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Introduction: We aimed to demonstrate the sensitivity of frozen section for patients with adult granulosa cell tumor (AGCT) and analyze the clinico-pathological factors that may be associated with sensitivity. Material methods: This is a multicenter study including data of 10 Gynecological Oncology Departments. Frozen-section results of patients who had ovarian AGCT at the final pathology report were retrospectively analyzed. The relation between clinico-pathological characteristics such as age, tumor size, Ca-125 level, presence of ascites, omental metastasis, menopausal status and peritoneal cytology, and the sensitivity of frozen section in patients with AGCT were evaluated. The sensitivity of frozen section diagnosis was determined by comparing the frozen section result with the final pathological diagnosis. Results: Frozen section results of 274 patients with AGCT were obtained. The median age of the patients was 52 years (range, 17–82 years). Totally, 144 (52.7%, n = 273) patients were postmenopausal. The median tumour size was 90 mm (range, 9–700 mm). The median preoperative Ca-125 level was 23 IU/mL (range, 2–995 IU/mL). The sensitivity of frozen section for detecting AGCT was 76.3%. Any association between the sensitivity of frozen section and menopausal status, presence of ascites, positive cytology, omental metastasis, tumor size, Ca-125 level, age could not be shown. Conclusion: It is important to know the diagnosis of AGCT intraoperatively, and we demonstrated the sensitivity of frozen-section for these tumors as 76.3%. [ABSTRACT FROM AUTHOR]

Collision tumors of the ovaries are rare, with only a few reports in the literature. Adult granulosa cell tumors are a relatively common primary tumor component of previously reported collision tumors. The combination of serous and mucinous tumors with adult granulosa cell tumors has been reported in several cases. On the other hand, mesonephric-like adenocarcinomas are rare neoplasms that commonly arise in the uterine corpus and ovaries. In this report, we present the case of a collision tumor composed of an adult granulosa cell tumor and mesonephric-like adenocarcinoma of the ovary in a 63-year-old woman. The initial magnetic resonance imaging findings showed a cystic mass with an internal hemorrhage, which suggested an adult granulosa cell tumor, and a solid mass with different enhancements. Microscopically, the tumor had two distinct components: An adult granulosa cell tumor and a mesonephric-like adenocarcinoma. Recognizing collision tumors consisting of slow-growing and aggressive tumors may prove beneficial in future diagnostic and treatment strategies. [ABSTRACT FROM AUTHOR]

Objective: The main feature of adult granulosa cell tumors (AGCT) is their capacity to secrete hormones, with nearly all of them capable of synthesizing oestradiol. The primary goal of this study is to identify synchronized endometrial pathologies, particularly endometrial cancer, in AGCT patients who had undergone a hysterectomy. Materials and Methods: The study cohort comprised retrospectively of 316 AGCT patients from 10 tertiary gynecological oncology centers. AGCT surgery consisted of bilateral salpingo‐oophorectomy, hysterectomy, peritoneal cytology, omentectomy, and the excision of any suspicious lesion. The median tumor size value was used to define the relationship between tumor size and endometrial cancer. The relationship between each value and endometrial cancer was evaluated. Results: Endometrial intraepithelial neoplasia, or hyperplasia with complex atypia, was detected in 7.3% of patients, and endometrial cancer in 3.1% of patients. Age, menopausal status, tumor size, International Federation of Gynecology and Obstetrics stage, ascites, and CA‐125 level were not statistically significant factors to predict endometrial cancer. There was no endometrial cancer under the age of 40, and 97.8% of women diagnosed with endometrial hyperplasia were over the age of 40. During the menopausal period, the endometrial cancer risk was 4.5%. Developing endometrial cancer increased to 12.1% from 3.2% when the size of the tumor was >150 mm in menopausal patients (p = 0.036). Conclusion: Endometrial hyperplasia, or cancer, occurs in approximately 30% of AGCT patients. Patients diagnosed with AGCT, especially those older than 40 years, should be evaluated for endometrial pathologies. There may be a relationship between tumor size and endometrial cancer, especially in menopausal patients. [ABSTRACT FROM AUTHOR]

Collision tumors of the ovaries are rare, with only a few reports in the literature. Adult granulosa cell tumors are a relatively common primary tumor component of previously reported collision tumors. The combination of serous and mucinous tumors with adult granulosa cell tumors has been reported in several cases. On the other hand, mesonephric-like adenocarcinomas are rare neoplasms that commonly arise in the uterine corpus and ovaries. In this report, we present the case of a collision tumor composed of an adult granulosa cell tumor and mesonephric-like adenocarcinoma of the ovary in a 63-year-old woman. The initial magnetic resonance imaging findings showed a cystic mass with an internal hemorrhage, which suggested an adult granulosa cell tumor, and a solid mass with different enhancements. Microscopically, the tumor had two distinct components: An adult granulosa cell tumor and a mesonephric-like adenocarcinoma. Recognizing collision tumors consisting of slow-growing and aggressive tumors may prove beneficial in future diagnostic and treatment strategies.

