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International Cancer Conference Journal Jul 2023Extraovarian adult granulosa cell tumor is a very uncommon neoplasm, which probably arises from the ectopic gonadal tissue along the embryonic root of the genital ridge....
Extraovarian adult granulosa cell tumor is a very uncommon neoplasm, which probably arises from the ectopic gonadal tissue along the embryonic root of the genital ridge. We report a new and rare case of an extraovarian adult granulosa cell tumor occurring in a 66-year-old woman who was presented with severe abdominal pain focused on the left iliac fossa. The immunohistopathology confirmed the diagnosis of a paratubal adult granulosa cell tumor. This paper illustrates the histogenetic origin of granulosa cell tumor, its clinicopathological and immunohistochemical features.
PubMed: 37251006
DOI: 10.1007/s13691-023-00603-z -
Abnormal Elevation of Anti-Mullerian Hormone and Androgen Levels Presenting as Granulosa Cell Tumor.Frontiers in Oncology 2021We report a rare subtype of adult cystic granulosa cell tumor (AGCT) characterized by elevated anti-Mullerian hormone and hyperandrogenism. A 35-year-old woman with...
We report a rare subtype of adult cystic granulosa cell tumor (AGCT) characterized by elevated anti-Mullerian hormone and hyperandrogenism. A 35-year-old woman with primary infertility, hyperandrogenism, and irregular menses who was previously diagnosed with polycystic ovarian syndrome was diagnosed with AGCT based on histopathological examination and FOXL2 genetic test after laparoscopy. Due to fertility aspirations, she underwent controlled ovarian stimulation followed by embryo cryopreservation before salpingo-oophorectomy, and two embryos were frozen-thawed and transferred after surgery. A healthy female infant was delivered at 40 weeks' gestation. Cystic granulosa cell tumors should be considered a differential diagnosis in patients with persistent ovarian cysts and hyperandrogenism. Younger patients with AGCT with fertility goals should consider active assisted reproduction measures to preserve fertility before treatment for AGCT.
PubMed: 33828986
DOI: 10.3389/fonc.2021.641166 -
The Journal of Pathology. Clinical... May 2021Adult-type granulosa cell tumors (aGCTs) account for 90% of malignant ovarian sex cord-stromal tumors and 2-5% of all ovarian cancers. These tumors are usually diagnosed...
Adult-type granulosa cell tumors (aGCTs) account for 90% of malignant ovarian sex cord-stromal tumors and 2-5% of all ovarian cancers. These tumors are usually diagnosed at an early stage and are treated with surgery. However, one-third of patients relapse between 4 and 8 years after initial diagnosis, and there are currently no effective treatments other than surgery for these relapsed patients. As the majority of aGCTs (>95%) harbor a somatic mutation in FOXL2 (c.C402G; p.C134W), the aim of this study was to identify genetic mutations besides FOXL2 C402G in aGCTs that could explain the clinical diversity of this disease. Whole-genome sequencing of 10 aGCTs and their matched normal blood was performed to identify somatic mutations. From this analysis, a custom amplicon-based panel was designed to sequence 39 genes of interest in a validation cohort of 83 aGCTs collected internationally. KMT2D inactivating mutations were present in 10 of 93 aGCTs (10.8%), and the frequency of these mutations was similar between primary and recurrent aGCTs. Inactivating mutations, including a splice site mutation in candidate tumor suppressor WNK2 and nonsense mutations in PIK3R1 and NLRC5, were identified at a low frequency in our cohort. Missense mutations were identified in cell cycle-related genes TP53, CDKN2D, and CDK1. From these data, we conclude that aGCTs are comparatively a homogeneous group of tumors that arise from a limited set of genetic events and are characterized by the FOXL2 C402G mutation. Secondary mutations occur in a subset of patients but do not explain the diverse clinical behavior of this disease. As the FOXL2 C402G mutation remains the main driver of this disease, progress in the development of therapeutics for aGCT would likely come from understanding the functional consequences of the FOXL2 C402G mutation.
Topics: Adult; Aged; Biomarkers, Tumor; Boston; British Columbia; CDC2 Protein Kinase; Class Ia Phosphatidylinositol 3-Kinase; Cyclin-Dependent Kinase Inhibitor p19; DNA Mutational Analysis; DNA-Binding Proteins; Europe; Female; Forkhead Box Protein L2; Genetic Predisposition to Disease; Granulosa Cell Tumor; Humans; Intracellular Signaling Peptides and Proteins; Middle Aged; Mutation; Neoplasm Proteins; Ovarian Neoplasms; Protein Serine-Threonine Kinases; Tumor Suppressor Protein p53; Whole Genome Sequencing
PubMed: 33428330
DOI: 10.1002/cjp2.198 -
Journal of Ovarian Research Feb 2020The aim of this study was to explore the clinicopathological characteristics of recurrent adult-type granulosa cell tumor of the ovary (AGCOT) and evaluated the...
