Search

To assess the efficacy and toxicity of paclitaxel and carboplatin (PC) compared to bleomycin, etoposide, and cisplatin (BEP) for treatment of newly diagnosed Stage IIA-IV or recurrent chemotherapy-naive ovarian sex cord-stromal tumors (SCST). This phase II noninferiority trial randomly assigned patients to receive PC (6 cycles P 175 mg/m2 and C AUC = 6 IV every 3 weeks), or BEP (4 cycles B 20 units/m2 IV push day 1, E 75 mg/m2 IV days 1–5, and cisplatin 20 mg/m2 IV days 1–5 every 3 weeks). The primary endpoint was progression- free survival (PFS). This trial is registered with ClinicalTrials.gov , NCT01042522. At the interim analysis, 63 patients (31 PC and 32 B.P. had accrued between Feb 8, 2010 and Apr 30, 2020. Median age was 48 years. 87% had granulosa cell tumors. 37% had measurable disease. The DSMB closed accrual early for futility of PC arm. The futility analysis was supported by an estimated HR = 1.11 [95% CI: 0.57 to 2.13] which exceeded the pre-determined threshold for non-inferiority (1.10). Median PFS was 27.7 months [11.2 to 41.0] for PC and 19.7 months for BEP [95% CI: 10.4–52.7]. PC patients had fewer grade 3 or higher adverse events (PC 77% vs BEP 90%). The study met its pre-specified criterion for stopping early for futility and so failed to demonstrate non-inferiority of PC versus BEP in ovarian SCSTs, in a non-inferiority test with a hazard ratio margin of 1.1. Both PC and BEP may be considered in patients with advanced/recurrent SCST. • Paclitaxel and carboplatin (PC) are well tolerated in patients with sex cord-stromal ovarian tumors (SCSTs). • Both PC and bleomycin/etoposide/cisplatin are regimens to be considered for patients with advanced/recurrent SCSTs. • No significant differences in outcomes or adverse effects were detected between these two regimens. [ABSTRACT FROM AUTHOR]

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

Ovarian fibroma is a rare benign tumor of the ovary that is composed of fusiform fibrous cell components. Ovarian fibroma can occur at any age, and it is more common in postmenopausal or postmenopausal women. The clinical manifestations of ovarian fibroma are not typical; they are usually characterized by no obvious symptoms and mostly accidental imaging findings. The density and signal of ovarian fibroma are generally uniform, and necrosis, cystic degeneration, and calcification are rare. We report a 25-year-old young woman who accidentally discovered a large calcified mass on the right side of the pelvic cavity during a computed tomography examination of the lumbar spine. The mass was pathologically confirmed as calcified ovarian fibroma.

Sertoli-Leydig cell tumors (SLCTs) are rare sex cord-stromal tumors, representing <0.5% of all ovarian tumors. We sought to describe prognostic factors, treatment and outcomes for individuals with ovarian SLCT. Individuals with SLCT were enrolled in the International Pleuropulmonary Blastoma/ DICER1 Registry and/or the International Ovarian and Testicular Stromal Tumor Registry. Medical records were systematically abstracted, and pathology was centrally reviewed when available. In total, 191 participants with ovarian SLCT enrolled, with most (92%, 175/191) presenting with FIGO stage I disease. Germline DICER1 results were available for 156 patients; of these 58% had a pathogenic or likely pathogenic germline variant. Somatic (tumor) DICER1 testing showed RNase IIIb hotspot variants in 97% (88/91) of intermediately and poorly differentiated tumors. Adjuvant chemotherapy was administered in 40% (77/191) of cases, and among these, nearly all patients received platinum-based regimens (95%, 73/77), and 30% (23/77) received regimens that included an alkylating agent. Three-year recurrence-free survival for patients with stage IA tumors was 93.6% (95% CI: 88.2–99.3%) compared to 67.1% (95% CI: 55.2–81.6%) for all stage IC and 60.6% (95% CI: 40.3–91.0%) for stage II-IV (p <.001) tumors. Among patients with FIGO stage I tumors, those with mesenchymal heterologous elements treated with surgery alone were at higher risk for recurrence (HR: 74.18, 95% CI: 17.99–305.85). Most individuals with SLCT fare well, though specific risk factors such as mesenchymal heterologous elements are associated with poor prognosis. We also highlight the role of DICER1 surveillance in early detection of SLCT, facilitating stage IA resection. • Most (92%, 175/191) ovarian Sertoli-Leydig cell tumors (SLCTs) present as FIGO stage I disease with a favorable prognosis. • FIGO stage I tumors with mesenchymal heterologous elements are at higher risk for recurrence when not receiving chemotherapy. • Somatic (tumor) DICER1 RNase IIIb hotspot variants were found in 97% of intermediately and poorly differentiated SLCTs. • More than half (58%, 91/156) of individuals were found to have a germline DICER1 pathogenic/likely pathogenic variant. • DICER1 surveillance recommendations facilitated detection of asymptomatic ovarian SLCT with nearly all resected as stage IA. [ABSTRACT FROM AUTHOR]

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

Sertoli cell tumors are a rare subtype of testicular tumors. This report describes a 55-year-old male who presented with scrotal pain and a palpable mass. Diagnostic imaging revealed a hypoechoic mass in the left epididymis and a hyperechoic mass in the right testis. A right testis-sparing surgical procedure was performed, and subsequent histopathological analysis confirmed the presence of a benign Sertoli cell tumor. The patient experienced an uncomplicated postoperative course and was discharged on the same day. This case underscores the viability of testis-sparing surgery in the management of rare testicular tumors, emphasizing its potential for preserving testicular function.