Adult granulosa cell tumors (AGCTs) are rare malignancies that accounts for approximately 1% of ovarian neoplasms. As there are currently no well-recognized models for predicting relapse-free survival (RFS), we performed a clinicopathological analysis to identify risk factors for AGCT recurrence. We investigated 130 patients with pathologically diagnosed AGCT as confirmed by the presence of the characteristic FOXL2 C402G mutation. Most patients had International Federation of Gynecology and Obstetrics stage I disease (n = 122, 95.3%). The 10-year RFS rate was 31.4% (22/70) and mean 10-year RFS was 74.4 (95% CI, 65.2–83.7) months. Ten patients experienced recurrence beyond the 10-year follow-up period. Undergoing fertility sparing surgery, an estrogen receptor-α (ERα) score (>0.25), and a Ki-67 index >15% were independent risk factors for recurrence in patients with stage I disease (bias-corrected C-index: 0.776). We constructed a nomogram with well-fitting calibration plots; the areas under the curve (AUCs) for 5-, and 10-year RFS prediction were 0.883 and 0.906 respectively. A simplified model with 3 predictive factors (ERα score, Ki-67 index, and primary surgical procedure) and 2 risk stratification subgroups (low- and high-risk) was constructed; its AUCs for 5-, and 10-year RFS prediction were 0.825 and 0.850 respectively. Kaplan-Meier survival curves showed significant differences in 10-year RFS between the low- and high-risk groups (p < 0.001). The type of primary surgical procedure, ERα score, and Ki-67 index are independent predictors of recurrence for patients with stage I AGCT. Our predictive model based on these factors showed good performance. • We evaluated recurrence risk in patients with adult granulosa cell tumors (AGCTs). • We focused on factors predicting recurrence in patients with stage I AGCT. • Independent predictors were the ERα score, Ki-67 index, and primary surgical procedure. • The histopathological characteristics were not associated with recurrence. • Our predictive model showed good reliability for predicting the risk of recurrence. [ABSTRACT FROM AUTHOR]

Identifying prognostic factors and evaluating the impact of adjuvant chemotherapy in patients with sex cord stromal tumors (SCST) is crucial. In this study, we aimed to address these challenges. We conducted a retrospective analysis of data from 13 centers of the French Rare malignant gynecological tumors (TMRG) network. We enrolled 469 adult patients with malignant SCST who received upfront surgery since 2011 to July 2015. 75% were diagnosed with adult Granulosa cell tumors, and 23% had another subtype. With a median follow-up of 6.4 years, 154 patients (33%) developed a first recurrence, 82 (17%) two recurrences, and 49 (10%) three recurrences. Adjuvant chemotherapy was administered in 14.7% of patients at initial diagnosis. In relapse, perioperative chemotherapy was administered in 58.5%, 28.2%, and 23.8% of patients, respectively, in the first, second, and third relapse. In the first-line therapy, age under 70 years, FIGO stage, and complete surgery were associated with longer progression-free survival (PFS). Chemotherapy had no impact on PFS in early-stage disease (FIGO I-II). The PFS was similar using BEP or other chemotherapy regimens (HR 0.88 [0.43; 1.81]) in the first-line therapy. In case of recurrence, PFS was statistically prolonged by complete surgery, but perioperative chemotherapy use did not impact PFS. Chemotherapy use did not impact survival in the first-line or relapse setting in SCST. Only surgery and its quality demonstrated benefit for PFS in ovarian SCST in any lines of treatment. • Surgery remains the mainstay of treatment for sex cord stromal tumors (SCST) in both the initial treatment and relapses. • Adjuvant Chemotherapy does not improve PFS for patients in 1st line setting with stage I-II but also in relapse setting • Adjuvant chemotherapy with BEP does not appear to improve PFS compared to other regimes. [ABSTRACT FROM AUTHOR]

Abstract Background Granulosa cell tumors (GCT) are rare malignant ovarian tumors. The two subtypes, adult and juvenile granulosa cell tumors, differ in clinical and molecular characteristics. GCT are low-malignant tumors and are generally associated with favorable prognosis. However, relapses are common even years and decades after diagnosis. Prognostic and predictive factors are difficult to assess in this rare tumor entity. The purpose of this review is to provide a comprehensive overview of the current state of knowledge on prognostic markers of GCT to identify patients with a high risk of recurrence. Methods Systematic research for adult ovarian granulosa cell tumors and prognosis revealed n = 409 English full text results from 1965 to 2021. Of these articles, n = 35 were considered for this review after title and abstract screening and topic-specific matching. A specific search for pathologic markers with prognostic relevance for GCT identified n = 19 articles that were added to this review. Results FOXL2 mutation and FOXL2 mRNA were inverse and immunohistochemical (IHC) expression of CD56, GATA-4 and SMAD3 was associated with reduced prognosis. IHC analysis of estrogen receptor, Anti-Mullerian hormone (AMH) and inhibin was not associated with prognosis for GCT. Analyses of mitotic rate, Ki-67, p53, β-catenin and HER2 revealed inconsistent results.

