Juvenile Granulosa Cell Tumor Of Ovary Research Articles

Juvenile granulosa cell tumor of the ovary: A rare cause of precocious puberty in a toddler

Ovarian tumors are a rare cause of sexual precocity in female children. Functional neoplasms of the ovary are relatively infrequent, and only 5% occur before puberty. Although ovarian juvenile granulosa cell tumor (GCT) is a rare tumor described infrequently in pediatrics, the most common presentation of this tumor is precocious puberty. We report a 1⅟2 year-old girl with isosexual precocious puberty, who presented with a rapid onset of premature menarche, pubic hair, and vaginal bleeding, with an abdominal mass on clinical examination. Ultrasonography of the pelvis and abdomen showed a heterogeneously hypoechoic solid mass with cystic areas and internal vascularity. The child underwent a left oophorectomy. Microscopic features of the resected mass were characteristic of juvenile GCTs. Even though the most common cause of precocious puberty in girls is idiopathic, functional ovarian tumors must be considered, especially when the onset is at an early age and puberty is rapidly progressive. Early-stage disease has a good prognosis, and adjuvant chemotherapy is not indicated.

Postpartum Juvenile Granulosa Cell Tumor: A Case Report

Granulosa Cell Tumors (GCTs) are extremely rare, sex cord-stromal tumors constituting only 1% to 2% of all ovarian malignancies. On the basis of age of onset and pathohistological characteristics, these tumors are subdivided into two distinct forms, the adult type (AGCT) and the juvenile type (JGCT), representing 95% and 5% of the tumors, respectively. Compared to the adult type, which is more common in the fifth decade, JGCT is rarely seen and the majority (90%) is reported in prepubertal individuals or those aged less than 30 years. We report an interesting case of a 24-years old woman with enormous ovarian juvenile granulosa cell tumor of the right ovary. Considering all the anamnestic data and ultrasound reports before and during the first pregnancy, where there has been no evidence for the presence of any tumor, we came to conclusion that the tumor grew rapidly during the first year since delivery. Maybe the tumor was present during the pregnancy or even before, but most probably it was not noticed because it small initial size or it was masked by the growing uterus at ultrasound. The first data for the tumor existence is 3 months before the surgical treatment.

Juvenile granulosa cell tumor associated with Ollier disease.

Prior case reports have described synchronous ovarian juvenile granulosa cell tumor (JGCT) and enchondromatosis in patients with Ollier disease and Maffucci syndrome. We present a case of a juvenile granulosa cell tumor with an IDH1 somatic mutation identified in the ovarian tissue in a 15-year-old female who presented with abnormal vaginal bleeding, several months of irregular menses, and a large multicystic adnexal mass. Multiple mixed lytic and sclerotic lesions were identified in the bones of the pelvis on imaging studies obtained during the work-up of her abdominal mass. Like previous reports in patients with undiagnosed enchondromatosis, these lesions were presumed to represent skeletal metastases; however, biopsy tissue revealed a hyaline cartilage neoplasm. Subspecialty review of the imaging findings revealed imaging features classic for Ollier disease involving the flat bones of the pelvis. It is important for radiologists to be familiar with the association between enchondromatosis and JGCT. When a female patient with enchondromatosis presents with a large, unilateral, mixed solid-cystic ovarian mass, the diagnosis of JGCT can be suggested. Alternatively, when a patient is diagnosed with JGCT, any skeletal lesions should be scrutinized for imaging features that suggest a hyaline cartilage neoplasm to avoid the misdiagnosis of skeletal metastases in a patient with previously undiagnosed Ollier disease or Maffucci syndrome. To our knowledge, this is the second reported confirmed case of an IDH1 somatic mutation identified in the ovarian tissue of a JGCT in a patient with Ollier disease.

Integrated Analysis of Ovarian Juvenile Granulosa Cell Tumors Reveals Distinct Epigenetic Signatures and Recurrent TERT Rearrangements.