Ovarian fibroma is a rare benign tumor of the ovary that is composed of fusiform fibrous cell components. Ovarian fibroma can occur at any age, and it is more common in postmenopausal or postmenopausal women. The clinical manifestations of ovarian fibroma are not typical; they are usually characterized by no obvious symptoms and mostly accidental imaging findings. The density and signal of ovarian fibroma are generally uniform, and necrosis, cystic degeneration, and calcification are rare. We report a 25-year-old young woman who accidentally discovered a large calcified mass on the right side of the pelvic cavity during a computed tomography examination of the lumbar spine. The mass was pathologically confirmed as calcified ovarian fibroma. Keywords:Ovarian fibroma, calcification, sex cord-stromal tumor: [ABSTRACT FROM AUTHOR]

Simple Summary: Fertility-sparing treatment (FST) is the gold standard for the majority of young women with non-epithelial ovarian cancer (NEOC). Its rarity and wide histological diversity lead to difficulties in assessing the oncological and reproductive outcomes. The aim of the study was to assess the recurrence rates and obstetric results of patients with NEOC. In a group of 146 patients, there was no difference in disease-free survival between the women with sex cord-stromal tumors (SCST) and germ cell tumors (GCT). The recurrence risk in the first two years after treatment exceeded the chance of childbearing. The cumulative incidence rate of childbearing rose continuously since the diagnosis. Chemotherapy was not related to the chance of having a child. FST can be offered to young women with NEOC regardless of their histology (SCST vs. GCT); however, pregnancy should be delayed until 2 years after receiving the treatment due to the increased risk of recurrence. Purpose: To assess the recurrence and birth rates among patients with non-epithelial ovarian cancer. Methods: The study included 146 patients with germ cell (GCT, n = 84) and sex cord-stromal tumors (SCST, n = 62), who underwent fertility-sparing surgery. Adjuvant chemotherapy was administered to 86 (58.9%) patients. Most cases (133 out of 146) were staged FIGO I. Results: The 5- and 10-year disease-free survival rates were 91% and 83%, respectively. The recurrence risk was not associated with tumor histology, stage or age. Twenty-four months after the treatment, the rate of recurrence was higher than the rate of childbearing. The childbearing rates kept rising after the treatment and exceeded the rate of recurrence after 2 years. The cumulative incidence rates of birth 36, 60 and 120 months after treatment were 13.24%, 20.75%, and 42.37%, respectively. Chemotherapy was not related to childbearing. The patients' age was related to the chance of childbearing. Conclusions: The prognoses of GCT and SCST are similar. Close follow-ups along with contraception should be offered to women during the first two years after treatment due to the increased risk of recurrence. After this period, relapses are rare and women can safely become pregnant. [ABSTRACT FROM AUTHOR]

DICER1 mutation has been linked to development of Sertoli-Leydig cell tumor and cystic nephroma, among other neoplasms. We present a unique case of recurrent ovarian Sertoli-Leydig cell tumor in a pediatric patient with a known DICER1 mutation and history of cystic nephroma. She underwent surgical staging and adjuvant chemotherapy, and her recurrences have been treated with chemotherapy, whole-abdomen radiation therapy, and further surgical debulking. This report adds to the small body of evidence about this rare but unexpectedly highly aggressive tumor, especially in the recurrent setting, and reminds the reader of the importance of cancer diagnosis in this population. [ABSTRACT FROM AUTHOR]

Microcystic stromal tumors (MCSTs) of the ovary are rare sex cord-stromal tumors that are considered benign neoplasms because almost all cases display unilateral, localized lesions and have benign outcomes, except for one recurrent case with familial adenomatous polyposis and another initial metastatic case with a CTNNB1 mutation. We report herein a sporadic case that relapsed as intra-abdominal spread 9 years and 1 month after primary left salpingo-oophorectomy for torsion of the ovarian tumor pedicle. The tumor relapsed as multiple disseminations at the subabdominal wall, Douglas pouch, and omentum. Histologically, the tumor cells formed microcysts and infiltrated the surrounding adipose tissue, similar to the invasive implants of ovarian epithelial borderline tumors. Mutation analysis of the recurrent tumor revealed a somatic CTNNB1 p.S33Y activated missense mutation and a germline KDR p.Q472H variant. In conclusion, long-term clinical follow-up may be needed to detect any recurrence of MCST, irrespective of familial adenomatous polyposis. [ABSTRACT FROM AUTHOR]

Granulosa cell tumor constitutes approximately 1% of all ovarian tumors. Extra ovarian spread can occur as a late recurrence. The authors reported a case of 41-year-old woman with adult-type granulosa cell tumor at sigmoid colon. The patient visited the outpatient department for a yearly medical check-up with no specific complaints. She had a history of ovarian cystectomy 12 years prior. A mass in left pelvic cavity was revealed upon transvaginal ultrasonography and computer tomography (CT). At the time of laparoscopy, a well-defined subserosa mass was detected at the antimesentericsideofthe sigmoid colon. The right and left ovaries appeared grossly normal. The tumor was successfully removed with laparoscopic sigmoidectomy. The pathologic findings were that of adult-type granulosa cell tumor, which was corresponding to the previous diagnosis made in the ovarian cystectomy specimen 12 years ago. The authors presented this case as an example of late recurrence of ovarian granulosa cell tumor in sigmoid colon, which could potentially be mistaken as other usual colonic tumors in the absence of previous history of ovarian tumor. [ABSTRACT FROM AUTHOR]

