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Background: Juvenile granulosa cell tumor (JGCT) of the ovary is a rare tumor with distinct clinicopathological and hormonal features primarily affecting young women and children. We conducted a complex clinicopathological, immunohistochemical, and molecular analysis of five cases of JGCT. Methods: The immunohistochemical examination was performed with 32 markers, including markers that have not been previously investigated. Moreover, DNA next-generation sequencing (NGS) and PTEN methylation analysis was performed. Result: We found the expression of calretinin, inhibin A, SF1, FOXL2, CD99, CKAE1/3, ER, PR, AR in all cases. WT1 was expressed in one case. Conversely, the expression of p16, OCT3/4, SALL4, GATA3, Napsin A, SATB2, MUC4, TTF1, and CAIX was completely negative. All tumors showed the wild-type pattern of p53 expression. Regarding predictive markers, all tumors were HER2 negative and did not express PD-L1. Mismatch repair proteins (MMR) showed no loss or restriction of expression, similarly to ARID1A, DPC4, BRG1, and INI1. The molecular analysis revealed AKT1 internal tandem duplication in two tumors. Two other cases exhibited mutations in TERT and EP400 and both developed recurrence. All AKT1-wild type tumors exhibited immunohistochemical loss of PTEN expression. However, no mutations, deletions (as assessed by CNV analysis), or promoter hypermethylation in the PTEN gene were detected. Conclusion: The results of our study further support the hypothesis that the pathogenesis of JGCT may be driven by activation of the PIK3/AKT/mTOR pathway. These findings could potentially have future therapeutic implications, as treatment strategies targeting the PTEN/mTOR pathways are currently under investigation. [ABSTRACT FROM AUTHOR]

Abstract Background Juvenile granulosa cell tumor (JGCT) of the ovary is a rare tumor with distinct clinicopathological and hormonal features primarily affecting young women and children. We conducted a complex clinicopathological, immunohistochemical, and molecular analysis of five cases of JGCT. Methods The immunohistochemical examination was performed with 32 markers, including markers that have not been previously investigated. Moreover, DNA next-generation sequencing (NGS) and PTEN methylation analysis was performed. Result We found the expression of calretinin, inhibin A, SF1, FOXL2, CD99, CKAE1/3, ER, PR, AR in all cases. WT1 was expressed in one case. Conversely, the expression of p16, OCT3/4, SALL4, GATA3, Napsin A, SATB2, MUC4, TTF1, and CAIX was completely negative. All tumors showed the wild-type pattern of p53 expression. Regarding predictive markers, all tumors were HER2 negative and did not express PD-L1. Mismatch repair proteins (MMR) showed no loss or restriction of expression, similarly to ARID1A, DPC4, BRG1, and INI1. The molecular analysis revealed AKT1 internal tandem duplication in two tumors. Two other cases exhibited mutations in TERT and EP400 and both developed recurrence. All AKT1-wild type tumors exhibited immunohistochemical loss of PTEN expression. However, no mutations, deletions (as assessed by CNV analysis), or promoter hypermethylation in the PTEN gene were detected. Conclusion The results of our study further support the hypothesis that the pathogenesis of JGCT may be driven by activation of the PIK3/AKT/mTOR pathway. These findings could potentially have future therapeutic implications, as treatment strategies targeting the PTEN/mTOR pathways are currently under investigation.

Abstract Background Stathmin, a cytosolic microtubule-destabilizing phosphoprotein involved in the regulation of mitosis, is widely expressed in various malignancies and acts as an adverse prognostic factor. Our research analyzed its immunohistochemical expression on a large cohort of ovarian sex cord-stromal tumors, evaluating its potential utility in differential diagnosis, prognosis, and therapeutic application. Methods We examined 390 cases of ovarian sex cord-stromal tumors including 281 adult granulosa cell tumors (AGCT), 5 juvenile granulosa cell tumors (JGCT), 33 Sertoli-Leydig cell tumors (SLCT), 50 fibromas/thecomas (F/T), 11 Leydig cell tumors/steroid cell tumors (LCT/SterCT), 5 sex-cord stromal tumors NOS (SCST-NOS), 3 Sertoli cell tumors (SCT), and 2 sclerosing stromal tumors (ScST). Immunohistochemical analysis was performed using TMAs. Results Strong expression (> 50%) was observed in all cases of AGCT, JGCT, SLCT, SCST-NOS, SCT and 1 ScST. The other case of ScST exhibited mild expression (5–10%). The negative cases included exclusively F/T and LCT/SterCT, with F/T showing 24% of negative cases and LCT/SterCT comprising 64% of negative cases. Conclusion The results of our study indicate that stathmin is neither a prognostic marker nor suitable for the differential diagnosis of challenging cases of ovarian sex cord-stromal tumors. However, its predictive value may be theoretically significant, as a decrease in stathmin expression potentialy influences response to chemotherapy treatment.

Testicular tumors are extremely rare, representing 1–1.5% of all neoplasms in men, and sex cord-stromal tumors account for about 5% of them. Histopathological diagnosis of such entities poses several challenges, mainly related to the fact that they can present in mixed forms and that immunohistochemical analyses can only be of partial help. We herein report a unique case of a collision sex cord-stromal tumor and discuss all the challenges faced in the diagnosis of such an entity. An accurate morphological examination of the entire lesion and a suitable immunohistochemical panel are essential for a correct diagnosis. [ABSTRACT FROM AUTHOR]

The current knowledge about the immunohistochemical features of adult granulosa cell tumor (AGCT) is mostly limited to the "traditional" immunohistochemical markers of sex cord differentiation, such as inhibin, calretinin, FOXL2, SF1, and CD99. Knowledge about the immunohistochemical markers possibly used for predictive purpose is limited. In our study, we focused on the immunohistochemical examination of 290 cases of AGCT classified based on strict diagnostic criteria, including molecular testing. The antibodies used included 12 of the "diagnostic" antibodies already examined in previous studies, 10 antibodies whose expression has not yet been examined in AGCT, and 7 antibodies with possible predictive significance, including the expression of HER2, PD-L1, CTLA4, and 4 mismatch repair (MMR) proteins. The results of our study showed expression of FOXL2, SF1, CD99, inhibin A, calretinin, ER, PR, AR, CKAE1/3, and CAIX in 98%, 100%, 90%, 78%, 45%, 41%, 94%, 82%, 26%, and 9% of AGCT, respectively. GATA3, SATB2, napsin A, MUC4, TTF1, and CD44 were all negative. PTEN showed a loss of expression in 71% of cases and DPC4 in 4% of cases. The aberrant staining pattern (overexpression) of p53 was found in 1% (3/268) of cases, 2 primary tumors, and 1 recurrent case. Concerning the predictive markers, the results of our study showed that AGCT is microsatellite stable, do not express PD-L1, and are HER2 negative. The CTLA4 expression was found in almost 70% of AGCT tumor cells. [ABSTRACT FROM AUTHOR]

