Adult Granulosa Cell Tumor Of Ovary Research Articles

Sensitivity of frozen section analysis in patients with ovarian adult granulosa cell tumor, a multi-center study.

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. 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. Frozen section results of 274 patients with AGCT were obtained. The median age of the patients was 52years (range, 17-82years). Totally, 144 (52.7%, n = 273) patients were postmenopausal. The median tumour size was 90mm (range, 9-700mm). The median preoperative Ca-125 level was 23IU/mL (range, 2-995IU/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. It is important to know the diagnosis of AGCT intraoperatively, and we demonstrated the sensitivity of frozen-section for these tumors as 76.3%.

Risk Factors and Clinical Outcomes of Recurrence in Adult Ovarian Granulosa Cell Tumors.

Granulosa cell tumors (GCTs) of the ovary are rare but clinically significant malignancies. Despite advances in treatment, recurrence has remained a substantial challenge. This study aimed to identify clinical outcomes and potential prognostic risk factors for recurrence in patients diagnosed with GCTs. In a retrospective cohort study, the ovarian cancer database of the gynecological tertiary referral cancer center, Mashhad University of Medical Sciences, Mashhad, Iran, was searched from August 2012 to August 2023 to find GCT cases. Demographic, clinical, pathological, intervention-related factors, follow-up, and survival findings were meticulously collected. Data were analyzed using SPSS v 23. Ninety-two patients with GCTs, including 86 AGCT and 6 JGCT subjects, were identified. Based on further analysis of AGCT patients, most patients were ages under 50 (58.1%), clinically presented pain (32.6%), and abnormal uterine bleeding (27.9%) as the most frequent symptoms. Stages IA (64.0%) and IC (20.9%) were common. Five-year overall and progression-free survival were 98.2% and 90.8%, respectively. With a median follow-up time of 72 (0.0-180) months, disease recurrence was observed in 19 patients (23.9%), and five patients (5.4%) died of the disease. Stage IV was a hazard factor of recurrence (HR = 7.62, 95%CI (1.89-30.63); p = 0.004). The present study provides valuable insights into the outcomes and potential risk factors for recurrence in ovarian AGCTs. It duplicates the importance of stage in the prognosis of AGCT patients and highlights the safety of fertility-sparing surgery in stage I and the lack of need to administer chemotherapy in stage IC.

An extensive immunohistochemical analysis of 290 ovarian adult granulosa cell tumors with 29 markers.

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

Clinicopathologic Characteristics of a Single-institution Cohort of Ovarian Adult Granulosa Cell Tumors, With Biomarker and Therapeutic Implications Utilizing the Detection of Androgen, Estrogen, and Progesterone Hormone Receptor Expression by Immunohistochemistry.

Adult granulosa cell tumors (AGCTs) are rare ovarian tumors with generally good prognosis after surgical resection; however, they do have recurrence potential. Therapeutic and management options for recurrences are currently limited, and the need for expanded adjuvant therapies is increasingly recognized. Anti-hormonal therapy is being explored as an option, which relies on the detection and assessment of hormone receptor expression (androgen, estrogen, and progesterone receptors) as a biomarker and therapeutic target. Our study identifies several clinicopathologic characteristics with significant associations for recurrence of AGCT, which were younger age, higher stage, and larger tumor size. Our study also demonstrates that androgen receptor (AR) expression may be utilized as a potential biomarker for hormonal therapy and that detection of AR expression in AGCT by immunohistochemistry (IHC) varies depending on the antibody clone used for testing. AR was detected in 95% of samples tested with antibodies derived from clone AR27. This detection rate is much higher than previously reported.

Defining the relationship between ovarian adult granulosa cell tumors and synchronous endometrial pathology: Does ovarian tumor size correlate with endometrial cancer?

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. 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. 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). 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.

DNA alterations in ovarian adult granulosa cell tumours: A scoping review protocol.

