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Biology of Reproduction Nov 2016Ovarian granulosa cell tumors (GCTs) are rare gynecologic tumors in women. Due to the rarity and limited research efforts invested, the etiology of GCTs remains poorly... (Review)
Review
Ovarian granulosa cell tumors (GCTs) are rare gynecologic tumors in women. Due to the rarity and limited research efforts invested, the etiology of GCTs remains poorly defined. A landmark study has discovered the mutation of forkhead box L2 (FOXL2) as a genetic hallmark of adult GCTs in the human. However, our understanding of the role of cell signaling in GCT development is far from complete. Increasing lines of evidence highlight the importance of TGF-beta (TGFB) superfamily signaling in the pathogenesis of GCTs. This review draws on findings using genetically modified mouse models and human patient specimens and cell lines to reveal SMAD3 activation as a potentially key converging point of dysregulated TGFB superfamily signaling and genetic aberrations in GCT development. It is anticipated that deciphering the role of TGFB superfamily signaling cascades in ovarian tumorigenesis will help develop new therapeutic approaches for GCTs by targeting core signaling elements essential for tumor initiation, growth, and progression.
Topics: Female; Granulosa Cell Tumor; Humans; Mutation; Ovarian Neoplasms; Smad3 Protein; Transforming Growth Factor beta
PubMed: 27683263
DOI: 10.1095/biolreprod.116.143412 -
International Journal of Surgery Case... Jul 2022Adult granulosa cell tumor (GCT) is a rare stromal cell neoplasm that most often arises from the ovary. Presenting symptoms are related to external compression of...
INTRODUCTION AND IMPORTANCE
Adult granulosa cell tumor (GCT) is a rare stromal cell neoplasm that most often arises from the ovary. Presenting symptoms are related to external compression of adjacent structures (mass effect) or secretion of hormones such as estrogen. Patients most commonly present with irregular menstruation, postmenopausal bleeding, and abdominal pain. Prolonged estrogen exposure can contribute to endometrial adenocarcinoma development in untreated patients. The highly vascular nature of GCTs can lead to hemorrhagic rupture in rare cases.
PRESENTATION OF CASE
We describe a case of adult GCT in a 44-year-old female with a history of irregular menstrual bleeding and anemia. The patient presented with shortness of breath and abdominal pain. Computed tomography (CT) scan demonstrated possible hemorrhagic ascites of unclear etiology and a pelvic mass. The patient was brought to the operating room in hemorrhagic shock for surgical exploration where she was found to have active bleeding of a ruptured ovarian tumor for which she underwent left salpingo-oophorectomy. Postoperative course was unremarkable, and pathology demonstrated ruptured GCT.
CLINICAL DISCUSSION
Although rare, ovarian tumors can present with massive bleeding following rupture. Granulosa cell tumors are surreptitious as they grow slowly, and symptoms such as distention, abdominal pain, and irregular vaginal bleeding are nonspecific.
CONCLUSION
CT findings demonstrating a pelvic mass in the setting of spontaneous intra-abdominal bleeding should raise clinical suspicion, particularly in patients with histories of menstrual abnormalities. Patients with suspected intra-abdominal hemorrhage due to any cause are best treated by prompt surgical exploration and aggressive resuscitation.
PubMed: 35724501
DOI: 10.1016/j.ijscr.2022.107317 -
American Journal of Translational... 2022This report describes a 17-year-old patient with ovarian granulosa cell tumor torsion, which is rare. The patient presented with lower abdominal pain for 1 day after...
This report describes a 17-year-old patient with ovarian granulosa cell tumor torsion, which is rare. The patient presented with lower abdominal pain for 1 day after defecation, accompanied by nausea and vomiting. Gynecological examination revealed a palpable mass of about 150 mm × 130 mm in the uterus. The mass had high surface tension, tight cysts, well-defined borders, and marked tenderness at its pedicle. Gynecological B-ultrasonography showed that the uterus was not compressed, and a mixed echo of about 152 mm × 112 mm was seen in the pelvic cavity. The initial diagnosis was ovarian tumor torsion. After explaining the condition to the patient's family, an emergent open resection of left ovarian tumor was performed. The postoperative pathology report indicated juvenile granulosa cell tumor. The patient's body temperature was normal, and there was no infection or thrombosis after operation.