This article discusses a less common group of testicular tumors, including sex cord-stromal tumors and gonadal stromal tumors. Among the sex cord-stromal tumors, we can distinguish androblastoma (Leydig cell tumor and Sertoli cell tumor), fibroma-thecoma group tumors, stromal tumors, and sex cord tumors. Based on a literature review, we present the epidemiology, diagnosis, and treatment of these testicular tumors. In our opinion, due to the rarity of this group of tumors and limited data in the EAU guidelines, this topic deserves attention, which is why we chose to explore it in our study. [ABSTRACT FROM AUTHOR]

Background: Stathmin, a cytosolic microtubule-destabilizing phosphoprotein involved in the regulation of mitosis, is widely expressed in various malignancies and acts as an adverse prognostic factor. Our research analyzed its immunohistochemical expression on a large cohort of ovarian sex cord-stromal tumors, evaluating its potential utility in differential diagnosis, prognosis, and therapeutic application. Methods: We examined 390 cases of ovarian sex cord-stromal tumors including 281 adult granulosa cell tumors (AGCT), 5 juvenile granulosa cell tumors (JGCT), 33 Sertoli-Leydig cell tumors (SLCT), 50 fibromas/thecomas (F/T), 11 Leydig cell tumors/steroid cell tumors (LCT/SterCT), 5 sex-cord stromal tumors NOS (SCST-NOS), 3 Sertoli cell tumors (SCT), and 2 sclerosing stromal tumors (ScST). Immunohistochemical analysis was performed using TMAs. Results: Strong expression (> 50%) was observed in all cases of AGCT, JGCT, SLCT, SCST-NOS, SCT and 1 ScST. The other case of ScST exhibited mild expression (5–10%). The negative cases included exclusively F/T and LCT/SterCT, with F/T showing 24% of negative cases and LCT/SterCT comprising 64% of negative cases. Conclusion: The results of our study indicate that stathmin is neither a prognostic marker nor suitable for the differential diagnosis of challenging cases of ovarian sex cord-stromal tumors. However, its predictive value may be theoretically significant, as a decrease in stathmin expression potentialy influences response to chemotherapy treatment. [ABSTRACT FROM AUTHOR]

Key Clinical Message We present a 39‐centimeter thecoma with ascites and elevated Ca‐125 values which is compatible with an atypical/incomplete Meigs' syndrome. Giant ovarian masses with elevated Ca‐125 values and ascites are an alarming combination, although Gynecologists should be aware that there are also benign entities that mimic advanced stage ovarian cancer.

Key Clinical Message: We present a 39‐centimeter thecoma with ascites and elevated Ca‐125 values which is compatible with an atypical/incomplete Meigs' syndrome. Giant ovarian masses with elevated Ca‐125 values and ascites are an alarming combination, although Gynecologists should be aware that there are also benign entities that mimic advanced stage ovarian cancer. [ABSTRACT FROM AUTHOR]

Para-testicular masses are a rare entity, and therefore the diagnosis and management nearly always lead to clinical doubts. Aside from the doubts that arise from these masses being uncommon, it is always necessary to rule out the malignancy process of them. Sexual cord tumors are extremely rare. Testicular fibroma of gonadal stromal origin is a proliferative process that can develop in para-testicular structures. The objective of our study is to present a rare case report of testicular fibroma of gonadal stromal origin as well as the well-documented diagnostic process and the successful therapeutic management that was subsequently carried out. We report a case of a 68-year old male who came in for a consult due to the casual finding of a nodule in his left testicle with normal tumor markers. Ultrasonography showed a nodular image that was well-defined with a diffusely homogeneous echotexture; it was also hypoechoic, vascularized and demonstrated hydrocele. MRI revealed a solid tumor with extrinsic growth to the left testicle and epididymis, and the lesion was relatively hyperintense in T1-weighted image and hypointense in T2. A surgical exeresis of the para-testicular tumor and hydrocelectomy was performed. The pathological anatomy and immunohistochemistry revealed a fibroma of gonadal stromal origin. Histopathological analysis made a diagnosis, although its clinical and radiological characteristics make it one of the differential diagnoses to consider in testicular tumors. Its characteristics, radiological and histopathological, allow for conservative management in clinical practice.

Introduction: Owing to their low incidence, no reliable statistics about prognostication derived from large sample sizes have been reported of malignant ovarian germ cell tumors (MOGCTs) and sex cord-stromal tumors (SCSTs). The present study aimed to investigate the clinicopathological prognostic factors and the survival trends of MOGCTs and SCSTs. Materials and Methods: Patients with MOGCTs and SCSTs were recorded in the Surveillance, Epidemiology, and End Results (SEER) database diagnosed between 2000 and 2019. Clinical, demographic, and treatment characteristics were compared between groups of MOGCTs and SCSTs. Cox risk regression analysis and Kaplan-Meier survival curves were used to compare overall survival (OS) and cancer-specific survival (CSS) and to assess the prognostic factors. Results: Information about 2,506 patients with MOGCTs and 1,556 patients with SCSTs was extracted from the SEER database, respectively. Aged <40 years and single were more common in patients with MOGCTs than in those with SCSTs. The vast majority of patients with MOGCTs and SCSTs underwent surgery (98.1% vs. 94.5%; p < 0.001), and women with MOGCTs were more likely to receive chemotherapy than women with SCSTs (56.1% vs. 32.2%; p < 0.001). For both patients before and after propensity-score matching, the 5-year OS rates of patients with SCSTs were lower than those of patients with MOGCTs (p < 0.05). In multivariate Cox regression analysis, both age and surgery were independent predictors of OS in patients with MOGCTs and SCSTs. FIGO staging was an independent predictor of CSS in MOGCT patients. Tumor size and chemotherapy were also independent predictors of CSS in patients with SCSTs. Conclusion: Compared to patients with SCSTs, those with MOGCTs tended to be younger and had a higher OS and CSS. Adjuvant chemotherapy after surgery did not prolong OS and CSS in patients with SCSTs. [ABSTRACT FROM AUTHOR]

Background: Ovarian tumors are common, ranking third in frequency after cervical and uterine cancer. According to the World Ovarian Cancer Coalition Atlas 2018, India has the second-highest incidence of ovarian carcinoma worldwide. In Chhattisgarh, ovarian malignancy accounts for 5.21% of all malignancies in females. Materials and Methods: The present descriptive observational cross-sectional study encompassed 108 cases of ovarian tumors. A histopathological examination was done, and data was compiled and analyzed. Observations and Results: Among the 108 ovarian tumors, 59.25% were noted in women aged 40–59 years. The primary presenting symptom was abdominal pain, reported by 57.40% of the cases. The majority of ovarian tumors were unilateral, the right side being more common. Primary ovarian tumors constituted 91.66%, while 8.33% were classified as secondary or metastatic ovarian tumors. Of 108 cases, 55.5% were malignant, 40.7% were benign, and 3.7% were borderline tumors. Surface epithelial tumors accounted for 73.14% of the cases; germ cell tumors constituted 9.25%, sex cord-stromal tumors were 7.4%, and mesenchymal tumors were 1.85%. Among surface epithelial tumors, serous cystadenocarcinoma was most common. Mature cystic teratoma was the most common germ cell tumor, and granulosa cell tumor was the most common sex cord-stromal tumor. Conclusion: Ovarian tumors were more commonly seen in the peri and postmenopausal age group. Primary malignant epithelial tumors were the most common type of ovarian tumor. The histopathological evaluation of ovarian tumors remains the gold standard for definitive diagnosis.

