Granulosa Cell Tumor Research Articles

SATB2 Cytoplasmic Expression is Characteristic of a Subset of Ovarian Stromal Cells and Sex Cord Stromal Tumors.

Special AT-rich sequence-binding protein 2 (SATB2) is a nuclear transcription factor that shows consistent nuclear staining in colorectal adenocarcinoma and osteosarcoma. Following the observation of cytoplasmic staining with this marker in luteinized ovarian stromal cells, we studied the expression of SATB2 in ovarian stromal cells, various types of follicular cysts, and sex cord-stromal tumors. Eighty-five cases were stained for SATB2. Ovarian hilar Leydig cells (n = 12), luteinized stromal cells (n = 10), corpora lutea (n = 4), luteinized follicular cysts (n = 4), and stromal hyperthecosis (n = 6) exhibited consistent, usually diffuse, granular cytoplasmic staining. In addition, Leydig cell tumors (n = 1) and steroid cell tumors (n = 4) showed diffuse cytoplasmic staining. SATB2 also exhibited cytoplasmic staining in most Sertoli-Leydig cell tumors (n = 16) and gynandroblastomas (n = 3) confined to the Leydig cell component. Adult granulosa cell tumors (n = 14), juvenile granulosa cell tumors (n = 3), sex cord tumors with annular tubules (n = 3), cellular fibromas (n = 3), sclerosing stromal tumors (n = 1), and thecomas (n = 1) were negative apart from cytoplasmic staining in associated luteinized stromal cells. SATB2 cytoplasmic staining has not been previously described in these lesions but is characteristic of a variety of ovarian stromal cells and sex cord-stromal tumors, in particular, those exhibiting luteinization or a Leydig or steroid cell component. SATB2 staining may be of value in identifying luteinized or Leydig cells when these are morphologically inconspicuous.

Early-onset gynecological tumors in DNA repair-deficient xeroderma pigmentosum group C patients: a case series

BackgroundXeroderma pigmentosum (XP) is a group of rare hereditary disorders with highly increased risk of skin tumors due to defective DNA repair. Recently we reported 34-fold increased risk of internal tumors in XP patients in comparison with general population. The molecular data and clinical practice on the internal tumors treatment in XP patients is limited and scarcely represented in the medical literature. In this work, we describe young patients with constitutive biallelic deactivation of the XPC gene developing gynecological tumors with somatic DICER1 mutations.MethodsWhole genome sequencing was used to analyze in detail somatic mutational landscape and driver events of these rare tumors.ResultsWe describe five early-onset gynecological tumors in four xeroderma pigmentosum group C (XP-C) young patients (11 to 19 years old) including vaginal embryonal rhabdomyosarcomas in monozygotic twin sisters, juvenile granulosa-cell tumor of the ovary and poorly differentiated stage IA Sertoli-Leydig cell tumor in 19-years old patient, and FIGO stage IC1 tumor of ovary in 13-years old patient. XP-C ovarian tumors harbor 4.4 times more single base substitutions than sporadic tissue-matched cancers and demonstrate XP-C specific mutation signature with strong transcriptional bias indicating inability of the cells to repair bulky DNA lesions of unknown etiology. A special mode of treatment was applied to avoid usage of chemotherapy which is toxic for XP patients.ConclusionsXP-C status should be accounted for prevention and specific treatment of gynecological tumors in young DNA repair-deficient XP patients.

TFE3 nuclear expression as a novel biomarker of ovarian sclerosing stromal tumors and associated with its histological morphology

