Search Results (51)

Testicular germ cell tumors (TGCTs) are the most common solid malignancy in young men and are highly curable, making reproductive and endocrine survivorship central concerns. Gonadal dysfunction is often attributed to orchiectomy and gonadotoxic therapy, yet semen and hormonal abnormalities may already be present at diagnosis. This narrative review synthesizes evidence obtained before orchiectomy and, where explicitly identified, broader pretreatment or pre-gonadotoxic evidence. Pre-orchiectomy studies generally report reduced sperm concentration, total sperm count, and progressive motility, together with impaired Sertoli and Leydig cell function. Tumor-derived human chorionic gonadotropin (hCG) can mask reduced Leydig reserve; in hCG-negative men, research-derived testosterone-to-luteinizing hormone and calculated free testosterone-to-luteinizing hormone ratios may aid risk stratification but lack standardized diagnostic cutoffs. Proposed contributors include testicular dysgenesis, contralateral impairment, germ cell neoplasia in situ, local tumor effects, and oxidative or proteomic alterations, although evidential support varies. These findings support fertility counseling at diagnosis, sperm cryopreservation before orchiectomy when feasible without delaying treatment, selected use of onco-microTESE when no usable ejaculate is available, and hCG-aware endocrine follow-up. Full article

Equine testicular disorders represent a diverse group of conditions that impact the longevity of a stallion’s breeding career. Stud farm veterinarians should be familiar with the variety of clinical presentations and diagnostic options for these conditions. This retrospective case series reports 57 cases of testicular abnormalities in stallions and donkeys presented to the clinic for further diagnostics and treatment. These disorders included neoplasia (three unilateral and one bilateral seminoma; two Sertoli cell tumors; two Leydig cell tumors; and one malignant mixed sex cord–stromal tumor), six cases of testicular hypoplasia and disorders of sexual development (DSDs), twenty-four cases of cryptorchidism with compensatory hypertrophy/hyperplasia, and two cases of monorchidism. Among the monorchid horses, one of these involved an abdominal retained testicle with a concurrent Leydig cell tumor, whereas the second presented a normally scrotal testis. Additional diagnoses consisted of testicular degeneration, including suspected anabolic steroid-induced hypogonadism, spermatic cord torsion, hydroceles, periorchitis, scrotal sarcoid associated with severe testicular degeneration, parasitic orchitis and periorchitis associated with Strongylus vulgaris and Setaria equina, one infectious epididymitis with orchitis in a donkey, and one case of ectopic adrenal cortical tissue within the testicular parenchyma. Rarely observed disorders included cystic ectasia of the rete testis in a cryptorchid testis and ischemic necrosis following failed laparoscopic castration without orchidectomy. This case series reviews the pathophysiology, clinical presentation, diagnostic techniques, and outcomes of various testicular diseases, providing a guide to facilitate case management in private practice. Additionally, it offers histopathologic descriptions of most cases, which are often missing from routine diagnostics but are crucial for definitive diagnosis. These findings demonstrate that horse testicular diseases encompass a wide range of neoplastic, developmental, degenerative, infectious, and parasitic conditions that can coexist and often go unnoticed until they progress. Full article

Total RNA was isolated from sections of healthy testes and Leydig cell tumors of mixed-breed dogs using TMA Master II device. The RNA-seq libraries were sequenced on the Illumina platform. Following differential expression analysis, Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Gene Set Enrichment Analysis (GSEA) were applied with quality control obtained using FastQC and Trimmomatic. This analysis revealed 1500 transcripts, including 982 upregulated and 168 downregulated genes. The results demonstrated that a significant proportion of these differentially expressed genes are directly involved in the control of sex steroid production (CYP11A1, STAR, and 3β-HSD3B1) or tube formation, angiogenesis, and extracellular matrix remodeling in interstitial cells (ESM1, FGG, and VEGFA). Moreover, we identified the upregulation of transcripts responsible for neurotransmitter or neuroendocrine signaling (SLC6A4, GRIN2C, GABRB3) and cholesterol metabolism and its regulation (GPX3, MSMO1, DHCR24). These genes were strongly associated with the phosphatidylinositol-3-kinase (PI3K)-Protein Kinase B (Akt) cascade and extracellular matrix interactions, features shared with various malignancies. Alterations in estrogen and relaxin signaling appear to be distinctive, understudied mechanisms specific to canine Leydig cell tumors. Concurrently, downregulated genes (e.g., DMRTC2, SEMA3C, ALOX12) were linked with cell differentiation, signaling and immunoregulatory pathway suppression involved in tumorigenesis. A complex transcriptomic profile of canine Leydig cell tumors was developed, revealing a conserved oncogenic core shared in some aspects with human malignancies alongside unique species-specific alterations. Findings seem to be useful for identifying novel diagnostic biomarkers and targeted therapies in veterinary oncology, establishing canine reproductive tissues as a valuable comparative biomedical model for research in human. Full article

