A single-center retrospective long-term analysis of 80 cases of ovarian Sertoli-Leydig cell tumors.
Ontology highlight
ABSTRACT:
SUBMITTER: Yang N
PROVIDER: S-EPMC8509968 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:BackgroundSertoli-Leydig cell tumors (SLCTs) represent less than 0.5% of ovarian tumors. Because of the rarity of this tumor and its peak in frequency at around 25 years of age, this study aimed to describe SLCT management strategies.ObjectiveThe objective of this study was to determine the management (i.e., conservative surgery and adjuvant chemotherapy) of ovarian SLCTs.ResultsThis retrospective analysis included 23 patients treated for ovarian SLCTs. A centralized pathologic review of the tumors was conducted. Patients were referred to or treated in our institution for an ovarian SLCT between 1994 and 2015. The median age at diagnosis was 33 years (range, 4-82 years). According to the 2014 Federation of Gynecology and Obstetrics classification, tumors were classified as stage Ia (n = 15: well differentiated, n = 1; of intermediate differentiation, n = 8; undifferentiated, n = 4; and undefined, n = 2), stage Ib (n = 1), stage Ic1 (n = 5), stage IIb (n = 1), and stage IIIc (n = 1). Surgery was conservative in 13 patients (Ia, n = 7; Ib, n = 1; Ic1, n = 5) and radical in 10 patients (Ia, n = 8; IIb, n = 1; IIIc, n = 1). Seven patients received adjuvant chemotherapy with a cisplatin-based regimen (Ia, n = 2; Ic1, n = 3; IIb, n = 1) or docetaxel + gemcitabine (IIIc, n = 1). Median follow-up was 61 months (range, 15-252 months). Eight patients experienced a relapse (Ia, n = 2; Ib, n = 1; Ic1, n = 3; IIb, n = 1; IIIc, n = 1). Of these, six had at least one peritoneal carcinomatosis, and four died (Ic1, n = 2; IIb, n = 1; and Ia, n = 1). Two patients had a local relapse (one uterus and one ovary) and survived without disease after relapse treatment. The median time between the initial treatment and relapse was 28 months (range 9-70).ConclusionConservative surgery was safe for patients with stage Ia ovarian SLCTs. The place of conservative surgery for stage Ic1 remains to be defined. The best chemotherapy regimen remains to be defined.Implications for practiceFor stage Ia disease, conservative surgery (in women of reproductive age) was safe and effective for treating ovarian Seroli-Leydig cell tumors. Adjuvant chemotherapy should be proposed for stage Ia when poor prognostic factors are present (poor differentiation, retiform pattern, or heterologous elements). For stage Ic1 and more severe stages, radical surgery and adjuvant chemotherapy should be considered. The combination of bleomycin, etoposide, and cisplatin was the most frequently used regimen, but the best chemotherapy regimen remains to be defined.
| S-EPMC6516129 | biostudies-literature
Project description:CONTEXT:Nontoxic multinodular goiter (MNG) is frequently observed in the general population, but little is known about the underlying genetic susceptibility to this disease. Familial cases of MNG have been reported, and published reports describe 5 families that also contain at least 1 individual with a Sertoli-Leydig cell tumor of the ovary (SLCT). Germline mutations in DICER1, a gene that codes for an RNase III endoribonuclease, have been identified in families affected by pleuropulmonary blastoma (PPB), some of whom include cases of MNG and gonadal tumors such as SLCTs. OBJECTIVE:To determine whether familial MNG with or without SLCT in the absence of PPB was associated with mutations in DICER1. DESIGN, SETTING, AND PATIENTS:From September 2009 to September 2010, we screened 53 individuals from 2 MNG and 3 MNG/SLCT families at McGill University for mutations in DICER1. We investigated blood lymphocytes and MNG and SLCT tissue from family members for loss of the wild-type DICER1 allele (loss of heterozygosity), DICER1 expression, and microRNA (miRNA) dysregulation. MAIN OUTCOME MEASURE:Detection of germline DICER1 gene mutations in familial MNG with and without SLCT. RESULTS:We identified and characterized germline DICER1 mutations in 37 individuals from 5 families. Two mutations were predicted to be protein truncating, 2 resulted in in-frame deletions, and 1 was a missense mutation. Molecular analysis of the 3 SLCTs showed no loss of heterozygosity of DICER1, and immunohistochemical analysis in 2 samples showed strong expression of DICER1 in Sertoli cells but weak staining of Leydig cells. miRNA profiling of RNA from lymphoblastoid cell lines from both affected and unaffected members of the familial MNG cases revealed miRNA perturbations in DICER1 mutation carriers. CONCLUSIONS:DICER1 mutations are associated with both familial MNG and MNG with SLCT, independent of PPB. These germline DICER1 mutations are associated with dysregulation of miRNA expression patterns.
