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Abstract Introduction Ovarian granulosa cell tumor (OGCT) is a rare female pathology with few available demographic data. Besides, there are no comprehensive clinical characteristics regarding the OGCT in Iran. Thus, this study aimed to assess the clinical features and survival rate of OGCT patients in Iran to expand the scope of knowledge in this field. Materials and methods In this 10-year retrospective study (2013–2023), the cases were gathered from the oncologic clinic of women (Imam Khomeini Hospital, Tehran, Iran). The patients with definite OGCT diagnosis were selected based on the inclusion and exclusion criteria including medical history, interfering backgrounds, demographic data, histopathological assessment, clinical and para-clinical features, survival rates, and all previous medical reports for definite diagnosis of OGCT along with approved pathology samples. Results The median age and BMI values of Iranian patients were 45 (19 ~ 83) years and 28.04 (19.4 ~ 48.0), respectively. The most common symptom was abdominal pain (56%) and 69.2% of cases were menopause. In 81.3% of cases, ovarian tumors were detected and metastasis was rare. Most patients (40.6%) underwent total abdominal hysterectomy and OGCT relapsing cases were seen in 13.2% of patients. The median of overall survival (OS) value using the Kaplan-Meier estimate was 52 months (95%CI:37.47–66.53), and the median of disease-free survival (DFS) was 45 months (95%CI: 28.88–61.12). There was a significant (p

Introduction: Ovarian granulosa cell tumor (OGCT) is a rare female pathology with few available demographic data. Besides, there are no comprehensive clinical characteristics regarding the OGCT in Iran. Thus, this study aimed to assess the clinical features and survival rate of OGCT patients in Iran to expand the scope of knowledge in this field. Materials and methods: In this 10-year retrospective study (2013–2023), the cases were gathered from the oncologic clinic of women (Imam Khomeini Hospital, Tehran, Iran). The patients with definite OGCT diagnosis were selected based on the inclusion and exclusion criteria including medical history, interfering backgrounds, demographic data, histopathological assessment, clinical and para-clinical features, survival rates, and all previous medical reports for definite diagnosis of OGCT along with approved pathology samples. Results: The median age and BMI values of Iranian patients were 45 (19 ~ 83) years and 28.04 (19.4 ~ 48.0), respectively. The most common symptom was abdominal pain (56%) and 69.2% of cases were menopause. In 81.3% of cases, ovarian tumors were detected and metastasis was rare. Most patients (40.6%) underwent total abdominal hysterectomy and OGCT relapsing cases were seen in 13.2% of patients. The median of overall survival (OS) value using the Kaplan-Meier estimate was 52 months (95%CI:37.47–66.53), and the median of disease-free survival (DFS) was 45 months (95%CI: 28.88–61.12). There was a significant (p < 0.05) relation between chemotherapy and left oophorectomy with OS. A significant (p < 0.05) correlation was also detected among the OGCT stage and left oophorectomy with DFS. Conclusion: OS and DFS values showed that the OGCT in Iranian patients can be treated in most cases using two main procedures of chemotherapy and oophorectomy. Parallel application of both procedures and associated outcomes are suggested for future studies. [ABSTRACT FROM AUTHOR]

Aim: To summarize the cytomorphology and immunocytochemistry features of OGCT in ascites or peritoneal washings. Methods: All cases of histology sections, cytology smears, cell block slides and immunohistochemical staining were reviewed. A panel of immunohistochemistry antibodies consisting of Inhibin, Calretinin, BerEP4 and MC was performed for diagnosis and differential diagnosis. Results: Seven positive cases (21.2%) in ascites and peritoneal washings were identified in 33 patients with OGCT, which is higher than early studies with positive rate of 7.4%. Clinicopathologic features including tumor size and the incidence of endometrial atypical hyperplasia or carcinoma (EAH/EC) displayed no statistical difference between groups with positive and negative cytology. Immunocytochemical results usually showed typical staining pattern with α‐inhibin, calretinin positive and BerEP4, MC negative. Features of granulosa cells, including nuclear hyperplasia and overlapping, can be observed in all seven positive cases. Nuclear grooves or small conspicuous nucleoli were occasionally observed in the smear. However, features of cell clusters mimicking Call‐Exner bodies, cytoplasmic vacuoles or single cell necrosis were not found on smear. Call‐Exner bodies and mitosis can only be found on cell blocks. All cases of follow‐up information were available and three cases displayed progression and there was a statistical difference between groups with positive and negative cytology. Conclusion: OGCT with positive cytology in ascites and peritoneal washings tend to have a larger tumor size and higher rates of disease progression. A panel of complementary biomarkers can greatly increase the detection rate and help in differential diagnosis in ascites or peritoneal washings of OGCT. [ABSTRACT FROM AUTHOR]