Metabolic dysfunction-associated steatotic liver disease (MASLD) and male hypogonadism (HG) are prevalent disorders that frequently coexist, suggesting a bidirectional “liver–testis axis” as a potential pathophysiological link. This review explores the mechanistic basis and clinical implications of this axis. Molecularly, metabolically stressed hepatocytes release an altered hepatokine signature—marked by reduced sex hormone-binding globulin (SHBG) and elevated fibroblast growth factor 21 (FGF21)—along with pro-inflammatory cytokines (e.g., interleukin-1 beta (IL-1β), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α)), which enter the systemic circulation. These factors may contribute to the impairment of Leydig cell steroidogenesis, the perturbation of blood–testis barrier integrity, and the disruption of spermatogenesis. Conversely, testicular dysfunction and subsequent testosterone deficiency promote visceral adiposity, worsen insulin resistance and amplify chronic inflammation, thereby accelerating hepatic steatosis and fibrosis. Clinically, these molecular interactions manifest as mutually worsening of MASLD and HG. Thus, the liver–testis axis establishes a framework that reveals the bidirectional crosstalk between hepatic metabolism and gonadal function, providing novel pathophysiological insights into these interconnected conditions. Full article

Hypospadias is a congenital malformation of the male external genitalia resulting from incomplete fusion of the urethral folds during embryonic development. The perineal form represents the most severe phenotype and is frequently associated with abnormalities such as cryptorchidism and penile hypoplasia. Although surgical correction is generally recommended in young dogs, the long-term clinical course of severe hypospadias under conservative management remains poorly documented. In this study, we describe an unusual canine case of severe perineal hypospadias that survived to geriatric age under conservative management and subsequently developed bilateral testicular tumors arising from cryptorchid testes. Despite recurrent urinary tract infections during early life, the patient maintained an acceptable quality of life with long-term supportive care, providing a rare clinical example of extended survival without surgical correction. Because no molecular material was available from the patient, publicly available mouse transcriptomic datasets related to genital tubercle development and Leydig cell differentiation were consulted only as contextual reference. These datasets illustrate established developmental regulators and steroidogenic pathways relevant to genital formation and testicular function but do not represent direct molecular findings from the reported case. This report primarily highlights the clinical course and management of severe hypospadias in a dog, while using existing transcriptomic knowledge solely to provide biological context. The findings should therefore be interpreted as descriptive and hypothesis-generating rather than as evidence of a direct mechanistic link between developmental abnormalities and endocrine tumorigenesis. Full article

Testicular tumors are the most common neoplasms of the canine male reproductive tract, corresponding to approximately 25% of all tumors in intact males. A large percentage of cases are characterized by one of three main tumor types: seminomas, interstitial Leydig cell tumors, or Sertoli cell tumors. Clinical importance is primarily associated with endocrine activity rather than malignant behavior; orchiectomy is the treatment of choice for most canine testicular cancers. Endocrine activity, particularly estrogen secretion, may result in feminization syndrome and, in severe cases, bone marrow suppression. The diagnostic approach combines physical examination, ultrasonography with hormonal assessment using endocrine testing (testosterone, estradiol, and T:E ratio), and/or tissue level evidence of the estrogen effect (preputial cytology). Management is centered on orchiectomy; unilateral surgery may be considered when the contralateral testis is clinically and ultrasonographically normal and when preservation of reproductive capacity or working ability is still a priority. Dogs with hormonally active tumors benefit from postoperative hematologic and endocrine monitoring. Recent advances in immunohistochemistry (IHC), such as Ki-67 and inhibin-α markers, and imaging techniques are improving tumor characterization and individualized clinical decision making. Full article