| S-EPMC3406486 | biostudies-literature
Project description:Analysis of the global gene expression in ovarian Sertoli-Leydig cell tumor samples with or without DICER1 RNase IIIb domain mutation
2015-10-01 | GSE71160 | GEO
Project description:Introduction Because of limited information of Sertoli–Leydig cell tumors (SLCTs), the objective aimed to describe clinical parameters, management and treatment results of SLCTs. Material and methods We retrospectively reviewed 15 cases with SLCTs, who were treated in the Affiliated Hospital of Qingdao University between 2009 and 2020. Data of clinical parameters and treatment was studied. Results The age ranged 25–69 years. Elevated testosterone was observed in 4 patients. FIGO-stage: 14 were at Ia(10 moderately differentiated, 3 poorly differentiated, 5 retiform pattern).1 was at Ic. Patients with retiform pattern were more likely to exhibit endocrine function (p = 0.019, w = 0.61) and tumor diameter was significantly bigger in no endocrine function (p = 0.012, d = 1.52). All patients received surgical treatment. 8 received postoperative chemotherapy. The median follow-up was 66 months (20–112 months). 1 patient relapsed within 36 months and received cytoreductive surgery. She survived without disease after recurrence treatment. Of 5 patients who performed fertility sparing surgeries with the desire of childbirth, 3 had full-term pregnancy and 1 experienced a miscarriage. Another one has not tried to conceive. Conclusion The prognosis of SLCTs is good. Our data showed patients with retiform pattern were more likely to exhibit endocrine function. The diameter of tumor was significantly bigger in no endocrine function. Conservative surgery is the preferred option for patients with the desire of fertility at stage Ia. Postoperative chemotherapy is advised to cases with high-risk factors, but the most effective chemotherapy regimen is still uncertain.
| S-EPMC8570032 | biostudies-literature
Project description:DICER1, an endoribonuclease required for microRNA (miRNA) biogenesis, is essential for embryogenesis and the development of many organs including ovaries. We have recently identified somatic hotspot mutations in RNase IIIb domain of DICER1 in half of ovarian Sertoli-Leydig cell tumors, a rare class of sex-cord stromal cell tumors in young women. These hotspot mutations lost IIIb cleavage activity of DICER1 in vitro and failed to produce 5p-derived miRNAs in mouse Dicer1-null ES cells. However, the oncogenic potential of these hotspot DICER1 mutations has not been studied. Here, we further revealed that the global expression of 5p-derived miRNAs was dramatically reduced in ovarian Sertoli-Leydig cell tumors carrying DICER1 hotspot mutations compared with those without DICER1 hotspot mutation. The miRNA production defect was associated with the deregulation of genes controlling cell proliferation and the cell fate. Using an immortalized human granulosa cell line, SVOG3e, we determined that the D1709N-DICER1 hotspot mutation failed to produce 5p-derived miRNAs, deregulated the expression of several genes that control gonadal differentiation and cell proliferation, and promoted cell growth. Re-expression of let-7 significantly inhibited the growth of D1709N-DICER1 SVOG3e cells, accompanied by the suppression of key regulators of cell cycle control and ovarian gonad differentiation. Taken together, our data revealed that DICER1 hotspot mutations cause systemic loss of 5p-miRNAs that can both drive pseudodifferentiation of testicular elements and cause oncogenic transformation in the ovary.