Background: Ovarian granulosa cell tumor (GCT) is a rare type of malignant sex-cord stromal tumor, with adult and juvenile types. The ovarian GCT initially presented as a giant liver mass clinically mimicking primary cholangiocarcinoma is exceedingly rare. Case Report: We report such a case of a 66-year-old woman who presented with right upper quadrant pain. Abdominal magnetic resonance imaging (MRI) and a subsequently fused positron emission tomography/computed tomography (PET/CT) showed a solid and cystic mass with hypermetabolic activity concerning intrahepatic primary cystic cholangiocarcinoma. A fine-needle core biopsy of the liver mass showed coffeebean-shaped tumor cells. The tumor cells were positive for Forkhead Box L2 (FOXL2), inhibin, Wilms tumor protein 1 (WT-1), steroidogenic factor 1 (SF1), vimentin, estrogen receptor (ER), and smooth muscle actin (SMA). The histologic features and immunoprofile supported a metastatic sex-cord stromal tumor favoring granulosa cell tumor, adult type. Strata next-generation sequencing test was performed on the liver biopsy and FOXL2 c.402C>G (p.C134W) mutation was present, consistent with granulosa cell tumor. Conclusion: To the best of our knowledge, this is the first documented case of ovarian granulosa cell tumor with FOXL2 mutation initially presenting as a giant liver mass clinically mimicking primary cystic cholangiocarcinoma. [ABSTRACT FROM AUTHOR]

Granulosa cell tumors of the ovary represent a rare subtype of ovarian malignancies which is usually associated with low recurrence rates due to the fact that is usually diagnosed in early stages of the disease. The aim of the current paper is to report the case of a 50 year old patient diagnosed with such a recurrence at four years after the initial diagnostic. Case report: the 50 year old patient was initially submitted to surgery for an ovarian tumor at that moment radical surgery being performed. Four years later she self referred to our service for diffuse abdominal pain and was diagnosed with a presumptive hematoma at the level of the mesosigmoid loop in association with increased values of serum inhibin. The patient was submitted to surgery, intraoperatively a ruptured tumor in association with mesosigmoidian hematoma being discovered; therefore the lesion was resected en bloc with the rectosigmoidian loop. The histopathological studies confirmed the presence of negative resection margins. In conclusion, although granulosa cell tumors of the ovary rarely develop distant metastases, isolated recurrences might occur and in such cases radical resection seem to be an effective therapeutic option. [ABSTRACT FROM AUTHOR]

Introduction. Granulosa cell tumors are rare neoplasms of the ovary with low malignancy potential and late recurrence. They originate from the granulose of the ovary stromal cells and have the ability to produce estrogen. The main treatment is surgical and implies hysterectomy with bilateral salpingooophorectomy, omentectomy, taking peritoneal biopsies, and cytological analysis of the peritoneal washing. When found in young women who have not given birth, a conservative approach can be considered. Fertility sparing surgery is safe only for early FIGO (Federation Internationale de Gynecologie et d’Obstetrique) stages IA tumors то IC, where it is necessary to make unilateral salpingo-oophorectomy and complete staging. Case outline. We present a case of young woman with granulosa cell tumor who was accidentally discovered, and after an adequate surgery and chemotherapy she gave a birth to a healthy child. Conclusion. Young women who have not given birth and who have been diagnosed with granulosa cell ovarian tumor can be treated conservatively after adequate disease staging and confirmation that the disease is at an early stage.