Uterus masculinus is a rare disorder of sexual development in males, characterized by the presence of tubular female genitalia. Diagnostic imaging reports of infected uterus masculinus are limited. We describe the ultrasonographic and computed tomographic findings in three dogs, all presenting with abdominal distension, pain, and systemic infection. Imaging consistently revealed a fluid-filled, bicornuate structure arising from the prostate. In two dogs, the horns extended through the inguinal rings to the scrotal testes; in the third, with a prior left orchiectomy, both horns were intra-abdominal, the right ending in a peritoneal mass. Surgery and histopathology confirmed infected uterus masculinus, with Escherichia coli isolated from urine in all dogs and from the structure in two. Two dogs had Leydig cell tumors, one with concurrent uterine neoplasia; the third had an ovarian or ovotesticular granulosa cell tumor. Although rare, infected uterus masculinus is potentially life-threatening and should be considered in male dogs with abdominal pain, distension, or systemic infection. This is the first case series describing combined ultrasonographic and tomographic features of infected uterus masculinus, including novel findings such as cervix-like mural narrowing and fluid–fluid levels. It is also the first imaging description of an ovarian or ovotesticular tumor in a dog with uterus masculinus. Full article

Testicular tumors are, after skin tumors, the most common neoplasms in male dogs. Among all animals, these tumors occur most frequently within dogs. The etiology remains unclear, although the ectopic (non-scrotal) positioning of the testicles has an influence on tumor development. The most common types of testicular tumors include seminomas, Sertoli cell tumors, and interstitial (Leydig) cell tumors. The aim of this study was a retrospective evaluation of preserved material. A total of 326 cases of testicular tumors in dogs, diagnosed between 2017 and 2024, were analyzed. A histological analysis of multiple unilateral testicular tumors was conducted, and the frequency of occurrence was determined. 27 instances (8.28%) of multiple tumors within the same testicle were identified. The most recurrent combination was seminoma and interstitial cell tumors—12 cases (44.44%), followed by Sertoli cell and Leydig cell tumors—6 cases (22.22%), and seminoma and Sertoli cell tumors—6 cases (22.22%). In three cases, the presence of three tumors within a single testicle was observed (11.11%). In one case, double tumors were found within both testicles. It was observed that malignant features, as in cases of single testicular tumors, are rare. Full article

Background and Objectives: NR5A1-related 46,XY differences of sex development (DSD) represent a heterogeneous group of conditions characterized by variable degrees of undervirilization, gonadal dysgenesis, and endocrine dysfunction. Mutations in the NR5A1 gene affect critical pathways of gonadal development and steroidogenesis, leading to complex diagnostic and management challenges. This narrative review aims to summarize the clinical spectrum, diagnostic algorithms, surgical management, and outcome data of pediatric NR5A1-related 46,XY DSD. Materials and Methods: A comprehensive search of PubMed, Scopus, and Web of Science databases was conducted, using terms related to NR5A1 mutations, ambiguous genitalia, gonadal dysgenesis, tumor risk, and surgical management. A total of 26 studies were initially identified, of which 16 met the inclusion criteria for pediatric patients (≤18 years) with confirmed 46,XY karyotype, NR5A1 mutation, and available clinical or surgical data. Results: NR5A1 mutations are associated with phenotypes ranging from complete female external genitalia to apparently normal males with later infertility. While Sertoli cell function during fetal life is often preserved, Leydig cell dysfunction leads to incomplete masculinization. Spontaneous virilization during puberty has been reported. Management of gonadal dysgenesis remains controversial: while streak-like intra-abdominal gonads carry high germ cell tumor risk, warranting early gonadectomy, well-formed testes may be preserved under strict surveillance. Conclusions: NR5A1-related 46,XY DSD requires individualized, multidisciplinary management integrating genetic, endocrine, surgical, and psychosocial expertise. Gonadectomy decisions should be risk-stratified and, when possible, delayed to allow patients to participate in decision-making. Early psychological support and lifelong follow-up are essential to optimize physical and psychosocial outcomes. Full article