Background: Granulosa cell tumors (GCTs) are rare neoplasia that account for less than 5 % of all the ovarian tumors. Juvenile GCT histotype is generally observed in adolescent and young women, representing a very rare disease, so only a paucity of data are present in literature. The aim of this study is to analyse the oncologic and fertility outcome in our case series of juvenile GCTs., Methods: Clinicopathological data were retrospectively collected and analysed from a cohort of 30 patients ovarian juvenile GCTs treated at IRCCS San Gerardo dei Tintori Hospital, Monza, between 1980 and 2024., Results: The median age of disease onset was 21.5. Among patients enrolled in the study, 80.0 % (24/30) were stage I (16/26, 1/26 and 7/26 of stage IA, IB and IC, respectively), 6.7 % (2/30) were stage II and 13.3 % stage III (4/30). In 86.7 % (26/30) of patients, a fertility-sparing surgery was carried out, while 13.3.% (4/30) of patients underwent radical surgery. Adjuvant chemotherapy was administered in 20.0 % (6/30) of cases, while 80.0 % (24/30) were followed only with surveillance. Three patients in thirty (10.0 %) relapsed and died of disease despite multi-therapeutic approaches. All of them had advanced stages of disease at time of diagnosis., Conclusions: Juvenile GCT appears to have a good prognosis at stage I disease. However, advanced stage represents a hard challenge for clinicians, showing a high rate of relapse and mortality., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: To evaluate the oncologic outcomes in patients with International Federation of Gynecology and Obstetrics (FIGO) stage I ovarian sex cordstromal tumors (SCSTs) who underwent fertility-sparing surgery (FSS) and the independent risk factors affecting overall survival (OS) and cancer-specific survival (CSS). Methods: Data were acquired from the Surveillance, Epidemiology, and End Results (SEER) database between 1973 and 2018. A total of 240 patients diagnosed with stage I ovarian SCSTs were divided into the definitive surgery group (N=116) and FSS group (N=124). The Kaplan-Meier analysis and Cox model were used to evaluate the overall survival (OS) and cancer-specific survival (CSS) of the two groups and assess the independent risk factors respectively. The Fine-Gray model evaluated cancer-specific mortality (CSM) and the independent risk factors that affected CSM. Results: Kaplan-Meier survival analysis showed no statistically significant differences in OS and CSS between the two groups (P>0.05). Univariate analysis of the Fine-Gray model also showed that there was no difference in the CSS between the two groups (P>0.05). However, from the 15th year postoperatively, the CSS of the FSS group decreased by 13.21% compared with that of the control group and by 17.49% in the 20th and 25th years postoperatively. The Cox proportional hazards model found that surgical methods ("defined surgery" vs "FSS"; HR=0.03259, P=0.0196) and FIGO stage ("stage IA" vs "stage IC"; HR=0.03073, P=0.0300) were independent risk factors for OS. The multivariate analysis of Fine-Gray model showed that the cancerspecific mortality of patients receiving definitive surgery was 40.1% lower than that of patients receiving FSS ("definitive surgery" vs "FSS"; HR=0.599, P=0.005), indicating that FSS might lead to higher tumor-specific mortality and lower CSS. However, age, race, laterality, history, FIGO stage, and tumor size had no significant influence on the tumor-specific mortality (P>0.05). Conclusions: FSS is considered for patients with stage I SCSTs with reproductive needs, but the follow-up period should not be less than 15 years. For patients with stage IC disease, FSS should be selected carefully, and close follow-up is necessary. Perhaps, definitive surgery after birth is a means to improve long-term survival rates. [ABSTRACT FROM AUTHOR]

Sex cord–stromal tumors are very rare ovarian tumors. Primary ovarian fibrosarcomas are a very rare type of sex cord–stromal tumors. They arise from superficial or deep connective tissues of fascia, tendon, periosteum, and scar. They can grow either slowly or rapidly forming a giant abdominal mass similar to epithelial tumors of the ovary. Fibrosarcomas are difficult to diagnose preoperatively. Tumor marker and radiological techniques play a trivial role in preoperative diagnosis of this rare variety of sex cord–stromal tumor. Often final diagnosis is made on histopathological and immunohistochemistry reporting. Histopathological features such as high mitotic count, nuclear atypia, and herringbone pattern arrangement of spindle cells confirm a diagnosis of malignant fibrosarcoma. Ki-67 index is considered a prognostic factor for fibromatous lesions of the ovary showing aggressive nature of tumor. We report a rare case of giant ovarian fibrosarcoma in a 40-year-old woman whose diagnosis was made histopathologically due to rarity of tumor.

About 5% of all ovarian tumors develop some form of hormonal activity. Only 1% of ovarian tumors will secrete androgens causing clinical hyperandrogenism. Most androgen-secreting neoplasms (ASN) derive from sex cord or stroma cells of the ovary and may affect both premenopausal and postmenopausal women. Typically, a patient will present reporting symptoms of rapidly increasing hyperandrogenization such as: hirsutism, acne, frontal/male pattern balding, and in severe cases even virilization. Sertoli-Leydig Cell Tumors are the most frequent ASN and constitute about 0.5% of all ovarian neoplasms. Typically affecting women under 30 years of age, these tumors are usually unilateral and benign. They are also the most common tumor in postmenopausal women suffering with hyperandrogenism. Other tumors originating from the sex-cord stroma are also known to develop in this population, but the incidence of these is much lower. Approaching suspected hyperandrogenemia and its related symptoms in a clinical setting can be a significant diagnostic challenge. When evaluating a patient for hyperandrogenism, it is important to assess the severity of symptoms but most of all it is critical to assess the time of onset and dynamics of symptom progression. Diagnostic tools including laboratory tests and imaging studies should also be engaged. When deriving a differential diagnosis for androgen-secreting ovarian tumors, adrenal gland tumors should be considered as well as typical endocrine pathologies including polycystic ovary syndrome, congenital adrenal hyperplasia, Cushing's disease, and acromegaly. Treatment options for an androgen-secreting ovarian tumors is mainly surgical, but in exceptional cases can involve pharmacotherapy alone. [ABSTRACT FROM AUTHOR]