Adult granulosa cell tumor (AGCT) is the most common sex cord-stromal tumor, accounting for about 1% of all ovarian tumors. It has a propensity for recurrences, especially late in the disease course. High-grade or sarcomatoid transformation has been rarely described in AGCT. We present a case of a 65 year old woman who presented with hemodynamic shock and bowel obstruction from a large pelvic mass. Histologic examination revealed predominantly high-grade epithelioid and spindled cells with high mitotic activity and necrosis. A minor component suggestive of AGCT was also identified. Molecular analysis confirmed the diagnosis of AGCT by revealing FOXL2 C134W mutations. Additionally, TP53 mutations were also detected which may contribute to the high-grade transformation. Our case is unique because the high-grade sarcomatous component constituted most of the tumor and the areas of "typical" AGCT were minor. Also, the clinical and operative findings did not suggest a specific site of origin leading to a broad differential diagnosis. High-grade transformation in AGCT is a rarely described phenomenon. The awareness of this presentation is helpful in reaching the correct diagnosis. Molecular analysis may be an extremely helpful adjunct in challenging cases. [ABSTRACT FROM AUTHOR]

Synchronous endometrial and ovarian carcinoma is a rare instance and it accounts for 50 to 70% of all synchronous female genital tract tumors. However, it is very rare to find synchronous endometrial carcinoma and ovarian sex cord–stromal tumor (thecoma). The present case is a 75-year-old woman with a complaint of post-menopausal vaginal bleeding. Radiologically, the magnetic resonance imaging (MRI) pelvis revealed altered signal intensity mass in the uterus. Frozen section and routine histopathological examination were done on radical hysterectomy. Microscopically, serous carcinoma involving uterine corpus and left Fallopian tube was identified along with the unusual finding of contralateral ovarian sex cord–stromal tumor (thecoma), which was confirmed on immunohistochemical examination. It is a very rare association and is first reported in the present study after a thorough search of the published literature. Their relationship based on a high level of estrogen produced by the hyperactive ovary is controversial as serous carcinomas are less hormone-dependent.

Spindle cell-rich testicular sex cord-stromal tumors (TSCSTs) comprise a group that includes mostly (but not exclusively): myoid gonadal stromal tumor (MGST), adult granulosa cell tumor (AGCT), and unclassified TSCST. These entities demonstrate histopathologic overlap, and prior genomic studies have failed to identify specific oncogenic drivers. Results of DNA sequencing suggest that different types of spindle cell-rich TSCSTs harbor a recurrent pattern of chromosomal gains. However, these results have not been validated by alternative methods and the extent of these changes within individual tumors remains unknown. We used a combination of commercially available fluorescence in-situ hybridization (FISH) probes (3q11.2, 6p24.3, 6q11.1, 6q23, 7q11.21-q11.22, 9p21.3, 11q13.3, 17p11.2) to enumerate a subset of chromosomes identified as altered (gained) in prior studies. We analyzed 10 cases (3 MGST, 4 unclassified TSCST, 3 AGCT), including 7 that had been previously sequenced. FISH demonstrated gains of chromosomes 3, 6, 7, 9, and 11 above the pre-established threshold (25%) in 50%, 80%, 70%, 20%, and 40% of cases, respectively, with gains of chromosome 17 being present in only 1 unclassified TSCST. The proportion of cells with chromosomal gains ranged from 26% to 60%. Tumors with available copy number data from prior genomic analyses showed a partial discordance between FISH and sequencing results. This study demonstrates that spindle-cell rich TSCSTs harbor a recurrent pattern of chromosomal gains, which are present in variable subsets of neoplastic cells. Further studies are needed to determine if these chromosomal changes represent a mechanism relevant for oncogenesis or a secondary event., Competing Interests: Declaration of competing interest The authors declare that they have no financial or intellectual conflicts of interest pertaining to the contents of this manuscript., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Gynecologic sex cord‐stromal tumors (SCSTs) arise from sex cords of the embryonic gonad and may display malignant behavior. We describe the cytomorphologic features of SCSTs in females, including adult and juvenile granulosa cell tumors (AGCTs and JGCTs), Sertoli‐Leydig cell tumors (SLCTs), and steroid cell tumors (SCTs). Methods: We retrieved available cytology slides from females with a histologic diagnosis of sex cord‐stromal tumor between 2009 and 2020 from institutional archives and reviewed their cytoarchitectural features. Results: There were 25, 2, 2, and 1 cytology specimens from 19, 2, 2, and 1 patients (aged 7‐90 years, median 57 years) with AGCT, JGCT, SLCT, and SCT, respectively. Features common to all SCSTs included 3‐dimensional groups, rosettes, rare papillary fragments, abundant single cells and naked nuclei. Rosettes and a streaming appearance of cell groups were only seen in AGCTs, which also rarely featured eosinophilic hyaline globules and metachromatic stroma. AGCTs exhibited high nuclear:cytoplasmic (N:C) ratios, with mild nuclear pleomorphism, uniform nuclei with finely granular chromatin, nuclear grooves and small nucleoli; in contrast, other SCSTs lacked rosettes and nuclear grooves and had generally lower N:C ratios, greater nuclear pleomorphism, coarse chromatin and more abundant cytoplasm. Mitotic figures, necrosis, and inflammation were rarely identified. Conclusions: AGCTs show cytomorphologic features that are distinct from those of other SCSTs. Careful evaluation of the cytological features and ancillary studies (eg, immunochemistry for FOXL2, inhibin and calretinin, or sequencing for FOXL2 mutations) can aid in the accurate diagnosis of these tumors. Adult granulosa cell tumors show cytomorphologic features that are distinct from those of other types of sex cord‐stromal tumor, including microfollicular structures, eosinophilic hyaline globules, and longitudinal nuclear grooves in tumor cells. Careful evaluation of the cytologic features and ancillary studies (eg, immunochemistry for FOXL2, inhibin, and calretinin, or sequencing for FOXL2 mutations) can aid in accurate diagnosis of these tumors. [ABSTRACT FROM AUTHOR]