PubMed: 36247268
DOI: No ID Found -
The Pan African Medical Journal 2017Granulosa cell tumors is classified into juvenile and adult types and comprise less than 5% of ovarian tumors in women and are much rarer in men which only 45 have been... (Review)
Review
Granulosa cell tumors is classified into juvenile and adult types and comprise less than 5% of ovarian tumors in women and are much rarer in men which only 45 have been previously reported. We report here a 40-year young man with a left testicular adult type granulosa cell tumor. The tumor measured 5.5X5X4cm; Immunohistochemical stains showed the tumor diffusely positive for inhibin and vimentin. Post operative CT scans shows a lomboaortic lymphnodes treated by four cycles of chemotherapy type BEP (bleomycin, etoposide, cisplatin). The thoraco abdominal CT scans post chemotherapy shows the disappearance of the right testicular nodule and the lomboaortic lymphnodes. 2 years after treatment, the patient is alive and well with no signs of recurrence. Our report highlights one more case of this very rare tumor of the testis, which is quite problematic In terms of prognosis and management, and for this reason seems to have attracted the interest of many researchers recently.
Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Cisplatin; Etoposide; Follow-Up Studies; Granulosa Cell Tumor; Humans; Male; Testicular Neoplasms; Tomography, X-Ray Computed
PubMed: 28674591
DOI: 10.11604/pamj.2017.26.198.11523 -
Radiology Case Reports Sep 2021Juvenile granulosa cell tumor (GCT) is a rare ovarian tumor in children, presenting with a multiloculated cystic pattern and irregular wall-thickening on imaging and...
Juvenile granulosa cell tumor (GCT) is a rare ovarian tumor in children, presenting with a multiloculated cystic pattern and irregular wall-thickening on imaging and serous cystadenoma (SCA) is also another rare benign cystic ovarian tumor in children. The appearance of two uncommon types of ovarian tumors on both sides in children is extremely rare. We report the case of a 4-year-old female presenting with symptoms of precocious puberty and diagnosed with juvenile GCT on the left ovary after surgical resection. However, during follow-up 1 year after GCT resection, she presented with another multiloculated cystic mass in the right ovary, and diagnosed as SCA after surgical resection and histopathologic evaluations. The appearance of cystic ovarian tumor after primarily GCT resection need to differentiate between the recurrence of the primarily GCT and other cystic ovarian tumors although it is very uncommon. Furthermore, the imaging features played a key role in the differential diagnosis between benign and malignant ovarian tumors.
PubMed: 34306284
DOI: 10.1016/j.radcr.2021.06.008 -
Gynecologic Oncology Reports May 2021Vaginal surgery is a classic and unique gynecologic procedure. However, the operation field is narrow, which may make surgery difficult to perform. While vaginoscopy or...
Vaginal surgery is a classic and unique gynecologic procedure. However, the operation field is narrow, which may make surgery difficult to perform. While vaginoscopy or vaginal endoscopy could be the solution of choice, they are mainly used for diagnosis due to the lack of adequate equipment to perform complicated surgery (Johary et al., 2015). Laparoscopy, especially single-port surgery, has been introduced in gynecologic surgery, and excellent equipment has been developed to perform complex surgical procedures through narrow inlets. And vaginal endoscopy using such single-port surgery devices, so-called vaginal natural orifice transluminal endoscopic surgery (vNOTES), has recently been introduced in the gynecologic field (Li and Hua, 2019 Aug) and allows the easier performance of endoscopic surgery through the vagina for ovarian cystectomy (Baekelandt, 2018 Feb 1), salpingo-oophorectomy (Baekelandt et al., 2018) and hysterectomy (Housmans et al., xxxx) for benign pathology. However, vNOTES has been used mainly as an alternative laparoscopic pathway to reduce abdominal wounds or bypass transabdominal approaches into the abdominal cavity. This report including the surgical video demonstrates the first case, to our knowledge, of successful tumor resection of a rare vaginal recurrence of ovarian granulosa cell tumor (Fujita et al., 2015 May, Levin et al., 2018) by pneumovaginoscopy using single-port surgery devices. A 39-year-old woman with an adult-type ovarian granulosa cell tumor had undergone left salpingo-oophorectomy. At 23 years after surgery, a recurrent mass was detected in her left vaginal wall. The patient had no history of pregnancy, and her vagina was too narrow to secure a good field of operation. Therefore, we underwent pneumovaginoscopic surgery. The total operating time was 88 min, and the blood loss volume was minimal. Complete tumor clearance (R0 resection) was achieved microscopically. There were no postoperative complications, and a one-year follow-up revealed no recurrence. Institutional Review Board approval was obtained through our local Ethics Committee of Kansai Medical University (#2019208).