Identifying and describing molecular alterations in tumors has become common with the development of high-throughput sequencing. However, DNA sequencing in rare tumors, such as ovarian adult granulosa cell tumor (aGCT), often lacks statistical power due to the limited number of cases in each study. Questions regarding personalized treatment or prognostic biomarkers for recurrence or other malignancies therefore still need to be elucidated. This scoping review protocol aims to systematically map the current evidence and identify knowledge gaps regarding DNA alterations, actionable variations and prognostic biomarkers in aGCT. This scoping review will be conducted based on Arksey and O'Malley's methodological framework and later modifications by JBI Evidence Synthesis. The protocol complies with Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for scoping reviews. All original publications describing molecular alterations of aGCT will be included. The search will be performed in May 2024 in the following databases: MEDLINE (Ovid), Embase (Ovid), Web of Science Core Collection and Google Scholar (100-top ranked). This scoping review will identify knowledge and gaps in the current understanding of the molecular landscape of aGCT, clinical trials on actionable variations and priorities for future research. As aGCT are rare, a possible limitation will be the small sample sizes and heterogenic study settings. The review protocol is registered at Open Science Framework under https://doi.org/10.17605/OSF.IO/PX4MF.

Adult ovarian granulosa cell tumors: analysis of outcomes and risk factors for recurrence

ObjectiveAdult granulosa cell tumors represent less than 5% of all ovarian malignancies. The aim of this study was to analyze the clinicopathological parameters and their impact on progression-free and overall...

The Prognostic Significance of Adjuvant Chemotherapy in Adult Ovarian Granulosa Cell Tumors: A Systematic Review and Meta-analysis.

This study aimed to evaluate the oncological and prognostic significance of adjuvant chemotherapy (CT) in patients with adult granulosa cell tumors of the ovary (AOGCT). We searched the Chinese National Knowledge Infrastructure, Clinical Trials, Wanfang Database, Web of Science, Cochrane Library, and MEDLINE electronic databases for articles published up to May 2023. Reference lists of the enrolled studies, Google Scholar, and scientific meeting reports were also manually searched. We enrolled 5641 patients with AOGCT from 33 eligible studies, including 1674 (29.7%) and 3967 (70.3%) patients in the CT and non-CT groups, respectively. Based on the cumulative results, adjuvant CT did not affect the risk of recurrence or progression (R/P) (odds ratio [OR]: 1.67, 95% confidence interval [CI]: 1.01-2.78, I2 = 63%, P = .05) and 5-year overall survival (OR: .86, 95% CI: .70-1.04, I2 = 0%, P = .12) of patients with AOGCT. However, adjuvant CT might reduce the 5-year disease-free survival (OR: 2.90, 95% CI: 1.19-7.08, I2 = 55%, P = .02). Sub-group analysis revealed that adjuvant CT did not affect the risk of R/P in patients with early-stage AOGCT (OR: .78, 95% CI: .43-1.43, I2 = 2%, P = .43) and advanced or recurrent AOGCT (OR: .78, 95% CI: .43-1.43, I2 = 2%, P = .43). This meta-analysis suggests that patients with AOGCT might not benefit from adjuvant CT, even those with advanced or recurrent disease. The results should be interpreted with caution because of the inherent limitations of retrospective studies.

Bisphenols S and F drive ovarian granulosa cell tumor invasion via a metabolic switch

Alterations in the metabolism of cancer cells are crucial for tumor growth and progression. However, the mechanism whereby environmental pollutants such as bisphenols F (BPF) and S (BPS) affect glucose metabolism through the glycolytic pathway, and therefore influence tumor progression, are unclear. Both bisphenols are endocrine-disrupting molecules that are used in plastics. As a consequence of their widespread use, these compounds have been detected in various human body fluids. Thus, hormone-sensitive cancers, such as ovarian cancers, are exposed to these compounds. In the present study, we aimed to determine the effects of the concentrations of BPS and BPF found in body fluids on the cell viability, glucose uptake, glycolysis, oxygen consumption, and invasion by the adult ovarian granulosa cell tumor (AGCT) cell line. We found that BPS and BPF increased the glucose uptake, hexokinase activity, proliferation, and invasion of the cells at environmentally relevant concentrations. Furthermore, we identified an inhibition of glycolysis in parallel with an increase in oxygen consumption, suggesting a BPS/BPF-induced switch from aerobic glycolysis to mitochondrial respiration. In summary, these findings demonstrate a new mechanism through which BPS and BPF promote ovarian granulosa cell tumor progression by increasing energy production through mitochondrial respiration. Thus, both bisphenols induced a metabolic switch that appears to be a stimulus for AGCT progression.