Objective: Granulosa cell tumor (GCT) of the ovary is an uncommon neoplasm with good prognosis. GCT is a rare ovarian malignancy originating from sex cord-stromal cells. The only clinically proven prognostic factor regarding recurrence is stage. In this study, we aimed to analyze the detailed clinical and histopathological prognostic parameters of this rare malignancy, based on the cases we experienced in our own clinic. Material and Methods: Forty-six patients who were followed up and treated with the diagnosis of granulosa cell ovarian tumor between 2010 and 2020 were evaluated retrospectively by scanning the patient archive files. Results: The median follow-up period was 52 months. The mean patient age was 55 years. The most common symptom was abdominal pain. The most common surgical procedure was total abdominal hysterectomy+bilateral salpingo-oophorectomy+pelvic/paraaortic lymph node dissection with 60.9% (n=28). Fertility sparing surgery was performed for 5 (10.9%) patients. In this study, a significant relationship was found between the survival and FIGO stage, nuclear atypia, mitotic rate. The rate of metastatic lymph nodes is very low in primary surgery and therefore may not be performed. Conclusion: GCT is one of the rare diseases of ovary. Since recurrence may occur even after many years, the follow-up period should be kept long. Stage is still the most important prognostic factor and is directly related to survival. In addition, the mitotic rate and nuclear atypia of the tumor may also be prognostic factors and have an impact on survival. [ABSTRACT FROM AUTHOR]

Ovarian granulosa cell tumor (GCT) is a rare, low‐grade malignant tumor that accounts for 70% of the sex cord‐stromal tumors. It has two histopathologic types with different clinical and biologic features: adult GCT and juvenile GCT. Most women diagnosed with the adult GCT have a favorable prognosis, with a 5‐year survival rate of 97%–98%, but adult GCT has a feature of late relapse; the recurrence time could be more than 20 years after diagnosis. Juvenile GCT has a survival rate of 97% in stage I and a 5‐year survival rate of 0%–22% in advanced stage with earlier recurrence than adult GCT. Consequently, the scenario emphasizes the need for early diagnosis, standardized treatment protocols, and long‐term follow up. However, there is a lack of consensus regarding accurate diagnosis of GCT and adjuvant treatment. Furthermore, GCT tends to occur in young women, which emphasizes the viability of fertility‐sparing surgery. The current review performed a systematic literature review of 60 articles to summarize the latest advances in GCT, with an emphasis on the molecular pathogenesis and survival after fertility‐sparing surgery. We found that young women with fertility‐sparing surgery had a desirable reproductive and survival outcome compared with those undergoing radical surgery. [ABSTRACT FROM AUTHOR]

Sex cord-stromal tumors (SCSTs) are ovarian tumors that generally present with an adnexal mass and signs/symptoms of hormone excess. Gynandroblastoma is a rare subtype of SCST with a combination of female and male sex cord differentiation. These tumors typically present in premenopausal women and are diagnosed at early stages with benign clinical courses. Here, we present a rare case of recurrent gynandroblastoma in a premenopausal woman with a DICER1 germline mutation. The patient was referred to our clinic for new symptoms of hormonal imbalance with a history of ovarian juvenile granulosa cell tumor (JGCT). Evaluation revealed a 5x5cm complex right adnexal mass and rising inhibin B. Patient underwent total abdominal hysterectomy with right salpingo-oophorectomy, omentectomy and right pelvic and para-aortic lymphadenectomy. Pathology showed a right ovarian gynandroblastoma. Somatic biallelic mutations in the RNase IIIb domain of DICER1 were identified; a 23-gene germline panel confirmed a germline DICER1 pathogenic variant. Cascade testing of her children documented that both daughters inherited the pathogenic variant. Testing for DICER1 mutations has important implications for individual and familial tumor risk assessment given what we know about DICER1 mutation and increased childhood cancer risk.