| S-EPMC4674484 | biostudies-other
Project description:Sertoli-Leydig Cell Tumors (SLCTs) are rare ovarian sex cord-stromal neoplasms, which predominantly affect adolescents and young female adults. The SLCTs clinical diagnosis and treatment remains challenging due to the rarity and the varied presentation. A large majority of SLCTs are unilateral, but also bilateral neoplasms have been reported, sometimes in the context of DICER1 syndrome. In fact, the most significant discovery regarding the molecular genetics basis of SLCTs was the finding of somatic and germline pathogenic variants in the DICER1 gene. The DICER1 protein is a key component of the micro-RNA processing pathway. Germline DICER1 pathogenic variants are typically inherited in an autosomal dominant pattern and are most often loss-of-function variants dispersed along the length of the gene. Contrarily, DICER1-related tumors harbor a characteristic missense "RNase IIIb hotspot" mutation occurring in trans, or, less frequently, loss of heterozygosity (LOH) event involving the wild-type allele. While DICER1 mutations have been identified in approximately 60% of SLCTs, especially in the moderately or poorly differentiated types, there are only a few case reports of ovarian SLCT with underlying germline DICER1 mutations. In this review, we focus on the molecular genetic features of SLCT, performing an extensive survey of all germline pathogenic variants modifying the whole sequence of the DICER1 gene. We point out that DICER1 genetic testing, coupled with an accurate variants classification and timely counseling, is of crucial importance in the clinical management of ovarian SLCT-affected patients.
| S-EPMC8123016 | biostudies-literature
Project description:BackgroundSpinal fibroblastic and myofibroblastic tumors (FMTs) are extremely rare. Few studies have reported on the features and outcomes of this condition that affects the axial skeleton. We explored the clinical characteristics and factors affecting the prognosis of spinal FMTs.MethodsWe retroactively assessed the survival of 51 patients with spinal FMTs who underwent surgical and adjuvant treatments in our center between April 2006 and September 2018. Factors affecting disease-free survival (DFS) and overall survival (OS) were analyzed using the Kaplan-Meier method. Variables with p value ≤ 0.05 were subjected to multivariate analysis using the Cox proportional hazards regression model. A two-sided P value < 0.05 was considered statistically significant.ResultsThe mean follow-up period was 50.8 ± 35.6 months (Range 4.2-172.6). Kaplan-Meier survival curves showed that the 5-year DFS was 10% (95% CI [31.09-42.56]) and the 5-year OS was 53% (95% CI [61.28-97.20]). Multivariate analysis showed that en bloc excision was associated with better DFS (HR 0.214, 0.011) and OS (HR 0.273, 0.043), radiotherapy negatively affected OS (HR 0.353, 0.033), and the recurrence and Ki-67 index <5% significantly affected DFS (HR 3.008, 0.008 and 2.754, 0.029).ConclusionsSpinal FMTs are rare. Surgery is the treatment of choice and en bloc excision is strongly recommended to improve outcomes. Disease recurrence and the Ki-67 marker are correlated with the progression of these tumors.
