MedWorm: Granulosa Cell Tumor

The C134W (402 C>G) FOXL2 mutation is absent in ovarian gynandroblastoma: insights into the genesis of an unusual tumour

Histopathology — Wed, 01 Feb 2012 05:00:00 +0100

Conclusions: This suggests that, despite their similar morphological appearances, the GCT‐like component of gynandroblastoma has a different molecular basis from conventional adult‐type GCT. This finding underscores a more general principle that morphological similarity does not necessarily indicate molecular identity. (Source: Histopathology)

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Molecular Pathogenesis of Granulosa Cell Tumors of the Ovary.

ENDOCR REV — Thu, 12 Jan 2012 05:00:00 +0100

Authors: Jamieson S, Fuller PJ Abstract Granulosa cell tumors of the ovary (GCT) comprise a distinct subset of ovarian cancers that account for approximately 5% of all ovarian malignancies. They are thought to arise from normal proliferating granulosa cells of the late preovulatory follicle and exhibit many morphological and biochemical features of these cells. GCT are distinct from other ovarian carcinomas in their hormonal activity; their ability to secrete estrogen, inhibin, and Müllerian inhibiting substance accounts for some of the clinical manifestations of the disease and also provides useful tumor markers for disease surveillance. Although considered to be of low malignant potential, GCT are commonly associated with slow, indolent disease progression, and frequent yet long...

An activating Pik3ca mutation coupled with Pten loss is sufficient to initiate ovarian tumorigenesis in mice

Journal of Clinical Investigation — Sat, 07 Jan 2012 01:06:50 +0100

Mutations in the gene encoding the p110α subunit of PI3K (PIK3CA) that result in enhanced PI3K activity are frequently observed in human cancers. To better understand the role of mutant PIK3CA in the initiation or progression of tumorigenesis, we generated mice in which a PIK3CA mutation commonly detected in human cancers (the H1047R mutation) could be conditionally knocked into the endogenous Pik3ca locus. Activation of this mutation in the mouse ovary revealed that alone, Pik3caH1047R induced premalignant hyperplasia of the ovarian surface epithelium but no tumors. Concomitantly, we analyzed several human ovarian cancers and found PIK3CA mutations coexistent with KRAS and/or PTEN mutations, raising the possibility that a secondary defect in a co-regulator of PI3K activity may be ...

A rare case of ovarian juvenile granulosa cell tumor without precocious pseudopuberty in an 11-month-old infant

Journal of Pediatric Surgery — Sun, 01 Jan 2012 05:00:00 +0100

We describe a new case of JGCT occurring in an 11-month-old girl, presenting without hormonal manifestations.. (Source: Journal of Pediatric Surgery)

Unexpected ovarian malignancy after conservative laparoscopic surgery: five case series in a half decade of experience

Archives of Gynecology and Obstetrics — Wed, 21 Dec 2011 20:07:58 +0100

Conclusion The main concern for laparoscopic management of ovarian masses is unexpected malignancy. However, with careful patient selection, proper technique and an experienced operator, laparoscopic treatment of ovarian masses is the best approach and should be implemented, with low risk of unexpected malignancy and recurrence. Content Type Journal ArticleCategory Gynecologic OncologyPages 1-4DOI 10.1007/s00404-011-2177-2Authors Noraziana Abd Wahab, Department of Obstetrics and Gynecology, Kulliyyah of medicine, Jalan Hospital, International Islamic University, 25710 Kuantan, Pahang, MalaysiaAmphan Chalermchockchareonkit, Department of Obstetrics and Gynecology, Thai-German Multidisciplinary Endoscopic Training Center, Faculty of Medicine Siriraj Hospital, Mahidol ...

Successful treatment of adult‐type granulosa cell tumor of the ovary by palliative radiotherapy

Journal of Obstetrics and Gynaecology Research — Mon, 19 Dec 2011 05:00:00 +0100

AbstractA 76‐year‐old woman underwent laparotomy at another hospital because of acute abdomen. Owing to strong attachment and dissemination of the tumor, it was unresectable. Adult‐type granulosa cell tumor (AGCT) was diagnosed based on pathological examination. Considering her poor condition, she was advised to receive total supportive care. However, she was lost to follow‐up after a few months. Subsequently, she visited our hospital with abdominal distension. A large abdominal tumor and liver metastasis was observed on abdominal computed tomography (CT). We selected palliative radiotherapy to relieve her of the symptoms. External beam radiotherapy was delivered to the affected data. No acute adverse effects were observed. We observed reduction in tumor size on postoperative abdom...