Response to Systemic Therapies in Ovarian Adult Granulosa Cell Tumors: A Literature Review.

Simple SummaryAdult granulosa cell tumors (aGCTs) are a rare subtype of ovarian cancer. First choice of treatment is surgery; when this is not possible, chemotherapy and anti-hormonal therapy are often used. There is limited evidence on the effect of systemic therapy in aGCT. The aim of our systematic review is to provide an overview of the response to chemotherapy and anti-hormonal therapy in patients with aGCT. We found very few articles reporting the response to chemotherapy and anti-hormonal therapy in only aGCT. The available data showed a moderate response to chemotherapy and anti-hormonal therapy, but if patients who achieve stable disease are also taken into account, the response is higher. This may mean that surgery can be postponed for a longer period of time.For adult granulosa cell tumors (aGCTs), the preferred treatment modality is surgery. Chemotherapy and anti-hormonal therapy are also frequently used in patients with recurrent aGCT. We aimed to review the existing literature on the response to chemotherapy and anti-hormonal therapy in patients with aGCT. Embase and MEDLINE were searched from inception to November 2021 for eligible studies. Objective response rate (ORR) was calculated as the total number of cases with a complete response (CR) or a partial response (PR). Disease control rate (DCR) was defined as the sum of cases with CR, PR or stable disease (SD). A total of 10 studies were included that reported on chemotherapy and 13 studies were included that reported on anti-hormonal therapy. The response rates of the 56 chemotherapy regimens that could be evaluated resulted in an ORR of 30% and DCR of 58%. For anti-hormonal therapy, the results of 73 regimens led to an ORR of 11% and a DCR of 66%. Evidence on systemic therapy in aGCT only is limited. For both chemotherapy and anti-hormonal therapy, the ORR is limited, but the response is considerably higher when patients achieving SD are included. New approaches are needed to provide more evidence and standardize treatment in aGCT.

Can adjuvant chemotherapy improve the prognosis of adult ovarian granulosa cell tumors?: A narrative review.

Adult granulosa cell tumors (aGCTs) are rare ovarian neoplasms with a relatively favorable prognosis. They follow an indolent course, characterized by a prolonged natural history and a tendency to late recurrences, Around a quarter of patients develop recurrence and More than 70% of women with recurrence die from their disease, The percentage of patients received chemotherapy increases over time, whether adjuvant chemotherapy improve the prognosis of aGCTs is equivocal? The purpose of this review is to summarize the previously published evidence to evaluate whether adjuvant chemotherapy improve the prognosis of aGCTs to provide guidance for clinical practice. EMBASE, PubMed, Web of Science, WanFang Data and Chinese National Knowledge Infrastructure are searched up to December 2020, used the search strategy of ovar* and granulosa cell* and (tumor* or tumour* or malignan* or cancer* or carcinom* or neoplasm*) and chemotherapy. The screening process was conducted strictly based on inclusion and exclusion criteria. Clinical studies based on human including randomized controlled trial, quasi-randomised controlled trials, nonrandomised trials cohort study and case control study were included without restriction of time. The percentage of patients received chemotherapy increases over time, but the benefit of adjuvant chemotherapy is lack of high-grade evidence of prospective study, based on the current retrospective studies, we still do not have the evidence to confirm the survival benefit of adjuvant chemotherapy in early stage, advanced stage or recurrent aGCT with no residual tumor, but for inoperable disseminated disease or disease with suboptimal cytoreduction, adjuvant chemotherapy maybe an Optable options. Multinational prospective randomised controlled trials are urgently needed to validate the role of adjuvant chemotherapy. Further research on molecular mechanisms and developing novel targeted medicines may improve the survival of aGCTs.