BACKGROUND
The aim of this study was to explore the clinicopathological characteristics of recurrent adult-type granulosa cell tumor of the ovary (AGCOT) and evaluated the treatment results to define the prognostic parameters for survival after recurrence.
RESULTS
A retrospective review of 40 patients with recurrent AGCOT, who were treated in the Cancer Hospital at the Chinese Academy of Medical Sciences from 2000 to 2015 was conducted. The impact of clinical and pathological characteristics, progression-free survival (PFS), and post-recurrence therapeutic approaches on prognosis were analyzed. Among the 40 recurrent patients, there were 10 cases where the relapse was uncontrolled, 24 cases had second relapses, and 6 cases without further relapses at the time of our follow-up. The median PFS was 61 months (range, 7-408 months), and the median time interval between the first and the second relapses (R-PFS) was 25 months (range, 0-94 months). The median time interval between the first relapse and death (R-OS) was 90 months (range, 2-216 months). PFS ≥ 61 months (P = 0.004) and post-recurrence therapeutic approach (P < 0.001) were independent risk factors for repeated recurrences. The age at recurrence (P = 0.031) and post-recurrence therapeutic approach (P = 0.001) were independent risk factors for death after recurrence.
CONCLUSION
Among patients with recurrent AGCOT, those with long PFS had good prognoses. Maximal cytoreductive effort should be made after recurrence. Complete resection and postoperative adjuvant chemotherapy may improve the prognosis of patients with recurrent AGCOT.
Topics: Adult; Female; Granulosa Cell Tumor; Humans; Male; Middle Aged; Neoplasm Recurrence, Local; Treatment Outcome; Young Adult
PubMed: 32059683
DOI: 10.1186/s13048-020-00619-6 -
Ginekologia Polska 2022The aim of this study is to share of the 20-year experience of a tertiary center about juvenile granulosa cell tumor (JGCT) and describe clinic manifestations,...
OBJECTIVES
The aim of this study is to share of the 20-year experience of a tertiary center about juvenile granulosa cell tumor (JGCT) and describe clinic manifestations, treatment, and outcome of patients who diagnosed JGCT.
MATERIAL AND METHODS
Five patients who diagnosed juvenile granulosa cell tumor between 2000 and 2020 were included in the study. The demographics, clinical findings and outcomes were retrospectively evaluated. Of the 5 patients in our study, one was in the premenarcheal girl. The common complaint in all of our patients was abdominal swelling. In preoperative imaging methods, all patients had unilateral adnexal mass and no signs in favor of metastasis. All patients were staged according to FIGO classification for ovarian tumors; 3 of patients had stage IA disease, one of patients had stage IC1 and one of patients had stage IC2. All patients underwent different surgecal procedures which is appropriate for their clinical manifestations. In addition to surgery 2 patients received adjuvant chemotherapy.
RESULTS
The median follow-up period of the patients was 60 mounts and recurrence was observed in two patients who were reoperated. We have no patients who died due to this disease.
CONCLUSIONS
Possible diagnosis of juvenile granulosa cell tumor should be kept in mind in a patient of young age with unilateral adnexal mass with benign features.
Topics: Female; Humans; Granulosa Cell Tumor; Retrospective Studies; Neoplasm Staging; Ovarian Neoplasms; Chemotherapy, Adjuvant
PubMed: 36748172
DOI: 10.5603/GP.a2022.0107 -
American Journal of Medical Genetics.... May 2020Ollier disease (OD) and Maffucci syndrome (MS) are characterized by multiple enchondromas. Patients with MS also have benign vascular overgrowths that become malignant...
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.
Topics: Adolescent; Adult; Child; Child, Preschool; Chondrosarcoma; Enchondromatosis; Female; Granulosa Cell Tumor; Humans; Infant; Infant, Newborn; Male; Middle Aged; Ovarian Neoplasms; Prognosis; Young Adult
PubMed: 32144835
DOI: 10.1002/ajmg.a.61530 -
International Journal of Molecular... Feb 2021Sirtuins (SIRTs) are NAD-dependent deacetylases that regulate proliferation and cell death. In the human ovary, granulosa cells express sirtuin 1 (SIRT1), which has also...
