Search Results (42)

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

Due to the complex anatomy of the pelvis, various tumors may arise in this region. Some of these tumors are well known and have distinctive features that allow them to be identified by magnetic resonance imaging (MRI). These include sacrococcygeal teratoma (SCT), the most prevalent congenital tumor in children, often diagnosed prenatally and most frequently occurring in this anatomical location, and ovarian teratoma, which in its mature form is the most common ovarian neoplasm in children and adolescents. Additionally, rhabdomyosarcoma (RMS), commonly found in the bladder in both genders and in the prostate in males, and Ewing sarcoma (ES), affecting the flat bones of the pelvis, are relatively common tumors. In this study, selected atypical pelvic tumors in children are presented. Most of them are tumors of the reproductive system, such as cervical cancer, small cell neuroendocrine carcinoma of the ovary, ES/primitive neuroectodermal tumor (PNET) of the ovary, diffuse large B-cell lymphoma (DLBCL) of the ovaries and ovarian Sertoli–Leydig cell tumor (SLCT) with RMS due to DICER1 syndrome. Additionally, tumors originating from the nervous system, including neuroblastoma (NBL) and plexiform neurofibroma (pNF), associated and not associated with neurofibromatosis type 1 (NF1), are discussed. Furthermore, Rosai–Dorfman disease involving the pelvic and inguinal lymph nodes is presented. By reviewing the literature and presenting our cases, we tried to find radiological features of individual tumors that would bring the radiologist closer to the correct diagnosis, ensuring the implementation of appropriate treatment. However, the MR images cannot be considered in isolation. Additional patient data, such as the clinical picture, comorbidities/syndromes, and laboratory test results, are necessary. Full article

Transferrin Receptor 2 (TfR2) is a homolog of Transferrin Receptor 1 (TfR1), involved in regulating intra and extracellular iron levels. Altered iron pathways have been associated with cancer onset and progression; however, their role in canine tumors remains poorly explored. This study investigated TfR2 immunohistochemical expression in non-neoplastic canine testis for the first time and in the most common types of canine testicular tumors: intratubular seminomas (ITSEMs), diffuse seminomas (DSEMs), Leydig cell tumors (LCTs), and Sertoli cell tumors (SCTs). Immunohistochemical analysis revealed a differential pattern of TfR2 expression according to tumor type, with high expression observed in ITSEMs and DSEMs, occasional expression in LCTs, and absence in SCTs. These results suggest that TfR2 may play a relevant role in canine seminoma development. Furthermore, the specific expression of TfR2 in seminomas highlights its potential as a therapeutic target, where its role in iron regulation and possible compensatory mechanisms warrant further investigation. Full article

This study aimed to describe the gross and histological features of multiple endocrine and non-endocrine neoplasia, including multiple PGLs found in two Boxer dogs. Additionally, the identified PGLs were immunohistochemically evaluated, and the subunits 2, 3, and 4 of the SDHD gene were screened for possible mutations. The tumors identified include aortic and carotid body PGLs, thyroid follicular-compact carcinoma, and subcutaneous lipomas. One case also had a Leydig cell tumor and adrenal cortex hyperplasia, while the other had H-type pancreatic carcinoma. Three out of 4 PGLs appeared benign, but one aortic body tumor showed malignant features with neoplastic emboli at its edge. Immunohistochemical analysis confirmed the neuroendocrine origin of all PGLs, with positive staining for Chromogranin A, NSE, and variable positivity for S100. No somatic mutations were found in exons 2, 3, and 4 of the SDHD gene in any of the evaluated PGLs. The absence of mutations in the evaluated SDHD gene subunits suggests the involvement of other genetic factors or pathways in the development of these tumors, warranting further investigation in this field. Full article

An ovarian Sertoli–Leydig cell tumor is a rare type of sex cord–stromal tumor of the ovary. Typically, it presents as abdominal pain or androgenic manifestations in women in the second to third decade of life. While cases of ovarian Sertoli–Leydig cell tumor associated with increased levels of alpha-fetoprotein are rare, they are reported to be the most common alpha-fetoprotein-producing ovarian non-germ cell tumor. We report the case of a 16-year-old patient, who presented with complaints of amenorrhea that had lasted for one year. Transabdominal ultrasound revealed the presence of a tumor in the right ovary, measuring 9.3 $\times$ 5.8 cm in size. The laboratory investigation showed an increased level of alpha-fetoprotein. The patient underwent laparoscopic right salpingo-oophorectomy. Histopathological examination confirmed the presence of a moderately differentiated (G2) Sertoli–Leydig cell tumor in the right ovary. For reproductive-age patients with disease confined to the ovary, fertility-sparing surgery is recommended. According to the current recommendations, the administration of adjuvant chemotherapy is indicated in cases of the presence of heterologous elements, poorly differentiated tumors, or FIGO stages IB–IV. As there were no high-risk factors and no residual disease in this case, there were no indications for further treatment with adjuvant chemotherapy. A recent follow-up visit showed that the patient is in complete remission. This report presents a detailed description of the findings, differential diagnosis, clinical course, chosen treatment, and prognosis. Also, a comprehensive literature review of ovarian Sertoli–Leydig cell tumors, focusing on their clinical presentation, laboratory findings, macroscopic and histopathological features, genetics, clinical management, prognostic factors and follow-up, is provided. Full article

