Granulosa cell tumor of the ovary: a series of 6 cases.

Granulosa cell tumor (GCT) is a rare ovarian malignancy that represents only 2-3% of all cases. There are two subtypes of GCT: juvenile/JGCT (5% of cases) and adult/AGCT (95% of cases). This study aimed to describe a series of 6 GCT cases. The 6 study patients were managed from June 2011 to November 2022 in a private oncology clinic located in Teresina (PI), Brazil. At diagnosis, the mean patient age was 47 years, and symptoms in 5 patients (83%) were pelvic pain and/or increased abdominal volume. The majority of the patients (N=4/67%) had no comorbidities or findings related to GCT on physical examination. The mean tumor size was 11 cm. Five (83%) tumors were stage Ia and one tumor (17%) was stage III. Regarding tumor subtype, 5 (83%) were AGCT and 1 (17%) was JGCT. Surgical treatment consisted of unilateral salpingo-ophorectomy in 2 patients (33%), total hysterectomy and bilateral salpingo-ophorectomy in 3 patients (50%), and cytoreduction (suboptimal) in 1 patient (17%). After a mean follow-up period of 62.7 months, 5 patients (83%) are still alive and free of disease. One (17%) died from disease progression after 126 months. In the current study, disease-free overall survival was 83%, in a mean follow-up period of 62.7 months.

Identification of prognostic factors and construction of nomogram to predict cancer-specific survival for patients with ovarian granulosa cell tumors.

BACKGROUND: Ovarian granulosa cell tumors (OGCTs) feature low incidence, indolent growth and late recurrence. Treatment for recurrent OGCTs is challenging. METHODS: The present study was designed to explore the prognostic factors and establish a nomogram to predict cancer-specific survival (CSS) for OGCTs patients. Enrolled in the study were 1459 eligible patients in the Surveillance, Epidemiology, and End Results (SEER) database, who were randomized to the training (n = 1021) or testing set (n = 438) at a ratio of 7:3. Univariate and multivariate Cox regression analyses were employed to screen the prognostic factors. The predictors were determined by using the Least absolute shrinkage and selection operator (LASSO) regression analysis. The model was constructed via the Cox proportional hazards risk regression analysis. The performance and clinical value of the nomograms was assessed with C-index, calibration plots, and decision curve analysis. RESULTS: Age, pTNM stage, tumor size, surgery of the primary tumor, surgery of regional lymph nodes (LNs), residual disease after surgery, and chemotherapy were considered as significant predictive factors for CSS in OGCTs patients. After screening, the prognostic factors except surgery of regional LNs and chemotherapy were employed to build the nomogram. With desirable discrimination and calibration, the nomogram was more powerful in predicting CSS than the American Joint Committee on Cancer staging system in clinical use. CONCLUSION: This novel prognostic nomogram, which comprises a stationary nomogram and a web-based calculator, offers convenience for clinicians in personalized decision-making including optimal treatment plans and prognosis assessments for OGCTs patients.

Adult-type granulosa cell tumor associated with elevated luteinizing hormone: Two rare case reports.

INTRODUCTION: Adult-type granulosa cell tumors (AGCTs), which account for 2% to 5% of all malignant ovarian tumors, are rare sex cord-stromal tumors that usually secrete excess estrogens, but they can also secrete androgens. PATIENT CONCERNS: We report 2 patients of childbearing age with AGCT who presented with the complaint of abnormal menstruation and elevated luteinizing hormone (LH), and mildly elevated testosterone. DIAGNOSIS: The ovarian tumors had hormonal activity. INTERVENTIONS: The 2 patients underwent laparoscopic left adnexectomy. The second patient underwent 4 cycles of chemotherapy with paclitaxel and carboplatin as adjuvant treatments. OUTCOMES: Their postoperative pathology confirmed AGCTs. Also, their menstrual cycle returned to normal, with normal serum LH and testosterone levels. There was no sign of recurrence. CONCLUSION: The cases suggest that elevated serum LH levels may be a sign of unknown tumors in cases of oligomenorrhea or secondary amenorrhea. It is useful to evaluate the serum levels of inhibin B and anti-Müllerian hormone to improve the early recognition of ovarian granulosa cell tumors.

FOXL2 Mutation Status in Sex Cord-stromal Tumors Cannot be Predicted by Morphology.