Sclerosing stromal tumors of the ovary are benign and tend to occur in youthful women with lobular structures at low frequencies. Three types of cells, including luteinized cells, short spindle myoid cells, and intermediate cells, are found in the lobules which abundant in the blood vessels. Currently, immunohistochemistry is used to detect normal follicles, sclerosing stromal tumors, granulosa cell tumors, and fibromas/thecomas. Our research results showed that transcription factor enhancer 3 (TFE3) was moderate to strong positive in the theca interna layer of normal follicles. TFE3 was expressed in seven out of eight sclerosing stromal tumors, mainly in luteinized cells. It did not express in 20 granulosa cell tumors. Of the nine fibromas/thecomas, TFE3 was weakly staining in 2 cases and negative in the remaining 7 cases. The expression of TFE3 was also weak in only one microcystic stromal tumor. 8 cases of sclerosing stromal tumors were analyzed by FISH using a TFE3 separation probe, and the results were negative. In short, as a nuclear transcription protein, TFE3 specifically expressed in sclerosing stromal tumors and could serve as a new marker for the diagnosis and differential diagnosis of sclerosing stromal tumors. Moreover, we speculate that TFE3 will promotes the formation of the vascular plexus after entry into the nucleus, which can further explain why sclerosing stromal tumors are different from other ovary sex-cord stromal tumors.

Behavioral Disorders in Mares with Ovarian Disorders, Outcome after Laparoscopic Ovariectomy: A Case Series.

Owner complaints of estrus-related behavior in mares are a common cause of referral for laparoscopic ovariectomy. Granulosa cell tumors are a common neoplastic condition affecting the equine ovary, causing behavioral changes at rest and reduced performance. The reported success rate of ovariectomy in treating behavioral disorders is 64-86%. The aim of this study was to retrospectively evaluate the long-term follow-up of laparoscopic ovariectomy in mares in our case series, focusing on the owner's perspective of the behavior of the mares after surgery. In addition, the histopathological features of the removed ovaries were investigated. The clinical records of mares that underwent laparoscopic ovariectomy between 2015 and 2022 were retrospectively reviewed. Owners complaining of poor behavior were interviewed about the main behavioral problem leading to referral and its eventual resolution after surgery. Eleven mares were included. The most common complaints were increased sensitivity on both flanks (10/11, 91%) and general riding problems (9/11, 82%). In 5/11 cases (45%), both ovaries were removed by laparoscopic ovariectomy. Histopathologic findings consistent with GCT/GTCT were found in five out of six examined ovaries (five granulosa theca cell tumors, GTCT). According to owner interviews, the scores assigned to each behavior improved significantly after surgery, regardless of histological findings. Although many factors can influence the behavior of horses, granulosa cell tumors (GCTs) proved to be a common cause and, as reported by the owners, ovariectomy resulted in improvement or complete resolution of the abnormal behavior.

Clinicopathological analysis of patients with molecularly confirmed stage I adult granulosa cell tumors and prediction of recurrence

ObjectiveAdult 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. MethodsWe investigated 130 patients with pathologically diagnosed AGCT as confirmed by the presence of the characteristic FOXL2 C402G mutation. ResultsMost 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). ConclusionsThe 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.

Clinical and ultrasonographic findings of ovarian tumours in bitches: A retrospective study

A retrospective study was carried out to investigate incidence, clinical signs and ultrasonographic findings of ovarian tumours in a population of dogs referred to the Veterinary Teaching Hospital of the University of Perugia (Italy) and Anicura Tyrus Veterinary Clinic (Terni, Italy). The period of study ranged from January 2005 to December 2021. A total of 1910 dogs were affected by neoplasia but only 35 of them (1.8%), of different breeds and ages, were found to have ovarian tumours. Ultrasound of the ovaries was performed based on clinical signs; the diagnosis was achieved after ultrasound findings prompted ovariohysterectomy and ovarian pathologic evaluation In our study, the age of bitches affected by ovarian neoplasia ranged from 3 to 20 years (mean 9.6 ± 3.8). The histopathological findings of ovarian masses identified 16 granulosa cell tumours (GCT) (46%), 7 adenomas (20%), 5 adenocarcinomas (14%), 2 teratomas (6%), 1 leiomyoma (3%), 1 luteoma (3%), 1 tecoma (3%), 1 dysgerminoma (3%), and 1 haemangiosarcoma (3%). In particular, with respect to clinical signs, 69% of bitches showed abnormalities of estrus cycle (short interestral interval, persistent estrus, prolonged interestral interval). The other main clinical signs included abdominal distention, palpable abdominal mass, vulvovaginal discharge, polyuria/polydipsia, mammary masses. When present, the laboratory abnormalities were slight anemia and leucocytosis with neutrophilia. The tumours were ultrasonographically classified as mainly solid: 12/35 (34%) (1 adenoma, 4 adenocarcinomas, 1 dysgerminoma, 1 haemangiosarcoma, 1 leyomioma, 1 luteoma, 1 GCT, 1 tecoma, 1 teratoma); solid with cystic component 13/35 (37%) (9 GCT, 2 Adenomas, 1 adenocarcinoma, 1 teratoma); and mainly cystic 10/35 (29%) (6 GCTs, 4 adenomas).In our study, the ultrasound examination allowed us to suspect ovarian neoplasia in asymptomatic subjects referred for breeding management or for preventive health check.On the basis of our data, we proposed to perform a complete periodic examination of the reproductive system once a year from 6 years. Nevertheless, the presence of ovarian neoplasms found in young subjects, during breeding management, suggest including routine ultrasound examination of the reproductive tract.