ObjectivesTo report the first series of testicular sex cord-stromal tumors (TSCSTs) with detailed clinicopathologic findings and long-term follow-up in the Chinese population.Patients and MethodsFrom 2008 to 2018, 15 patients with TSCST were included in our study. The tumors were analyzed for epidemiological parameters, clinical characteristics, tumor markers, therapy, and follow-up data.ResultsThe median age of the patients was 28 years (range, 13–80 years). Para-aortic lymph node metastases were detected in 2 patients after radiological evaluation. Orchiectomy was performed in all patients, and the median diameter of the tumor was 1.5 cm (range, 0.5–5.0 cm). Nine Leydig cell tumors (LCTs), 5 Sertoli cell tumors (SCTs), and 1 unclassified type were confirmed after pathologic evaluation. Thirteen patients (86.7%) were categorized as stage I, and 2 patients (13.3%) were categorized as stage II. The median clinical follow-up was 39.0 months (range, 5–97 months), which showed 10 alive patients, such as 1 patient with progression at 40 months after orchiectomy. The 3- and 5-year progression-free survivals were 100 and 90.0%, respectively.ConclusionTesticular sex cord-stromal tumor at stages I and II is a rare subtype with benign behavior and a favorable prognosis in the Chinese population. However, lymph node metastases may be the dominant risk factor for patients with TSCST.

Abstract Objective To evaluate the role of clinical features and preoperativemeasurement of cancer antigen 125 (CA125), human epididymis protein(HE4), and carcinoembryonic antigen (CEA) serum levels in women with benign and malignant non-epithelial ovarian tumors. Methods One hundred and nineteen consecutive women with germ cell, sex cordstromal, and ovarian leiomyomas were included in this study. The preoperative levels of biomarkers were measured, and then surgery and histopathological analysis were performed. Information about the treatment and disease recurrence were obtained from the medical files of patients. Results Our sample included 71 women with germ cell tumors (64 benign and 7 malignant), 46 with sex cord-stromal tumors (32 benign and 14 malignant), and 2 with ovarian leiomyomas. Among benign germ cell tumors, 63 were mature teratomas, and, amongmalignant, fourwere immatureteratomas. Themost common tumors in the sex cordstromal group were fibromas (benign) and granulosa cell tumor (malignant). The biomarker serum levels were not different among benign andmalignant non-epithelial ovarian tumors. Fertility-sparing surgeries were performed in 5 (71.4%) women with malignant germ cell tumor. Eleven (78.6%) patients with malignant sex cord-stromal tumors were treated with fertility-sparing surgeries. Five women (71.4%) with germ cell tumors and only 1 (7.1%) with sex cord-stromal tumor were treated with chemotherapy. One woman with germ cell tumor recurred and died of the disease and one woman with sex cord-stromal tumor recurred. Conclusion Non-epithelial ovarian tumors were benign in the majority of cases, and the malignant caseswere diagnosed at initial stages with good prognosis. Themeasurements of CA125, HE4, and CEA serum levels were not useful in the preoperative diagnosis of these tumors.

The current knowledge about the immunohistochemical features of adult granulosa cell tumor (AGCT) is mostly limited to the "traditional" immunohistochemical markers of sex cord differentiation, such as inhibin, calretinin, FOXL2, SF1, and CD99. Knowledge about the immunohistochemical markers possibly used for predictive purpose is limited. In our study, we focused on the immunohistochemical examination of 290 cases of AGCT classified based on strict diagnostic criteria, including molecular testing. The antibodies used included 12 of the "diagnostic" antibodies already examined in previous studies, 10 antibodies whose expression has not yet been examined in AGCT, and 7 antibodies with possible predictive significance, including the expression of HER2, PD-L1, CTLA4, and 4 mismatch repair (MMR) proteins. The results of our study showed expression of FOXL2, SF1, CD99, inhibin A, calretinin, ER, PR, AR, CKAE1/3, and CAIX in 98%, 100%, 90%, 78%, 45%, 41%, 94%, 82%, 26%, and 9% of AGCT, respectively. GATA3, SATB2, napsin A, MUC4, TTF1, and CD44 were all negative. PTEN showed a loss of expression in 71% of cases and DPC4 in 4% of cases. The aberrant staining pattern (overexpression) of p53 was found in 1% (3/268) of cases, 2 primary tumors, and 1 recurrent case. Concerning the predictive markers, the results of our study showed that AGCT is microsatellite stable, do not express PD-L1, and are HER2 negative. The CTLA4 expression was found in almost 70% of AGCT tumor cells., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Aim: Sex cord-stromal tumors are relatively uncommon tumors which constitute approximately 8% of all primary ovarian neoplasms. Morphologic differentiation of non-SCST from SCSTs can be challenging due to microscopic overlap. Immunohistochemistry is beneficial in challenging cases. Inhibin and calretinin have limited sensitivity and specificity, a more sensitive marker is required. SF-1 is known as a promising immunohistochemical marker in the differentiation of SCST from non-SCST ovarian tumors. For this purpose, various non-SCSTs (metastatic and non-metastatic) having morphologic overlap with SCSTs, and multiple SCSTs were stained with SF-1 antibody to elucidate its importance in morphologically challenging cases. Materials and Methods: Twenty-three SCST, 40 non-SCSTs, and an ectopic adrenal tissue were stained with SF-1, and also the percentage and the intensity were scored. SF-1 immunoreactivity was seen in all 23 SCST with varying degrees of intensity and percentage. In contrast, non-SCSTs were negative in all regarding to SF-1. Ectopic adrenal gland tissue and ovarian stroma are positive as non-tumoral lesions. Results: In our series, SF-1 immunoreactivity was seen in all 23 SCST and ectopic adrenal tissue with varying degrees of intensity and diffuseness. In contrast, non-SCSTs were all negative concerning SF-1. In addition; we observed nuclear positivity with SF-1 in 15-75% of the sclerosing stromal tumor cells, whereas inhibin and calretinin were negative in all 4 cases. Conclusion: Our data shows that SF-1 is a nuclear, reliable and surrogate marker for all SCSTs, and can be used routinely. [ABSTRACT FROM AUTHOR]