Adult granulosa cell tumor (AGCT) is characterized by the somatic FOXL2 p.C134W mutation, and recurrences have been associated with TERT promoter and KMT2D-truncating mutations. Conversely, the molecular underpinnings of the rare juvenile granulosa cell tumor (JGCT) have not been well elucidated. To this end, we applied a tumor-only integrated approach to investigate the genomic, transcriptomic, and epigenomic landscape of 31 JGCTs to identify putative oncogenic drivers. Multipronged analyses of 31 JGCTs were performed utilizing a clinically validated next-generation sequencing (NGS) panel targeting 580 cancer-related genes for genomic interrogation, in addition to targeted RNA NGS for transcriptomic exploration. Genome-wide DNA methylation profiling was conducted using an Infinium Methylation EPIC array targeting 866,562 CpG methylation sites. We identified frequent KMT2C-truncating mutations along with other mutated genes implicated in the switch/sucrose nonfermentable (SWI/SNF) chromatin remodeling complex, in addition to previously reported hotspot AKT1 and DICER1 mutations. Targeted transcriptome sequencing revealed recurrent TERT rearrangements (13%) involving partners CLPTM1L or DROSHA, and differential gene expression analysis showed FGFR1 upregulation in the TERT non-rearranged JGCTs under direct promoter control. Genome-wide DNA methylation rendered a clear delineation between AGCTs and JGCTs at the epigenomic level, further supporting its diagnostic utility in distinguishing among these tumors. This is the largest comprehensive molecular study of JGCTs, where we further expand our current understanding of JGCT pathogenesis and demonstrate putative oncogenic drivers and TERT rearrangements in a subset of tumors. Our findings further offer insights into possible targeted therapies in a rare entity.

Ovarian Juvenile Granulosa Cell Tumor Case Report.

Abdominal pain, ascites, ovarian juvenile granulosa cell tumor, point-of-care ultrasound.

Ollier's disease associated with ovarian juvenile granulosa cell tumor and triple X syndrome: A letter to the editor.

Ollier's disease associated with ovarian juvenile granulosa cell tumor and triple X syndrome: A letter to the editor.

Retrospective analysis of clinicopathological characteristics of 19 ovarian juvenile granulosa cell tumor cases.

To describe the clinical and pathological characteristics, diagnosis, treatment, and outcomes of juvenile granulosa cell tumor (JGCT). We retrospectively analyzed the data of 19 patients with histopathologically confirmed juvenile granulosa cell tumors treated in two medical centers in Wuhan city of China between 1999 and 2019. Totally, 19 patients were included during the period. The median age at diagnosis was 8.25 years (range, 0.25-28 years). The most common clinical presentation was abdominal pain, five out of 10 prepubertal children presented with precocious puberty. Three patients underwent radical surgery (including total hysterectomy, bilateral salpingo-oophorectomy, omentectomy, and pelvic and para-aortic lymphadenectomy), the other 16 patients had fertility-sparing surgery (cystectomy or ipsilateral salpingo-oophorectomy with or without omentectomy and lymphadenectomy). Eighteen patients had the international federation of gynecology and obstetrics (FIGO) stage I tumors, one patient had FIGO stage II disease. Twelve patients received postoperative adjuvant chemotherapy. The median follow-up time from the time of diagnosis was 35 months (range, 13-250 months). One patient experienced relapse and died of the disease 32 months after the initial diagnosis. Eighteen patients were alive and had not experienced recurrence during the follow-up period. The reproductive age patients that received fertility-sparing surgery had regular menstruation. A majority of JGCTs are diagnosed as FIGO stage I tumors and have favorable clinical outcomes. Adjuvant chemotherapy seems to improve outcomes for patients with advanced-stage JGCTs; however, the value of chemotherapy in stage Ic patients is still unknown. Fertility sparing surgery should be considered in young patients who wish to bear children.

Juvenile Granulosa Cell Tumors of the Ovary

To explore the clinical and pathologic features of ovarian juvenile granulosa cell tumors (JGCTs). Clinical data, histopathologic observations, immunohistochemical results, FOXL2 mutation status, and follow-up information of 7 JGCT cases were studied. The patients most commonly presented with abdominal distension and pain (5 cases), followed by precocious puberty (1 case) and a pelvic mass (1 case). Six patients had stage I disease, and 1 had stage IV disease. The microscopic examinations typically showed lobular growth punctuated by variably sized and shaped follicles. Rare features included a reticular-cystic appearance mimicking a yolk sac tumor (2 cases), a lobular appearance similar to a sclerosing stromal tumor (1 case), strands and cords (1 case), pseudopapillary appearance (2 cases), spindle cell appearance (1 case), microcystic appearance (1 case), hobnail cells (1 case), and rhabdomyoid cells (1 case). No FOXL2 mutation was encountered. After a median follow-up of 53 months, only 1 patient with a strongly diffuse TP53-positive tumor died of the disease, and 2 successfully had babies. JGCT is a rare neoplasm with a wide morphologic spectrum and is easily confused with other tumors. Familiarity with the characteristics, rare atypical appearances, and immunohistochemical results may aid in obtaining a correct diagnosis.