Granulosa-cell tumors (GCTs) are the most common type of malignant ovarian sex cord-stromal tumor (SCST). The histopathologic diagnosis of these tumors can be challenging. A recurrent somatic mutation of the forkhead box L2 (FOXL2) gene has been identified in adult GCT. In this retrospective single-center study of 44 SCST, a morphologic review together with analysis of FOXL2 C134W was evaluated in relation to tumor morphology. In addition, TERT promoter mutation testing was performed. Twelve of 36 cases got an altered diagnosis based on morphology alone. The overarching architectural growth pattern in 32/44 (72.7%) tumors was diffuse/solid with several tumors showing markedly heterogeneous architecture. In correlation to FOXL2 C134W mutation status, cytoplasmic color, and nuclear shape, differed between the FOXL2 C134W positive and FOXL2 C134 W negative groups, but these differences were not significant when comparing them separately. Nineteen of 44 cases underwent TERT promoter sequencing with a positive result in 3 cases; 2 adult GCTs and 1 cellular fibroma. Three patients developed a recurrence of which 2 were FOXL2 C134W positive adult GCTs and the third was an unclassified SCST. In conclusion, the morphologic and immunohistochemical diagnosis of different SCSTs is challenging and one cannot reliably identify FOXL2 mutation-positive tumors solely by morphologic features. Therefore, broad use of molecular analysis of the FOXL2 C134W mutation is suggested for SCSTs, and further studies are needed to evaluate the clinical outcome of these tumors as well as the diagnostic and prognostic implications of TERT promoter mutations.

Successful intra-abdominal resection of a 24 kg ovarian granulosa cell tumor in a Warmblood mare.

Background: Granulosa cell tumors (GCTs) are the most common ovarian tumors in mares. The classical presentation of a GCT is a unilaterally enlarged ovary appearing as a multicystic honeycomb mass. In rare cases, GCTs cause hemoperitoneum as a result of the rapid growth of the tumor. The clinical diagnosis of GCT is usually based on history, rectal examination, ultrasonographic examination, and serum hormone analysis, and surgical removal of the affected ovary is the treatment of choice. The different surgical approaches are based on the dimension of the GCT. Case Description: A 7-year-old mare was referred to the department for horses due to suspicion of a large colon impaction. The mare presented with clinical signs of colic, fever, and signs of hypovolemic shock. Rectal and ultrasonographic examination showed hemoperitoneum and a honey-comb mass within the abdomen, and a GCT as the cause of an acute hemoperitoneum was diagnosed based on the serum level of anti-Müllerian hormone. After stabilization of the mare, the GCT was removed through a ventral midline incision. Because of the enormous dimensions of the GCT, intra-abdominal partial resection of the tumor using a tenotomy knife was necessary to exteriorize the ovarian pedicle. At 3 months follow-up, the mare was ridden for her intended use. Conclusion: This report provides an approach to an uncommon case of a very large and heavy GCT.

Acute Large Ovarian Cyst After Surgical Resection of Juvenile Granulosa Cell Tumor Stage 1C.

Juvenile granulosa cell tumors (JGCTs) are rare, though carry significant burden of morbidity and mortality. A 15-year-old menstruating female with abdominal pain was diagnosed with a large 22.3 cm pelvic mass. CA-125 and LDH were elevated. Exploratory laparotomy was undertaken due to lesion size, and left salpingo-oophorectomy with omentectomy was completed. Pathology confirmed JGCTs with focal disruption, consistent with Stage IC disease. Six weeks postoperatively, the patient experienced recurrent abdominal pain and ultrasound revealed a 7.9 cm right ovarian cystic structure. Given size and nodularity, management was discussed with a multidisciplinary team. Serial ultrasounds demonstrated resolution of the cyst. Workup for ovarian masses in pediatric patients has added complexity of fertility preservation. Once ovarian torsion is ruled out, imaging and laboratory studies are completed to characterize the mass. In pediatric patients with cancer of the Mullerian structures and risk of infertility, decision-making can be challenging and is best managed with a multidisciplinary approach.

Detection of FOXL2 C134W Mutation Status by a Novel BaseScope In Situ Hybridization Assay is Highly Sensitive and Specific for Adult Granulosa Cell Tumors.

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

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.

An unusual coincidence of giant cervical leiomyoma and incidental ovarian granulosa cell tumor: A case report.

