Granulosa Cell Tumor Research Articles

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.

Juvenile granulosa cell tumor of the ovary: A retrospective analysis of 12 cases

Juvenile granulosa cell tumor of the ovary: A retrospective analysis of 12 cases

Tumor of the Granulosa of the Ovary About a Case

Ovarian granulosa tumors are very rare; they belong to the group of sex cord and stromal tumors. Their slow evolution in the adult forms which are more frequent (95%) and less aggressive than the much rarer juvenile forms. The exact etiology of these tumors is unknown, but higher than normal estrogen levels are frequently found in women with ovarian granulosa cell tumors. A woman's menstrual status with excess estrogen is related to the presence of certain symptoms such as: early puberty in young women, increase in the size of the abdomen, menstrual cycle disorders in pre menopause or bleeding abnormal uteri in postmenopausal women. The most frequent ultrasound aspect is the solid-cystic aspect and pathological examination remains the diagnostic key. The treatment is essentially surgical, but sometimes associated with complementary therapies such as: chemotherapy, radiotherapy, hormone therapy. Recurrences occur late, hence the importance of post-therapeutic follow-up. Some aggressive forms relapse and progress more rapidly, which justifies rigorous therapeutic monitoring. The prognostic factors for recurrence identified in the literature are the FIGO stage, the presence of residual tumor and the tumor size. We report a case of observation and we draw attention to the epidemiological, clinical particularities, as well as the various prognostic factors in order to carry out a better therapeutic management.

Diagnostic value and safety of medical thoracoscopy under local anesthesia for unexplained diffuse interstitial lung disease: A retrospective study.

ObjectiveWe aimed to explore the safety and diagnostic value of medical thoracoscopic lung biopsy in patients with unexplained diffuse interstitial lung disease (ILD) in a single center pilot study.MethodWe retrospectively analyzed clinical and pathological diagnostic data from 52 patients with diffuse ILD undergoing medical thoracoscopic lung biopsy.ResultsForty-four cases of diffuse ILD were confirmed pathologically, giving a diagnostic rate of 84.6%. Among these 44 patients, 11 patients were diagnosed with cancer, including eight patients with lung adenocarcinoma, three patients with metastases; two from a gastrointestinal malignancy, and one from a granulosa cell tumor of the ovary. There were 17 cases of idiopathic interstitial pneumonia, including nine cases of usual interstitial pneumonia (UIP), four cases of non-specific interstitial pneumonia (NSIP), three cases of cryptogenic organizing pneumonia (COP), and one case of acute interstitial pneumonia (AIP). There were 12 cases of rare interstitial pneumonias, which included six cases of pulmonary alveolar proteinosis, one case each of pulmonary Langerhans cell histiocytosis (LCH) and pulmonary lymphangiomyomatosis, two cases of nodular sarcoidosis, and two cases of chronic eosinophilic pneumonia. We recorded various complications, including bleeding, infection, and pneumothorax. A total of 28 patients (53.8%) experienced at least one of the above complications, but there were no deaths associated with biopsy.ConclusionsMedical thoracoscopic lung biopsy appears a safe and effective method for diagnosing diffuse ILD of unknown cause but further prospective studies, with larger numbers, including comparison with other established techniques are required.

Ovarian granulosa cell tumor – case report and literature review

Gigantic (>10 cm) ovarian cysts are a rare finding in gynecology. In literature, there are only a few cases of giant ovarian cysts reported, mainly in older patients. Granulosa cell tumor (GCT) of the ovary is frequently a hormonally active, stromal cell neoplasm with the ability to produce sex steroids, such as estrogens. We report the case of a 61-year-old postmenopausal woman with a giant left ovarian cyst measuring 39 x 28 cm. The excision of the giant left ovarian cyst was performed, with intraoperative histologic examination; the result was granulosa cell tumor. We continued the surgery with a total abdominal hysterectomy and bilateral salpingo-oophorectomy and complete staging. On the final histopathological report the result was granulosa cell tumor of the ovary. The management of these high-risk ovarian tumors should have a strict follow up in order to avoid complications.