Orotic acid induces apoptotic death in ovarian adult granulosa tumour cells and increases mitochondrial activity in normal ovarian granulosa cells

Orotic acid (OA) is a natural product that acts as a precursor in the pyrimidine nucleotide biosynthesis pathway. Most studies concerning administration of OA focus on its therapeutic effects; however, its effect on tumours is unclear. We aimed to determine whether treatment with OA influences the viability and apoptosis of normal (HGrC1) and tumour-derived (KGN) human ovarian granulosa cells. The effects of OA (10–250 μM) on viability and apoptosis of both cell lines were determined by using alamarBlue and assessing caspase-3/7 activity, respectively. Annexin V binding and loss of membrane integrity were evaluated in KGN cells. The cell cycle and proliferation of HGrC1 cells were assessed by performing flow cytometric and DNA content analyses, respectively. The influence of OA (10 and 100 μM) on cell cycle- and apoptosis-related gene expression was assessed by RT-qPCR in both cell lines. Mitochondrial activity was analysed by JC-1 staining in HGrC1 cells. In KGN cells, OA reduced viability and increased caspase-3/7 activity, but did not affect mRNA expression of Caspase 3, BAX, and BCL2. OA enhanced proliferation and mitochondrial activity in HGrC1 cells without activating apoptosis. This study demonstrates that the anti-cancer properties of OA in ovarian granulosa tumour cells are not related to changes in apoptosis-associated gene expression, but to increased caspase-3/7 activity. Thus, OA is a promising therapeutic agent for ovarian granulosa tumours. Further, our results suggest that differences in basal expression of cell cycle- and apoptosis-related genes between the two cell lines are responsible for their different responses to OA.

Adult-Type Granulosa Cell Tumor of the Testis: A Report of a Case and a Discussion of the Literature

Testicular granulosa cell tumors (TGCTs) are rare tumors of sex cord-stromal origin. TGCTs are classified into two main categories, the adult type and the juvenile type. The adult type is extremely rare, with only 93 known cases reported in the literature. Herein, we present a report of a case of a 30-year-old male patient who presented with a testicular mass and underwent radical inguinal orchiectomy; the pathology examination revealed an adult-type granulosa tumor. Additionally, we review the literature to summarize the scientific knowledge of an entity barely described worldwide.

Mixed sex cord-stromal tumor (gynandroblastoma) with malignant morphology involving both ovaries: a case report.

Mixed sex cord-stromal tumors, which consist of poorly differentiated Sertoli cells and Leydig cells and juvenile granulosa cell tumor tissue, are extremely rare. Most of these tumors are unilateral and stage I at the time of diagnosis; nonetheless, according to the available relevant English-language literature, these tumors maintain a malignant potential. We herein report a case involving a 15-year-old girl diagnosed with a mixed sex cord-stromal tumor (gynandroblastoma with juvenile granulosa cell tumor component). Left salpingo-oophorectomy was initially performed, and the diagnosis of a juvenile granulosa cell tumor was established. Right salpingo-oophorectomy was performed 1 year later, at which time the specimen showed a different growth pattern involving epithelioid cells and tubules, resembling a Sertoli-Leydig cell tumor. Immunohistochemical staining was performed and the specimen was compared with that obtained 1 year earlier. We concluded that the tumors were linked and most likely constituted a gynandroblastoma (mixed form of sex cord-stromal tumor). Although this is an extremely uncommon ovarian tumor, it should be considered when diverse tumor morphology is identified. Bilateral metachronous involvement of the ovaries is possible. The grade of the Sertoli-Leydig cell component may influence the prognosis of such a tumor.