Tumor progression studied by analysis of cellular features of serial ascitic ovarian carcinoma tumors. Adenocarcinoma, chicken, coelomic effusion, granulosa cell tumor, Oil red O, ovarian carcinoma, pancytokeratin, sex cord-stromal tumor Keywords: adenocarcinoma; chicken; coelomic effusion; granulosa cell tumor; Oil red O; ovarian carcinoma; pancytokeratin; sex cord-stromal tumor EN adenocarcinoma chicken coelomic effusion granulosa cell tumor Oil red O ovarian carcinoma pancytokeratin sex cord-stromal tumor 305 308 4 07/01/21 20210601 NES 210601 CASE PRESENTATION A 3-year-old female chicken was presented to the Zoological Medicine Service at the University of Florida with severe crop distention and lethargy. [Extracted from the article]

Adult‐type granulosa cell tumors (aGCTs) account for 90% of malignant ovarian sex cord‐stromal tumors and 2–5% of all ovarian cancers. These tumors are usually diagnosed at an early stage and are treated with surgery. However, one‐third of patients relapse between 4 and 8 years after initial diagnosis, and there are currently no effective treatments other than surgery for these relapsed patients. As the majority of aGCTs (>95%) harbor a somatic mutation in FOXL2 (c.C402G; p.C134W), the aim of this study was to identify genetic mutations besides FOXL2 C402G in aGCTs that could explain the clinical diversity of this disease. Whole‐genome sequencing of 10 aGCTs and their matched normal blood was performed to identify somatic mutations. From this analysis, a custom amplicon‐based panel was designed to sequence 39 genes of interest in a validation cohort of 83 aGCTs collected internationally. KMT2D inactivating mutations were present in 10 of 93 aGCTs (10.8%), and the frequency of these mutations was similar between primary and recurrent aGCTs. Inactivating mutations, including a splice site mutation in candidate tumor suppressor WNK2 and nonsense mutations in PIK3R1 and NLRC5, were identified at a low frequency in our cohort. Missense mutations were identified in cell cycle‐related genes TP53, CDKN2D, and CDK1. From these data, we conclude that aGCTs are comparatively a homogeneous group of tumors that arise from a limited set of genetic events and are characterized by the FOXL2 C402G mutation. Secondary mutations occur in a subset of patients but do not explain the diverse clinical behavior of this disease. As the FOXL2 C402G mutation remains the main driver of this disease, progress in the development of therapeutics for aGCT would likely come from understanding the functional consequences of the FOXL2 C402G mutation. [ABSTRACT FROM AUTHOR]

Abstract Background To investigate MRI for differentiating benign from malignant sex cord-stromal tumors of the ovary (SCSTs) emphasizing on the value of diffusion-weighted (DW) magnetic resonance (MR) imaging. Methods This retrospective study included 29 benign SCSTs in 28 patients and 13 malignant SCSTs in 13 patients. DW imaging as well as conventional MR imaging was performed. Signal intensity on DW imaging was assessed and apparent diffusion coefficient (ADC) value was measured. In addition, T2 signal intensity and contrast enhancement pattern were also assessed and compared between benign and malignant SCSTs. Results Both of the T2 hypointensity and mild enhancement were specific to benign SCSTs. The majority of malignant SCSTs showed high signal intensity on DW imaging, whereas most benign SCSTs showed low or moderate signal intensity (p = 0.000). Fibromas were the tumors with the lowest observed ADC value (0.470 × 10− 3 mm2/s). Sclerosing stromal tumors were the tumors with the highest observed ADC value (2.291 × 10− 3 mm2/s). ADC value of solid component was significantly lower in malignant SCSTs (0.825 ± 0.129 × 10− 3 mm2/s) than in benign SCSTs (1.343 ± 0.528 × 10− 3 mm2/s) when fibromas were excluded (p = 0.024). T2, DCE and DW imaging has a limited value on the differential diagnosis of the benign and malignant SCSTs with an accuracy of 69.0%,71.4% and 78.1% respectively. Combination of T2, DCE and DW imaging permitted the distinction with an accuracy of 88.0%. Conclusions It is more helpful for distinction of the benign and malignant SCSTs by combining of T2, DCE and DW imaging than using each of the three sequences independently.

Purpose: To investigate the epidemiology, clinico-pathological characteristics and outcomes of patients diagnosed with malignant ovarian Sertoli-Leydig cell tumors (SLCTs) in comparison to granulosa cell tumors (GCTs). Methods: The National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) database were accessed and patients diagnosed with a malignant SLCT and GCT between 1988 and 2013 were selected. Demographic and clinico-pathological characteristics were compared using the Mann–Whitney and chi-square tests. Overall (OS) and cancer-specific survival (CSS) rates were estimated with the Kaplan–Meier method and compared with the log-rank test. Cox hazard models were constructed to control for confounders. Results: A total of 175 and 1361 patients diagnosed with SLCT and GCT, respectively, were identified. Compared to patients with GCT, those with SLCT were younger (median age 32 vs. 51 years, p < 0.001) and more likely to present with larger tumors (median size 15 vs 9.5 cm, p < 0.001) confined to the ovary (77.5% vs 69.2%, p = 0.031). Patients with SLCTs had worse CSS compared to those with GCTs, p < 0.001 (5-year rate was 76.2% vs 90.7%). After controlling for the presence of extra-ovarian disease and tumor size (≤ 10 vs > 10 cm), SCLTs were associated with a worse cancer-specific mortality compared to GCTs. Conclusions: SLCTs are extremely rare, commonly arise in premenopausal patients. They are associated with a poorer prognosis compared to GCT. [ABSTRACT FROM AUTHOR]