Ovarian Toxicity Induced by Aluminum Chloride: Alteration of Cyp19a1, Pcna, Puma, and Map1lc3b genes Expression

Aluminum (Al) is an abundant metal with wide application in our daily lives including medicine, industry, cosmetics, and packaging. After entrance to the body, aluminum binds to transferrin and reaches different tissues. Al is a metalloestrogen that can lead to oxidative stress (OxS) and endocrine disruption. No detailed study can be found addressing the effect of Al on the ovary and granulosa cells (GCs). In this study, the focus is on the treated ovaries and GCs of NMRI mice exposed to low, middle, and high doses of aluminum chloride (AlCl3) via in vitro and in vivo assays. The steroidogenic, proliferative, apoptotic, and autophagic-related genes were examined. Up-regulated expression of steroidogenic and proliferative genes was detected. The observed apoptotic and autophagic genes had variable expression. Interrupted ovarian structure, disrupted folliculogenesis, presence of Call-Exner bodies, overexpression of steroidogenic gene, and unbalanced apoptosis/autophagy and proliferation resembled features of granulosa cell tumor (GCT).

PERITONEAL CARCINOMATOSIS SECONDARY TO OVARIAN CANCER: IMAGING FINDINGS

Summary: Peritoneal lesions are a relatively common site of metastases, particularly from tumors of the abdomen and pelvis, which generally carry a poor prognosis, often with a signicant impact on treatment. One of the tumors implicated in peritoneal metastasis is ovarian cancer. Ovarian cancer is the fth most commonly diagnosed cancer among women worldwide and the second most common gynecologic malignancy. Despite clinical screening, ovarian cancer in more than 60% of those affected is diagnosed at an advanced stage with a reported 5-year survival rate of 37% (stage III disease) or 25% (stage III disease). IV). Therefore, ovarian cancer is one of the deadliest cancers affecting women. Ovarian tumors are classied according to the origin of the tumor into epithelial tumors (serous and mucinous tumors, endometrioid and clear cell carcinomas, Brenner's tumor), germ cell tumors (mature and immature teratomas, dysgerminoma, endodermal sinus tumor, carcinoma embryonic), sex cord - stromal tumors (brothecoma; granulosa cell, sclerosing stroma and Sertoli-Leydig cell tumors) and metastatic tumors. Metastases to the ovary are relatively common with a documented incidence of 5% to 30% of all malignant ovarian masses. Ovarian cancer metastases differ from other tumors: they are primarily peritoneal rather than parenchymal in location. These implants are usually isodense in tomography, in relation to the viscera, which makes their detection difcult. For this, a multidisciplinary approach is used, such as physical examination, tumor marker levels and diagnostic images. Such as CT, magnetic resonance imaging (MRI) and positron emission tomography (PET). Objective: Describes ovarian metastasis in a patient with no signicant history, emphasizing peritoneal lesions, through a clinical case. Design: Prospective, observational in a single center. Methodology: This is a systematic review of ovarian metastasis, detailing its clinical characteristics and short-term complications. The information and images obtained belong to the medical personnel in charge of the case, whose reinforcements are provided by the Excel, Word and JPG statistical package.

Analysis of Outcomes and Prognostic Factors after Fertility-Sparing Surgery in Patients with Early Stage Juvenile Granulosa Cell Tumor of the Ovary: Experience from a Tertiary Center