Metastatic Leydig cell tumors (LCT) are rare, difficult to treat malignancies without known underlying moleculargenetic events. We profiled 27 LCT cases using NGS and immunohistochemistry. Our study identified TERT gene fusions as a main genetic alteration and a potential therapeutic target in LCT. TOP1 and AR expressions may guide decisions on chemo-and/or hormone therapy for selected individual patients. Objective: Metastatic Leydig cell tumors (LCT) are rare, difficult-to-treat malignancies without known underlying molecular-genetic events. An index case of metastatic LCT showed an LDLR-TERT gene fusion upon routine genetic profiling for detection of therapeutic targets, which was then followed by an investigation into a cohort of additional LCTs. Patients and Methods: Twenty-nine LCT (27 male and 2 female patients) were profiled using next-generation sequencing and immunohistochemistry. Results: TERT gene fusions were detected only in testicular metastatic LCTs, in 3 of 7 successfully analyzed cases (RMST:TERT,LDLR:TERT, and B4GALT5:TERT). TOP1 and CCND3 amplifications were identified in the case with a B4GALT5:TERT fusion. A TP53 mutation was detected in 1 metastatic tumor without a TERT fusion. Five primary (4 testicular and 1 ovarian) LCTs showed multiple gene amplifications, without a consistent pattern. A single metastatic ovarian LCT showed BAP1 mutation and copy number amplifications affecting the NPM1, PCM1, and SS18 genes. At the protein level, 4 of 7 metastatic and 6 of 10 primary testicular LCTs overexpressed Topo1. Androgen receptor was overexpressed in 10 of 13 primary testicular tumors and 2 of 5 metastatic testicular LCTs (without detectable ARv7 messenger RNA or ARv7 protein). Only 1 metastatic testicular LCT exhibited a high tumor mutational burden; all tested cases were microsatellite instability stable and did not express programmed cell death ligand 1. Conclusions: Our study for the first time identified TERT gene fusions as a main genetic alteration and a potential therapeutic target in metastatic LCTs. Topo1 and androgen receptor may guide decisions on chemotherapy and/or hormone therapy for selected individual patients. [ABSTRACT FROM AUTHOR]

Ovarian Sertoli-Leydig cell tumors (SLCTs) are uncommon sex cord-stromal tumors. Moreover, SLCTs with heterologous mesenchymal elements are extremely rare and usually associated with poor differentiation and prognosis. Herein, the authors describe a case of SLCT involving the right ovary in a 16-year-old girl who presented with acute lower abdominal pain and fever. Serum investigation demonstrated abnormally elevated level of alpha-fetoprotein (AFP), slightly elevation of testosterone, and CA125 concentration. Right salpingo-oopherectomy was performed due to ovarian tumor torsion and then histopathological analysis revealed a poorly differentiated Sertoli-Leydig cell tumor with heterologous rhabdomyosarcomatous elements. A brief review of the literature was conducted to explore the management options for patients with SLCTs and the prognosis. [ABSTRACT FROM AUTHOR]

Rationale: Sex cord-stromal tumors (SCST) are hormonally active and rare. The aim was to describe their endocrinological presentation and outcomes., Method: Patients (< 19 years) registered in the TGM13 registry between 2014 and 2021 for SCST were selected., Results: Sixty-three ovarian SCST (juvenile granulosa tumor (JGT) n = 34, Sertoli-Leydig cell tumor (SLCT) n = 17, other SCST n = 12) were included. Median age was 13.1 years (0.4-17.4). Germline DICER1 pathogenic variant was present in 9/17 SLCT. Sixty-one were FIGO stage I (IC n = 14). Adjuvant chemotherapy was administered for 15. Seven had recurrence (FIGO IA n = 3, IX n = 2, III n = 2), leading to one death. With a median follow-up of 42 months (2.5-92), the 3-year progression-free survival (PFS) was 89% (95% CI 76%-95%). Median age was 6.4 years (0.1-12.9) among the 15 testicular SCST (Leydig cell tumor n = 6, JGT n = 5, Sertoli cell tumor n = 3, mixed SCST n = 1). Tumor-nodes-metastases (TNM) stage was pSI in 14. Eight underwent a tumorectomy, 7 an orchiectomy. None experienced recurrence. Endocrinological data were reviewed for 41 patients (18 prepubescent). Endocrine symptoms were present at diagnosis in 29/34 females and 2/7 males (gynecomastia). After a median follow-up of 11 months, 15 patients had persistent endocrine abnormalities: gynecomastia/breast growth (2 males, 1 prepubescent female), precocious/advanced puberty (4 prepubescent females), and hirsutism/menstruation disorders/voice hoarseness/hot flashes (8 pubescent females). The mean height at the last follow-up was within normal ranges (+0.3 standard deviation)., Conclusions: SCSTs have a favorable prognosis. Tumorectomy appears safe with testicular primary. Endocrinological disorders, common at diagnosis, may persist warranting endocrinological follow-up., (© 2024 Wiley Periodicals LLC.)

Background: Sertoli‐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. Objective: The objective of this study was to determine the management (i.e., conservative surgery and adjuvant chemotherapy) of ovarian SLCTs. Results: This 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). Conclusion: Conservative 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 Practice: For 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. Sertoli‐Leydig cell tumors (SLCT) represent less than 0.5% of ovarian tumors. Because of the rarity of this tumor, this study aimed to determine appropriate SLCT management strategies and indications for conservative surgery and adjuvant chemotherapy. [ABSTRACT FROM AUTHOR]

Fibromas/fibrothecomas are considered to be benign ovarian tumors. We describe a rare case of recurrent fibrothecoma with a clinically malignant course. A 42-year-old woman, with no family history of malignancy, operated multiple times for tumor that recurred three times within 4 years despite radical surgical removal. Initially, she presented with 9×7×10 cm right ovarian mass, frozen section was consistent with fibrothecoma and thus right salpingoophorectomy was performed. At the last two recurrences, she was found to have recurrent multiple abdomino-pelvic fibrothecomas and two long major operations were performed. This malignant behavior of a benign tumor is very rare. Further genetic analysis and immunohistochemistry studies are recommended to be conducted. Furthermore, new modalities of treatment should be considered, eg, high-intensity focused ultrasound and/or hormonal treatment. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study was to determine the incidence of new primary malignancies after adult-type granulosa cell tumor (AGCT) and the incidence of AGCT after breast and uterine cancer using nationwide population-based registry data. Methods: We used the Finnish Cancer Registry to identify all patients diagnosed with AGCT in 1968 to 2013 (n = 986). The number of subsequent primary malignancies among women with AGCT and the number of AGCTs in women with previous breast or uterine cancer were compared with the expected number of cases and expressed as standardized incidence ratios (SIRs). Results: There were 122 cases of subsequent cancers diagnosed at least 6 months after the primary diagnosis of AGCT (SIR, 1.09; 95% confidence interval [CI], 0.91–1.3). In particular, the observed number of cancers of the soft tissue (SIR, 4.13; 95% CI, 1.33–12.8), thyroid (SIR, 3.42; 95% CI, 1.54–7.62), and leukemia (SIR, 2.67; 95% CI, 0.98–5.82) exceeded the number of expected cases. The SIR for breast cancers after AGCT was 1.26 (95% CI, 0.92–1.73), and the SIR for AGCT after breast cancer was 1.59 (95% CI, 1.04–2.29). The risk for subsequent AGCT was more than 2-fold in breast cancer patients younger than 50 years, and over 15 years after primary diagnosis. Conclusions: There is an increased risk for thyroid and soft tissue cancer as well as leukemia after AGCT, which may be associated with late effects of carcinogenic treatments and possibly shared risk factors. After breast cancer, the risk for AGCT was higher, which may indicate a shared hormonal etiology. [ABSTRACT FROM AUTHOR]