Transvaginal ultrasound in evaluation and follow-up of ovarian granulosa cell tumors

ObjectiveUltrasound features of granulosa cell tumors of the ovary are still poorly defined. The aim of this study is to widen current knowledge on the role of sonographic gray scale...

Juvenile granulosa cell tumor: An interim report from the international ovarian and testicular stromal tumor (OTST) registry.

6064 Background: Juvenile granulosa cell tumors (JGCT) are rare sex cord-stromal tumors which occur primarily in children and adolescents. Methods: All individuals or proxy caregivers provided informed consent/assent for participation in the International OTST Registry. Clinical data was collected. When available, pathology was centrally reviewed. Staging was evaluated using the International Federation of Gynecology and Obstetrics (FIGO) classification. Kaplan-Meier survival analyses and exact permutation tests were performed. Results: Forty-two individuals with ovarian JGCT were enrolled. Median age at diagnosis was 9 years (range 0-27). Most individuals had Stage I disease (Stage Ia=16; Stage Ib=1; Stage Ic=16). Seven individuals presented with higher stage (Stage II=2; Stage III=5). Stage was unknown for 2 individuals. Three-year overall survival (OS) was 88% (CI 77%, 100%) and event-free survival (EFS) was 69% (CI 54%, 88%). At median follow-up time of 25 months (range 0-416), 9 patients (Stage Ia=1, Stage Ic=5, Stage III=3) had recurrent disease. Use of post-operative adjuvant chemotherapy varied by stage and timing of rupture. Of those with Stage Ic JGCT, 2/7 with preoperative rupture and 3/9 with intraoperative rupture recurred. Among individuals with recurrence, median time to recurrence was 11.5 months (range 3-19). Four of 9 individuals with recurrence survived (no evidence of disease n=2; alive with disease n=2). All individuals who died presented with extrapelvic recurrence. Median time from recurrence to death was 10 months (range 2-53). In individuals with recurrence, advanced stage at diagnosis (HR 5.1; p-value 0.087) and recurrence outside the tumor bed (HR Infinity; p-value 0.048) were associated with inferior OS. Three-year OS for individuals with recurrence was 57% (CI 30%, 100%). Conclusions: Low stage JGCT is associated with a favorable prognosis, however, recurrence is associated with lower survival rate. Within this series, recurrences presented within 2 years of diagnosis. Novel strategies are needed to address recurrent and extrapelvic disease.

Natural history of Ollier disease and Maffucci syndrome: Patient survey and review of clinical literature.

Ollier disease (OD) and Maffucci syndrome (MS) are characterized by multiple enchondromas. Patients with MS also have benign vascular overgrowths that become malignant in 8.5% of cases. OD is characterized by multiple enchondromas, typically unilateral in distribution with a predilection for the appendicular skeleton. MS is characterized by multiple enchondromas bilaterally distributed in most of the cases. Both disorders feature multiple swellings on the extremity, deformity around the joints, limitations in joint mobility, scoliosis, bone shortening, leg-length discrepancy, gait disturbances, pain, loss of function, and pathological fractures. About 50% of patients with OD or MS develop a malignancy, such as chondrosarcoma, glioma, and ovarian juvenile granulosa cell tumor. To better understand the natural history of OD and MS, we reviewed 287 papers describing patients with OD and MS. We also created a survey that was distributed directly to 162 patients through Facebook. Here, we compare the review of the cases described in the literature to the survey's responses. The review of the literature showed that: the patients with OD are diagnosed at a younger age; the prevalence of chondrosarcomas among patients with OD or MS was ~30%; in four patients, vascular anomalies were identified in internal organs only; and, the prevalence of cancer among patients with OD or MS was ~50%. With these data, health care providers will better understand the natural history, severity, and prognosis of these diseases and the prevalence of malignancies in these patients. Here, we recommend new guidelines for the care of patients with OD and MS.