Introduction: This study aimed to describe the clinicopathological characteristics of recurrent adult granulosa cell tumor and identify the risk factors for recurrence. Material and methods: Seventy recurrent adult granulosa cell tumor patients treated in Peking Union Medical College Hospital between 2000 and 2020 were retrospectively reviewed. The primary outcomes were progression-free survival after first recurrence (PFS-R), overall survival after first recurrence (OS-R) and recurrence frequency. The Kaplan-Meier analysis, univariate and multivariate Cox proportional hazard analysis, and the Prentice, Williams and Peterson counting process (PWP-CP) model were adopted. Results: There were 70 patients included in the study, and recurrence occurred twice in more than 71% of patients, and 49.9% of patients relapsed = three times. The recurrence pattern in over half of the patients at first recurrence was multifocal and distant disease, and abdominal or pelvic mass and liver metastasis were the most common. The 5-year PFS-R was 29.3%, and the 10-year PFS-R was 11.3%; the 5-year OS-R was 94.9%, and the 10-year OS-R was 87.9%. Kaplan-Meier analysis demonstrated that patients with distant recurrence and PFS1 (PFS when first recurrence occurred) =60 months had worse PFS-R (p = 0.017, 0.018), and patients with PFS-R = 34 months had worse OS-R (p = 0.023). It demonstrated that PFS1 = 60 months (hazard ratio, HR 1.9, 95% confidence interval [CI]: 1.1-3.4, p = 0.028) was an independent risk factor for PFS-R, and local lesion at recurrence (HR 0.488, 95% CI: 0.3-0.9, p = 0.027) was an independent protective factor for PFS-R. In addition, it demonstrated that PFS-R = 33 months (HR 5.5, 95% CI: 1.2-25.3, p = 0.028) was an independent risk factor for OS-R. The PWP-CP analysis showed that laparoscopic operation (at each operation) could significantly increase recurrence times (p = 0.002, HR = 3.4), and no existence of gross residual lesion (R0) at each recurrence operation could significantly decrease recurrence frequency (p < 0.001, HR <0.001). Conclusions: The recurrence pattern in patients with recurrent adult granulosa cell tumor was characterized as late and repeated, multifocal, and distant relapse. It has been demonstrated that PFS1 = 60 months and distant lesion at recurrence are independent risk factors for PFS-R, and PFS-R = 33 months is an independent risk factor for OS-R. The PWP-CP model showed that the transabdominal approach and surgery reaching R0 could significantly decrease the recurrence frequency. [ABSTRACT FROM AUTHOR]

Objective: To illustrate the clinical course of a rare case of recurrent adult granulosa cell tumor (AGCT) and discuss the features and management for recurrences. Case report: A 56-year-old female was first diagnosed with AGCT in 2008 and had uneventful, regular follow-ups until 2013. Recurrence was suspected and proven by computed tomography-guided biopsy. After undergoing complete cytoreductive surgery (CRS) followed by adjuvant megestrol acetate then leuprolide acetate, another recurrence sprouted at the presacral area in 2017. On both occasions, CRS with no visible residual tumor were attained. The patient has remained in complete remission to date with progestin therapy. Conclusion: There are currently no standardized tumor markers, imaging exams, or therapies for managing AGCT recurrences. Whole exome sequencing analysis of our patient suggested possible association with triosephosphate isomerase 1 mutation. Regular follow-ups with at least two types of imaging exams and indefinite hormone therapy are crucial for this patient's remission.

Background: Granulosa cell tumors (GCT) are rare malignant ovarian tumors. The two subtypes, adult and juvenile granulosa cell tumors, differ in clinical and molecular characteristics. GCT are low-malignant tumors and are generally associated with favorable prognosis. However, relapses are common even years and decades after diagnosis. Prognostic and predictive factors are difficult to assess in this rare tumor entity. The purpose of this review is to provide a comprehensive overview of the current state of knowledge on prognostic markers of GCT to identify patients with a high risk of recurrence. Methods: Systematic research for adult ovarian granulosa cell tumors and prognosis revealed n = 409 English full text results from 1965 to 2021. Of these articles, n = 35 were considered for this review after title and abstract screening and topic-specific matching. A specific search for pathologic markers with prognostic relevance for GCT identified n = 19 articles that were added to this review. Results: FOXL2 mutation and FOXL2 mRNA were inverse and immunohistochemical (IHC) expression of CD56, GATA-4 and SMAD3 was associated with reduced prognosis. IHC analysis of estrogen receptor, Anti-Mullerian hormone (AMH) and inhibin was not associated with prognosis for GCT. Analyses of mitotic rate, Ki-67, p53, β-catenin and HER2 revealed inconsistent results. [ABSTRACT FROM AUTHOR]