Objective To examine the potential of ARX as a novel biomarker of ovarian endometriosis and other ovarian pathologies. Methods The mRNA level of ARX in ovarian endometriosis and normal endometrium samples was determined by real-time PCR, while the protein level was determined by Western blotting and immunohistochemical staining. Immunohistochemical analysis was performed on nearly 200 tissue samples of different ovarian pathologies. GraphPad Prism was used for statistical analysis. Results The expression of ARX was significantly increased in ovarian endometriosis samples as compared to normal endometrium. Also Western blotting data showed higher ARX levels in the ovarian endometriosis samples versus normal endometrium. Immunohistochemical analysis revealed that the protein is localized in the ovarian stroma and does not originate from endometriosis. Further immunohistochemical analysis performed on several different non-neoplastic and neoplastic ovarian tissue samples revealed that in the non-neoplastic ovary ARX protein is present only in the stromal cells and their derivates (luteinized stromal cells, theca and Leydig cells) and not in granulosa cells, oocites, surface epithelium or rete ovarii, while all stromal and sex cord tumors showed strong nuclear staining for ARX. All other primary or metastatic epithelial tumors of the ovary were ARX negative. Conclusions ARX is not associated with endometriosis and cannot be used as a biomarker for ovarian endometriosis. ARX is present in ovarian stroma and cells derived from ovarian stroma as well as in all types of sex cord-stromal tumors of the ovary and could thus be used as a marker for sex cord-stromal differentiation in ovarian tumors. [ABSTRACT FROM AUTHOR]

Objective: The aim of this retrospective population-based study was to investigate the oncologic safety of fertility-sparing surgery (FSS) for premenopausal women with malignant sex cord-stromal tumors (SCSTs) confined to the ovary. Methods: A cohort of women aged 18 to 49 years and diagnosed with a stage I malignant SCST between 1984 and 2013 was drawn from the National Cancer Institute's Surveillance, Epidemiology, and End Results database. Based on site-specific surgery codes, women who had FSS, defined as unilateral oophorectomy/tumor resection without hysterectomy, and definite surgery were identified. Cancer-specific survival and overall survival were evaluated after generation of Kaplan-Meier curves, whereas comparisons between the 2 groups were made with the log-rank test. Results: A total of 255 women who met the inclusion criteria were identified; 161 (63.1%) underwent FSS whereas 94 (36.9%) had definitive surgery (bilateral salpingo-oophorectomy and hysterectomy). Median follow-up was 104 months. Cancer-specific survival (P = 0.015) but not overall survival (P = 0.76) was superior for women who had definite surgery. Conclusions: In this retrospective population-based cohort of premenopausal women with SCSTs confined to the ovary, FSS was associated only with a worse long-term cancer-specific survival compared with definitive surgery. Women undergoing FSS for early stage SCSTs should be extensively counseled and closely monitored. [ABSTRACT FROM AUTHOR]

Objective The aim of this retrospective population-based study was to investigate the prevalence of lymph node metastasis in patients with apparent early stage malignant sex cord-stromal tumors (SCSTs) and the effect of regional lymph node sampling/lymphadenectomy (LND) on their survival. Methods A cohort of patients diagnosed with malignant SCSTs between 1988 and 2012 was drawn from the National Cancer Institute's Surveillance, Epidemiology, and End Results database. Overall and Cancer Specific Survival, stratified by performance of LND, were calculated following generation of Kaplan-Meier curves. Comparisons were made using the log-rank and Breslow tests. A multivariate Cox proportional analysis was performed to determine the effect of LND on overall mortality. Results A total of 1156 patients with SCST met the inclusion criteria; 1000 (86.5%) and 156 (13.5%) patients had apparent stage I and II disease, respectively. LND was performed in 572 (49.5%) patients. Lymph node metastases were pathologically confirmed in 19 patients (3.3%). Five-year cancer specific survival (CSS) was similar, 92.7% and 94.7%, for patients who did or did not undergo LND, respectively. According to multivariate analysis overall mortality did not differ between the two groups after controlling for age, histology and apparent stage. Conclusions Regional lymphatic mode metastasis in patients with apparent early stage SCSTs is uncommon and lymphadenectomy did not confer a survival benefit in this cohort. [ABSTRACT FROM AUTHOR]

Testicular germ cell tumors (TGCTs) and sex cord-stromal tumors (SCSTs) are the most common testicular neoplasms. The morphologic spectrum of such tumors is wide, with several histologic subtypes within each group. Testicular tumors often represent a diagnostic challenge, requiring proper identification of their biologic potential for accurate risk stratification and selection of therapy. In the era of precision medicine, molecular biomarkers are increasingly assuming a critical role in the management of patients with cancer. Given the overall rarity of certain types of testicular neoplasms, progress in biomarker research has been relatively slow. However, in recent years, we have witnessed a multitude of important contributions, including both tissue-based and liquid biopsy biomarkers, stemming from important discoveries of tumor pathobiology, accurate histopathological analysis, multi-institutional studies, and genome-wide molecular analyses of specific tumor subtypes. In this review, we provide an overview of the progress in molecular biomarkers of TGCTs and SCSTs, focusing on those with greatest potential for clinical application. In TGCTs, developmental biology has been the key to understanding these tumors and identifying clinically useful biomarkers (from classical serum tumor markers to pluripotency factors and circulating microRNAs of the 371-373 cluster). For SCSTs, studies have focused on tissue biomarkers only, and genome-wide investigations have recently contributed to a better understanding of rare phenotypes and the aggressive biological behavior of some tumors within this nosologic category. Several new biomarkers are moving toward clinical implementation in this field. Therefore, the practicing pathologist should be aware of their strengths and limitations in order to utilize them properly and maximize their clinical benefits., (Copyright © 2023 United States & Canadian Academy of Pathology. Published by Elsevier Inc. All rights reserved.)