P13 Ovarian granulosa cell tumors treated with estrogen blockade and CDK4/6 inhibitors: A case series

P13 Ovarian granulosa cell tumors treated with estrogen blockade and CDK4/6 inhibitors: A case series

Deep convolutional neural networks for multiple histologic types of ovarian tumors classification in ultrasound images.

This study aimed to evaluate and validate the performance of deep convolutional neural networks when discriminating different histologic types of ovarian tumor in ultrasound (US) images. Our retrospective study took 1142 US images from 328 patients from January 2019 to June 2021. Two tasks were proposed based on US images. Task 1 was to classify benign and high-grade serous carcinoma in original ovarian tumor US images, in which benign ovarian tumor was divided into six classes: mature cystic teratoma, endometriotic cyst, serous cystadenoma, granulosa-theca cell tumor, mucinous cystadenoma and simple cyst. The US images in task 2 were segmented. Deep convolutional neural networks (DCNN) were applied to classify different types of ovarian tumors in detail. We used transfer learning on six pre-trained DCNNs: VGG16, GoogleNet, ResNet34, ResNext50, DensNet121 and DensNet201. Several metrics were adopted to assess the model performance: accuracy, sensitivity, specificity, FI-score and the area under the receiver operating characteristic curve (AUC). The DCNN performed better in labeled US images than in original US images. The best predictive performance came from the ResNext50 model. The model had an overall accuracy of 0.952 for in directly classifying the seven histologic types of ovarian tumors. It achieved a sensitivity of 90% and a specificity of 99.2% for high-grade serous carcinoma, and a sensitivity of over 90% and a specificity of over 95% in most benign pathological categories. DCNN is a promising technique for classifying different histologic types of ovarian tumors in US images, and provide valuable computer-aided information.

Abnormal mare behaviour is rarely associated with changes in hormonal markers of granulosa cell tumours: A retrospective study.

Abnormal or undesired mare behaviours are often assumed to be associated with ovarian abnormalities. We aimed to determine the incidence of abnormal behaviours and their association with concentrations of one or more ovarian hormones associated with a granulosa cell tumour (GCT). Retrospective descriptive. A total of 2914 hormonal profile samples submitted with the words behave, behaviour, or behaving in the submission history were analysed. The association between reported abnormal behaviours and concentrations of testosterone, anti-Müllerian hormone (AMH), inhibins and inhibin-B were assessed. Statistical analysis was performed using a Chi-squared test of association. Of the 2914 cases that were submitted due to behaviour issues, 2506 (86%) did not have any of the measured hormones reach GCT-like concentrations. The remaining 408 cases had either one (63%), two (25.5%), or three (11.5%) hormones with concentrations consistent with those from confirmed GCT cases. Testosterone had the lowest percent of GCT-like values among the cases (7.7%), compared with AMH (9.4%), inhibins (9.6%) and inhibin B (8.7%). Stallion-like behaviour was significantly associated with increased concentrations of all four hormones. In contrast, aggression, oestrous and other abnormal behaviours were significantly less likely to be associated with increased concentrations of the hormones. Retrospective study, using sample submission history. Overall, the abnormal behaviours among mares, except the stallion-like behaviour, were not associated with increased ovarian hormones. These results highlight the common misassumption about the involvement of the ovaries in 'abnormal behaviours' or 'undesirable behaviours' of mares.