Study ObjectiveThe objective of the study was to analyze the oncological outcomes and prognostic factors in patients with early-stage juvenile granulosa cell tumor (JGCT) who underwent fertility-sparing surgery. Design, Setting, and ParticipantsAll patients with early-stage JGCT who underwent fertility-sparing surgery between January 1995 and December 2017 were reviewed retrospectively. InterventionsNone. Main Outcome MeasuresThe risk factors for recurrence and death in patients with early-stage JGCT were identified. ResultsThirty-five patients were eligible for the current study. The median age was 17 years (range: 4-30 years), and 10 patients were premenarchal. Nine patients were International Federation of Obstetrics and Gynecology stage IA, and 26 were stage IC. Eight subjects underwent complete staging, whereas 28 had no staging at their initial surgery. In those without initial staging, 3 patients who received initial unilateral salpingo-oophorectomy (USO) and 6 with initial cystectomy underwent secondary surgery for staging or USO with staging, respectively. At the time of the secondary staging operation, 1 of the subjects (treated with USO at initial surgery) was found to be stage III and was excluded from this study. Therefore, 8 patients underwent secondary staging surgery performed by laparoscopic surgery, and none of them suffered recurrence during follow-up. Fourteen of the 16 patients with complete staging surgery underwent lymphadenectomy, and none of them had lymph node metastasis. Thirty-one patients received adjuvant chemotherapy after surgery. Eight patients had disease recurrence after a median follow-up time of 51 months (range: 6-229 months), with a median time to recurrence of 4.5 months (range: 2-52 months). Six patients died of their disease. The 5-year disease-free and overall survival rates were 74.8% and 84.3%, respectively. Univariate analysis showed that incomplete staging surgery was associated with increased risk of recurrence (P = 0.029). Adjuvant chemotherapy was not associated with disease-free survival. Four patients had a total of 6 pregnancies, resulting in 6 live births. ConclusionComplete surgical staging is recommended for early-stage JGCT, but lymph node dissection can be omitted. Laparoscopic restaging surgery is feasible for patients with incomplete staging at initial surgery. However, the prognosis of patients with relapsed JGCT remains poor.

Imaging findings of uterine adenosarcoma with sarcomatous overgrowth: two case reports, emphasizing restricted diffusion on diffusion weighted imaging

BackgroundAdenosarcoma is classified as a mixed epithelial and mesenchymal tumor composed of a benign epithelial component and a malignant stromal component. The stromal component in adenosarcoma is usually low grade, and consequently the prognosis is relatively favorable. While, adenosarcoma with sarcomatous overgrowth (SO) is defined as an adenosarcoma in which the sarcomatous component constitutes more than 25% of the tumor. The stromal component is also high-grade sarcoma showing greater nuclear pleomorphism and mitotic activity, thus, it is associated with worse prognosis. MRI findings of adenosarcoma without SO have been described in previous literatures but the imaging findings in adenosarcoma with SO may be poorly defined. Therefore we present two cases of uterine adenosarcoma with SO.Case presentationPatient 1 was a 76-year-old woman referred to our hospital with complaint of abdominal distension and postmenopausal bleeding. Patient 2 was a 57-year-old woman with complaint of lower abdominal pain and abnormal uterine bleeding. On magnetic resonance imaging (MRI), T2 weighted imaging showed a large, heterogeneous high-intensity mass with hyperintense tiny cysts that expanded the uterine cavity and extended into the cervical canal for both patients. On diffusion-weighted imaging (DWI), both masses appeared as high signal intensity. Patient 2 also had a right ovarian adult granulosa cell tumor that may have contributed to development of the adenosarcoma. Patient 1 recurred with peritoneal sarcomatosis 6 months after surgery and died of the disease. Patient 2 also recurred with a left upper lung metastasis 3 months after surgery.ConclusionsDWI may depict pathological changes produced by SO of adenosarcoma as high signal intensity, even though SO does not seem to change MRI findings of adenosarcoma on other sequences. Therefore, DWI could potentially predict SO in presumptive adenosarcoma on MRI and the patient’s prognosis. It is also important for pathologists to know if SO can arise in adenosarcoma because they need to examine the tumor thoroughly to determine the percentage of SO component in the tumor volume when SO is present.

Gene cascade analysis in human granulosa tumor cells (KGN) following exposure to high levels of free fatty acids and insulin