Objective: To report the natural history and prognosis of the uncommon Sertoli–Leydig cell tumor (SLCT) of the ovary. Materials and Methods: A 20-year retrospective review was conducted by the Taiwanese Gynecologic Oncology Group (TGOG), including nine tertiary medical centers from different regions in Taiwan. The medical records for 40 cases of ovarian SLCT were collected. Pathology reviews were carried out by a panel of expert pathologists. Results: After pathological review, 17 patients were subsequently excluded because the pathology slides were unavailable in five cases, and discrepant results from the initial diagnosis were found in 12 cases (34%). For the remaining 23 patients, the median age was 41 years. The most common symptom was irregular vaginal bleeding followed by an abdominal mass or amenorrhea. Most of the tumors were unilateral and confined to the right ovary, with an average size of 8.2 cm. Preoperative serum markers were available for 12 patients and were elevated for three patients. All patients underwent primary surgery. Six patients accepted adjuvant chemotherapy, and bleomycin, etoposide, and cisplatin were used in four of them. Clinical follow-up information was available in 21 patients with a median of 19 months. Eighty-two percent of patients were alive and free of disease up to the date of the last follow-up. Two patients died of the disease. Conclusion: This study demonstrates the extreme rarity of ovarian SLCT in Taiwan. Histological discordance between the diagnosis and central review proves the need for expertise review before treatment. For an improved understanding of the biological behavior and treatment strategy for this unique tumor, international collaboration is imperative.

Ovarian sex cord-stromal tumors (OSCSTs) are a rare group of ovarian neoplasms that can be benign or malignant. They are classified into pure sex cord tumors, pure stromal tumors, and mixed SCST. The most common malignant OSCSTs are adult granulosa cell tumors. In contrast to the more common ovarian epithelial malignancies, OSCSTs present in younger patients, often at early stages, with better prognoses. Imaging features are variable, and pathology is required for diagnosis. However, certain tumors demonstrate characteristic imaging appearances that can be useful in narrowing the differential diagnosis., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Se presenta el raro caso de una mujer de 20 años con un tumor del estroma gonadal específico del ovario, variedad tumor de los cordones sexuales, con túbulos anulares no asociado a síndrome de Peutz-Jeghers. Se revisa la literatura sobre el manejo de esta entidadA twenty years-old woman with an unusual variant of ovarian sex cord-stromal tumor, a sex cord tumor with annular tubules non-associated to Peutz-Jeghers syndrome, is reported. A review of the literature in the management of this unfrequent entity is also presented

Testicular cancer is rare overall but comprises the most common solid malignancy diagnosed in young men aged ∼20-40 years. Most testicular neoplasms generally fall into 2 broad categories: germ cell tumors (GCTs; ∼95%) and sex cord-stromal tumors (SCSTs ∼5%). Given the relative rarity of these tumors, diagnostic biomarkers are highly relevant for their diagnosis. Over the past several decades, diagnostic biomarkers have improved dramatically through targeted immunohistochemical and molecular characterization. Despite these recent advances, most markers are not perfectly sensitive or entirely specific. Therefore, they need to be used in combination and interpreted in context. In this review, we summarize tissue-based biomarkers relevant to the pathologist, with a focus on practical diagnostic issues that relate to testicular GCT and SCST., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: The Sertoli and Leydig cell tumor is an unusual neoplasm that belongs to the sex cord-stromal tumors. Generally these tumors are associated with good prognosis. These tumors usually present virilizing symptoms such as oligomenorrhea or amenorrhea, hirsutism, voice raucity, laryngeal protuberance and clitoromegaly. Case presentation: A 12 year old girl referred acute abdominal pain with no other clinical manifestations. An abdominal ultrasound showed a semisolid mass suggestive of ovarian tumor. The diagnosis was confirmed by a computed tomography. A unilateral salpingo oophorectomy was performed and the pathologist reported a Sertoli-Leydig tumor with intermediate differentiation. The outcome was excellent. Conclusions: These tumors represent a rare condition in children. However, they can occur at any age, therefore it is important to acknowledge the clinical manifestations, diagnostic approach and therapeutic options. In this case the patient presented unusual symptoms which makes it more interesting. [ABSTRACT FROM AUTHOR]

Abstract: Objective: Ovarian sex cord-stromal tumors (SCSTs) are rare and their diagnosis is often difficult to establish. Recently, immunostaining and molecular analysis for Forkhead box L2 (FOXL2) have been developed in this pathology. This study aims to assess the benefit of an algorithm incorporating these new tools for a better diagnosis and classification of SCSTs Methods: Seventy-two tumors with a potential diagnosis of SCSTs were addressed by 37 different pathologists to one French rare ovarian tumor expert center, member of the Rare Malignant Ovarian Tumor network (TMRO). Then a “second opinion” (SO) through an algorithm incorporating immunostaining (IHC) and molecular analysis of FOXL2 was performed for all these cases. This algorithm was then validated by all pathologists of the TMRO network. Results: After a second opinion including molecular analysis and immunostaining for FOXL2 the initial diagnosis was changed in 15 of 72 samples (21%). FOXL2 mutation was present in 44 out of 47 adult granulosa cell tumors (94%), in 3 out of 8 Thecomas (37%), in 1 out of 10 Sertoli–Leydig cell tumors (SLSTs) (10%) and in 3 out of 5 undifferentiated-SCSTs (Und-SCSTs) (60%). Immunoexpression of FOXL2 was available in 45 cases of SCSTs: FOXL2 was expressed in 44 of them (98%). Conclusions: A second opinion in an expert center for all cases of SCSTs is fundamental to get an optimal classification of these rare tumors. This second opinion could be performed with an algorithm which integrates FOXL2 mutation and expression status of FOXL2 in order to standardize the practice. [Copyright &y& Elsevier]