Sirtuins (SIRTs) are NAD-dependent deacetylases that regulate proliferation and cell death. In the human ovary, granulosa cells express sirtuin 1 (SIRT1), which has also been detected in human tumors derived from granulosa cells, i.e., granulosa cell tumors (GCTs), and in KGN cells. KGN cells are an established cellular model for the majority of GCTs and were used to explore the role of SIRT1. The SIRT1 activator SRT2104 increased cell proliferation. By contrast, the inhibitor EX527 reduced cell numbers, without inducing apoptosis. These results were supported by the outcome of siRNA-mediated silencing studies. A tissue microarray containing 92 GCTs revealed nuclear and/or cytoplasmic SIRT1 staining in the majority of the samples, and also, SIRT2-7 were detected in most samples. The expression of SIRT1-7 was not correlated with the survival of the patients; however, SIRT3 and SIRT7 expression was significantly correlated with the proliferation marker Ki-67, implying roles in tumor cell proliferation. SIRT3 was identified by a proteomic analysis as the most abundant SIRT in KGN. The results of the siRNA-silencing experiments indicate involvement of SIRT3 in proliferation. Thus, several SIRTs are expressed by GCTs, and SIRT1 and SIRT3 are involved in the growth regulation of KGN. If transferable to GCTs, these SIRTs may represent novel drug targets.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Carbazoles; Cell Line, Tumor; Down-Regulation; Gene Expression Regulation, Neoplastic; Gene Silencing; Granulosa Cell Tumor; Heterocyclic Compounds, 2-Ring; Humans; Middle Aged; RNA, Messenger; RNA, Small Interfering; Sirtuin 1; Sirtuin 3; Young Adult
PubMed: 33669567
DOI: 10.3390/ijms22042047 -
Endocrinology Apr 2023Granulosa cell tumors (GCTs) are rare ovarian tumors comprising an adult and a juvenile subtype. They have a generally good prognosis, but the survival rate drastically... (Review)
Review
Granulosa cell tumors (GCTs) are rare ovarian tumors comprising an adult and a juvenile subtype. They have a generally good prognosis, but the survival rate drastically declines in patients with late-stage or recurring tumors. Due to the rarity of GCTs, the tumor type is largely understudied and lacks a specific treatment strategy. Estrogen receptor beta (ERβ/ESR2) has been found to be highly expressed in GCTs, which could be of therapeutic importance since it can be targeted with small molecules. However, its role in GCTs is not known. In this review, we summarize the current knowledge about the action of ERβ in the ovary and discuss its prospective role in GCTs.
Topics: Female; Humans; Estrogen Receptor beta; Granulosa Cell Tumor; Neoplasm Recurrence, Local; Ovarian Neoplasms
PubMed: 37075218
DOI: 10.1210/endocr/bqad063 -
Journal of Veterinary Diagnostic... Nov 2022Granulosa cell tumors (GCTs) are common ovarian neoplasms in the mare and bitch that can be challenging to diagnose on histopathology. Inhibin has long been the standard...
Granulosa cell tumors (GCTs) are common ovarian neoplasms in the mare and bitch that can be challenging to diagnose on histopathology. Inhibin has long been the standard immunohistochemical (IHC) marker for GCTs; however, anti-Müllerian hormone (AMH) has not been evaluated widely as an IHC marker in the bitch and mare. We compared the efficacy of AMH and inhibin as IHC markers in canine and equine GCTs. We selected retrospectively 18 equine and 15 canine cases. All equine tumors were dominated by a cystic pattern; canine tumors often had solid patterns. Both inhibin and AMH had similar punctate cytoplasmic patterns of immunolabeling, although labeling intensity was variable; distribution and intensity of labeling were unrelated to the histomorphologic pattern. Labeling for AMH occurred in 12 of 15 canine and 18 of 18 equine cases. Labeling for inhibin occurred in 15 of 15 canine and 18 of 18 equine cases. AMH in equine GCTs often had stronger immunolabeling than inhibin, and granulosa cells were labeled more extensively. Inhibin and AMH performed comparably in bitches, but AMH had more diffuse immunolabeling than inhibin in mares.
Topics: Animals; Horses; Female; Dogs; Granulosa Cell Tumor; Inhibins; Anti-Mullerian Hormone; Retrospective Studies; Ovarian Neoplasms; Biomarkers; Dog Diseases; Horse Diseases
PubMed: 36113168
DOI: 10.1177/10406387221124589 -
The Journal of Veterinary Medical... Apr 2021A retrospective study involving eight African pygmy hedgehogs histopathologically diagnosed with granulosa cell tumors was conducted. The age at onset was 2.2-4.5 years,...
A retrospective study involving eight African pygmy hedgehogs histopathologically diagnosed with granulosa cell tumors was conducted. The age at onset was 2.2-4.5 years, with a median age of 3.6 years. The most common clinical signs were hematuria and abdominal distension, which were observed in >50% cases. Exploratory laparotomy was performed in all cases, and ovariohysterectomy or excision of the abdominal mass was performed. Patients with only hematuria survived for >250 days after surgery, whereas those with initial ascites showed recurrence of ascites or tumor growth and survived for approximately 130 days after surgery. Intraperitoneal injection of carboplatin was performed in three recurrent cases. In one of these three cases, the tumor mass disappeared. Hence, carboplatin can be considered a potential antineoplastic drug for the treatment of granulosa cell tumors.
Topics: Animals; Female; Granulosa Cell Tumor; Hedgehogs; Neoplasm Recurrence, Local; Ovarian Neoplasms; Retrospective Studies
PubMed: 33597318
DOI: 10.1292/jvms.20-0521