DICER1 syndrome is a hereditary cancer predisposition syndrome, characterized by a large range of benign and malignant neoplasms. Patients with DICER1 syndrome have a broad phenotype, with pleuropulmonary blastoma, Sertoli–Leydig cell tumor, cystic nephroma, cervical embryonal rhabdomyosarcoma, cystic lung lesions, and thyroid follicular nodular disease being the most prevalent manifestations. The syndrome is caused by loss-of-function germline variants in the DICER1 gene, and DICER1-related tumors are characterized by second somatic hotspot variants in the RNase IIIb domain of DICER1. DICER1 encodes an endoribonuclease, which is important for RNA interference. This review describes the molecular mechanism of DICER1 function and the pathogenetic mechanisms of tumorigenesis. The purpose of this review is to describe the pathogenesis, genotype–phenotype correlation and tissue specificity of DICER1 syndrome. We conclude that there is a lack of knowledge about the exact molecular mechanisms of DICER1 function and more research is needed to determine the exact role of this altered protein in relation to pathogenesis. Full article

Mycosis is caused by, among other factors, filamentous fungi, ubiquitous molds belonging to Aspergillus spp. which are often opportunistic pathogens. Over 100 species of Aspergillus have been described. The most common species responsible for diseases in humans and animals are Aspergillus fumigatus and Aspergillus niger, with Aspergillus flavus and Aspergillus clavatus being somewhat rarer. Aspergillus causes a range of diseases, from localized colonization and hypersensitivity reactions, through chronic necrotizing infections, to rapidly progressing angioinvasion and dissemination, leading to death. Testicular mycosis is extremely rarely described in both humans and animals. No studies in the literature report a simultaneous occurrence of testicular tumors and fungal infection of the organ, so the aim of this paper was to describe, for the first time, a case of two independent testicular tumors coexisting with testicular mycosis. A histopathological examination was performed on the left testicle of a male dog, specifically a mixed-breed dog resembling a husky weighing 22 kg and with an age of 8 years. Bilateral orchidectomy was performed for medical reasons due to the altered outline of the left testicle, leading to scrotal deformation. The dog did not show any clinical signs of illness, and the testicles were not painful. The right testicle, according to the operating veterinarian, showed no macroscopic changes, so histopathological verification was not performed. Microscopic imaging of the changes clearly indicated the coexistence of a tumor process involving Leydig cells (Leydigoma, interstitial cell tumor, ICT), Sertoli cells (Sertolioma), and fungal infection of the testis. The case suggests the possibility of the coexistence of tumor processes, which may have impaired local immune response of the tissue, with an infectious, in this case fungal, inflammatory process. Based on the literature, this paper is the first report on the occurrence of two independent histotype testicular tumors and their associated mycosis. Full article

(1) Background: Sertoli–Leydig cell tumors (SLCTs) are rare ovarian neoplasms that account for less than 0.5% of all ovarian tumors. They usually affect young women and often present with androgenic symptoms. We report a unique case of a 40-year-old woman diagnosed with both SLCT and clear cell papillary renal cell carcinoma (CCP-RCC), a rare tumor association with unclear pathogenesis. (2) Methods: Both tumors were treated surgically. The diagnostic workup included hormonal testing, imaging studies, and extensive genetic testing, including DICER1 mutation analysis and multiplex ligation-dependent probe amplification (MLPA), as well as the examination of a next-generation sequencing (NGS) panel covering ~280 cancer-related genes. (3) Results: Histopathologic examination confirmed a well-differentiated SLCT and CCP-RCC. No pathogenic variants in DICER1 were identified by WES or MLPA. No clinically relevant changes were found in the extended NGS panel either, so a known hereditary predisposition could be ruled out. The synchronous occurrence of both tumors without genomic alterations could indicate a sporadic event or as yet unidentified mechanisms. (4) Conclusions: This case highlights the importance of a multidisciplinary approach in the management of rare tumor compounds. The exclusion of DICER1 mutations and the absence of genetic findings adds new evidence to the limited literature and underscores the importance of long-term surveillance and further research into potential shared oncogenic pathways. Full article