Ovarian cancer is the most common pediatric gynecologic malignancy. When diagnosed in children, ovarian cancers present unique challenges that differ dramatically from those faced by adults. Here, we review the spectrum of ovarian cancers found in young women and girls and discuss the biology of these diseases. A number of advances have recently shed significant new understanding on the potential causes of ovarian cancer in this unique population. Particular emphasis is placed on understanding how altered expression of non-coding RNA transcripts known as microRNAs play a key role in the etiology of ovarian germ cell and sex cord-stromal tumors. Emerging transgenic models for these diseases are also reviewed. Lastly, future challenges and opportunities for understanding pediatric ovarian cancers, delineating clinically useful biomarkers, and developing targeted therapies are discussed. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the oncologic outcomes in patients with International Federation of Gynecology and Obstetrics (FIGO) stage I ovarian sex cord-stromal tumors (SCSTs) who underwent fertility-sparing surgery (FSS) and the independent risk factors affecting overall survival (OS) and cancer-specific survival (CSS)., Methods: Data were acquired from the Surveillance, Epidemiology, and End Results (SEER) database between 1973 and 2018. A total of 240 patients diagnosed with stage I ovarian SCSTs were divided into the definitive surgery group (N=116) and FSS group (N=124). The Kaplan-Meier analysis and Cox model were used to evaluate the overall survival (OS) and cancer-specific survival (CSS) of the two groups and assess the independent risk factors respectively. The Fine-Gray model evaluated cancer-specific mortality (CSM) and the independent risk factors that affected CSM., Results: Kaplan-Meier survival analysis showed no statistically significant differences in OS and CSS between the two groups (P>0.05). Univariate analysis of the Fine-Gray model also showed that there was no difference in the CSS between the two groups (P>0.05). However, from the 15th year postoperatively, the CSS of the FSS group decreased by 13.21% compared with that of the control group and by 17.49% in the 20th and 25th years postoperatively. The Cox proportional hazards model found that surgical methods ("defined surgery" vs "FSS"; HR=0.03259, P=0.0196) and FIGO stage ("stage IA" vs "stage IC"; HR=0.03073, P=0.0300) were independent risk factors for OS. The multivariate analysis of Fine-Gray model showed that the cancer-specific mortality of patients receiving definitive surgery was 40.1% lower than that of patients receiving FSS ("definitive surgery" vs "FSS"; HR=0.599, P=0.005), indicating that FSS might lead to higher tumor-specific mortality and lower CSS. However, age, race, laterality, history, FIGO stage, and tumor size had no significant influence on the tumor-specific mortality (P>0.05)., Conclusions: FSS is considered for patients with stage I SCSTs with reproductive needs, but the follow-up period should not be less than 15 years. For patients with stage IC disease, FSS should be selected carefully, and close follow-up is necessary. Perhaps, definitive surgery after birth is a means to improve long-term survival rates., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Sun, Zhi and Fan.)

This study evaluates the immunoreactivity of 12 sex cord–stromal tumors of nonhuman primates (11 granulosa cell tumors and 1 luteoma). The markers selected are used in the characterization of gonadal tumors in dogs and other species, including cytokeratins AE1/AE3, GATA-4, inhibin-α, neuron-specific enolase, protein gene product 9.5, and vimentin. A normal nonhuman primate ovary was used as a control and to optimize immunolabeling. Staining was graded as follows: 0 (nonstaining), 1+ (< 10% positive cells), 2+ (10%–50% positive cells), and 3+ (> 50% positive cells). Calretinin, GATA-4, neuron-specific enolase, and vimentin were the most consistently expressed markers (12 of 12). Cytokeratins AE1/AE3 were also consistently expressed (11 of 12). Inhibin-α and protein gene product 9.5 were expressed in 8 and 10 sex cord–stromal tumors, respectively. Results indicate that immunoreactivity of nonhuman primate sex cord–stromal tumors is similar to that observed in other species and that calretinin, GATA-4, and neuron-specific enolase are the most consistently expressed markers in nonhuman primate sex cord–stromal tumors. [ABSTRACT FROM PUBLISHER]

Abstract: Objective: Pleuropulmonary blastoma (PPB) is a childhood cancer arising from pleuropulmonary mesenchyme. This neoplasm is a sentinel disease in a familial tumor syndrome recently found to be associated with germline mutations in DICER1. Observations of ovarian sex cord-stromal tumors (OSCST) in PPB kindreds led to further study. We sought to characterize ovarian tumors seen in probands and families with PPB and PPB-related conditions and define germline DICER1 status. Methods: Patient and family records of pathology-reviewed PPB cases enrolled in the International PPB Registry (IPPBR) were searched for ovarian tumors. Ovarian tumor pathology specimens were obtained and centrally reviewed. Germline DNA from patients with ovarian tumors was tested for DICER1 mutations. Three additional OSCST patients registered in the IPPBR were also tested for mutations in DICER1. Results: Among 296 kindreds including 325 children with PPB, we observed three children with both PPB and Sertoli–Leydig cell tumors (SLCT)/Sertoli cell tumors. Among family members of PPB patients, we identified six OSCST (three SLCT, one Sertoli cell tumor, one juvenile granulosa cell tumor, one gynandroblastoma). Age at ovarian tumor diagnosis was youngest in PPB probands and younger in family members than in OSCST in general. Germline DICER1 mutations were identified in four of six patients with OSCST from PPB kindreds and in two of three children with OSCST and no personal or family history of PPB. Conclusions: Primary ovarian neoplasms, particularly OSCST, are a manifestation of the familial PPB syndrome and may be the initial clinical presentation of DICER1 mutations within a family. [Copyright &y& Elsevier]

Abstract: Purpose: Testicular sex cord-stromal tumors (SCSTs) are very rare in children and include a variety of neoplasms with different clinical features and biologic behavior. Aim of the study was to report the clinical findings and results observed in a series of patients with testicular SCST, registered in a multi-institutional Italian network on rare tumors in children and adolescents. Materials and Methods: The records of 11 patients, enrolled in 6 Italian centers from January 2000 to December 2008, were reviewed. The Children''s Oncology Group (COG) staging system was adopted. Chemotherapy was recommended in patients with incomplete surgery or metastatic disease. Results: A testicular mass was the most common symptom. All patients underwent primary removal of the tumor; orchiectomy with high ligation of spermatic cord was performed in 7 and tumor enucleation in 4. At histology, 4 patients had Leydig cell tumors, 4 juvenile granulosa cell tumors, 1 Sertoli cell tumor, 1 incompletely differentiated SCST, and 1 SCST with an intermediate pattern Sertoli cell tumor/mixed form. The histology of 8 of 11 cases was reviewed and investigated through immunohistochemical stains. Ten children were in stage I; 1 patient, who did not undergo hemiscrotectomy after enucleation through a transscrotal access, was considered stage II. All the patients are in first complete remission (mean follow-up, 59 months; range, 8-94). Conclusions: Our experience confirmed the rarity of testicular SCST. They have to be considered in the differential diagnosis of testicular solid masses, taking into account that hormonal signs are present in a minority of cases. All patients were cured with surgery alone. The sparing surgery represented a choice in selected cases. [Copyright &y& Elsevier]

Abstract: Sex cord-stromal tumors including granulosa cell tumor, thecoma, Sertoli stromal cell tumor and steroid cell tumor are noted for their hormonal activity. However, there are many kinds of ovarian tumors other than sex cord-stromal tumors and tumor-like conditions with endocrine manifestations. Cross-sectional imaging, especially MR, can provide precise features of ovarian tumors and uterine morphological change even in a clinically latent excess of estrogen. In this article, we demonstrate typical imaging findings of ovarian tumors with hormonal activity. We also shortly explain the mechanism of the virilization and hyperestrogenism caused by ovarian tumors and tumor-like conditions. [Copyright &y& Elsevier]