Maternal metabolic disorders such as obesity and diabetes are detrimental factors that compromise fertility and the success rates of medically assisted procreation procedures. During metabolic stress, adipose tissue is more likely to release free fatty acids (FFA) in the serum resulting in an increase of FFA levels not only in blood, but also in follicular fluid (FF). In humans, high concentrations of palmitic acid and stearic acid reduced granulosa cell survival and were associated with poor cumulus-oocyte complex (COC) morphology. Obesity and high levels of circulating FFA were also causatively linked to hampered insulin sensitivity in cells and compensatory hyperinsulinemia. To provide a global picture of the principal upstream signaling pathways and genomic mechanisms involved in this metabolic context, human granulosa-like tumor cells (KGN) were treated with a combination of palmitic acid, oleic acid, and stearic acid at the higher physiological concentrations found in the follicular fluid of women with a higher body mass index (BMI) (≥ 30.0 kg/m2). We also tested a high concentration of insulin alone and in combination with high concentrations of fatty acids. Transcription analysis by RNA-seq with a cut off for fold change of 1.5 and p-value 0.05 resulted in thousands of differentially expressed genes for each treatment. Using analysis software such as Ingenuity Pathway Analysis (IPA), we were able to establish that high concentrations of FFA affected the expression of genes mainly related to glucose and insulin homoeostasis, fatty acid metabolism, as well as steroidogenesis and granulosa cell differentiation processes. The combination of insulin and high concentrations of FFA affected signaling pathways related to apoptosis, inflammation, and oxidative stress. Taken together, our results provided new information on the mechanisms that might be involved in human granulosa cells exposed to high concentrations of FFA and insulin in the contexts of metabolism disorders.

Extracts of Anogeissus leiocarpus and Dillenia indica Inhibit the Growth of MCF-7 Breast Cancer and COV434 Granulosa Tumor Cells by Inducing Apoptosis and Autophagy

Background: Dillenia indica L. (Dilleniaceae) and Anogeissus leiocarpus (DC.) Guill. & Perr. (Combretaceae) are used in traditional Nigerian medicine to treat various forms of cancer. This study investigated the cytotoxic effects of these plant extracts using COV434 granulosa tumor and MCF-7 breast cancer cells. Methods: Samples of D. indica and A. leiocarpus were collected in Ibadan, Nigeria, air-dried, and extracted with methanol. Cell viability and cytotoxicity were determined using CellTiter-Glo® 2.0 assay at concentrations from 1 to 100 μg/mL. Caspase activity and apoptosis were determined using Caspase-Glo® 3/7, Caspase-Glo® 8, and ApoTox-Glo™ triplex assays, and qPCR. Autophagy was measured using a Cyto-ID Autophagy Detection Kit. Results: In COV434, aqueous partitions of A. leiocarpus root (ALR-Aq) and stem bark (ALS-Aq) had IC50s of 23.5 and 26.7 μg/mL, respectively. In MCF-7 cells, the ALR MeOH extract had IC50 of 12.75 μg/mL, while the DIS-Aq had IC50 of 65.28 μg/mL. None of the extracts inhibited the growth of human osteoblasts or rat myoblasts at similar concentrations. Treatment with ALR-Aq and DIS-Aq induced mitochondrial apoptosis in MCF-7 and COV434. Both ALR-Aq and DIS-Aq induced autophagy in COV434 cells, while ALR-Aq induced autophagy in MCF-7 cells. Ellagic acid (IC50 of 3.27μg/mL in COV434 cells) was isolated from ALR-Aq using bioassay-guided fractionation. Conclusion: DIS-Aq and ALR-Aq induced apoptosis in MCF-7 and COV434 cancer cells. Ellagic acid was isolated as the active constituent. Taken together, these data suggest that both plant extracts have strong anti-proliferative effects, and further investigation for their anticancer effects is warranted.

Biochemical markers of ovarian stromal cell tumors

Ovarian stromal cell tumors are a rare group of neoplasms that characterized by an ambiguous prognosis and biological activity associated with the hypersecretion of a number of substances. The review presents the latest data on the biochemical diagnosis of tumors of the stroma of sex cord, including granulosa cell tumor of the ovary. The importance of hormones,

Significance of peritoneal washing cytology in the accurate staging of malignant ovarian tumors.