The Impact of Surgery &amp; Chemo in Treating Sex Cord-Stromal Tumors

The Impact of Surgery &amp; Chemo in Treating Sex Cord-Stromal Tumors

Serum vascular endothelial growth factor associated with the progression of granulosa cell tumor: a report of two cases

BackgroundGranulosa cell tumors (GCTs) account for approximately 2% of ovarian malignancies and are considered a rare type of ovarian cancer. GCTs are characterized by irregular genital bleeding after menopause due to female hormone production as well as late recurrence around 5–10 years after initial treatment. In this study, we investigated two cases of GCTs to find a biomarker that can be used to evaluate the treatment and predict recurrence.Case presentationCase 1 was a 56-year-old woman who presented to our hospital with abdominal pain and distention. An abdominal tumor was found, and GCTs were diagnosed. Serum vascular endothelial growth factor (VEGF) levels decreased after surgery. Case 2 involved a 51-year-old woman with refractory GCTs. Carboplatin–paclitaxel combination therapy and bevacizumab were administered after the tumor resection. After chemotherapy, a decline in VEGF levels was observed, but serum VEGF levels increased again with disease progression.ConclusionsVEGF expression may be of clinical importance in GCTs as a clinical biomarker for disease progression, which may be used to determine the efficacy of bevacizumab against GCTs.

Progress on correlation between pathological features and prognosis of adult granulosa cell tumor of the ovary

成人型粒层细胞瘤（adult granulosa cell tumor，AGCT）是卵巢最常见的性索间质肿瘤。AGCT患者大多数为Ⅰ期，尽管有较高的5年及10年生存率，但其易复发，尤其具有远期复发的特点。肿瘤分期、肿瘤破裂和肿瘤残留是重要的预后因素。但是，AGCT肿瘤病理特征与预后的相关性却尚不明确，存在较多争议。本文旨在明确AGCT肿瘤大体、组织病理、免疫组织化学、分子病理各项特征与预后之间的相关性研究进展。.

ЮВЕНИЛЬНАЯ ГРАНУЛЕЗОКЛЕТОЧНАЯ ОПУХОЛЬ ЯИЧНИКА У РЕБЕНКА: КЛИНИЧЕСКОЕ НАБЛЮДЕНИЕ И ОБЗОР ЛИТЕРАТУРЫ

Juvenile granulosa cell tumor of the ovaries is a rare disease in pediatric oncology. Mostly seen in girls and young women in premenarchal age (median age 10 y/o) and is more aggressive than the adult type, but has a favorable prognosis, especially in its early stages. Large reviews and studies include patients with bot adult and juvenile types granulosa cell tumor. Due to the limited cohort of pediatric patients, there are no standards for the treatment of juvenile granulosa cell tumor in pediatric practice. Therefore, diagnosis, treatment, and long-term follow-up for this disease are based on recommendations for an adult cohort. Adjuvant chemotherapy as a curative option is used in advanced stages above the FIGO IC. For the IC stage, the issue of prescribing adjuvant chemotherapy remains debatable. Article represents analysis of the bibliographical data of the largest studies on the treatment of this disease as well as clinical case of a 15 y/o patient with juvenile granulosa cell tumor of the right ovary who had received complex treatment in the Oncological Department of the Morozov Children’s City Clinical Hospital (Moscow, Russia).

ЮВЕНИЛЬНАЯ ГРАНУЛЕЗОКЛЕТОЧНАЯ ОПУХОЛЬ ЯИЧНИКА У РЕБЕНКА: КЛИНИЧЕСКОЕ НАБЛЮДЕНИЕ И ОБЗОР ЛИТЕРАТУРЫ

Juvenile granulosa cell tumor of the ovaries is a rare disease in pediatric oncology. Mostly seen in girls and young women in premenarchal age (median age 10 y/o) and is more aggressive than the adult type, but has a favorable prognosis, especially in its early stages. Large reviews and studies include patients with bot adult and juvenile types granulosa cell tumor. Due to the limited cohort of pediatric patients, there are no standards for the treatment of juvenile granulosa cell tumor in pediatric practice. Therefore, diagnosis, treatment, and long-term follow-up for this disease are based on recommendations for an adult cohort. Adjuvant chemotherapy as a curative option is used in advanced stages above the FIGO IC. For the IC stage, the issue of prescribing adjuvant chemotherapy remains debatable. Article represents analysis of the bibliographical data of the largest studies on the treatment of this disease as well as clinical case of a 15 y/o patient with juvenile granulosa cell tumor of the right ovary who had received complex treatment in the Oncological Department of the Morozov Children’s City Clinical Hospital (Moscow, Russia).