RATIONALE: Leiomyomas are the most common benign tumors of smooth muscle origin in women. They are most frequently found in the submucosal tissue of the uterine corpus; however, they also occur in other areas of the uterus, including the cervix. Their size usually varies between 0.5 to 1.0 cm; however, they can reach great dimensions. A strong correlation between the onset and growth of leiomyomas and estrogen levels was observed. Granulosa cell tumor (GCT) is an infrequent sex cord-stromal ovarian neoplasm. Despite their malignancy, GCTs have a good long-term prognosis. In this study, we present a unique case of coincidence of 2 tumors: leiomyoma of rare location (cervix uteri) and extraordinary size (9, 04 cm diameter) with an adult granulosa cell tumor. PATIENT CONCERNS: A 67-year-old Caucasian woman was transported from an emergency ward to a gynecological surgery department due to a massive vaginal hemorrhage. DIAGNOSES: Preliminary examination showed a presence of an enormous uteri cervix tumor. INTERVENTIONS: Initially, the patient underwent physical and ultrasound examinations. To prevent further bleeding, an urgent surgery (hysterectomy) with bilateral salpingo-oophorectomy was performed. OUTCOME: Postoperative histopathological examination revealed a cervical leiomyoma and the incidental occurrence of an adult GCT in the right ovary. LESSONS: This case shares an interesting coincidence between a rare variant of leiomyoma and GCT. The study suggests that the potential reason for this can be estrogen secreted by the GCT, which causes the enormous size of the patient's cervical leiomyoma and the severe vaginal bleeding. Therefore, we advise it is important in abnormal cases to search for other hidden explanations, as in cases of GCT.

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

BACKGROUND: Granulosa 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 PRESENTATION: Case 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. CONCLUSIONS: VEGF 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.

Atypical Presentation of Granulosa Cell Tumor in an Adolescent: A Case Report.

BACKGROUND: Granulosa cell tumors (GCTs) frequently present with elevated levels of estrogen and inhibin. Most diagnoses in the pediatric and adolescent population are juvenile-type GCTs; adult-type GCTs in this population are rare. CASE: We describe a 14-year-old female who presented with a large adnexal mass and clinical hyperandrogenism. Laboratory evaluation revealed elevated levels of free and total testosterone, low-normal estradiol, and mildly elevated alpha-fetoprotein (AFP). Other tumor markers, including inhibin, were within normal limits. Intraoperative assessment with unilateral oophorectomy, pathology, and imaging resulted in a diagnosis of a stage IA adult-type GCT. SUMMARY AND CONCLUSION: GCTs often result in elevated estrogen and inhibin B levels; however, this case demonstrates that non-classic elevations in testosterone and normal inhibin levels should not eliminate concern for a GCT, particularly in the setting of a large ovarian mass.

Testosterone elevation in ovarian adult granulosa cell tumor: A case report and review of the literature.

RATIONALE: Adult granulosa cell tumors (AGCT) mainly secret estrogen, but few androgens. It is rarer to have amenorrhea and hyperandrogenemia as clinical features. Here, we report a rare case of right side AGCTs with amenorrhea and hyperandrogenemia in a 19-year-old female. PATIENT CONCERNS: The 19-year-old patient was admitted to our hospital due to amenorrhea for more than 1 year, and discovery of pelvic mass for 4 months. The gynecological ultrasound and computed tomography (CT) cannot define the nature of the mass. Surprisingly, an elevation in testosterone levels was also measured. DIAGNOSIS AND INTERVENTIONS: The present patient underwent laparoscopic right salpingo-oophorectomy and partial omentectomy and biopsy of the peritoneum. OUTCOMES: After the surgery, the testosterone value was down to normal. The patient menstrual cramps on August 13, 2021. Her clitoris is smaller than the front. Up to August 1, 2022, there was no obvious sign of recurrence. LESSONS: Androgen-secreting AGCT is rare. We hope that this case can strengthen gynecologists' early diagnosis and treatment of this disease and improve the prognosis.

AMH producing purely cystic virilizing adult granulosa cell tumor in 17 years old girl: a case report and review of literatures.

BACKGROUND: Androgen-producing granulosa cell tumor in adolescent girl is rare condition and clinical characteristics are not fully elucidated. CASE PRESENTATION: Seventeen years old girl complained of secondary amenorrhea was referred to our out-patient consultation. Markedly elevated serum testosterone, LH, and AMH levels were noted. Mild hirsutism and clitoromegaly were presented. Transabdominal ultrasonography and MRI revealed cystic mass occupied pelvic cavity probably originated from left ovary. Right ovary showed polycystic appearance. Laparoscopic left ovarian cystectomy was performed. After the surgery, her menstruation resumed along with normalized hormonal parameters, and clinical hyperandrogenism were improved. Since the scarcity of cellular lining of inner cyst wall, definitive pathological diagnosis was difficult. After the consultation with gynecological pathologist, the tumor was diagnosed as sex cord stromal tumor, highly suspicious for adult granulosa cell tumor. Residual left salpingo-oophorectomy was performed by additional laparoscopic surgery. Her serum testosterone and AMH levels were remained low with regular menstrual cycles and no evidence of recurrence. CONCLUSIONS: Androgen-producing cystic granulosa cell tumor is rare gynecological disorders, which need both gynecologic oncological and endocrinological approach. Its clinical manifestations may bring some clues to the pathogenesis of ovulatory dysfunctions, such as polycystic ovary syndrome.

