutic strategies in these patients. Testicular germ cell tumors (TGCTs) are cancers with very good prognosis, even in the metastatic setting, with high curative potential mainly attributed to the introduction of cisplatin-based chemotherapy. However, approximately 15% of the patients develop platinum-refractory disease and suffer multiple relapses. Therefore, there is an unmet need for novel therapeutic agents with improved efficacy and minimal long-term side effects. Recent advances in the development of immunotherapeutic agents, particularly immune checkpoint inhibitors (ICIs), have offered an opportunity to test their activity in various tumor types, including GCTs. This review aims to analyze the immune microenvironment of these tumors and present the most recently available data from studies that have tested immunotherapeutic agents against GCTs. The majority of the available knowledge derives from case reports or small cohort studies, particularly those involving ICIs of the PD-1/PD-L1 axis alone or in combination with anti-CTLA-4 monoclonal antibodies. Other immunotherapeutic targeted approaches, including antibody-drug conjugates, antibody prodrugs, vaccines, tyrosine kinase inhibitors, chimeric antigen receptor (CAR) T-cell therapy, have biological rationales and have shown preliminary activity or are currently being tested. Growing evidence on these and other approaches will assist in broadening the currently limited treatment armamentarium against platinum-refractory TGCTs. [ABSTRACT FROM AUTHOR]

Mesotheliomas of the tunica vaginalis testis are rare malignant tumors that can present as a scrotal mass or hydrocele. These tumors are typically aggressive with high rates of recurrence and metastasis. Suspected risk factors for malignant mesothelioma include asbestos exposure, chronic inflammation, trauma, and persistent hydrocele. We report the case of a malignant epithelioid mesothelioma of the tunica vaginalis testis that presented as a finding at hydrocelectomy and was ultimately treated with radical inguinal orchiectomy. This patient was on chronic immunosuppression therapy with tacrolimus and mycophenolate mofetil secondary to a kidney transplant but had none of the common risk factors for mesothelioma formation. To our knowledge, this is the first case describing a possible connection between chronic immunosuppression and mesothelioma of the tunica vaginalis. However, future studies are needed to investigate this association and discern whether this could have played a role in our patient or if his mesothelioma formation was coincidental. [ABSTRACT FROM AUTHOR]

Testicular and scrotal abnormalities can occur in children, adolescents, and adults. The lesions, often accompanied by pain and swelling/enlargement of the scrotum, can cause anxiety in patients and their parents. Regardless of age, proper diagnosis is based on adequate anamnesis and physical examination. Color Doppler ultrasound is the first-line test in the differential process of testicular and scrotal diseases. Testicular and scrotal lesions require differentiation for benign and malignant processes as well as therapeutic management, including urgent surgical intervention. The aim of this paper is to present the most common causes of testicular and scrotal abnormalities in pediatric and adult patients and to outline the symptoms and diagnostic and therapeutic management. [ABSTRACT FROM AUTHOR]