Adult-type ovarian granulosa cell tumors (AGCTs) are hormonally active neoplasms with limited epidemiological data available. We evaluated the effect of parity and postmenopausal hormone therapy (HT) use on the risk of AGCT in a population-based case-control setting. We identified all women diagnosed with AGCT during 1994–2015 (n = 505) from the Finnish Cancer Registry. For each case, five controls matched for age were selected from the National Population Registry, which also provided data on parity and ages at deliveries. Information on postmenopausal HT by different regimens (estradiol-only, sequential estrogen-progestin and continuous estrogen-progestin) was obtained from nationwide Prescription Register. The association between parity, ages at deliveries, HT use, and AGCT incidence was evaluated by odds ratios (ORs) using a conditional logistic regression model and stratified by age at index date (<55 years or ≥ 55 years). Parity and age at first or last delivery had no significant effect on AGCT risk. Systemic postmenopausal HT had been used by 20.4% of women who were later diagnosed with AGCT. The risk for subsequent AGCT was significantly decreased among users of estradiol-only therapy for at least five years (OR 0.28; 95% confidence interval 0.08–0.94) and continuous estradiol-progestin therapy for 6 months to 5 years (0.23; 0.08–0.71). Unlike in epithelial ovarian cancer, AGCT development is not clearly associated with parity, and users of postmenopausal HT do not seem to carry an excess risk for AGCT formation. • Adult-type granulosa cell tumors (AGCTs) are hormonally active neoplasms with limited epidemiological data available • AGCT development is not clearly associated with parity or age at deliveries • Use of postmenopausal hormone therapy does not increase the risk for subsequent AGCT [ABSTRACT FROM AUTHOR]

The aim of this study was to elucidate the clinicopathological features of ovarian granulosa cell tumors (GCTs) and to identify the prognostic factors. The Japanese Society of Gynecologic Oncology (JSGO) conducted an observational retrospective cohort study of women with GCTs enrolled in the Gynecological Tumor Registry of the Japan Society of Obstetrics and Gynecology (JSOG) between 2002 and 2015. Clinicopathological features, including lymph node metastasis, were evaluated. In addition, we performed a prognostic analysis of patients between 2002 and 2011 for whom survival data were available. Kaplan–Meier and multivariate Cox proportional hazards analyses were performed. We identified 1426 patients with GCTs. Of the 222 patients who underwent lymph node dissection, 10 (4.5%) had lymph node metastasis. The incidence of lymph node metastasis in patients with pT1, pT2, and pT3 was 2.1%, 13.3%, and 26.7%, respectively (p < 0.001). Prognostic analysis was performed on 674 patients. In the multivariate Cox regression analysis, residual disease after initial surgery (hazard ratio (HR) = 10.39, 95% confidence interval (CI) = 3.15–34.29) and lymph node metastasis (HR = 5.58, 95% CI = 1.62–19.19) were independent risk factors for cancer-specific survival. In the initial surgery for GCTs, lymph node dissection can be omitted if the operative finding is pT1. In cases of pT2 or higher, lymph node dissection should be considered. Debulking is critical for achieving no gross residual tumor at the end of the surgery. • This was an observational retrospective cohort study involving Japanese women. • Prognostic factors of ovarian granulosa cell tumors (GCTs) were identified. • If the operative finding is pT1, lymph node dissection can be omitted in initial surgery. • Debulking is critical for achieving no gross residual tumor at the end of the surgery. [ABSTRACT FROM AUTHOR]

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.

Granüloza hücreli tümör, seks kord stromal kaynaklı, nadir görülen ve sıklıkla östrojen gibi seks steroidleri sentezleyebilen bir over tümörüdür. Bu çalışmada, kırk sekiz yaşında karın ağrısı ve genel durum bozukluğu nedeniyle acil servisimize başvuran ve preoperatif dönemde yapılan karın muayenesinde akut karın tablosu mevcut olan bir bayan hastayı sunuyoruz. Hastaya çekilen manyetik rezonans (MR) görüntülemede, sol adneksiyal alanda 56x55 mm boyutlarında kistik lezyon ve karın ve pelvis içinde solid ve kistik alanlar içeren kitlesel lezyon izlendi. Hastamızın cerrahi eksplorasyon sonrası sol overinde sigmoid kolonu penetre ederek akut karın içi kanamaya yol açmış kistik tümöral kitle tespit edildi. Biz olgumuza anterior rezeksiyon ve bilateral salpingo-ooferektomi uyguladık. Histopatoloji sonucu sigmoid kolonu invaze etmiş sol overde granüloza hücreli tümör saptanmıştır. Bu olgu sunumunda, overin granüloza hücreli tümör vakası ve klinik görünümü literatür verileri ışığında gözden geçirildi.