Sex cord–stromal tumors of the testes are rare malignancies as compared to germ cell tumors. Pure Sertoli cell tumors are still rare representing

We report a case of microcystic stromal tumor (MCST) resected by laparoscopy. MCST is a very rare ovarian tumor with distinctive microcystic features and a characteristic stromal tumor immunophenotype. The present case was a 26-year-old woman who underwent laparoscopic surgery for suspected endometrial cyst of the left ovary. The mass was 8 cm in size and contained bloody fluid, and after attempting cystectomy, we eventually performed left salpingo-oophorectomy with a final postoperative pathological diagnosis of MCST. Although MCST has not yet been associated with malignancy, there are reported links to mutations in the β-catenin gene, and long-term prognosis is still unknown. As MCST resection by laparoscopy has not yet been fully described in the literature, the current case provides an example of when an unexpected, potentially malignant mass is encountered during routine cystectomy and details its subsequent management laparoscopically.

Objective To explore the preoperative diagnostic value of MRI for ovarian sex cord-stromal tumors (SCSTs). Methods A retrospective analysis was performed on the MRI data of 52 patients in our hospital with pathologically documented ovarian SCSTs. Results Among the 43 patients， 35 were with theca cell tumor， which was solid or cystic-solid， mainly with low signals on T1WI and T2WI. The larger ones were accompanied by patchy high signals， and the enhanced scan showed mild to moderate intensity enhancement. Another 10 cases were with granular cell tumor，which was cystic-solid，with iso-low signals on T1WI and high signals on T2WI ， and enhancement was found in the solid part and no enhancement in the cystic part. The rest 7 cases were with sclerosing stromal tumor，which was solid or cystic-solid，with isosignal on T1WI and medium signal with heterogeneity on T2WI，and low signal ring could be seen around while continuous enhancement of enhanced scanning was obvious. Conclusion MRI allows clear display of the structural and cytological characteristics of ovarian SCSTs， supporting its application in preoperative diagnosis of ovarian SCSTs. [ABSTRACT FROM AUTHOR]

Testicular tumors apart from those in the germ cell family are uncommon and are mostly sex cord-stromal tumors and may pose a major diagnostic challenge. This review focuses on the clinicopathologic features of these uncommon neoplasms, pertinent differential diagnoses, relevant immunohistochemical and molecular findings as well as the recent updates proposed by the World Health Organization (WHO). Contrast between these neoplasms as seen in the male and female gonad will also be made when warranted. The commonest sex cord-stromal tumor of the testis is the Leydig cell tumor which, when seen in children, is often associated with sexual precocity. The histologic features are generally those of an easily recognized oxyphilic neoplasm but various peculiarities such as microcysts and spindling of the tumor cells may case diagnostic difficulty on occasion. In the male, in contrast to the female, the most common sex cord-stromal tumor of epithelial nature is the Sertoli cell tumor. Most of these fall in the not otherwise specified category and are usually characterized by a diagnostically helpful at least focal hollow or solid tubular pattern. Occasional malignant Sertoli cell tumors have a predominantly diffuse pattern sometimes interrupted by septa with a lymphocytic infiltrate that can cause seminoma to be mimicked. Rare Sertoli cell tumors are associated with marked sclerosis. The so-called large cell calcifying Sertoli cell tumor, may be sporadic or associated with manifestations of the Carney syndrome. A distinctive entity referred to as intratubular hyalinizing Sertoli cell neoplasia occurs in the testis of young boys with Peutz-Jeghers syndrome. It is often bilateral, microscopic and associated with gynecomastia. Testicular granulosa cell tumors are much rarer than their ovarian counterparts but can be similarly subdivided into adult and juvenile forms. In the male, the juvenile granulosa cell tumor has a particularly striking tendency to occur in the first 6 months of life. The primitive appearance of the nuclei and brisk mitotic activity of the juvenile granulosa cell tumor may result in a misdiagnosis of a more malignant neoplasm. The histologic spectrum of the adult granulosa cell tumor is as seen in the more common female examples. Pure stromal tumors of the testis are much less common than similar tumors in the ovary and the well-known thecoma is remarkably rare in the testis. Fibromas of stromal derivation in the testis should be distinguished from fibromas that originate from the tunica albuginea and from examples of the non-neoplastic process nodular pseudotumor. [ABSTRACT FROM AUTHOR]

Juvenile granulosa cell tumor (JGCT) is an extremely rare ovarian tumor that has been associated with Maffucci syndrome. It both secretes hormone and has been postulated to grow in response to hormone. We present a case of a 33-year-old G1P0 asymptomatic woman with a history of Maffucci syndrome found to have a left adnexal mass on routine ultrasonography at 13 weeks gestation. This case demonstrates the sonographic and magnetic resonance imaging (MRI) features of JGCT, as well as the natural progression of the tumor during pregnancy. A follow-up ultrasound 3 weeks after initial diagnosis demonstrated marked growth in size and vascularity of the tumor, prompting unilateral salpingo-oophorectomy. Histopathological findings confirmed the diagnosis of JGCT. • Juvenile granulosa cell tumor (JGCT) is extremely rare in the general population, but it is a diagnosis that must be considered in patients with Maffucci syndrome and Ollier disease. • JGCT is hormonally sensitive and exhibit rapid growth during pregnancy, therefore, early diagnosis is vital. • Tumor markers have to be interpreted with caution during pregnancy. As a result, imaging plays an important role in the diagnosis of JGCT. [ABSTRACT FROM AUTHOR]