ABSTRACTObjectives:To identify the percentage of ovarian cancers with positive peritoneal cytology and to correlate the positive cytology with the prognostic factors.Methods:This retrospective, cross-sectional study, evaluated the data of surgical specimens of malignant ovarian tumors, received in the Department of Pathology, Dow University of Health Sciences over a period of three years. The peritoneal cytology was correlated with these prognostic parameters: the size of the tumor, stage, capsular invasion, omental, and lymph node metastasis.Results:Eighty malignant ovarian tumors were diagnosed. Serous carcinoma was the most common ovarian tumor, diagnosed in 24(30.0%) cases, followed by endometrioid carcinoma in 17(21.25%) and Granulosa cell tumor in 11 (13.75%) cases. The mean age of the patients was 41.91 years (range 7-71 years). The mean size of the tumors was 10.03 cm (SD 5.62 cm). The ovarian capsular invasion was present in 27(33.75%) tumors. Peritoneal cytology was positive in 10/24 cases, with a detection rate of 41.66%. Omentum was involved in 12/34(35.29%) cases. Lymph node dissection was performed in three cases, two were reported as positive for metastasis. Peritoneal cytology significantly correlated with the tumor size (p=0.045), and with ovarian capsular invasion (p=0.054) and omental metastasis (p=0.052). Most of the tumors were staged as FIGO stage IA.Conclusion:Peritoneal cytology correlates with the tumor size, stage, and omental metastasis of the malignant ovarian tumors. It should be routinely performed at the time of surgery for the optimal staging of the patients.

Prognostic predictors in recurrent adult granulosa cell tumors of the ovary: a systematic review and meta-analysis.

Ovarian adult granulosa cell tumours are low-grade malignant sex cord-stromal neoplasm with a low recurrence rate. Prognostic factors for recurrence include tumor stage, tumor rupture in Stage I neoplasms and the presence of residual tumors after surgery. However, in recurrent tumors, prognostic factors for overall survival (OS) are lacking. In the present paper, we conducted a systematic meta-analysis with the aim to assess prognostic factors for OS in patients with recurrent GCT. Electronic databases were searched for all studies assessing prognostic factors in recurrent adult granulosa cell tumor of the ovary. Student T test, Fisher's exact test and Kaplan-Meier survival analysis with long-rank test were used to assess differences among groups; a p value < 0.05 was considered significant. Eleven studies analyzing 102 recurrent tumors were included in the systematic review. Tumor stage and localization of recurrent tumors were significantly associated with OS on Kaplan-Meier analysis; Cox regression analysis showed a HR of 0.879 for the stage II, of 3.052 for the stage III, and of 2.734 for stage IV tumor was significantly associated with OS (p = 0.037); observed HRs for abdominal and thoracic locations were of 2.405 and of 4.024, respectively. In conclusion, the present article emphasizes the prognostic significance of tumor stage > II and extrapelvic anatomic sites of recurrences in patients with recurrent granuolase cell tumors of the ovary.

FOXL2C134W : much ado about something!†.

Recent studies have suggested that the unique FOXL2C134W mutation, which is pathognomonic for adult granulosa cell tumours of the ovary, is a tumour suppressor gene. In a recent issue of The Journal of Pathology, a detailed study by Pilsworth et al seeks to rebut the proposition that the FOXL2C134W mutation, which uniquely characterises adult granulosa cell tumours of the ovary, leads to reduced transcript levels with the implication that FOXL2 is a tumour suppressor gene. The study provides compelling evidence that both wild-type and mutant FOXL2 transcripts and protein are expressed at equivalent levels. In the context of other recent studies, one is drawn to the conclusion that FOXL2C134W is a gain-of-function mutation whose impact is mediated through enhanced interactions with the SMAD transcription factor complex. © 2021 The Pathological Society of Great Britain and Ireland.

Characteristics of granulosa cell tumor at Dr. Soetomo general hospital from 2014 to 2019