Abstract Background Granulosa cell tumors (GCTs) are derived from proliferating granulosa cells of the ovarian follicle. They are known for their late recurrence and most patients with an aggressive form die from their disease. There are no treatment options for this slowly proliferating tumor besides surgery and chemotherapy. In a number of tumors, analogs of the second mitochondria-derived activator of caspases (SMAC), alone or in combination with other molecules, such as TNFα, are evolving as new treatment options. SMAC mimetics block inhibitor of apoptosis proteins (IAPs), which bind caspases (e.g. XIAP), or activate the pro-survival NF-κB pathway (e.g. cIAP1/2). Expression of IAPs by GCTs is yet not fully elucidated but recently XIAP and its inhibition by SMAC mimetics in a combination therapy was described to induce apoptosis in a GCT cell line, KGN. We evaluated the expression of cIAP1 in GCTs and elucidated the effects of the SMAC mimetic BV-6 using KGN as a model. Results Employing immunohistochemistry, we observed cIAP1 expression in a tissue microarray (TMA) of 42 GCT samples. RT-PCR confirmed expression of cIAP1/2, as well as XIAP, in primary, patient-derived GCTs and in KGN. We therefore tested the ability of the bivalent SMAC mimetic BV-6, which is known to inhibit cIAP1/2 and XIAP, to induce cell death in KGN. A dose response study indicated an EC50 ≈ 8 μM for both, early ( 80) passages, which differ in growth rate and presumably aggressiveness. Quantitative RT-PCR showed upregulation of NF-κB regulated genes in BV-6 stimulated cells. Blocking experiments with the pan-caspase inhibitor Z-VAD-FMK indicated caspase-dependence. A concentration of 20 μM Z-VAD-FMK was sufficient to significantly reduce apoptosis. This cell death was further substantiated by results of Western Blot studies. Cleaved caspase 3 and cleaved PARP became evident in the BV-6 treated group. Conclusions Taken together, the results show that BV-6 is able to induce apoptosis in KGN cells. This approach may therefore offer a promising therapeutic avenue to treat GCTs.

Abstract Background To describe magnetic resonance imaging (MRI) features of ovarian granulosa cell tumors (OGCTs) and compare with other sex cord-stromal tumors (OSCs) in ovary. Methods MR findings of 18 patients with surgically confirmed ovarian granulosa cell tumor were retrospectively reviewed by two radiologists with consensus reading. All MR examinations were prospectively performed within one month. Clinical and imaging characteristics of OGCTs were evaluated and compared with OSCs (control group). Results In 18 patients, 20 ovarian granulosa cell tumors were detected on MRI. Sixteen tumors appeared as solid or mostly solid mass (16/20), while 4 tumors as cystic mass. Pathological pelvic fluid was detected in 1 OGCT (1/18) and 11 OSCs (11/34) (p = 0.031).On T2 weighted imaging (T2WI), most of OGCTs displayed hyperintense signal and mixed signal (19/20); on T1 weighted imaging (T1WI), 11 OGCTs (11/20) displayed similar signal as on T2WI imaging. The lesion signal between OGCT and OSC differed significantly on both T1WI (p = 0.017) and T2WI (p = 0.002). Tumoral bleeding was detected in 6 OGCTs on MRI. On diffusion weighted imaging (DWI) images, OGCTs mostly appeared as high signal (16/20). Average apparent diffusion coefficient (ADC) value derived from DWI images in the OGCT group (0.84 ± 0.26× 10− 3 mm2/s was less than the control group (1.22 ± 0.47 × 10− 3 mm2/s) with statistical difference (p = 0.002). Conclusions MRI could provide important information in OGCT diagnosis. ADC value might be useful in differentiating OGCT from OSC.