Objective: To investigate the role of adjuvant chemotherapy (CT) in the management of ovarian non-granulosa cell (GC) sex cord-stromal tumors (SCSTs). Methods: The National Cancer Database was accessed and patients diagnosed between 2004 and 2013 with a malignant non-GC SCST were selected. Overall survival (OS) was evaluated with Kaplan-Meier curves and compared with the log-rank test. Multivariate survival analysis was performed with Cox regression. Factors associated with the administration of CT were evaluated with the chi-square test and binary logistic regression. Results: A total of 391 patients were identified. The majority had a Sertoli-Leydig cell tumor (SLCT) (73.2%) and early stage disease (84.8%). A total of 203 (51.9%) patients received CT. Advanced disease stage, younger age, high-grade histology, White race, large tumor size and SLCT histology were associated with administration of CT. For patients with early stage disease, there was no difference in OS between those who did (n=134) and did not receive CT (n=157), p=0.40; 5-year OS rates were 81.7% and 84.6%, respectively. No mortality benefit was observed (hazard ratio=0.73; 95% confidence interval=0.38-1.4) after controlling for tumor histology. Median OS of women with advanced stage disease who received CT (n=41) was 34.96 months compared to 15.51 months for those who did not (n=11), p=0.013. Conclusion: Adjuvant CT was associated with improved survival for patients with advanced stage non-GC SCSTs. No clear benefit was found for those with early stage disease. [ABSTRACT FROM AUTHOR]

A small subset of testicular sex cord-stromal tumors, designated as Sertoli-stromal cell tumors (SSCTs), comprises a mixture of Sertoli, spindle, and/or Leydig cells. The clinicopathologic features of these tumors have not been studied in any detail, and their molecular features are unknown. We, therefore, assessed the morphologic and genomic features of 14 SSCTs, including 1 tumor with features similar to the ovarian Sertoli-Leydig cell tumor (SLCT) with retiform tubules. The median age of the patients was 24 years (range, 10-55 years), and the median tumor size was 2.3 cm (range, 0.7-4.7 cm). All tumors showed Sertoli-like sex cord cells arranged in variably developed tubular structures, typically also forming nests and cords. These imperceptibly blended with a neoplastic spindle cell stroma or, in the SLCT, vacuolated to eosinophilic Leydig cells. Genomic analysis demonstrated the presence of a hotspot loss-of-function DICER1 mutation in the SLCT (patient 1) and hotspot gain-of-function CTNNB1 mutations in the tumors of patients 2 and 3, with both CTNNB1 variants being interpreted as possible subclonal events. The mutations were the only relevant findings in the tumors of patients 1 and 2, whereas the tumor of patient 3 harbored concurrent chromosomal arm-level and chromosome-level copy number gains. Among the remaining 11 tumors, all of those that had interpretable copy number data (9 tumors) harbored multiple recurrent chromosomal arm-level and chromosome-level copy number gains suggestive of a shift in ploidy without concurrent pathogenic mutations. The results of the present study suggest that CTNNB1 mutations (likely subclonal) are only rarely present in SSCTs; instead, most of them harbor genomic alterations similar to those seen in testicular sex cord-stromal tumors with pure or predominant spindle cell components. A notable exception was a testicular SLCT with morphologic features identical to the ovarian counterpart, which harbored a DICER1 mutation., (Copyright © 2023 United States & Canadian Academy of Pathology. Published by Elsevier Inc. All rights reserved.)

Background Ovarian sex cord-stromal tumors (OSCST) include juvenile granulosa cell tumors (JGCT), Sertoli-Leydig cell tumor (SLCT) and gynandroblastoma (GAB) among others. These ovarian sex cord-stromal tumors as well as other tumors including pleuropulmonary blastoma (PPB) may be associated with DICER1 mutations. We sought to describe the clinical and genetic findings from the first 107 individuals enrolled in the International Ovarian and Testicular Stromal Tumor Registry. Methods Medical and family history were obtained for individuals consecutively enrolled in the International Ovarian and Testicular Stromal Tumor Registry. Pathology was centrally reviewed. DICER1 sequencing was performed on blood and tumor tissue. Results Of the 107 participants, 49 had SLCT, 25 had JGCT and 5 had GAB. Nearly all (36/37) SLCTs and 4/4 GAB tested had a DICER1 mutation in an RNase IIIb domain hotspot; approximately half of these individuals had a predisposing germline DICER1 mutation. Metachronous SLCTs were seen in 3 individuals with germline DICER1 mutations. Other DICER1 -associated conditions were seen in 19% of patients with SLCT or GAB. Three children of women with SLCT were diagnosed with PPB based on genetic testing and clinical screening during the course of this study. All were diagnosed with PPB in its earliest and most curable form (Type I), were treated with surgery alone, and are alive without evidence of disease. Conclusions Recognition of the distinct genetic basis for a group of these tumors improves precise classification in difficult cases and promotes mutation-based screening and early detection. [ABSTRACT FROM AUTHOR]