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Aromatase inhibitors in the treatment of recurrent ovarian granulosa cell tumors: Brief report and review of the literature

Journal of Obstetrics and Gynaecology Research — Mon, 05 Dec 2011 05:00:00 +0100

We present a heavily pre‐treated, multi‐operated patient who experienced significant tumor shrinkage following treatment with an aromatase inhibitor for her recurrent granulosa cell tumor. (Source: Journal of Obstetrics and Gynaecology Research)

Measuring anti-Müllerian hormone for the assessment of ovarian reserve: When and for whom is it indicated?

Maturitas — Fri, 18 Nov 2011 05:00:00 +0100

Abstract: Our understanding of female reproductive function has been hampered by our inability to directly assess the number of non-growing primordial follicles present in the ovary, the ovarian reserve. Female reproductive hormones (FSH and LH, the inhibins and steroids) reflect the activity of the larger growing follicles and thus are largely informative of peri-ovulatory ovarian activity. In contrast anti-Müllerian hormone (AMH) is a product of the granulosa cells of small growing follicles, whose number (and therefore circulating AMH concentrations) is reflective of the ovarian reserve. AMH declines with age in adult women, and emerging data suggest a relationship with remaining reproductive lifespan and age at the menopause. Early studies demonstrated that AMH concentrations are stab...

Short RNA Duplexes Elicit RIG-I-Mediated Apoptosis in a Cell Type- and Length-Dependent Manner.

Science Signaling — Thu, 17 Nov 2011 07:36:01 +0100

Authors: Ishibashi O, Ali MM, Luo SS, Ohba T, Katabuchi H, Takeshita T, Takizawa T Abstract Short double-stranded RNAs (dsRNAs) induce type I interferon (IFN)-mediated innate immune responses. In functional studies with short interfering RNAs or synthetic mimics of microRNA precursors in vitro, we found that short dsRNAs readily induced apoptosis in cells derived from human granulosa cell tumors, but not in other cell types. Apoptosis was independent of the sequence of the dsRNA, but depended on its length, and was induced by 23- and 24-nucleotide (nt) dsRNAs, but not by shorter dsRNAs (<22 nt) or by the long dsRNA polyinosinic-polycytidylic acid. Microarray analysis revealed that apoptosis was accompanied by the increased expression of IFN-stimulated genes; however, several lin...

Proceedings of the 2011 National Toxicology Program Satellite Symposium.

Toxicologic Pathology — Wed, 16 Nov 2011 05:00:00 +0100

This article presents summaries of the speakers' presentations, including diagnostic or nomenclature issues that were presented, along with select images that were used for audience voting or discussion. Some lesions and topics covered during the symposium include: proliferative lesions from various fish species including ameloblastoma, gas gland hyperplasia, nodular regenerative hepatocellular hyperplasia, and malignant granulosa cell tumor; spontaneous cystic hyperplasia in the stomach of CD1 mice and histiocytic aggregates in the duodenal villous tips of treated mice; an olfactory neuroblastoma in a cynomolgus monkey; various rodent skin lesions, including follicular parakeratotic hyperkeratosis, adnexal degeneration, and epithelial intracytoplasmic accumulations; oligodendroglioma and ...

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Journal of Pediatric Surgery — Tue, 01 Nov 2011 04:00:00 +0100

In the article “Medico-legal observations concerning a mortal case of 4 granulosa cell tumor of the ovary in an 8-month-old infant” (J Pediatr Surg 2011;46:1679-82), there was an error in the order of the authors. The correct byline is as follows: Mariano Paternoster, Vincenzo Graziano, Alessandro Settimi, Pierpaolo Di Lorenzo, F. Alicchio, and Ciro Esposito. (Source: Journal of Pediatric Surgery)

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FOXL2 mutation and large-scale genomic imbalances in adult granulosa cell tumors of the ovary

Cancer Genetics and Cytogenetics — Tue, 01 Nov 2011 04:00:00 +0100

This study provides the first correlation of FOXL2 mutation status and genomic imbalances in AGCTs, and it further elucidates the mechanisms for mutant allele imbalance in cancer. (Source: Cancer Genetics and Cytogenetics)

A long-term follow-up study of 176 cases with adult-type ovarian granulosa cell tumors.