Background: Granulosa cell tumor (GCT) is a rare type of ovarian malignancy with poor prognosis of recurrence. Anti-Mullerian hormone (AMH) is a promising serum biomarker for early diagnosis GCT, therefore we assessed its accuracy and clinical value.Methods: A meta-analysis was performed to estimate the diagnostic accuracy. We searched the PubMed, Cochrane Literature Library and EMBASE database. After filtering, five studies met our criteria. Two independent reviewers extracted data and total 421 serum samples (70 GCT serum samples and 351 controls) were included in our analysis. The pooled values of sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR) and Summary receiver operating characteristic (SROC) were calculated to assess the accuracy.Results: The pooled estimated for AMH were sensitivity: 0.89 (95 % CI 0.78-0.95), specificity: 0.93 (95 %CI 0.83-0.97). The area under the SROC was 0.93 (95 %CI 0.91-0.95).Conclusion: Serum AMH can be used as a biomarker in clinical diagnosis of GCT with high accuracy. [ABSTRACT FROM AUTHOR]

To evaluate the role of laparoscopic (LPS) and laparotomic (LPT) re-staging in patients with incompletely surgically staged ovarian granulosa cell tumors (OGCT). We conducted a medical chart retrospective analysis of all patients with sex cord stromal tumors (SCSTs) who were managed in our division between March 1994 and March 2017. After a complete review of surgical and pathological notes, patients with incomplete staging were restaged according to the FIGO guidelines. Statistical analysis was conducted using Statistical Package version 20.0 for Windows (SPSS, Inc., Chicago, Illinois). Out of a total of 170 patients SCSTs, 84 patients (49,5%) received primary surgery that included a hysterectomy; 86 patients (50,5%) underwent fertility-sparing surgery. Eighty-one patients (48%) with diagnosis of OGCT were incompletely surgically staged at another institution. We evaluated our results in terms of laparoscopic approach (56 patients) and open treatment (25 patients). Among the IA patient's group, 1 was upstaged to IIB stage and 2 to IIIB; among patients with IC stage, 1 was upstaged to IIA, 2 to IIB and 1 to IIIB stage. Adjuvant chemotherapy was given to the upstaged patients with final stage IIB-IIIC. No statistically significant difference between laparoscopy and open-surgery was detected in terms of upstaged patients after second surgery (p = 0,36). According to our series, laparoscopic restaging compared to the open approach seems to be a feasible and efficient technique to complete surgical staging in patients with GCTs incorrectly staged. Surgical restaging seems to upstage a considerable number of OGCT, mainly in the initial stage IC group of patients. However, the impact of restaging on final outcome and survival remains to be demonstrated. • Ovarian granulosa cell tumor (OGCT) represents 3% to 5% of all ovarian neoplasms. • FIGO stage is one of the most important prognostic factors in OGCTs. • Re-staging operation is a reoperation after incomplete evaluation during initial surgery. • To our knowledge, there is no report concerning laparoscopic and laparotomic restaging of OGCT published to date. • Surgical restaging seems to have a role in the management of OGCT, mainly in initial stage IC group of patients. [ABSTRACT FROM AUTHOR]

Abstract Background Granulosa cell tumor of the ovary is the most frequent sex cord stromal tumor and represents 2 to 5% of all primary ovarian cancers. Ovarian granulosa cell tumor is a malignant tumor with slow progression and in some cases this tumor is hormonally active. The recurrence of granulosa cell tumor often happens after 5 years. Case presentation We describe two cases of postmenopausal women with adult-type granulosa cell tumors of the ovary. Patient 1 is a 49-year-old European woman with a recurrent tumor; patient 2 is a 55-year-old European woman without recurrence of tumor. Urinary steroid profiles of patient 1 were monitored during a 5-year period starting from before an operation (13 samples). In patient 2, the urinary steroid profiles were monitored during a 3-year period starting from after an operation (six samples). The 24-hour urinary samples were examined and the urinary concentration of 20 androgen, progesterone, and corticoid metabolites was quantitatively determined by gas chromatography-mass spectrometry with selected ion-monitoring mode. Conclusions Based on these cases a correlation could be observed between increased levels of the urinary steroids and the recurrence of ovarian granulosa cell tumor; therefore, we concluded that a urinary steroid profile could be a more effective method to follow-up such patients compared to the traditional serum hormones determinations supplemented with conventional tumor markers.