Imaging findings of uterine adenosarcoma with sarcomatous overgrowth: two case reports, emphasizing restricted diffusion on diffusion weighted imaging

BackgroundAdenosarcoma is classified as a mixed epithelial and mesenchymal tumor composed of a benign epithelial component and a malignant stromal component. The stromal component in adenosarcoma is usually low grade, and consequently the prognosis is relatively favorable. While, adenosarcoma with sarcomatous overgrowth (SO) is defined as an adenosarcoma in which the sarcomatous component constitutes more than 25% of the tumor. The stromal component is also high-grade sarcoma showing greater nuclear pleomorphism and mitotic activity, thus, it is associated with worse prognosis. MRI findings of adenosarcoma without SO have been described in previous literatures but the imaging findings in adenosarcoma with SO may be poorly defined. Therefore we present two cases of uterine adenosarcoma with SO.Case presentationPatient 1 was a 76-year-old woman referred to our hospital with complaint of abdominal distension and postmenopausal bleeding. Patient 2 was a 57-year-old woman with complaint of lower abdominal pain and abnormal uterine bleeding. On magnetic resonance imaging (MRI), T2 weighted imaging showed a large, heterogeneous high-intensity mass with hyperintense tiny cysts that expanded the uterine cavity and extended into the cervical canal for both patients. On diffusion-weighted imaging (DWI), both masses appeared as high signal intensity. Patient 2 also had a right ovarian adult granulosa cell tumor that may have contributed to development of the adenosarcoma. Patient 1 recurred with peritoneal sarcomatosis 6 months after surgery and died of the disease. Patient 2 also recurred with a left upper lung metastasis 3 months after surgery.ConclusionsDWI may depict pathological changes produced by SO of adenosarcoma as high signal intensity, even though SO does not seem to change MRI findings of adenosarcoma on other sequences. Therefore, DWI could potentially predict SO in presumptive adenosarcoma on MRI and the patient’s prognosis. It is also important for pathologists to know if SO can arise in adenosarcoma because they need to examine the tumor thoroughly to determine the percentage of SO component in the tumor volume when SO is present.

Nuclear Localization of SMAD3 as an Independent Predictor of Recurrence in Ovarian Adult Granulosa Cell Tumor

Nuclear Localization of SMAD3 as an Independent Predictor of Recurrence in Ovarian Adult Granulosa Cell Tumor

Assessment of predictive biomarker prevalence in molecularly defined adult-type ovarian granulosa cell tumors.

5567 Background: The FDA has separately approved pembrolizumab for all advanced solid tumors with either microsatellite instability or high tumor mutational burden (≥10 mutations per megabase), and homologous recombination deficiency is an established biomarker for response to poly ADP ribose polymerase inhibitors in epithelial ovarian cancer. The detection of these predictive biomarkers in adult-type ovarian granulosa cell tumors could identify novel treatment strategies in this rare disease. The primary objective of this study was to determine the prevalence of established predictive biomarkers among molecularly defined adult-type ovarian granulosa cell tumors. Methods: With institutional review board approval, we performed a cross-sectional study examining de-identified FoundationOne companion diagnostic molecular profiles for 423 women with molecularly defined (FOXL2 c.C402G positive) adult type ovarian granulosa cell tumors. The dataset was comprised of coding variants for up to 406 genes as well as genomic signatures including microsatellite instability, tumor mutational burden, and genome wide loss of heterozygosity. PD-L1 expression by immunohistochemistry was also available for a subset of tumors. Descriptive statistics were used for comparison between groups and all statistical tests were two-sided. Results: Women in this cohort had a mean age of 57 years (range 24-87) at the time of sample submission for molecular profiling. The median tumor mutational burden was 1.3 mutations per megabase [mut/Mb] (range 0-8.8 mut/Mb). TP53-mutated aGCT had a higher tumor mutation burden than TP53 non-mutated tumors (median 2.4 mut/Mb, 95% CI 1.7-3.0 mut/Mb vs median 1.3 mut/Mb, 95% CI 1.5-1.9 mut/Mb; P=.02). All 384 tumors with available microsatellite instability testing were microsatellite stable. Sixty-seven tumors had PD-L1 expression measured and of these 94% (63/67) were negative with the remainder “low positive.” No tumors were positive for genome wide loss of heterozygosity. Apart from FOXL2 c.C402G, the most frequent short variants were TERT promoter mutations (-124C>T: 190/423, 45.0%; -146C>T: 39/423, 9.2%). Other frequently observed variants included truncating mutations in KMT2D/MLL2 (71/423, 16.8%), pathogenic TP53 mutations (35/423, 8.3%), CDKN2A/B deletions (43/423, 10.2%), and activating PIK3CA mutations (23/423, 5.4%). Conclusions: No women with molecularly defined adult-type ovarian granulosa cell tumors in this large cross-sectional study would be eligible for FDA-approved pembrolizumab based on either microsatellite instability or high tumor mutational burden. No tumors exhibited evidence of homologous recombination deficiency and molecularly targetable mutations were rare. The development of novel precision treatment options remains a critical unmet need for this rare disease.