PubMed: 33748384
DOI: 10.1016/j.gore.2021.100743 -
Taiwanese Journal of Obstetrics &... Jan 2022Only a few cases of early-stage ovarian granulosa cell tumor (GCT) with lung metastasis have been previously documented in the literature. We present a case of stage IA... (Review)
Review
OBJECTIVE
Only a few cases of early-stage ovarian granulosa cell tumor (GCT) with lung metastasis have been previously documented in the literature. We present a case of stage IA adult-type ovarian GCT with late pelvic recurrence and lung metastasis and review the relevant literature.
CASE REPORT
A 71-year-old female who underwent total abdominal hysterectomy and bilateral salpingo-oophorectomy for an ovarian GCT in her early 50s presented with pelvic recurrence 16 years later. Lung metastasis was accidentally discovered during a preoperative computed tomography scan of the pelvic tumor. The patient received surgical resection and adjuvant chemotherapy. She remains alive and healthy without evidence of disease after 12 months of follow up.
CONCLUSION
This case illustrates the importance of long-term follow-up for early-stage GCTs. It also highlights the requirement of extended examination for possible extra-abdominal/pelvic tumors.
Topics: Aged; Female; Granulosa Cell Tumor; Humans; Lung Neoplasms; Neoplasm Metastasis; Neoplasm Recurrence, Local; Ovarian Neoplasms; Salpingo-oophorectomy
PubMed: 35181019
DOI: 10.1016/j.tjog.2021.10.002 -
Molecular Endocrinology (Baltimore, Md.) Jul 2015The forkhead box (FOX), FOXO1 and FOXO3, transcription factors regulate multiple functions in mammalian cells. Selective inactivation of the Foxo1 and Foxo3 genes in...
The forkhead box (FOX), FOXO1 and FOXO3, transcription factors regulate multiple functions in mammalian cells. Selective inactivation of the Foxo1 and Foxo3 genes in murine ovarian granulosa cells severely impairs follicular development and apoptosis causing infertility, and as shown here, granulosa cell tumor (GCT) formation. Coordinate depletion of the tumor suppressor Pten gene in the Foxo1/3 strain enhanced the penetrance and onset of GCT formation. Immunostaining and Western blot analyses confirmed FOXO1 and phosphatase and tensin homolog (PTEN) depletion, maintenance of globin transcription factor (GATA) 4 and nuclear localization of FOXL2 and phosphorylated small mothers against decapentaplegic (SMAD) 2/3 in the tumor cells, recapitulating results we observed in human adult GCTs. Microarray and quantitative PCR analyses of mouse GCTs further confirmed expression of specific genes (Foxl2, Gata4, and Wnt4) controlling granulosa cell fate specification and proliferation, whereas others (Emx2, Nr0b1, Rspo1, and Wt1) were suppressed. Key genes (Amh, Bmp2, and Fshr) controlling follicle growth, apoptosis, and differentiation were also suppressed. Inhbb and Grem1 were selectively elevated, whereas reduction of Inha provided additional evidence that activin signaling and small mothers against decapentaplegic (SMAD) 2/3 phosphorylation impact GCT formation. Unexpectedly, markers of Sertoli/epithelial cells (SRY [sex determining region Y]-box 9/keratin 8) and alternatively activated macrophages (chitinase 3-like 3) were elevated in discrete subpopulations within the mouse GCTs, indicating that Foxo1/3/Pten depletion not only leads to GCTs but also to altered granulosa cell fate decisions and immune responses. Thus, analyses of the Foxo1/3/Pten mouse GCTs and human adult GCTs provide strong evidence that impaired functions of the FOXO1/3/PTEN pathways lead to dramatic changes in the molecular program within granulosa cells, chronic activin signaling in the presence of FOXL2 and GATA4, and tumor formation.
Topics: Adult; Animals; Carcinogenesis; Female; Forkhead Box Protein O1; Forkhead Box Protein O3; Forkhead Transcription Factors; Gene Expression Profiling; Gene Expression Regulation, Neoplastic; Gonadotropins; Granulosa Cell Tumor; Humans; Immunohistochemistry; Integrases; Keratin-8; Lectins; Mice, Knockout; Middle Aged; Models, Biological; PTEN Phosphohydrolase; SOX9 Transcription Factor; Smad Proteins; beta-N-Acetylhexosaminidases
PubMed: 26061565
DOI: 10.1210/me.2015-1103 -
Journal of Ovarian Research Dec 2018Ovarian granulosa cell tumors (GCTs) are divided into adult GCT (AGCT) and juvenile GCT (JGCT). The AGCT is more common type, conversely, less than 5% of tumors are the... (Review)
Review
BACKGROUND
Ovarian granulosa cell tumors (GCTs) are divided into adult GCT (AGCT) and juvenile GCT (JGCT). The AGCT is more common type, conversely, less than 5% of tumors are the JGCT and occur in mainly premenarchal girls and in women younger than 30 years. Although JGCT have different histologic features compared to AGCT, the two types have similar imaging features because they have similar gross appearance. Therefore, it is difficult to distinguish two types by radiologic findings. In addition, it has not been described about the growth rate of JGCTs in past literatures. The aims of this report were to describe a case of rapidly growing JGCT arising in adult with difficulty in diagnosing and to review the literatures.