Pathohistological findings in bilateral removed ovaries of mares with behavioral problems

Unwanted behavior is a common presenting problem in mares which often challenges veterinarians. Behavioral problems associated with cyclicity in absence of neoplastic ovarian pathology are often treated with oestrus suppression (Aurich and Kaps, Reprod.Dom.Anim. 2022;00:1-9). However, most options are cost-intensive, might have severe side effects or reversibility is not clearly determined yet. Therefore, bilateral ovariectomy (bOE) is often chosen due to the benefited surgical procedure. Studies evaluating effects of bOE on unwanted behavior in mares from the owner´s perspective revealed an improvement (Melgaard et al., Animals 2020;10:1210). However, there is a lack of histopathological explanation for this phenomenon. Therefore, the aim of the present study was to evaluate bilateral removed ovaries histopathologically in mares with behavioral problems. We hypothesized, that there are non-neoplastic changes in ovaries histologically detectable, which could be responsible for unwanted behavior in mares. In a retrospective case series, ovaries of 20 mares after bOE (OE) via standing laparoscopy using routine procedures (Röcken et al., Vet. Surge. 2011;40:1009-1014) were compared with granulosa cell tumors (GCT, n=10). Samples from removed ovaries were fixed in formaldehyde for further histological evaluation. One additional representative sample of each ovary was sent to a commercial laboratory for histopathological diagnosis of GCT by a Board-certified pathologist.Immunohistochemical evaluation was carried out using Kiel 67 (ki67), Aromatase (AR) and Anti-Muellerian Hormone (AMH) as diagnostic marker. Intensity of staining for ki67, AR and AMH was classified as -, +, ++, and +++ for no, low (<40%), moderate (40-70%) and high (70-100%) expression, respectively. Immunolabeling for ki67, AR and AMH was most intense in granulosa cells of antral and early atretic follicles in OE. In GCT, immunolabeling for AR and AMH was additionally highly intense in Leydig-like cells. In OE, ovaries of 3 mares initially categorized as GCT could not be confirmed and were therefore regarded as early stages due to upregulated ki67 in presence of a corpus luteum. Measurements of AMH in serum performed before surgery were above the reference value in all mares of GCT and in 6/20 (30%) in OE. In GCT, 8/10 (80%) and in OE, 16/20 (80%) mares showed behavioral abnormalities before surgery, which were not correlated with increased AMH in serum. Serum AMH values were not correlated with high expression of AMH in 9 mares, where granulosa cells of antral follicles could be evaluated. All, but one mare, benefit from bOE regarding behavior as reported from the owner. In the present study, immunostaining with ki67, AR or AMH showed no clear difference between OE and GCT. Further investigations regarding different immunohistochemical staining are warranted to find marker for non- or early neoplastic changes related to improvement of behavior in mares after bOE.

The impact of adjuvant platinum-based chemotherapy in early adult granulosa cell tumor of the ovaries: A meta-analysis of comparative studies.