Gynecologic Oncology — Wed, 19 Oct 2011 04:00:00 +0100

CONCLUSIONS: The outcomes of patients with GCTs were good, with nearly to 95% of patients surviving 5 and 10years. The prognosis was related to initial stage, presence of residual tumor after initial surgery, and tumor size (> 13.5cm). Different surgical methods and/or adjuvant therapy appear not to affect the outcome. PMID: 22019525 [PubMed - as supplied by publisher] (Source: Gynecologic Oncology)

Autoimmune mediated regulation of ovarian tumor growth.

Gynecologic Oncology — Sun, 16 Oct 2011 04:00:00 +0100

CONCLUSIONS: Our results indicate that induction of ovarian-specific autoimmunity may serve as an effective way to prevent the emergence of autochthonous ovarian tumors and control the growth of established ovarian malignancies. PMID: 22004903 [PubMed - as supplied by publisher] (Source: Gynecologic Oncology)

WT1 Expression in the Female Genital Tract

Advances in Anatomic Pathology — Sat, 15 Oct 2011 19:38:22 +0100

The Wilms tumor gene 1 (WT1) has been reported in normal tissues and many neoplasms of the female genital tract. This review discusses WT1 expression in the female genital tract and its potential utility in the differential diagnosis of neoplasms that occur at this location. WT1 is of value in the differential diagnosis of synchronous serous carcinomas arising in the ovary/fallopian tube/peritoneum and endometrium, as strong WT1 positivity in both tumors points toward an extrauterine origin. In addition, WT1 can be used to distinguish sex cord stromal tumors (WT1 positive) from endometrioid carcinomas (OECs). WT1 expression is not helpful in the differential diagnosis of ovarian serous carcinomas (OSCs) and transitional carcinomas, as both are typically positive and has limited value in th...

Serum Vascular Endothelial Growth Factor A (VEGF) Is Elevated in Patients with Ovarian Granulosa Cell Tumor (GCT), and VEGF Inhibition by Bevacizumab Induces Apoptosis in GCT in Vitro.

The Journal of Clinical Endocrinology and Metabolism — Wed, 12 Oct 2011 04:00:00 +0100

Conclusions:These data suggest an autocrine role for VEGF in GCT and encourage clinical studies on anti-VEGF treatments in this disease. PMID: 21994955 [PubMed - as supplied by publisher] (Source: The Journal of Clinical Endocrinology and Metabolism)

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Third‐line chemotherapy with tyrosine kinase inhibitor (imatinib mesylate) in recurrent ovarian granulosa cell tumor: Case report

Journal of Obstetrics and Gynaecology Research — Wed, 28 Sep 2011 04:00:00 +0100

We report a case of a 60‐year‐old woman with a heavily pretreated recurrent, c‐kit positive, GCT of the ovary who underwent an experimental therapy with imatinib, a tyrosine kinase inhibitor. Imatinib (400 mg/day during the first 2 months; 800 mg/day after) was given, without notable side‐effects. Monthly positron emission tomography–computed tomography scan evaluations were performed revealing a marked reduction of disease after 6 months of treatment. To our knowledge this is the first case of highly recurrent and unresponsive GCT of the ovary responding to imatinib. Further studies evaluating this drug in recurrent and/or aggressive GCT are warranted. (Source: Journal of Obstetrics and Gynaecology Research)

Tamoxifen: Granulosa cell tumour of the ovary: case report

Reactions — Sun, 18 Sep 2011 23:35:47 +0100

(Source: Reactions)