CASE PRESENTATION
A 38-year-old woman, presented with abdominal distension and frequent urination, was found to have a pelvic mass measuring approximately 12 cm on ultrasonography. On magnetic resonance imaging (MRI), right ovarian multiloculated cystic mass accompanied with hemorrhagic foci was demonstrated. Although the presumptive diagnosis of GCT was made based on MR findings, the intraoperative differential diagnoses included GCT, yolk sac tumor or malignant mucinous tumor due to cytologic atypia and lack of the typical findings for AGCT such as nuclear grooves and Call-Exner bodies. As a result, abdominal simple total hysterectomy, bilateral oophoro-salpingectomy, partial omentectomy and appendectomy were performed. Moreover, she had a history of laparoscopic uterine myomectomy about one year before, and during that surgery bilateral ovaries were found to be macrospically normal. Therefore, it was suspected the tumor became enlarged within the short period of time.
CONCLUSIONS
Even though it is difficult to distinguish two types of GCT by imaging findings, in some cases without typical findings for AGCT pathologically, MRI could provide useful information in accurately diagnosing JGCT. Moreover, in this case, the tumor growth rate seemed to be rapid regardless of its borderline malignant potential. It may be related with nuclear atypia and high mitotic rate of the tumor.
Topics: Adult; Female; Granulosa Cell Tumor; Humans; Magnetic Resonance Imaging; Ovarian Neoplasms
PubMed: 30547828
DOI: 10.1186/s13048-018-0474-0 -
Gynecologic Oncology Reports Apr 2023To report a case of stage IIIB juvenile granulosa cell tumor (JGCT) complicating pregnancy in a 33 year-old (y.o.) woman.
OBJECTIVE
To report a case of stage IIIB juvenile granulosa cell tumor (JGCT) complicating pregnancy in a 33 year-old (y.o.) woman.
METHODS
Retrospective review of the clinical data, imaging studies, and pathology reports of a case of JGCT diagnosed during pregnancy. Patient consent was obtained for review and presentation of the case. A literature review was conducted.
RESULTS
A 33 y.o., gravida 3, para 1 was incidentally found to have an 8 cm left ovarian mass on an anatomy scan at 22 weeks gestation. Four days later, she presented to labor and delivery triage with abdominal pain. An ultrasound revealed an 11 cm heterogeneous, solid mass in the left adnexa and free fluid at this level. The diagnosis of degenerating fibroid was made based on her clinical presentation and she was discharged. A follow up outpatient MRI revealed a 15 cm left ovarian mass consistent with a primary malignant ovarian neoplasm with moderate ascites and omental, left cul de sac, and probable paracolic gutter implantation. She re-presented 2 weeks later with an acute abdomen and was admitted for a gynecologic oncology consult. Pre-op tumor markers showed an elevated inhibin B. She underwent an exploratory laparotomy, left salpingo-oophorectomy, omental biopsy, and small bowel resection at 25 weeks gestation. Intra-op findings included a ruptured tumor and metastases. Tumor reductive surgery was completed to R0. Pathology revealed a JGCT, FIGO stage IIIB. The pathology and management were reviewed in collaboration with an outside institution. Chemotherapy was delayed until after delivery with monthly MRI surveillance. She underwent induction of labor at 37 weeks followed by an uncomplicated vaginal delivery. She received 3 cycles of bleomycin, etoposide, and cisplatin starting six weeks postpartum. Last known contact was over five years after the initial diagnosis with no evidence of recurrent disease.
CONCLUSION
JGCTs account for 5% of granulosa cell tumors and 3% are diagnosed after age 30. JGCT is an uncommon neoplasm in pregnancy. 90% are stage I at diagnosis, but advanced stage tumors are aggressive often resulting in recurrence or death within 3 years of diagnosis. We present a surgically treated case with delay in chemotherapy until after delivery with a good outcome after 5 years of follow up.
PubMed: 36992983
DOI: 10.1016/j.gore.2023.101164