Outcomes of fertility-sparing surgery in ovarian juvenile granulosa cell tumor.

To analyze the clinical characteristics, diagnosis, and treatment of ovarian juvenile granulosa cell tumor. The clinical and pathological data of six patients with ovarian juvenile granulosa cell tumor was collected. The mean age of disease onset was 20.5 years (range 12 to 33). All six patients had an adnexal mass located laterally in the pelvis, and two developed ascites. All patients had fertility-sparing surgery with complete staging. The mean size of the tumors was 15.3 cm (range 5 to 35). Ovarian sex cord stromal tumors were diagnosed or highly suspected from the frozen sections for all patients. Five patients received three to six courses of postoperative adjuvant chemotherapy, with three receiving a bleomycin/etoposide/cisplatin regimen and two receiving a paclitaxel/carboplatin regimen. The five stage I patients had no recurrence with 52 to 155 months of follow-up. The patient with stage IIIB disease had a recurrence 55 months' later and underwent reoperation and chemotherapy. This patient remained disease-free 30 months after the reoperation. Fertility-sparing surgery is the treatment of choice for ovarian juvenile granulosa cell tumor and the overall prognosis is good.

Clinicopathological Evaluation of Ovarian Juvenile Granulosa Cell Tumor: Is Fertility-Sparing Surgery Safe?

Objective: To retrospectively investigate the clinicopathological characteristics of ovarian juvenile granulosa cell tumors (JGCTs) and to evaluate the safety of fertility-sparing surgery. Methods: In this study, surgically treated patients with JGCTs diagnosed between January 2004 and October 2018 in our center were identified. Clinicopathological data, survival outcomes, and recurrence rates were examined in these patients. Results: A total of 8 patients were included. All patients were premenarchal girls or young women (age range, 9–32 years). Irregular vaginal bleeding was the most common presenting symptom. Of them, seven patients were classified with Stage I JGCTs, and they underwent fertility-sparing surgery. One patient who had Stage IIIC JGCT and had completed childbearing underwent complete surgery. Seven patients received adjuvant chemotherapy. The median follow-up duration in the total cohort was 64 months (range, 2–117 months). The overall survival rate in the fertility-sparing group was 100%, whereas the patient with Stage IIIC JGCT died 1 month after the treatment. Conclusions: Fertility-sparing surgery might not show a negative impact on oncologic outcomes. Fertility sparing could be considered a modified option for patients with Stage I JGCTs. However, due to the limited number of patients, the conclusion must be interpreted with caution, and larger or multicenter studies are needed before conclusions can be drawn.

The association of enchondromatosis with malignant transformed chondrosarcoma and ovarian juvenile granulosa cell tumor (Ollier disease)

ObjectiveOvarian juvenile granulosa cell tumor has an interesting association with multiple enchondromatosis (Ollier disease and Maffucci syndrome) and should be considered a leading diagnosis when an ovarian mass is found in young patients with these conditions. Besides the association with nonskeletal malignancies, there is a high risk of malignant transformation of enchondroma in chondrosarcoma as was also the case in this instance. Case ReportThe report uses multiple images to document the representative and characteristic markers of multiple enchondromas in a 22-year-old patient with Ollier disease complicated by malignant transformation of chondrosarcoma and in whom the disease is associated with ovarian juvenile granulosa cell tumor of the right ovary. ConclusionIt is important to recognize that when the female patient presents with enchondromatosis and a large unilateral multilocular-solid ovarian mass, the specific diagnosis of granulosa cell tumor can be made with high accuracy.