5547 Background: Adult granulosa cell tumors (AGCT) are the most common type of malignant ovarian sex chord stromal tumors but only comprise 2 to 5 percent of all malignant ovarian neoplasms. Most granulosa cell tumors have an indolent growth pattern, and prognosis depends on the disease stage at diagnosis and the presence of residual disease after surgery. Though these tumors have metastatic potential, their tendency for late relapses is well documented. Despite the lack of supporting data, the National Cancer Centers Network recommends platinum-based adjuvant chemotherapy (AC) for Stage I with intermediate and high-risk features. Most studies have failed to show any benefit of AC with disease-free or overall survival. However, several of these studies were small, and some had short median follow-ups. Others included advanced stages and the juvenile variant of the disease. Therefore, we conducted this meta-analysis to evaluate the impact of AC on disease recurrence in a stage I enriched AGCT. Methods: A review of the medical literature was conducted using online databases. Inclusion criteria consisted of English language, diagnosis of AGCT, studies with a preponderance of stage I, comparative studies of AC versus none, and studies that reported recurrence rates. Studies that had a preponderance of advanced stages or juvenile variants were excluded. A meta-analysis using the fixed effects and random effects models was conducted. Results: Seven retrospective comparative studies with a total of 500 patients were included. The average median age was 47 years, and the average median follow-up was 58 months. Approximately 79% of the sample were stage I, and 79% of stage I were IC. Most AC regimens used were BEP and EP, though it varied among the regions. Platinum-based AC in early-stage AGCT failed to impact recurrence rates compared to clinical observation (HR=1.39, 95%CI 0.86-2.25, I2=48%, p=0.18). Conclusions: This is the first meta-analysis to show that adding platinum-based adjuvant chemotherapy to surgery does not improve the recurrence rate in early AGCT. Therefore, in the absence of evidence supporting any benefit of AC in this disease, recommendations to use AC should be re-evaluated, especially since the risk of platinum-based AC with or without Bleomycin is well-documented and carry potentially serious side effects.

Impact of cytoreductive surgery on survival outcomes for recurrent adult-type granulosa cell tumors of the ovary.

5573 Background: Adult-type granulosa cell tumor of the ovary (aGCT) is a rare tumor that often relapses and the optimal management strategy is not known. Cytoreductive surgery (CRS) offers an attractive option for disease confined to the abdomen/pelvis. However, few studies have evaluated the role of CRS compared to systemic therapy alone. Thus, the study objective was to determine the impact of secondary, tertiary, and quaternary CRS on survival outcomes for patients with relapsed aGCT. Methods: This was an IRB-approved retrospective cohort study that evaluated all patients with relapsed aGCT who were enrolled in the Rare Gynecologic Malignancy Registry at MD Anderson. Study inclusion criteria were patients who had histology-proven aGCT, were above 18 years of age, had at least one documented relapse, and had received treatment or treatment planning at MD Anderson. Progression-free survival (PFS) endpoints were the outcomes of interest and were defined as follows: PFS2 was defined from first recurrence to subsequent progression or death (PFS2), PFS3 was defined as second relapse/progression to third relapse/progression or death, and PFS4 was similarly defined. PFS2, PFS3, and PFS4 were estimated with methods of Kaplan and Meier and were modeled via cox proportional hazards regression. Analyses were performed among those with resectable disease at time of disease progression. Results: Among the 369 aGCT patients identified from January 1970 to October 2022, 162 met the study inclusion criteria for analysis. The mean age of diagnosis was 44.4 years old and the majority were initially diagnosed with stage 1 disease (72.8%). The median follow-up time for all patients was 5.86 years (range 0.09 – 34.27). At the first relapse, there were 151 patients who had resectable disease with 128 who underwent secondary CRS. PFS2 was significantly improved among those who underwent CRS compared to those who did not (HR 0.50, 95% CI 0.30 – 0.81; p = 0.005) with the median PFS2 difference being 18.24 months (p = 0.006). At the second relapse/progression, there were 120 patients with resectable disease with 52 who underwent tertiary CRS. PFS3 was significantly improved among those who underwent CRS compared to those who did not (HR 0.57, 95% CI 0.39 – 0.84; p = 0.004) with the median PFS3 difference being 6 months (p = 0.01). At the third relapse/progression, there were 96 patients with resectable disease with 46 who underwent quaternary CRS. There was a trend towards improved PFS3 among those who underwent CRS compared to those who did not (HR 0.69, 95% CI 0.45 – 1.06; p = 0.09). The use of systemic or hormonal therapy did not confer additional PFS benefit among those who underwent CRS. Conclusions: For relapsed, resectable aGCT, CRS may offer a beneficial impact on PFS. Future studies should evaluate the role of CRS on survival outcomes.