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]

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Granulosa cell tumors of the ovary are rare ovarian neoplasms developing from ovarian stromal cells. They are characterized by insidious growth, low malignancy potential, and late recurrence. Due to the production of estrogen by these tumors, the frequent symptoms that occur in these patients develop as a result of hyperestrogenism. Standard treatment involves surgery in all patients. Fertility-sparing surgery is considered safe in young patients only in case of early-stage IA and IC tumors, where it is necessary to perform a unilateral salpingo-oophorectomy and complete staging. Surgical staging includes peritoneal washing, multiple peritoneal biopsies, omental biopsy, and biopsy of any suspicious area. [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.

Ovarian granulosa cell tumor (GCT) has different recurrence periods, which dramatically decreases after the 5-year survival period. Prognosis evaluation has important clinical values and is a research hotspot. Prognosis evaluation methods include logistic regression, Chi-square analysis, and other traditional statistical methods; however, these techniques cannot solve problems, such as limited samples and ambiguous prognosis-related pathologic features, and have poor reliability and validity of assessment results. In this study, an artificial intelligence theory was introduced, and the prognosis evaluation of ovarian GCT based on co-forest intelligence model was proposed to find a method applicable to the pathological data of ovarian GCT with limited samples and ambiguous prognosis features. First, data preprocessing of ovarian GCT samples was performed. This procedure included deleting unqualified data and standardizing and normalizing data. Second, prognosis evaluation of ovarian GCT was accomplished by using co-forest intelligence algorithm. Finally, the validity of the proposed prognosis evaluation method was verified by 75 patients with ovarian GCT in the West China Second Hospital of Sichuan University. Results indicate that: (1) the accuracy of prognosis evaluation based on the feature set selected by Log-Rank test increases by 12.1% compared with that (4.1%) based on the direct use of standardized and normalized feature set, and (2) the co-forest algorithm can be used for the model analysis of small pathological datasets of ovarian GCT. Moreover, this method can be used to explore effective characteristics from the candidate feature dataset through automatic learning with prediction accuracy of up to 95.7%. This study reveals the reliability and effectiveness of the proposed prognosis evaluation method of ovarian GCT based on co-forest intelligence model. Conclusions are beneficial for clinicians to accurately understand the development laws of ovarian GCT, take the initiative to master the diagnosis and treatment, and increase the long-term survival rate of patients. [ABSTRACT FROM AUTHOR]

Background: Granulosa cell tumor of the ovary is the most frequent sex cord stromal tumor and represents 2 to 5% of all primary ovarian cancers. Ovarian granulosa cell tumor is a malignant tumor with slow progression and in some cases this tumor is hormonally active. The recurrence of granulosa cell tumor often happens after 5 years.Case Presentation: We describe two cases of postmenopausal women with adult-type granulosa cell tumors of the ovary. Patient 1 is a 49-year-old European woman with a recurrent tumor; patient 2 is a 55-year-old European woman without recurrence of tumor. Urinary steroid profiles of patient 1 were monitored during a 5-year period starting from before an operation (13 samples). In patient 2, the urinary steroid profiles were monitored during a 3-year period starting from after an operation (six samples). The 24-hour urinary samples were examined and the urinary concentration of 20 androgen, progesterone, and corticoid metabolites was quantitatively determined by gas chromatography-mass spectrometry with selected ion-monitoring mode.Conclusions: Based on these cases a correlation could be observed between increased levels of the urinary steroids and the recurrence of ovarian granulosa cell tumor; therefore, we concluded that a urinary steroid profile could be a more effective method to follow-up such patients compared to the traditional serum hormones determinations supplemented with conventional tumor markers. [ABSTRACT FROM AUTHOR]