Fancf‐deficient mice are prone to develop ovarian tumors

The Journal of Pathology — Wed, 07 Sep 2011 04:00:00 +0100

AbstractFanconi Anemia (FA) is a rare recessive disorder marked by developmental abnormalities, bone marrow failure, and a high risk for the development of leukemia and solid tumors. The inactivation of FA genes, in particular FANCF, has also been documented in sporadic tumors in non‐FA patients. To study whether there is a causal relationship between FA pathway defects and tumor development, we have generated a mouse model with a targeted disruption of the FA core complex gene Fancf. Fancf‐deficient mouse embryonic fibroblasts displayed a phenotype typical for FA cells: they showed an aberrant response to DNA crosslinking agents as manifested by G2 arrest, chromosomal aberrations, reduced survival and an inability to monoubiquitinate FANCD2. Fancf homozygous mice were viable, born fol...

Fancf‐deficient mice are prone to develop ovarian tumours

The Journal of Pathology — Wed, 07 Sep 2011 04:00:00 +0100

AbstractFanconi anaemia (FA) is a rare recessive disorder marked by developmental abnormalities, bone marrow failure, and a high risk for the development of leukaemia and solid tumours. The inactivation of FA genes, in particular FANCF, has also been documented in sporadic tumours in non‐FA patients. To study whether there is a causal relationship between FA pathway defects and tumour development, we have generated a mouse model with a targeted disruption of the FA core complex gene Fancf. Fancf‐deficient mouse embryonic fibroblasts displayed a phenotype typical for FA cells: they showed an aberrant response to DNA cross‐linking agents as manifested by G2 arrest, chromosomal aberrations, reduced survival, and an inability to monoubiquitinate FANCD2. Fancf homozygous mice were viable,...

Fancfdeficient mice are prone to develop ovarian tumors

The Journal of Pathology — Tue, 06 Sep 2011 23:00:00 +0100

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Fine needle aspiration cytology in ovarian lesions: an institutional experience of 584 cases

Cytopathology — Wed, 24 Aug 2011 23:00:00 +0100

Conclusion: FNAC has a high specificity for diagnosis of ovarian/adnexal lesions but greater experience is required for the accurate subtyping of neoplasms and sensitivity is limited by inconclusive/inadequate results. (Source: Cytopathology)

Either Kras activation or Pten loss similarly enhance the dominant-stable CTNNB1-induced genetic program to promote granulosa cell tumor development in the ovary and testis

Oncogene — Sun, 21 Aug 2011 23:00:00 +0100

Authors: J S Richards, H-Y Fan, Z Liu, M Tsoi, M-N Laguë, A Boyer & D Boerboom (Source: Oncogene)

Prediction of benignity of solid adnexal masses

Archives of Gynecology and Obstetrics — Fri, 19 Aug 2011 16:01:14 +0100

Conclusion We present a retrospective study of both surgical and nonsurgical management of solid ovarian masses. None of the sonographically diagnosed benign-appearing solid adnexal masses were subsequently proved to be malignant either at pathology or by clinical course, suggesting that ultrasound can accurately predict benignity in these masses and that conservative management is an option in these patients. Content Type Journal ArticleCategory General GynecologyPages 1-6DOI 10.1007/s00404-011-2062-zAuthors Shengfu Wang, Department of Radiology, Wayne State University School of Medicine, Detroit Medical Center, 4201 St. Antoine, DRH 3L-8, Detroit, MI 48201, USASamuel Johnson, Department of Radiology, Wayne State University School of Medicine, Detroit Medical Cent...

Early Pregnancy Complicated With Juvenile Granulosa Cell Tumor.

The American Journal of the Medical Sciences — Wed, 10 Aug 2011 23:00:00 +0100

CONCLUSION:: Treatment options and a review of the literature related to JGCTs are discussed. PMID: 21841464 [PubMed - as supplied by publisher] (Source: The American Journal of the Medical Sciences)

Correlation of FOXL2 mutation status with genomic imbalances in adult granulosa cell tumors of the ovary

Cancer Genetics and Cytogenetics — Mon, 01 Aug 2011 04:00:00 +0100

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Anti-Müllerian hormone inhibits growth of AMH type II receptor-positive human ovarian granulosa cell tumor cells by activating apoptosis