| S-EPMC7749654 | biostudies-literature
Project description:BackgroundLong-term effects of assisted reproductive technology (ART) on ovarian tumor risk are unknown.MethodsThis nationwide cohort study comprises 30 625 women who received ovarian stimulation for ART in 1983-2000 and 9988 subfertile women not treated with ART. Incident invasive and borderline ovarian tumors were ascertained through linkage with the Netherlands Cancer Registry and the Dutch Pathology Registry until July 2018. Ovarian tumor risk in ART-treated women was compared with risks in the general population and the subfertile non-ART group. Statistical tests were 2-sided.ResultsAfter a median follow-up of 24 years, 158 invasive and 100 borderline ovarian tumors were observed. Ovarian cancer risk in the ART group was increased compared with the general population (standardized incidence ratio [SIR] = 1.43, 95% confidence interval [CI] = 1.18 to 1.71) but not when compared with the non-ART group (age- and parity-adjusted hazard ratio [HR] = 1.02, 95% CI = 0.70 to 1.50). Risk decreased with higher parity and with a larger number of successful ART cycles (resulting in childbirth, Ptrend = .001) but was not associated with the number of unsuccessful ART cycles. Borderline ovarian tumor risk was increased in ART-treated women compared with the general population (SIR = 2.20, 95% CI = 1.66 to 2.86) and with non-ART women (HR = 1.84, 95% CI = 1.08 to 3.14). Risk did not increase with more ART cycles or longer follow-up time.ConclusionsIncreased ovarian cancer risk in ART-treated women compared with the general population is likely explained by nulliparity rather than ART treatment. The increased risk of borderline ovarian tumors after ART must be interpreted with caution because no dose-response relationship was observed.
| S-EPMC8168156 | biostudies-literature
Project description:Sertoli cells are somatic cells in testis essential for spermatogenesis, that support the development, maturation, and differentiation of germ cells. Sertoli cells are metabolically highly active and physiologically regulated by external signals, particularly factors in the blood stream. In disease conditions, circulating pathological signals may affect Sertoli cells and consequentially, alter germ cells and fertility. While the effects of stress on reproductive cells have been well studied, how Sertoli cells respond to stress remains poorly characterized. We used a mouse model of early postnatal stress to assess the effects of stress on Sertoli cells. We developed an improved strategy based on intracellular stainings and obtained enriched preparations of Sertoli cells from exposed males. We show that adult Sertoli cells have impaired electron transport chain (ETC) pathways and that several components of ETC complexes particularly complex I, III, and IV are persistently affected. We identify serum as potential mediator of the effects of stress on Sertoli cells by showing that it can recapitulate ETC alterations in primary cells. These results highlight Sertoli cells as cellular targets of stress in early life that can keep a trace of exposure until adulthood.
| S-EPMC9638847 | biostudies-literature
Project description:Ependymoma is the third most common brain tumor in children, but there is a paucity of large studies with more than 10 years of follow-up examining the long-term survival and recurrence patterns of this disease. We conducted a retrospective chart review of 103 pediatric patients with WHO Grades II/III intracranial ependymoma, who were treated at Dana-Farber/Boston Children's Cancer and Blood Disorders Center and Chicago's Ann & Robert H. Lurie Children's Hospital between 1985 and 2008, and an additional 360 ependymoma patients identified from the Surveillance Epidemiology and End Results (SEER) database. For the institutional cohort, we evaluated clinical and histopathological prognostic factors of overall survival (OS) and progression-free survival (PFS) using the log-rank test, and univariate and multivariate Cox proportional-hazards models. Overall survival rates were compared to those of the SEER cohort. Median follow-up time was 11 years. Ten-year OS and PFS were 50 ± 5% and 29 ± 5%, respectively. Findings were validated in the independent SEER cohort, with 10-year OS rates of 52 ± 3%. GTR and grade II pathology were associated with significantly improved OS. However, GTR was not curative for all children. Ten-year OS for patients treated with a GTR was 61 ± 7% and PFS was 36 ± 6%. Pathological examination confirmed most recurrent tumors to be ependymoma, and 74% occurred at the primary tumor site. Current treatment paradigms are not sufficient to provide long-term cure for children with ependymoma. Our findings highlight the urgent need to develop novel treatment approaches for this devastating disease.
| S-EPMC5658456 | biostudies-literature