Introduction We would like to present a rare case of metastatic renal tumor. Case presentation A 60‐year‐old woman presented to our department with a left renal tumor. She underwent a total hysterectomy and right adnexal resection for a stage IA ovarian granulosa cell tumor approximately 15 years ago, followed by left adnexal resection and postoperative chemotherapy with gemcitabine and paclitaxel 6 years ago. She received six courses of gemcitabine and carboplatin to treat a stage IC clear cell adenocarcinoma of the ovary. The patient was diagnosed with the left renal tumor and underwent a laparoscopic left nephrectomy. Immunostaining was positive for α‐inhibin and SF‐1 and showed FOXL2 402C→G (C134W) mutation. Finally, the patient was diagnosed with renal metastasis of a granulosa cell tumor. Conclusion To our knowledge, this is a very rare case of renal metastasis of a granulosa cell tumor with the FOXL2 mutation in an adult.

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.)

Objective: Adult-type granulosa cell tumors (GCT) are sex cord-stromal tumors and often accompanied with abdominal distention and hyperestrogenism-related symptoms. Adult-type GCT-presenting ascites and pleural effusion is extremely rare. Case report: A 56-year-old perimenopausal woman presented with abdominal distention and abnormal vaginal spotting. Ultrasound and abdominal computed tomography showed a complex cystic mass in the left ovary accompanied with bilateral pleural effusion and ascites. The patient underwent total abdominal hysterectomy, bilateral salpingo-oophorectomy, left pelvic lymph node dissection, omentectomy and appendectomy. Final histopathological diagnosis was adult-type GCT. The patient had postoperative hormone and anti-angiogenesis agent therapy with free of disease. Conclusion: Ovarian cystic complex mass accompanied with ascites and pleural effusion often results from malignant ovarian tumors or benign ovarian fibroma. Based on the aforementioned report, the rare types of ovarian tumors, such as adult-type granulosa cell tumor of the ovary should be taken into consideration.

Therapeutic options for recurrent adult granulosa cell tumors (AGCT) are limited. After examining the hormonal pathways involved in FOXL2-mutated granulosa cell tumor development, a novel treatment regimen was utilized for recurrent AGCT: a combination of an androgen receptor antagonist, a gonadotropin-releasing hormone receptor agonist, and an aromatase inhibitor for hormonal blockade. In this case series, seven patients at our institution were treated with bicalutamide 50 mg orally once daily, Leuprolide acetate 7.5 mg intramuscular (IM) injection every 4 weeks, and a daily oral aromatase inhibitor. These patients had recurrent AGCT with androgen receptor positive tumors and had failed prior aromatase inhibitor therapy. All patients had undergone multiple surgical resections and many cycles of chemotherapy. Patients were monitored for toxicities and for response to treatment. Of the seven patients receiving the triple therapy, six saw clinical benefit. Two patients demonstrated a partial response and four patients had stable disease. One patient had progressive disease on the regimen. For the two patients who had a partial response to the triple therapy, there was strong expression of the androgen receptor (AR) noted on tumor immunohistochemistry. This drug combination was well-tolerated except for severe hot flashes in one patient. In conclusion, the triple therapy combination of an androgen receptor antagonist, aromatase inhibitor, and GnRH agonist demonstrated measurable responses in patients with recurrent AGCTs after multiple previous treatments. A prospective clinical trial is planned to further investigate these findings.

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]

Adult-type ovarian granulosa cell tumors (AGCTs) are very rare tumors that account for

Abstract Background Adult granulosa cell tumor (aGCT) is a rare type of stromal cell malignant cancer of the ovary characterized by elevated estrogen levels. aGCTs ubiquitously harbor a somatic mutation in FOXL2 gene, Cys134Trp (c.402C

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]