Laboratory Investigation AOP — Sun, 31 Jul 2011 23:00:00 +0100

Anti-Müllerian hormone inhibits growth of AMH type II receptor-positive human ovarian granulosa cell tumor cells by activating apoptosis Laboratory Investigation advance online publication, August 1, 2011. doi:10.1038/labinvest.2011.116 Authors: Mikko Anttonen, Anniina Färkkilä, Hanna Tauriala, Marjut Kauppinen, David T MacLaughlin, Leila Unkila-Kallio, Ralf Bützow & Markku Heikinheimo (Source: Laboratory Investigation AOP)

Medico-legal observations concerning a mortal case of granulosa cell tumor of the ovary in an 8-month-old infant

Journal of Pediatric Surgery — Sun, 31 Jul 2011 23:00:00 +0100

Granulosa cell tumor is a gonadal sex steroid hormone-secreting tumor presenting with symptoms and signs of precocious pseudopuberty . It usually occurs before 20 years of life but is very rare in neonates and infants . Considering that until now, few cases have been reported in the literature, we describe a case that demanded our attention. We analyzed the clinical and pathologic features of a case of granulosa cell tumor of the ovary that occurred in an 8-month-old little infant who died after spontaneous rupture of an undiagnosed tumor. The case was brought to our attention during a medico-legal proceeding initiated to ascertain an episode of suspected medical malpractice. Considering that court actions against surgeons and pediatricians are going to become an increasing problem in pedi...

Biological and clinical significance of anti-Müllerian hormone determination in blood serum of the mare

Theriogenology — Fri, 29 Jul 2011 04:00:00 +0100

The objectives of the present study were to validate a heterologous enzyme immunoassay for determination of serum AMH in the horse, and to determine concentrations of AMH in the blood of mares during the estrous cycle, pregnancy, and in mares with granulosa-cell tumors. Mares with normal estrous cycles (n = 6) and pregnant mares (n = 6) had blood samples collected throughout one interovulatory period and monthly throughout gestation, respectively. Mares diagnosed with GCT had blood samples taken before (n = 11) and after ovariectomy (n = 5). Tumors were sectioned and fixed for immunohistochemistry and snap frozen for immunoblot analyses and RT-qPCR. In normal cyclic mares and in pregnant mares, there was no effect of cycle stage or month of gestation on serum AMH concentrations. In GCT mar...

Pregnancy concomitant with metastatic adult granulosa cell tumor

Archives of Gynecology and Obstetrics — Sat, 25 Jun 2011 15:51:23 +0100

Conclusions The case is an unusual presentation of metastatic adult granulosa cell tumor at child bearing age. Although rapidly progressing, successful prolongation of pregnancy till 30 weeks of gestation was possible with the judicious use of chemotherapy. Fetal and maternal outcomes were favorable. Content Type Journal ArticlePages 1-5DOI 10.1007/s00404-011-1958-yAuthors R. Agarwal, Department of Obstetrics and Gynaecology, UCMS and GTB Hospital, Delhi, IndiaG. Radhakrishnan, Department of Obstetrics and Gynaecology, UCMS and GTB Hospital, Delhi, IndiaA. G. Radhika, Department of Obstetrics and Gynaecology, UCMS and GTB Hospital, Delhi, IndiaJ. Jain, Department of Oncology, Delhi State Cancer Institute, Delhi, IndiaS. Sharma, Department of Pathology, UCMS and...

Silent existence: A retroperitoneal tumor had an unexpected origin

American Journal of Obstetrics and Gynecology — Tue, 21 Jun 2011 23:00:00 +0100

A 63-year-old woman was referred to our institute, because a lesion of the pancreatic tail, an incidental finding during a general health examination, was progressively enlarging. At the time of admission, she did not have abdominal pain, bowel discomfort, or weight loss. Her physical examination was unremarkable, except for a surgical scar located low on the abdomen. She had undergone hysterectomy and left salpingo-oophorectomy 9 years earlier because of postmenopausal vaginal bleeding. Pathologic examination of that surgical specimen showed uterine leiomyomas and a granulosa cell tumor (GCT) of the left ovary. (Source: American Journal of Obstetrics and Gynecology)

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Excessive Ovarian Production of Nerve Growth Factor Elicits Granulosa Cell Apoptosis by Setting in Motion a Tumor Necrosis Factor alpha/Stathmin-Mediated Death Signaling Pathway.