A white, lobular mass was found in the right ovary of a pregnant Risso's dolphin (Grampus griseus) at necropsy. The mass was unilateral and occupied most of the pre-existing ovarian tissue. Histologically, the mass was composed of diffuse sheets of polyhedral cells with abundant eosinophilic cytoplasm and oval nuclei, separated by fibrous connective tissue. Only a few ovarian follicles were observed at the periphery of the mass. Immunohistochemically, the large eosinophilic cells were positive for vimentin and negative for pan-cytokeratins. Based on the histopathological features, the present case was diagnosed as luteoma. In human medicine, luteoma of pregnancy, a tumor-like proliferative lesion occurring in pregnant women, is well described. In veterinary medicine, luteoma associated with pregnancy has never been described. The present study would provide useful information for understanding the characteristics of luteoma in animals. [ABSTRACT FROM AUTHOR]

Extraovarian sex cord-stromal tumor is an exceedingly uncommon entity that may cause a diagnostic dilemma clinically. We report a case of extraovarian fibroma with minor sex cord elements arising in the left broad ligament. The patient was a 66-year-old woman presenting with an intra-abdominal solid mass near the left ovary on magnetic resonance imaging. The tumor was located in the left broad ligament in contact with the left ovary and fallopian tube based on laparotomy findings. Histological examination revealed that the tumor was a fibroma that contained cell nests with aggregates resembling the Call-Exner bodies of granulosa cell tumors and irregularly shaped cell nests composed of undifferentiated sex cord-type cells. Cellular atypia or mitotic figures were not identified in any of the components. It was speculated that the possible site of origin of this tumor might be a supernumerary ovary in the broad ligament that was thought to be derived from embryonic remnants. [ABSTRACT FROM AUTHOR]

We report a case of microcystic stromal tumor (MCST) resected by laparoscopy. MCST is a very rare ovarian tumor with distinctive microcystic features and a characteristic stromal tumor immunophenotype. The present case was a 26-year-old woman who underwent laparoscopic surgery for suspected endometrial cyst of the left ovary. The mass was 8 cm in size and contained bloody fluid, and after attempting cystectomy, we eventually performed left salpingo-oophorectomy with a final postoperative pathological diagnosis of MCST. Although MCST has not yet been associated with malignancy, there are reported links to mutations in the β-catenin gene, and long-term prognosis is still unknown. As MCST resection by laparoscopy has not yet been fully described in the literature, the current case provides an example of when an unexpected, potentially malignant mass is encountered during routine cystectomy and details its subsequent management laparoscopically. [ABSTRACT FROM AUTHOR]

Steroid cell tumor not otherwise specified (SCT-NOS) is a rare type of sex cord-stromal tumor with malignant potential. A 19-year-old woman underwent laparoscopic bilateral cystectomy, and postoperative pathology showed bilateral ovarian SCT-NOS. She had recurrence of the right tumor 8 years after the surgery, with shortened menstrual cycles, elevated testosterone and prolactin concentrations, and impaired glucose metabolism. We performed a laparoscopic right salpingo-oophorectomy. Testosterone and prolactin concentrations rapidly decreased and returned to the normal range after surgery. Subsequently, she had regular menstrual cycles and good glycemic control. The findings in our case suggest that there is a possibility of late recurrence in SCT-NOS. Therefore, we suggest that the postoperative follow-up period should be 10 years for this condition.

Sertoli cell tumor (SCT) is the second most common type of sex cord-stromal tumor in men, and ∼10% exhibit malignant behavior. Although CTNNB1 variants have been described in SCTs, only a limited number of metastatic cases have been analyzed, and the molecular alterations associated with aggressive behavior remain largely unexplored. This study evaluated a series of nonmetastasizing and metastasizing SCTs using next-generation DNA sequencing to further characterize their genomic landscape. Twenty-two tumors from 21 patients were analyzed. Cases were divided into metastasizing SCTs and nonmetastasizing SCTs. Nonmetastasizing tumors were considered to have aggressive histopathologic features if they exhibited ≥1 of the following: size >2.4 cm, necrosis, lymphovascular invasion, ≥3 mitoses per 10 high-power fields, severe nuclear atypia, or invasive growth. Six patients had metastasizing SCTs, and the remaining 15 patients had nonmetastasizing SCTs; 5 nonmetastasizing tumors had ≥1 aggressive histopathologic feature(s). Gain-of-function CTNNB1 or inactivating APC variants were highly recurrent in nonmetastasizing SCTs (combined frequency >90%), with arm-level/chromosome-level copy number variants, loss of 1p, and CTNNB1 loss of heterozygosity occurring exclusively in CTNNB1-mutant tumors with aggressive histopathologic features or size >1.5 cm. Nonmetastasizing SCTs were almost invariably driven by WNT pathway activation. In contrast, only 50% of metastasizing SCTs harbored gain-of-function CTNNB1 variants. The remaining 50% of metastasizing SCTs were CTNNB1-wild-type and harbored alterations in the TP53, MDM2, CDKN2A/CDKN2B, and TERT pathways. These findings suggest that ∼50% of aggressive SCTs represent progression of CTNNB1-mutant benign SCTs, whereas the remaining ones are CTNNB1-wild-type neoplasms that exhibit alterations in genes of the TP53, cell cycle regulation, and telomere maintenance pathways., (Copyright © 2023 United States & Canadian Academy of Pathology. Published by Elsevier Inc. All rights reserved.)