Objective: ovarian granulosa cell tumor (OGCT) is a kind of infrequent ovarian malignant tumor with limited epidemiological data available. we established a predictive nomograph to verify the clinical prognosis., Methods: 1005 diagnosed with ovarian granulosa cell tumor (OGCT) were extracted from Surveillance, Epidemiology, and End Results (SEER) public database from 2000-2018. Kaplan-Meier analysis was applied to distinguish risk factors, univariate and multivariate Cox analyses were used to determine the independent prognostic factors for cancer-specific survival (CSS) of OGCT patients. The obtained prognostic variables were combined to construct a nomogram model for predicting CSS in OGCT patients., Results: Model performance was detected and evaluated with ROC curves and calibration plots. Data collected from 1005 patients were divided into two groups: training cohort(n=703,70%) and validation cohort(n=302,30%). The multivariate Cox model identified five covariates including age, marital status, AJCC stages, surgery and chemotherapy as independent interfering factors of CSS. The nomogram has shown a promising and excellent accuracy in evaluating 3 -, 5 -, 8-year CSS in OGCT patients. In terms of the CSS of the training cohort, the AUC values of the 3 -, 5 -, 8-year ROC curves were 0.819,0.8,0.819, while in terms of the CSS of the validation cohort, the AUC values of the validation cohort were 0.822,0.84,0.823, respectively. All the calibration curves showed pleasant consistency between predicted and actual survival rates. The nomogram model established in the study can improve the veracity of prognosis prediction, thereby improving the accuracy of individualized survival risk assessment, and providing targeted and constructive recommendations for specific treatment options., Conclusion: Age, advanced clinical stage, widower and without surgery therapy are independent risk factors for poor prognosis and the nomogram we constructed can help clinicians efficiently recognize high-risk OGCT patients to guide targeted therapies and improve their outcomes., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest., (Copyright © 2023 Elsevier Masson SAS. All rights reserved.)

Background: Ovarian granulosa cell tumor (GCT) is a rare type of malignant sex-cord stromal tumor, with adult and juvenile types. The ovarian GCT initially presented as a giant liver mass clinically mimicking primary cholangiocarcinoma is exceedingly rare., Case Report: We report such a case of a 66-year-old woman who presented with right upper quadrant pain. Abdominal magnetic resonance imaging (MRI) and a subsequently fused positron emission tomography/computed tomography (PET/CT) showed a solid and cystic mass with hypermetabolic activity concerning intrahepatic primary cystic cholangiocarcinoma. A fine-needle core biopsy of the liver mass showed coffee-bean-shaped tumor cells. The tumor cells were positive for Forkhead Box L2 (FOXL2), inhibin, Wilms tumor protein 1 (WT-1), steroidogenic factor 1 (SF1), vimentin, estrogen receptor (ER), and smooth muscle actin (SMA). The histologic features and immunoprofile supported a metastatic sex-cord stromal tumor favoring granulosa cell tumor, adult type. Strata next-generation sequencing test was performed on the liver biopsy and FOXL2 c.402C>G (p.C134W) mutation was present, consistent with granulosa cell tumor., Conclusion: To the best of our knowledge, this is the first documented case of ovarian granulosa cell tumor with FOXL2 mutation initially presenting as a giant liver mass clinically mimicking primary cystic cholangiocarcinoma., (Copyright © 2023, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background: Ovarian granulosa cell tumors (GCTs) are the most frequent sex cord-stromal tumors. Several studies have shown that a somatic mutation leading to a C134W substitution in the transcription factor FOXL2 appears in more than 95% of adult-type GCTs. Its pervasive presence suggests that FOXL2 is the main cancer driver gene. However, other mutations and genomic changes might also contribute to tumor formation and/or progression. Methods: We have performed a combined comparative genomic hybridization and transcriptomic analyses of 10 adult-type GCTs to obtain a picture of the genomic landscape of this cancer type and to identify new candidate co-driver genes. Results: Our results, along with a review of previous molecular studies, show the existence of highly recurrent chromosomal imbalances (especially, trisomy 14 and monosomy 22) and preferential co-occurrences (i.e. trisomy 14/monosomy 22 and trisomy 7/monosomy 16q). In-depth analyses showed the presence of recurrently broken, amplified/duplicated or deleted genes. Many of these genes, such as AKT1, RUNX1 and LIMA1, are known to be involved in cancer and related processes. Further genomic explorations suggest that they are functionally related. Conclusions: Our combined analysis identifies potential candidate genes, whose alterations might contribute to adult-type GCT formation/progression together with the recurrent FOXL2 somatic mutation. [ABSTRACT FROM AUTHOR]