Reproduction — Sun, 05 Jun 2011 23:00:00 +0100

Authors: Garcia-Rudaz C, Dorfman M, Nagalla S, Svechnikov K, Soder O, Ojeda SR, Dissen GA Excessive nerve growth factor (NGF) production by the ovary, achieved via a transgenic approach, results in arrested antral follicle growth, reduced ovulatory capacity, and a predisposition to cyst formation in response to mildly elevated LH levels. Two salient features in these mutant mice (termed 17NF) are an elevated production of 17-alpha hydroxyprogesterone (17-OHP4), testosterone (T4) and estradiol (E2) in response to gonadotropins, and an increased frequency of granulosa cell (GC) apoptosis. Here we show that the increase in steroidal response is associated with enhanced expression of Cyp17a1, Hsd17b, and Cyp19a1, which encode the enzymes catalyzing the synthesis of 17-OHP4, T4 and E2, resp...

FOXL2 C402G mutation detection using MALDI-TOF-MS in DNA extracted from Israeli granulosa cell tumors.

Gynecologic Oncology — Wed, 01 Jun 2011 23:00:00 +0100

CONCLUSIONS: Our results indicate that the FOXL2 mutations can be reliably detected by MALDI-TOF-MS genotyping. MALDI-TOF-MS genotyping is a simple, robust and highly sensitive method to detect FOXL2 C402G mutation. Our results confirm previous studies reporting over 95% prevalence of FOXL2 mutation in GCT. Furthermore, we suggest that testing for the presence of the FOXL2 C402G mutation may improve diagnostic accuracy. PMID: 21640373 [PubMed - as supplied by publisher] (Source: Gynecologic Oncology)

Fine needle aspiration cytology in sclerosing stromal tumor of the ovary: A series of three cases

Diagnostic Cytopathology — Tue, 31 May 2011 16:24:05 +0100

We present FNAC findings in a series of three cases of SST and discuss the cytomorphological features. We have described Call‐Exner like bodies in one of our cases and hence, suggest that these may not be an exclusive feature of granulosa cell tumor. Diagn. Cytopathol. 2011; © 2011 Wiley‐Liss, Inc. (Source: Diagnostic Cytopathology)

Prognostic significance of FOXL2 mutation and mRNA expression in adult and juvenile granulosa cell tumors of the ovary

Modern Pathology AOP — Thu, 26 May 2011 23:00:00 +0100

Authors: Emanuela D'Angelo, Ana Mozos, Daiei Nakayama, Iñigo Espinosa, Lluis Catasus, Josefina Muñoz & Jaime Prat (Source: Modern Pathology AOP)

Adult granulosa cell tumor presenting as metastases to the pleural and peritoneal cavity

Diagnostic Cytopathology — Wed, 25 May 2011 23:00:00 +0100

We report a case of AGCT presenting as stage IV disease with exfoliation of malignant cells in the pleural and ascitic fluid with exudative effusions. We wish to emphasize on cytomorphologic features of AGCT to differentiate the same from malignant epithelial tumors. A precise diagnosis in such a case may be possible on serous body fluid cytology with a combined clinical and cytopathologic approach. Diagn. Cytopathol. 2011; © 2011 Wiley‐Liss, Inc. (Source: Diagnostic Cytopathology)

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Ovarian sex cord-stromal tumors, pleuropulmonary blastoma and DICER1 mutations: A report from the International Pleuropulmonary Blastoma Registry.

Gynecologic Oncology — Sat, 16 Apr 2011 23:00:00 +0100

CONCLUSIONS: Primary ovarian neoplasms, particularly OSCST, are a manifestation of the familial PPB syndrome and may be the initial clinical presentation of DICER1 mutations within a family. PMID: 21501861 [PubMed - as supplied by publisher] (Source: Gynecologic Oncology)

Patterns of spread and recurrence of sex cord-stromal tumors of the ovary.