DICER1 tumor predisposition syndrome is a genetic condition that increases the risk of developing certain cancer types. While thyroid tumors are the main tumors caused by this condition in adult oncology, children and adolescents with DICER1 germline mutations may suffer from a broader spectrum of tumors, including Sertoli-Leydig cell tumors, pleuropulmonary blastomas, embryonal rhabdomyosarcomas, and pineoblastomas. Although these diseases—many of which are hallmark tumors of DICER1 syndrome and rarely occur sporadically—have been known for several years, the more recent identification of DICER1 mutations in embryonal tumors with multilayered rosettes (ETMR) and DICER1-associated intra- and extracranial sarcomas has expanded the spectrum of tumor types potentially linked to DICER1 syndrome. This review sought to investigate the presence and characteristics of DICER1 mutations in rare CNS tumors and to discuss their potential implications for early recognition of DICER1-related syndromes. To address this, we conducted a comprehensive systematic literature review and analyzed data from our nationwide German database (CNS-InterREST) regarding these entities. When present, DICER1 mutation status, mutation type (somatic vs. germline), and localization within the gene were recorded. Demographic and clinical data—including age at diagnosis and tumor localization—were also evaluated where available. We found that the prevalence of DICER1 mutations in the cohort of ETMR patients included in the CNS-InterREST study was exceedingly low (1/31). The distribution of DICER1 mutations in patients with ETMR or intracranial sarcomas is comparable to that in other previously identified DICER1-mutant tumors. Our literature review demonstrates that within the 248 cases, which include three intracranial DICER1-mutated neoplasias and one reference group, most somatic mutations accumulate in the RNase IIIb domain, while germline mutations are usually evenly distributed throughout the gene. Overall, further research is necessary to unravel the cell-of-origin of the respective tumor types and whether other, hitherto undescribed, genetic factors may contribute to the development of ETMR and DICER1-associated intracranial sarcomas. Full article

Background and Clinical Significance: Paratubal Leydig cell nodules are rare incidental findings that present diagnostic challenges. Case Presentation: A 45-year-old female with a history of hypertension and diabetes mellitus presented with fever and chills following an episode of severe dysmenorrhea and menorrhagia. The patient reported heavy menstrual bleeding, persisting for 2–3 years. Physical examination revealed erythema of the perineum and whitish vaginal discharge, with no cervical lesions. Imaging revealed a 15 cm right ovarian cyst. Laboratory investigations showed elevated C-reactive protein (6.37 mg/L) and CA125 (88.82 U/mL) levels, whereas other tumor markers were within normal limits. A pelvic ultrasound revealed a retroverted uterus and a large ovarian mass suggestive of malignancy. The patient underwent a right salpingo-oophorectomy, during which a 15 cm ovarian tumor adherent to the right pelvic sidewall was excised. Histopathological examination revealed an endometriotic cyst with endometrial glandular epithelium positive for estrogen receptor and focal mucinous metaplasia. CD10-positive endometrial stromal cells and paratubal cysts were also observed. Additionally, a small Leydig cell tumor originated from the ovarian hilum was identified and confirmed by positive staining for inhibin, calretinin, and androgen receptors, as well as negative estrogen receptor staining. The postoperative recovery was uneventful, and at the five-week follow-up, the patient’s hormonal levels were normal, and there were no complications. Conclusions: This case highlights the importance of thorough histopathological evaluation in managing ovarian masses and the potential coexistence of benign and rare pathological entities, such as Leydig cell tumors. Full article

DICER1 syndrome (DICERs) represents a tumor predisposition genetic syndrome, inherited in an autosomal dominant manner. Germline loss-of-function variants of the DICER1 gene lead to impaired processing of microRNA, gene expression, and increased risk of tumorigenesis. Although pleuropulmonary blastoma (PPB) is the hallmark of the syndrome, multiple extrapulmonary malignant and non-malignant conditions have also been described, including multinodular goiter (MNG) and sex-cord stromal tumors. MNG is one of the most common components and is associated with an increased risk of thyroid carcinoma. Sertoli–Leydig cell tumor (SLCT) represents the most prevalent type of sex-cord stromal tumor associated with the syndrome, whereas juvenile granulosa cell tumor (JGCT) is considered to be a very rare phenotype. They both may present with abdominal pain due to mass effect and menstrual irregularities in case of hormone production. Although they exhibit low rates of mortality, recurrence rates highly depend on the grade of malignancy. Herein, we report a novel pathogenic DICER1 variant associated with MNG, bilateral ovarian SLCT, and JGCT in a young Greek patient. Clinicians should be aware of a potential germline DICER1 variant when evaluating MNG in young patients, especially if it coexists with other neoplasms. Full article