FOXL2 is a transcription factor that is essential for ovarian development. Somatic mutations of FOXL2 are associated with ovarian granulosa cell tumorigenesis. In the present study, the expression of FOXL2 was suppressed by microRNAs using the Ago2 knockdown method in COV434 cells. Online bioinformatics tools were utilized to predict that FOXL2 expression may be repressed by miR-30 family members, and dual luciferase assay and western blotting were performed to demonstrate that FOXL2 is a target gene of miR-30a, which is relatively abundant in COV434 cells. Furthermore, miR-30a overexpression upregulates BCL2A1, IER3 and cyclin D2 expression by inhibiting FOXL2. miR-30a is known to function as a tumor suppressor in breast cancer, small cell lung cancer and colorectal carcinoma; however, the present study revealed an opposing function of miR-30a as an oncogene. [ABSTRACT FROM AUTHOR]

Aim The aim of this study was to retrospectively report our experience (efficacy/morbidity) with cytoreductive surgery+hyperthermic intraperitoneal chemotherapy ( CRS+ HIPEC) for the management of recurrent/relapsed ovarian granulosa cell tumors ( OGCT). Material and Methods From 2010 to 2013, six patients underwent CRS+ HIPEC. CRS was performed with standard peritonectomy procedures and visceral resections directed towards complete elimination of tumors from the abdominopelvic cavity. HIPEC was performed with cisplatin (50 mg/m2) and doxorubicin (15 mg/m2) and allowed to circulate in the abdominopelvic cavity for 90 min at 41.0-42.2°C. Results Cytoreduction completeness ( CC-0) was achieved in all except one patient ( CC-1). Five patients had OGCT recurrences in abdomen+pelvis and one patient in abdomen only. No grade V morbidity ( Clavien- Dindo classification) occurred. Two patients developed lung atelectasis, which was managed by mere chest physiotherapy (grade I). One patient developed urinary tract infection (grade II) and another patient developed pneumonia (grade II) - both of which were managed by antibiotics. One patient developed splenic bed and anterior abdominal wall collections requiring ultrasound-guided aspiration without general anesthesia (grade III). One patient developed pulmonary embolism requiring intensive care-unit management (grade IV). Four chemo-naïve patients received adjuvant chemotherapy whereas the remaining two previously chemo-exposed patients received no adjuvant therapy. All patients were alive and disease-free without proof of recurrence/relapse at 40, 32, 27, 24, 20 and 16 months. The average interval of follow-up after CRS+ HIPEC was roughly 27 months (range: 16-40 months). Conclusion CRS+ HIPEC appears to be an efficacious and morbidly well-tolerated therapeutic modality for recurrent/relapsed OGCT. Long-term follow-up data and further research are needed. [ABSTRACT FROM AUTHOR]

This report describes a 17-year-old patient with ovarian granulosa cell tumor torsion, which is rare. The patient presented with lower abdominal pain for 1 day after defecation, accompanied by nausea and vomiting. Gynecological examination revealed a palpable mass of about 150 mm × 130 mm in the uterus. The mass had high surface tension, tight cysts, well-defined borders, and marked tenderness at its pedicle. Gynecological B-ultrasonography showed that the uterus was not compressed, and a mixed echo of about 152 mm × 112 mm was seen in the pelvic cavity. The initial diagnosis was ovarian tumor torsion. After explaining the condition to the patient's family, an emergent open resection of left ovarian tumor was performed. The postoperative pathology report indicated juvenile granulosa cell tumor. The patient's body temperature was normal, and there was no infection or thrombosis after operation., Competing Interests: None., (AJTR Copyright © 2022.)

The article presents a case study of a 41-year-old woman who had an emergency laparotomy with left salpingo-oophorectory for her left ovarian tumor in 2004. The patient was diagnosed with granulosa cell tumor (GCT) adult type FIGO Stage IC based on immunohistochemical analysis. She underwent surgery, chemotherapy, and radiotherapy with no recurrence of tumor seven years after the treatment.