MALIGNANT JUVENILE AND ADULT OVARIAN GRANULOSA CELL TUMORS IN PEDIATRIC PATIENTS - REPORT OF TWO CASES

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.

Magnetic Resonance Imaging of Recurrent Adult Granulosa Cell Tumor of the Ovary: A Retrospective Analysis of 11 Cases.

ObjectiveThe aim of the study was to characterize magnetic resonance imaging findings in patients with recurrent ovarian adult granulosa cell tumors (AGCTs).MethodsClinical and magnetic resonance imaging manifestations of recurrent AGCTs were evaluated in 11 patients.ResultsInitial recurrences of AGCT were diagnosed between 13 months and 30 years (mean, 11.3 years). Recurrent tumors were located in the pelvic peritoneum, the abdominal peritoneum, the retroperitoneum, and bone. The number of recurrent tumors varied from 1 to 5. Tumors varied in morphology and all margins were well circumscribed. The internal structures noted were as follows: multilocular cystic and solid and cystic. Furthermore, internal hemorrhage and sponge-like multicystic components were identified.ConclusionsOvarian AGCTs recurred in the pelvic peritoneum, abdominal peritoneum, and the retroperitoneal lymph nodes. Large recurrent AGCTs were commonly well circumscribed, round or lobulated, and multilocular cystic or solid and cystic. Moreover, they frequently included internal hemorrhage and sponge-like multicystic components.

Rare DICER1 and Absent FOXL2 Mutations Characterize Ovarian Juvenile Granulosa Cell Tumors.

FOXL2 somatic mutation occurs in a high percentage of ovarian adult granulosa cell tumors and DICER1 mutations in a high proportion of Sertoli-Leydig cell tumors. These mutations have only been studied in a limited number of juvenile granulosa cell tumors (JGCTs), and their occurrence and frequency in these neoplasms is controversial. We aimed to determine the frequency of FOXL2 and DICER1 mutations in a large cohort of 50 JGCTs, and to evaluate the prognostic impact of these mutations. A FOXL2 hotspot mutation was found in 2/50 JGCTs. Review of these 2 cases reclassified them as adult granulosa cell tumors. Thus, FOXL2 mutation was absent from our large cohort of JGCTs. DICER1 mutations in the RNase IIIb domain were found in 4 cases. After review of the mutated cases, 1 was reclassified as a gynandroblastoma with a prominent JGCT component. Thus, DICER1 mutations were detected in 3/47 (6%) of pathologically confirmed JGCTs. Our results show that FOXL2 mutations are not present in JGCT, whereas a small percentage of these neoplasms exhibit DICER1 mutations.