Ovarian Granulosa Cell Tumor Initially Presenting as a Giant Liver Mass Radiologically Mimicking Primary Cystic Cholangiocarcinoma.

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.

A 12-Year-Old Girl with Juvenile Granulosa Cell Tumor of the Ovary, Presenting with Adolescent Hyperprolactinemia, Galactorrhea, and Amenorrhea.

BACKGROUND Juvenile-type granulosa cell tumors (JGCTs) are a rare subtype of sex cord stromal tumor with a characteristic histology that is commonly found in the first 3 decades of life. It most commonly presents with symptoms of hyperestrogenism, which may present as precocious pseudopuberty or as menstruation-related symptoms, allowing for early detection of the tumor. CASE REPORT We present the case of a 12-year-old girl who presented to her primary care provider (PCP) with secondary amenorrhea with intermittent abdominal pain, who underwent an ultrasound for further evaluation, which revealed a large incidental pelvic mass. She was admitted to the Emergency Department (ED) and had findings of galactorrhea and hyperprolactinemia on examination. Imaging studies demonstrated a large ovarian mass measuring 15.0×9.0×18.8 cm that was resected, and subsequent pathology results showed JGCT stage 1A. CONCLUSIONS Prognosis of granulosa cell tumors (GCT) largely depends on its initial size, stage at diagnosis, residual tumors after surgery, and the subtype of GCT. If the patient is of reproductive age, fertility-sparing surgical options must be considered and patients must be regularly monitored for recurrence. JGCTs can present with minimal to no symptoms of precocious puberty in young girls but may present with amenorrhea, which may be considered normal for their developmental age. Although JGCTs are rare, they are important to include in differential diagnoses of younger female patients with abdominal pain, especially if accompanied by hormonal irregularities.

Cytomorphology and immunocytochemical features of ovarian granulosa cell tumors in ascites or peritoneal washings: A retrospective review.

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.

Bilateral Peutz-Jeghers-Associated Sex Cord Tumor With Annular Tubules Combined With Unilateral Adult Granulosa Cell Tumor: A Case Report.

Sex cord tumor with annular tubules (SCTATs) is a rare sex cord stromal tumor in the ovary. SCTAT combined with adult granulosa cell tumor (AGCT) is even rarer. Here, we report a unique case of ovarian tumors with mixed AGCT and SCTAT components. Due to the unusual coexistence, molecular testing was separately performed on each ovary. Both SCTAT and AGCT components were found to have STK11 germline mutation. Furthermore, the AGCT component had an additional FOXL2 somatic mutation. Based on medical history and molecular testing we conclude that the ovarian tumors were associated with Peutz-Jeghers syndrome (PJS). Thus, we present the first report of bilateral PJS-associated SCTAT combined with unilateral AGCT.

Composite FOXL2 Mutation-positive Adult Granulosa Cell Tumor and Serous Borderline Tumor of the Ovary.

We report a case of a cystic ovarian neoplasm in a 76-yr-old female composed of 2 distinct and intimately associated components: a macrocystic adult granulosa cell tumor (AGCT) and a serous borderline tumor. The granulosa cell nature of the tumor was confirmed with positive immunohistochemical staining for inhibin, calretinin, and WT1, while the neoplastic nature of the granulosa cell proliferation was supported by the presence of a point mutation of the FOXL2 gene. A review of 19 previously reported mixed AGCT and epithelial neoplasms of the ovary is included. Of the eight mixed AGCT and epithelial tumors, including our case, that were tested for FOXL2 mutation, 4 of the 5 mutation-positive cases were notable for demonstrating a macroscopically visible nodule or mass of AGCT at the time of gross examination, while 2 of the 3 mutation-negative cases lacked a mass-producing granulosa cell component. This feature by itself may be sufficient to predict the true neoplastic nature of the granulosa cell proliferation. This is the first reported case of a composite neoplastic AGCT and serous borderline tumor. We also discuss the current histogenetic models for these rare mixed AGCT and epithelial tumors.