Adult-type granulosa cell tumor with splenic metastasis: a rare case

Abstract Background The aim of this study was to explore the clinicopathological characteristics of recurrent adult-type granulosa cell tumor of the ovary (AGCOT) and evaluated the treatment results to define the prognostic parameters for survival after recurrence. Results A retrospective review of 40 patients with recurrent AGCOT, who were treated in the Cancer Hospital at the Chinese Academy of Medical Sciences from 2000 to 2015 was conducted. The impact of clinical and pathological characteristics, progression-free survival (PFS), and post-recurrence therapeutic approaches on prognosis were analyzed. Among the 40 recurrent patients, there were 10 cases where the relapse was uncontrolled, 24 cases had second relapses, and 6 cases without further relapses at the time of our follow-up. The median PFS was 61 months (range, 7-408 months), and the median time interval between the first and the second relapses (R-PFS) was 25 months (range, 0–94 months). The median time interval between the first relapse and death (R-OS) was 90 months (range, 2–216 months). PFS ≥ 61 months (P = 0.004) and post-recurrence therapeutic approach (P < 0.001) were independent risk factors for repeated recurrences. The age at recurrence (P = 0.031) and post-recurrence therapeutic approach (P = 0.001) were independent risk factors for death after recurrence. Conclusion Among patients with recurrent AGCOT, those with long PFS had good prognoses. Maximal cytoreductive effort should be made after recurrence. Complete resection and postoperative adjuvant chemotherapy may improve the prognosis of patients with recurrent AGCOT.

Aim: To present the clinicopathologic findings of the second case of androgen-secreting adult granulosa cell tumor (AGCT) in a woman with polycystic ovary syndrome (PCOS) and discuss in the light of the literature. Methods: Description of a case and discussion of the literature. Results: A patient with oligomenorrhea, amenorrhea and hirsutism who was diagnosed as PCOS and treated by oral contraceptive for three years, then left ovarian solid and liquid mass was found and pathologically confirmed to be androgen-secreting AGCT after left oophorectomy. She got regular menstrual cycle and gave birth naturally, but clinical features of PCOS reappeared after breastfeeding. Conclusion: Androgen-secreting AGCT and PCOS have similar clinical features of hyperandrogenism, it is difficult to diagnose androgen-secreting AGCT when both diseases occur in the same patient. If the size of cystic mass in androgen-secreting AGCT is too small to differentiate from PCOM on imaging, pathological examination after surgery may be the only way to find the disease. [ABSTRACT FROM AUTHOR]

We report that a case of adult testicular granulosa cell tumor in a 40-year-old man who presented with a palpable testicular mass. The sectioned surface of the testis revealed a well-circumscribed, yellowish tan, solid mass with hemorrhagic foci. Histologically, the tumor was arranged in solid nests, trabeculae, gyriform, pseudopapillae and macro-and microfollicles in a fibrocollagenous stroma. The tumor cells were ovoid or carrot-shaped with scant cytoplasm and nuclear grooves. Immunohistochemically, the tumor cells were diffusely strongly positive for estrogen receptor, progesterone receptor, androgen receptor, CD10, CD56, calretinin and vimentin, and multifocally positive for inhibin, synaptophysin and cytokeratin.

Adult granulosa cell tumor (AGCT) and sex cord tumor with annular tubules (SCTAT) are distinct sex cord stromal tumors with different molecular signatures. We present a unique case of an incidental ovarian tumor with mixed AGCT and SCTAT morphologic patterns. Due to the unusual co-occurrence, molecular testing was separately performed on both components. Despite minimal overlap in morphology, both the SCTAT and AGCT components were found to have an identical mutation profile, including the prototypical FOXL2 p.C134W mutation characteristic of AGCT. We thus present the first report of AGCT with SCTAT-like pattern. [ABSTRACT FROM AUTHOR]

Adult-type ovarian granulosa cell tumors (AGCTs) are very rare tumors that account for <5% of all ovarian carcinomas. AGCTs have low malignancy potential and rarely metastasize 5–30 years after the initial diagnosis. Because time has passed from the first surgery and because recurrence develops in various locations, the differential diagnosis is difficult. In particular, tumors developing in the greater omentum are encountered rarely, and it is necessary to carefully consider the differential diagnosis, including primary and secondary neoplasms. Although CT is useful to detect omental tumors, the diagnosis requires invasive procedures. We report a case of AGCT recurrence in the greater omentum that was resected during laparoscopic cholecystectomy. A patient visited our hospital with right-sided abdominal pain. The CT revealed gallbladder stones, a ureteral stone, and a right abdominal mass. The diagnosis of the abdominal tumor was difficult on the basis of blood biochemical testing, gastrointestinal endoscopy, or image inspection. Although the patient underwent several previous surgeries and there were no findings of malignancy with positron emission tomography, we chose to resect the tumor for combined diagnosis and treatment during laparoscopic cholecystectomy. Intraoperative findings showed that the tumor originated from the greater omentum, and the tumor was diagnosed as AGCT recurrence by pathology. A recurrence of AGCT in the greater omentum is very rare, and laparoscopic surgery was safe and useful for resection, in our case. [ABSTRACT FROM AUTHOR]