Iron is a key element in spermatogenesis; its metabolic pathway in the testis is strictly regulated. Alterations in iron metabolism are linked to various diseases, including cancer, and changes in iron metabolism-related proteins have been observed in multiple human, mouse and canine tumors. There is limited knowledge about iron metabolism in canine non-neoplastic and neoplastic testes. This study aimed to explore the immunohistochemical expression of molecules involved in iron uptake and storage [Transferrin Receptor 1 (TfR1), ferritin (FTH1), nuclear receptor coactivator 4 (NCOA4)] and PCNA in canine non-neoplastic and neoplastic testicular samples. Non-neoplastic testes showed moderate TfR1 expression in developing germ cells and Sertoli cells, high NCOA4 cytoplasmic immunostaining in the Sertoli cells and occasional cytoplasmic immunopositivity for FTH1 in the spermatogonia and Sertoli cells. In contrast, Leydig cell tumors (LCTs) and Diffuse Type Seminoma (DSEM) exhibited increased expression of TfR1, along with higher PCNA expression, suggesting a higher iron need for proliferation. Intratubular Type Seminoma (ITSEM) showed a higher FTH1 expression, indicating greater iron storage, while the increased NCOA4 expression in the LCTs and DSEM suggested ferritinophagy to release iron for proliferation. Sertoli cell tumors (SCTs) showed only NCOA4 expression. These preliminary findings highlight potential molecular targets for developing new anti-neoplastic treatments in canine testicular tumors. Full article

Objective: The objective of this study was to prospectively assess the extent to which magnetic resonance imaging (MRI) can differentiate malignant from benign lesions of the testis. Materials and Methods: All included patients underwent multiparametric testicular MRI, including diffusion-weighted imaging (DWI) and subtraction dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI). Subsequently, all patients underwent a histopathological examination via orchiectomy or testicular biopsy/partial resection. The Kolmogorov–Smirnov test, t-test, Mann–Whitney U test, Fisher’s exact test, and logistic regression were applied for statistical analysis. Results: We included 48 male patients (median age 37.5 years [range 18–69]) with testicular tumors. The median tumor size on MRI was 2.0 cm for malignant tumors and 1.1 cm for benign tumors (p < 0.05). A statistically significant difference was observed for the type (type 0-III curve, p < 0.05) and pattern of enhancement (homogeneous, heterogeneous, or rim-like, p < 0.01) between malignant and benign tumors. The minimum apparent diffusion coefficient (ADC) value was 0.9 for benign tumors and 0.7 for malignant tumors (each ×10³ mm²/s, p < 0.05), while the mean ADC was 0.05. The mean ADC value was significantly lower for malignant tumors; the mean ADC value was 1.1 for benign tumors and 0.9 for malignant tumors (each ×10³ mm²/s, p < 0.05). The sensitivity, specificity, positive predictive value, and negative predictive value of multiparametric MRI for differentiating malignant from benign testicular lesions were 94.3%, 76.9%, 91.7%, and 83.3%, respectively. The surgical procedures performed included orchiectomy (n = 33; 71.7%) and partial testicular resection (n = 11; 23.9%). Histopathology (HP) revealed malignancy in 35 patients (72.9%), including 26 with seminomas and 9 with non-seminomatous germ cell tumors (NSGCTs). The HP was benign in 13 (27.1%) patients, including 5 with Leydig cell tumors. Conclusions: Malignant and benign tumors differ in MRI characteristics in terms of the type and pattern of enhancement and the extent of diffusion restriction, indicating that MRI can be an important imaging modality for the accurate diagnosis of testicular lesions. Full article