Long-term survival in a patient with an advanced ovarian juvenile granulosa cell tumor with para-aortic lymph node metastasis

Long-term survival in a patient with an advanced ovarian juvenile granulosa cell tumor with para-aortic lymph node metastasis

Juvenile Granulosa Cell Tumor of the Ovary: A Clinicopathologic Study

Study ObjectiveTo report on the clinical characteristics and outcome of pediatric patients with juvenile granulosa cell tumor (JGCT) of the ovary. Design, Setting, Participants, Interventions, and Main Outcome MeasuresPatients with histopathologically confirmed ovarian JGCT diagnosed between 1990 and 2016 were identified. Data on the clinical presentation, surgical management, oncologic management, laboratory investigation, follow-up, and outcome were collected. Tumors were staged according to the International Federation of Gynecology and Obstetrics criteria. ResultsEight patients were diagnosed with ovarian JGCT during the study period. The median age at presentation was 3 years (range, 0.7-14 years). Precocious puberty was the presenting symptom in all five prepubertal children; abdominal distension due to mass effect was the presenting symptom in three children older than 9 years of age. In patients who had preoperative serologic testing, estradiol (n = 3) and inhibin (n = 3) levels were elevated. Five patients had stage I disease, and three had stage III. All stage I patients underwent salpingo-oophorectomy as the only treatment. Stage III patients received adjuvant chemotherapy. After a median follow-up of 6.2 years, six patients (75%) were alive without evidence of disease. One stage I patient with germline p53 mutation and phosphatase and tensin homolog mutation, died because of subsequent liposarcoma. One patient with stage IIIB disease developed recurrence detected according to an elevated inhibin serum level, and died due to progressive disease despite receiving multiple chemotherapy regimens. ConclusionJuvenile granulosa cell tumor has a favorable prognosis in patients with stage I disease after surgical resection alone. Adjuvant chemotherapy might be indicated in patients with higher-stage tumors.

Long-term Remission in a Female With Multiple Relapsed Juvenile Granulosa Cell Tumor

A 4 ½-year-old female was diagnosed with ovarian juvenile granulosa cell tumor stage IA. After complete tumor resection she received 4 courses of chemotherapy due to unfavorable histopathologic features (high mitotic index, high microvessel density, blood vessel invasion). One year after diagnosis, she experienced paraaortic lymph node relapse treated with surgery, local radiotherapy, and conventional and high-dose chemotherapy. A second, paratracheal lymph node relapse 7 months later necessitated surgical removal and radiotherapy. Subsequently an adjuvant antiangiogenesis-based treatment including paclitaxel, bevacizumab, thalidomide, and pegylated interferon was initiated and continued for 2 years. The female is now in third complete remission 6 years after second relapse.

Ovarian juvenile granulosa cell tumor in a 20-month-old infant

Ovarian juvenile granulosa cell tumor in a 20-month-old infant

Massive Ascites as the Only Sign of Ovarian Juvenile Granulosa Cell Tumor in an Adolescent: A Case Report and a Review of the Literature

Ovarian neoplasms are relatively rare in childhood and adolescence; only 5% to 8% of the cases are of sex cord stromal origin. Granulosa cell tumors are a group of estrogen producing sex cord stromal tumors of the ovary. They occur in 95% of the cases in adults, and only about 5% of the cases, which differ in histologic characteristics, are of juvenile type. A 13-year-old girl is reported who presented with massive abdominal distention and ascites. An abdominopelvic computed tomography scan showed a predominantly cystic mass lesion with septations arising from the left ovary. All tumor markers were normal, but serum inhibin level was increased. The patient underwent mass resection with salpingoophorectomy. Histopathology was compatible with the juvenile granulosa cell tumor. Interestingly, menarche was started in the patient soon after the surgery. To the best of our knowledge, massive ascites as the only clinical manifestation in the juvenile granulosa cell tumor has not reported as yet.

Childhood Ovarian Juvenile Granulosa Cell Tumor

Ovarian juvenile granulosa cell tumor (JGCT) is an extremely rare sex cord-stromal tumor that is most commonly encountered in prepubertal girls and young women. In this study, 3 cases of childhood JGCT are reported. The main causes of hospitalization were abnormal abdominal signs and syndromes. Imaging findings indicated masses with multiple cysts and solid components in the abdominal cavities. Diagnosis was confirmed by histopathology. Tumors were excised completely, and all cases have a good outcome in the follow-up (2 to 13 y) without any adjuvant chemotherapy or radiotherapy. This data suggests that children with JGCT might have a variety of initial clinical manifestations. Pathologic examination especially immunohistochemical staining could help to diagnose JGCT. For children, adjuvant treatment may not be necessary if the tumor can be excised completely in early stage.