Background: Adult granulosa cell tumor (aGCT) is a rare type of stromal cell malignant cancer of the ovary characterized by elevated estrogen levels. aGCTs ubiquitously harbor a somatic mutation in FOXL2 gene, Cys134Trp (c.402C < G); however, the general molecular effect of this mutation and its putative pathogenic role in aGCT tumorigenesis is not completely understood. We previously studied the role of FOXL2C134W, its partner SMAD3 and its antagonist FOXO1 in cellular models of aGCT.Methods: In this work, seeking more comprehensive profiling of FOXL2C134W transcriptomic effects, we performed an RNA-seq analysis comparing the effect of FOXL2WT/SMAD3 and FOXL2C134W/SMAD3 overexpression in an established human GC line (HGrC1), which is not luteinized, and bears normal alleles of FOXL2.Results: Our data shows that FOXL2C134W/SMAD3 overexpression alters the expression of 717 genes. These genes include known and novel FOXL2 targets (TGFB2, SMARCA4, HSPG2, MKI67, NFKBIA) and are enriched for neoplastic pathways (Proteoglycans in Cancer, Chromatin remodeling, Apoptosis, Tissue Morphogenesis, Tyrosine Kinase Receptors). We additionally expressed the FOXL2 antagonistic Forkhead protein, FOXO1. Surprisingly, overexpression of FOXO1 mitigated 40% of the altered genome-wide effects specifically related to FOXL2C134W, suggesting it can be a new target for aGCT treatment.Conclusions: Our transcriptomic data provide novel insights into potential genes (FOXO1 regulated) that could be used as biomarkers of efficacy in aGCT patients. [ABSTRACT FROM AUTHOR]

Abstract Background To evaluate the association between adjuvant chemotherapy and clinical outcomes in patients with stage IC adult granulosa cell tumor (AGCT). Methods We performed a retrospective study of patients with stage IC AGCT diagnosed at our hospital from January 1985 to September 2015. We analyzed descriptive statistics, and performed univariate and multivariate and Kaplan–Meier survival analyses. Results Sixty stage IC AGCT patients were identified, including 28 in the no adjuvant chemotherapy group (NACG) and 32 in the adjuvant chemotherapy group (ACG). The median follow-up time was 88 months (range: 9–334 months). Sixteen patients developed recurrences, including nine in the NACG and seven in the ACG groups. Univariate analysis identified incomplete surgical staging and initial treatment place as associated with disease-free survival (DFS) (P = 0.003 and 0.038, respectively). Incomplete surgical staging remained a risk factor for recurrence in multivariate analysis (hazard ratio (HR) = 3.883, 95% confidence interval (CI): 1.123–13.430, P = 0.032). The 5-year DFS rates in the NACG and ACG groups were 76.3% and 87.5% respectively (P = 0.197). Adjuvant chemotherapy was thus not associated with improved DFS. Furthermore, the number of chemotherapy cycles was not associated with recurrence rate (≤3 cycles vs. > 3 cycles, HR = 0.613, 95% CI: 0.112–3.351, P = 0.572). Conclusion Administration of adjuvant chemotherapy does not improve DFS in patients with stage IC AGCT. Further studies with larger samples involving multi-institutional collaboration are needed to validate new treatment regimens for this disease.

Juvenile ovarian granulosa cell tumor is a sex chord stromal tumor derived from granulosa cells. It rarely occurs in children. Although it is usually classified as a benign tumor in children due to its good prognosis after surgical intervention, it is a malignant tumor and can be deadly, especially if recurrence occurs. We report two rare cases. The first one is a five-year-old girl with a malignant juvenile ovarian granulosa cell tumor stage 3 FIGO, presenting with abdominal pain in the inferior part of the abdomen and very early pubertal development. On physical examination, she was at stage two puberty. The second case is a 12 years old girl presenting with two periods monthly. An 8.3/5.4cm mass was found at the pelvic region on ultrasound examination. Exploratory laparoscopy with histological examination led to the diagnosis of stage 2A FIGO, combined juvenile and adult ovarian granulosa cell tumor. Conclusion: Precocious puberty accompanying abdominal pain or more than a period in a month is a pointer to juvenile and adult ovarian granulosa cell tumor requiring immediate investigations and patient management. Early diagnosis with the assistance of inhibin test and a FISH test of p53(17p13) aids better management of patients with Juvenile ovarian granulosa cell tumor, preventing tumor recurrence for a favorable outcome. Juvenile and adult ovarian granulosa cell tumors in pediatric female patients can present in different forms but gearing towards menstruation abnormalities. [ABSTRACT FROM AUTHOR]