The aim of the present study was to investigate tumor characteristics, treatment, recurrence, and prognosis in both Granulosa Cell Tumor types.A retrospective review study of 38 patients in a single institute; We identified patients with GCTs diagnosed between 2014 and 2019 in the Regional General Dr. Soetomo Hospital. Surgical outcome, pathological findings and follow-up data were analyzed. Statistical analyses were conducted using Fisher exact test and Kaplan-Meier survival curves and compared with the log-rank test. The prevalence of AGCT subtypes as the most common type occurring in 97% of cases. The median age at diagnosis among patients with AGCT is 47.5 years (range 41-59), and most women are premenopausal and multiparous. In our literature review Stage 1 disease is 76% with Overall Survival (OS) for 5years is 89.7%. FIGO stage and adjuvant therapy was not shown a positive correlation with recurrency (p &amp;#62;0.05). Rate of recurrence in AGCT is reported to be as high as 5.26%.GCT is a rare low malignant tumor, majority of patients present with early-stage disease and generally have a favorable prognosis. Stage is not considered as the most important prognostic factor. The role of adjuvant chemotherapy treatment is debatable as it was not shown to reduce recurrence rates. Long-term surveillance including routine clinical follow-up and tumor markers serial evaluation is mandatory to evaluate recurrency.

Luteoma in two mares treated by ovariectomy

Summary A 15‐year‐old Paint mare (Case 1) and a 15‐year‐old Arabian mare (Case 2) were presented for aggressive and undesired behaviour. Reproductive evaluation revealed, initially, an enlarged ovary with a smaller/normal sized contralateral ovary in each case. Granulosa cell tumour (GCT) panel testing revealed elevated inhibin B in both cases and elevated anti‐Mullerian hormone (AMH) levels only in Case 1 determined from currently established reference ranges. Based on a presumptive diagnosis of GCT, bilateral standing ovariectomy was elected for both mares. In each case neoplastic tissue consistent with luteoma was detected only on histological examination in the smaller/normal sized left ovary; the right ovary appearing normal. Long‐term follow‐up was performed 1 year and 5 years post‐operatively by telephone. The owners were satisfied with the outcome and each patient demonstrated resolution of aggressive stallion‐like behaviour. Each case returned to the owners' intended use. In conclusion, luteoma should be considered as a differential diagnosis for ovarian neoplasms in horses related to behavioural abnormalities, even in normal‐sized ovaries.

Characterization of an incipient granulosa cell tumour in a Holstein cow: Steroid hormone receptors and coregulators expression.

The objective of this study was to describe a case of a granulosa cell tumour (GCT) of incipient formation and to characterize it by its immunohistochemical pattern and hormonal profile. The case presented corresponds to a 7-year-old Holstein cow without reproductive disorders. No alterations were observed at rectal palpation, neither in the ultrasonography nor in the hormonal profile. A GCT concomitant with normal follicular development was diagnosed. Through a panel of immunohistochemical markers, a highly differentiated pattern could be determined in the GCT, which preserves the expression of steroid receptors (ESR1, ESR2 and PR) typical of granulosa cells, but does not express the enzymes for the synthesis of androgens (CYP17A1) and oestrogens (CYP19A1). In addition, the expression of co-regulators of steroid hormone receptors and neuroendocrine markers was described for the first time in a GCT in cattle. These results increase the information about GCTs in cattle before the ovarian function is compromised.

Adult Granulosa Cell Tumor in Pregnancy: A New Case and a Review of the Literature.

Granulosa cell tumors are rare ovarian tumors that can arise during pregnancy. We present a new case of recurrent adult granulosa cell tumor (AGCT) in pregnancy and a systematic review of the literature. The new case described is a 41-year-old woman G5P1122 with a prior history of AGCT that was referred to our center at 29 weeks because of a symptomatic abdominal mass, compatible with a possible recurrence of AGCT. At 36 + 3 weeks, she underwent a cesarean delivery for preterm labor and a total hysterectomy with a radical surgical staging. A healthy female infant was delivered. The patient received a platinum-based chemotherapy, with a 26-month follow-up negative for recurrence. Analyzing our case with the four identified by the literature review, three were recurrent and two were primary AGCT. Only one required surgery for AGCT at 15 weeks, while another underwent chemotherapy in pregnancy. In the other three cases, surgery for AGCT was done at the time of cesarean delivery. There were three cases of preterm delivery. All five pregnancies resulted in the birth of live babies with weight adequate for gestational age. In conclusion, AGCT diagnosed in pregnancy is rare, reported in only five cases. All gave birth to live babies in the third trimester, and maternal outcome at up to 18 months showed no recurrence.