DICER1 syndrome, a rare autosomal dominant genetic disorder, stems from mutations in the DICER1 gene, disrupting RNA interference and leading to various tumors. These tumors, affecting organs like the lung, kidney, ovaries, and brain, pose diagnostic challenges due to diverse presentations. Understanding DICER1-associated tumors, including pleuropulmonary blastoma, ovarian Sertoli–Leydig cell tumors, and others, is vital for early detection and management. Surgical resection, chemotherapy, and targeted therapies are primary treatment modalities, with genetic counseling playing a crucial role. Multidisciplinary care is essential for optimal management, offering hope for improved outcomes in affected individuals. Full article

Background: DICER1, a cancer predisposition syndrome (CPS), seems to escape timely diagnosis in pediatric patients. Case report 1: A 16-year-old female patient was referred to the endocrinology ward due to a large goiter. Her medical history indicated normal sexual maturation, with menarche occurring at 13.5 years. Over the past 2.5 years, she had developed pronounced androgenic symptoms, including a deepened male voice; facial, back, and neckline acne; hirsutism; and menstrual irregularities leading to secondary amenorrhea. A thyroid ultrasound identified a multinodular goiter (MNG) with cystic–solid lesions containing calcifications. An abdominal ultrasound identified a 5.7 × 6.9 cm solid mass in the right adnexal region, displacing the uterus to the left. Histopathological examination confirmed a Sertoli–Leydig cell tumor. The patient was subjected to a total thyroidectomy. Histopathology revealed benign follicular cell-derived neoplasms. Thyroid follicular nodular disease (TFND) was diagnosed bilaterally. DNA analysis using NGS, confirmed via the Sanger method, revealed a pathogenic heterozygotic variant c.2953C>T [p.Gln985*] in exon 18 of the DICER1 gene. Case report 2: A 12-year-old male patient was admitted to the pediatric surgery unit due to a 33 mL goiter. A month prior to his admission, the patient discovered a palpable nodule in his neck, accompanied by hoarseness. An ultrasound revealed MNG. Molecular analysis revealed a pathogenic heterozygotic variant c.2782C>T [p.Gln928*] in exon 17 of the DICER1 gene. Subsequently, a total thyroidectomy was performed, and histopathological examination revealed TFND bilaterally. Conclusions: Recent advances in genetic evaluation and in histological approaches indicate that MNG/TFND, although rare in the pediatric population, when accompanied by characteristic ultrasound and histopathological features, and by additional features such as androgenization, may warrant assessment also of the DICER1 gene within CPS molecular panel screening. Full article

Androgen insensitivity syndrome (AIS) is a rare Mendelian disorder caused by mutations of the androgen receptor (AR) gene on the long arm of the X chromosome. As a result of the mutation, the receptor becomes resistant to androgens, and hence, karyotypically male patients (46,XY) carry a female phenotype. Their cryptorchid gonads are prone to the development of several types of tumors (germ cell, sex cord stromal, and others). Here, we report a 15-year-old female-looking patient with primary amenorrhea who underwent laparoscopic gonadectomy. Histologically, the patient’s gonads showed Sertoli cell hamartomas (SCHs) and adenomas (SCAs) with areas of Sertoli–Leydig cell tumors (SLCTs) and a left-sided paratesticular leiomyoma. Rudimentary Fallopian tubes were also present. The patient’s karyotype was 46,XY without any evidence of aberrations. Molecular genetic analysis of the left gonad revealed two likely germline mutations—a pathogenic frameshift deletion in the AR gene (c.77delT) and a likely pathogenic missense variant in the RAC1 gene (p.A94V). Strikingly, no somatic mutations, fusions, or copy number variations were found. We also performed the first systematic literature review (PRISMA guidelines; screened databases: PubMed, Scopus, Web of Science; ended on 7 December 2023) of the reported cases of patients with AIS showing benign or malignant Sertoli cell lesions/tumors in their gonads (n = 225; age: 4–84, mean 32 years), including Sertoli cell hyperplasia (1%), Sertoli cell nodules (6%), SCHs (31%), SCAs (36%), Sertoli cell tumors (SCTs) (16%), and SLCTs (4%). The few cases (n = 14, 6%; six SCAs, four SCTs, two SLCTs, and two SCHs) with available follow-up (2–49, mean 17 months) showed no evidence of disease (13/14, 93%) or died of other causes (1/14, 7%) despite the histological diagnosis. Smooth muscle lesions/proliferations were identified in 19 (8%) cases (including clearly reported rudimentary uterine remnants, 3 cases; leiomyomas, 4 cases). Rudimentary Fallopian tube(s) were described in nine (4%) cases. Conclusion: AIS may be associated with sex cord/stromal tumors and, rarely, mesenchymal tumors such as leiomyomas. True malignant sex cord tumors can arise in these patients. Larger series with longer follow-ups are needed to estimate the exact prognostic relevance of tumor histology in AIS. Full article