Background: The aim of this study was to explore the clinicopathological characteristics of recurrent adult-type granulosa cell tumor of the ovary (AGCOT) and evaluated the treatment results to define the prognostic parameters for survival after recurrence. Results: A retrospective review of 40 patients with recurrent AGCOT, who were treated in the Cancer Hospital at the Chinese Academy of Medical Sciences from 2000 to 2015 was conducted. The impact of clinical and pathological characteristics, progression-free survival (PFS), and post-recurrence therapeutic approaches on prognosis were analyzed. Among the 40 recurrent patients, there were 10 cases where the relapse was uncontrolled, 24 cases had second relapses, and 6 cases without further relapses at the time of our follow-up. The median PFS was 61 months (range, 7-408 months), and the median time interval between the first and the second relapses (R-PFS) was 25 months (range, 0–94 months). The median time interval between the first relapse and death (R-OS) was 90 months (range, 2–216 months). PFS ≥ 61 months (P = 0.004) and post-recurrence therapeutic approach (P < 0.001) were independent risk factors for repeated recurrences. The age at recurrence (P = 0.031) and post-recurrence therapeutic approach (P = 0.001) were independent risk factors for death after recurrence. Conclusion: Among patients with recurrent AGCOT, those with long PFS had good prognoses. Maximal cytoreductive effort should be made after recurrence. Complete resection and postoperative adjuvant chemotherapy may improve the prognosis of patients with recurrent AGCOT. [ABSTRACT FROM AUTHOR]

Granulosa cell tumors represent only 1% of the total number of ovarian tumors. "Coffee bean" nuclei represent an extremely rare feature of these tumors. We presented the case of a 66 year-old patient that was hospitalized for abdominopelvic pain, lately to be diagnosticated with an Adult Granulosa Cell Tumor. The histopathological analysis revealed Call- Exner corpuscles and Coffee Bean" nuclei. Positive S100 marker was a particular finding in the immunohistochemical profile. Treatment strategy for this kind of cases should include surgery and adjuvant treatment and a strict follow-up of the patient for at least 5-10 years. [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]

Objective: The objectives of this study were to conduct a retrospective review of patients with adult granulosa cell tumors (AGCTs) to validate the effect of full surgical staging and adjuvant chemotherapy, and to identify the factors influencing disease-free survival (DFS) and overall survival (OS). Material and Methods: The database and patient files available at our gynecological oncology department were searched to identify women who had undergone primary surgery for an ovarian tumor and whose final diagnosis was stage I/II AGCT. A total of 41 patients with earlystage AGCT were included in the analysis. Results: The majority of the cases were Stage I AGCT (63.4%). The median OS of the patients was 54.3 months. Full stage surgery, age, and lymphadenectomy were not independent risk factors for the involvement of lymph nodes in AGCTs. For patients with full surgical staging, pelvic and para-aortic lymphadenectomy were not independent prognostic factors for DFS and OS. Conclusion: Initial stage, age, lymphadenectomy, and full stage surgery did not influence DFS, OS, or recurrence of AGCTs. Furthermore, age, bilaterality, and preoperative ultrasound image did not influence the involvement of lymph nodes in AGCTs. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study is to evaluate the long-term outcome of ovarian recurrent granulosa cell tumors (GCTs) in a large series of patients treated in Taiwanese Gynecologic Oncology Group (TGOG) centers and to define the prognostic parameters for survival. Materials and methods: A retrospective multi-institutional review of patients with recurrent ovarian GCTs treated in TGOG centers was conducted. The clinical and pathological characteristics, treatment, and outcomes of patients with ovarian recurrent GCTs were analyzed using Kaplan-Meier and Cox proportional hazards analyses to determine the predictors for survival. Results: A total of 44 patients from 16 medical centers were identified between January 1994 and December 2010. The median disease-free survival (DFS), postrecurrence survival, and overall survival (OS) were 61.5 months (range, 3.7–219.3 months), 55.8 months (range, 4.6–193.7 months), and 115.3 months (range, 17.2–390.6 months), respectively. In multivariate analysis, DFS (> 61.5 months versus ≤ 61.5 months, hazard ratio (HR) 0.15, 95% confidence interval (CI) 0.03–0.78, p = 0.024) at the initial operation after diagnosis of relapse was the only predictor that correlated with OS. Conclusion: DFS after the initial operation was the only important predictor for overall survival in patients with recurrent GCTs, regardless of treatment, suggesting that the natural behavior of the tumor is a critical factor for patients with recurrent GCTs.