Application of molecular analysis in differential diagnosis of ovarian adult granulosa cell tumors

Objective: To investigate the application value of molecular detection in the differential diagnosis of ovarian adult granulosa cell tumors (AGCT) by analyzing FOXL2, AKT1 and DICER1 mutations in these tumors. Methods: A total of 48 cases of ovarian sex cord-stromal tumor (SCST) were selected from July 2012 to June 2019 in Beijing Obstetrics and Gynecology Hospital, including 21 adult granulosa cell tumors (AGCT), 15 fibromas/fibrothecomas, 8 Sertoli-Leydig cell tumors (SLCT) and 4 other types of ovarian SCST. Genomic DNA was extracted from the formalin-fixed paraffin-embedded tissue sections. Polymerase chain reaction amplification for FOXL2, AKT1 and DICER1 genes was performed, followed by sequencing using capillary electrophoresis. Fisher exact test was used to compare the prevalence difference of FOXL2, AKT1 and DICER1 mutations among the groups. P<0.05 was considered significant. Results: Eighteen of the 21 (85.7%) AGCT harbored FOXL2 mutation. Compared with other SCST (13.0%, 3 of 23; including fibromas/fibrothecomas and SLCT), FOXL2 mutation was significantly higher in AGCT (P<0.001). In addition, FOXL2 mutation was also detected in one fibrothecoma, two SLCT and two gynandroblastomas. DICER1 mutation was identified in four of eight SLCT, and these cases were moderately to poorly differentiated. FOXL2 mutation was found in one SLCT with DICER1 mutation. There was no DICER1 mutation in other ovarian SCST. No AKT1 mutation was detected in all the patients. Conclusions: FOXL2 mutation is a highly specific biomarker for adult AGCT and may be helpful to resolve problematic cases. Diagnosis should also be taken into consideration of the clinical and histological features as FOXL2 mutation is also found in other SCST. The detection of DICER1 mutation is helpful for the differential diagnosis of ovarian SLCT. Synchronous DICER1 and FOXL2 mutation in the SLCT has been observed, and its significance needs to be further studied.

"Coffe Bean" Nucleic in a Rare Case of Ovarian Adult Granulosa Cell Tumor

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. A positive S100 marker was a particular finding in the immunohistochemical profile. Treatment strategy for this kind of case should include surgery and adjuvant treatment and a strict follow-up of the patient for at least 5-10 years.

Adult ovarian granulosa cell tumor: Role of systemic chemotherapy and surgical treatment.

e18083 Background: Granulosa cell tumor (GCT) are rare sex cord-stromal tumours. Their frequency is approximately 3% - 5% of all malignant ovarian tumors, and the incidence is from 0.6 to 2.1 cases per 100 000 women per year. According to the histological features, GCT are divided into two types: adult and juvenile. In the 2014 WHO histological classification, GCT were divided into borderline, which included the GCT of the juvenile type, and the malignant GCT of the adult type (AGCT). Despite the definition of AGCT not as borderline, but as low-grade malignant tumors, there are no specific recommendations for the surgical and drug treatment in such patients. Main method of treatment is surgical. Role of systemic treatment due to rarity of AGCT and late recurrence still has not determined. Methods: Data of 93 patients in our institution who were diagnosed with AGCT I-IV stage of the disease between 1980 and 2017 were evaluated. The data were obtained from the files of the patients, electronic database of the gynecologic oncology clinic, operation notes, and pathology records. Results: Stage of the disease, the spread of the tumor beyond the capsule and the number of mitoses of more than 10 significantly influenced the OS rates (p &lt; 0.05). The average time before the onset of the first relapse in IA, IB stage was 134.5 months, in IC stage - 67.4 months, in II-IV stage - 34.3 months. Stage of the disease is an independent prognostic factor for the occurrence of a relapse of the disease. In stage I disease there was no influence of the volume of surgical treatment and adjuvant chemotherapy on DFS and the duration of disease-free period (p &gt; 0.05). The duration of the non-progressive period was some, but not significantly more when performing optimal cytoreduction for the recurrence of the disease, and did not depend on the implementation regimen and adjuvant chemotherapy. Conclusions: There were not found significant difference in the overall and relapse-free survival of patients with ovarian AGCT, depending on the options of surgical and drug treatment they underwent. Studies showed that hormones play a critical role in the pathogenesis and treatment of GCT, especially in some ineffective cases for radiotherapy and chemotherapy. Additional multicenter randomized trials are needed to clarify the effectiveness of the various options for surgical and drug treatment of adult GCT patients.