Adult granulosa cell tumors (AGCTs) are a molecularly distinct group of malignant ovarian sex cord-stromal tumors (SCSTs) characterized by a nearly ubiquitous c.402C>G/p.C134W mutation in FOXL2 (hereafter referred to as "C134W"). In some cases, AGCT exhibits marked morphologic overlap with other SCSTs and has an identical immunophenotype, and molecular testing may be necessary to help confirm the diagnosis. However, molecular testing is time consuming, relatively expensive, and unavailable in many pathology laboratories. We describe the development and validation of an in situ hybridization (ISH) custom BaseScope assay for the detection of the FOXL2 C134W mutation. We evaluated 106 ovarian SCSTs, including 78 AGCTs, 9 juvenile granulosa cell tumors, 18 fibromas (cellular and conventional), and 1 SCST, not otherwise specified, as well as 53 epithelial ovarian tumors (42 endometrioid carcinomas and 11 carcinosarcomas) and 1 STK11 adnexal tumor for the presence or absence of FOXL2 wild-type and FOXL2 C134W RNA expression via BaseScope-ISH. Fifty-one tumors had previously undergone DNA sequencing of the FOXL2 gene. Across the entire cohort, the FOXL2 C134W probe staining was positive in 77 of 78 (98.7%) AGCTs. Two of 81 (2.5%) non-AGCTs also showed positive staining, both of which were epithelial ovarian tumors. The assay worked in tissue from blocks >20 years old. There was 100% concordance between the FOXL2 sequencing and BaseScope-ISH results. Overall, assessment of FOXL2 mutation status by custom BaseScope-ISH demonstrated 98.7% sensitivity and 97.5% specificity for the diagnosis of AGCT. BaseScope-ISH for FOXL2 C134W represents a reasonable alternative to sequencing, is quicker and less expensive, and is more easily incorporated than molecular testing into many pathology laboratories. It also has the advantage of requiring less tissue, and the neoplastic cells can be directly visualized on stained sections., (Copyright © 2023 United States & Canadian Academy of Pathology. Published by Elsevier Inc. All rights reserved.)

Background: Granulosa cell tumor of testis is a rare tumor accounting for less than 4% of adult testicular tumors though they account for nearly 30% of childhood testicular tumors. Due to the rarity of these tumors, exact etiology, pathogenesis, prognostic factors and best treatment approach are not well known. The molecular events in pathogenesis of these stromal tumors have begun to unravel and these developments put forth a reasonable and scientific explanation for the association of these tumors with developmental anomalies like undescended testis. However, many questions remain unanswered. Materials and Methods: We performed a retrospective analysis of clinicopathological features of all Granulosa Cell Tumors of testis from our archives in addition to an extensive literature search using PUBMED with the key words "Granulosa Cell Tumor, testis". Results: We found six cases in our archives, two of which were of juvenile type and four of adult type. One out of these six cases presented with metastases. All cases underwent radical orchidectomy. Morphology and immunohistochemistry were classical in all cases and there was no diagnostic dilemma. Literature search revealed 63 cases of testicular Granulosa Cell Tumor in addition to highlighting the similarities in the biology and the dissimilarities in the clinical behavior as compared to ovarian Granulosa Cell Tumor. Conclusion: Testicular Granulosa Cell Tumor is a rare tumor, which although histologically similar to its ovarian counterpart, differs in clinical behavior. Further detailed investigations are needed to reveal the mystery behind the differing clinical behavior despite histological and immunohistochemical similarity between the testicular and ovarian Granulosa Cell Tumors.

Introduction: Adult granulosa cell tumor (AGCT) is a rare ovarian sex-cord malignancy notorious for late recurrences and metastases. The cytologic features of AGCT at the metastatic sites have been documented sporadically. Hence, knowledge of the characteristic cytomorphologic features is essential for an accurate diagnosis and distinguishing it from its pathologic mimics, especially at the metastatic sites., Materials and Methods: This was a retrospective study conducted over six years. The cytopathology electronic database was searched for the fine needle aspirates (FNA) reported as metastatic AGCT. A detailed cytomorphologic assessment was done for multiple cytologic features, including overall cellularity, cellular arrangement of the tumor cells, cell size, cell shape, nuclear pleomorphism, nuclear grooving, chromatin pattern, nucleolar prominence, mitotic figures, amount and character of cytoplasm, and the extracellular background., Results: There were 6 cases reported as metastatic AGCT on aspiration cytology. The smears in all the cases were cellular, with tumor cells arranged in loose aggregates, three-dimensional clusters, perivascular papillary fronds, and scattered singly. The most consistent cytologic features included microfollicular arrangement of monomorphic tumor cells with round-oval nuclei, fine chromatin, longitudinal nuclear grooving, and scant cytoplasm. Typical Call-Exner bodies and metachromatically stained extracellular hyaline material were noted sporadically. None of the smears showed anaplasia, prominent macronucleoli, atypical mitoses, or necrosis., Conclusions: The current study not only outlines the distinct cytologic attributes of AGCTs across various metastatic locations but also highlights its prevalent cytologic mimics. Additionally, it outlines key clinicopathologic traits that can aid in distinguishing and precisely diagnosing these tumors through cytological analysis., Competing Interests: None., (AJTR Copyright © 2023.)