Gynecologic Oncology — Thu, 07 Apr 2011 23:00:00 +0100

CONCLUSIONS.: This study confirms the finding that lymph node metastasis are rare in sex-cord stromal tumors. These findings support the hypothesis that routine lymphadenectomy provides limited additional information in the management of these patients and can be omitted from the primary surgical staging procedure or secondary restaging procedures. PMID: 21481441 [PubMed - as supplied by publisher] (Source: Gynecologic Oncology)

Non-epithelial ovarian tumours: a review of selected patterns that mimic epithelial tumours and other high-grade malignancies

Diagnostic Histopathology — Tue, 08 Mar 2011 00:00:00 +0100

Abstract: Non-epithelial ovarian tumours exhibit a diverse array of growth patterns that can mimic epithelial ovarian cancers or other high-grade malignancies. This review highlights selected morphologic features that may assist in the differential diagnosis, as well as recent advances in immunohistochemistry. Steroidogenic factor-1 is a novel marker for sex cord-stromal differentiation and is useful in the diagnosis of granulosa cell tumour. SALL4 is a novel marker of primitive germ cell tumours and is useful in the diagnosis of yolk sac tumour. Distinction of primary versus metastatic origin of carcinoid tumour is important and gross and microscopic features are more accurate to this end than immunohistochemistry, except for the value of TTF-1 in pulmonary or cervical neuroendocrine tumo...

Ovarian Pathology for the Pediatric Urologist

Urology — Mon, 24 Jan 2011 00:00:00 +0100

Conclusions: At our centers, an ovarian condition is encountered an average of 1.3 times per year. As management of pediatric ovarian cysts and masses is controversial, pediatric urologists should be familiar with the diagnosis and treatment of such conditions. (Source: Urology)

Minireview: Roles of the Forkhead Transcription Factor FOXL2 in Granulosa Cell Biology and Pathology.

Endocrinology — Wed, 19 Jan 2011 00:00:00 +0100

Authors: Pisarska MD, Barlow G, Kuo FT The forkhead transcription factor (FOXL2) is an essential transcription factor in the ovary. It is important in ovarian development and a key factor in female sex determination. In addition, FOXL2 plays a significant role in the postnatal ovary and follicle maintenance. The diverse transcriptional activities of FOXL2 are likely attributable to posttranslational modifications and binding to other key proteins involved in granulosa cell function. Mutations of FOXL2 lead to disorders of ovarian function ranging from premature follicle depletion and ovarian failure to unregulated granulosa cell proliferation leading to tumor formation. Thus, FOXL2 is a key regulator of granulosa cell function and a master transcription factor in these cells. PMID:...

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Adult testicular granulosa cell tumor: a review of the literature for clinicopathologic predictors of malignancy.

Archives of Pathology and Laboratory Medicine — Sat, 01 Jan 2011 00:00:00 +0100

Authors: Hanson JA, Ambaye AB Abstract Adult testicular granulosa cell tumors are rare sex cord-stromal tumors of which only 28 have been previously reported. As compared with their ovarian counterparts, these tumors may follow a more aggressive course because the proportion of malignant cases is higher. To date, there are no clinical or pathologic features that definitively predict malignancy. We reviewed all prior case reports for features that may predict their malignant potential. Tumor size greater than 5.0 cm is the only feature statistically associated with malignancy. Mitotic count, tumor necrosis, patient age, and the presence of gynecomastia do not, at present, predict benign versus malignant behavior. PMID: 21204721 [PubMed - in process] (Source: Archives of Pathology a...

Nuclear localization of E‐cadherin but not beta‐catenin in human ovarian granulosa cell tumours and normal ovarian follicles and ovarian stroma

Histopathology — Sat, 01 Jan 2011 00:00:00 +0100

Conclusions: We have confirmed frequent nuclear localization of E‐cadherin but not beta‐catenin in human ovarian GCT, ovarian follicles and stroma. There is no evidence of misregulated Wnt/beta‐catenin signalling (represented by nuclear expression of beta‐catenin) in human ovarian GCT. Nuclear translocation of E‐cadherin might contribute to ovarian folliculogenesis or granulosa/stromal cell differentiation. (Source: Histopathology)

Standing Hand‐Assisted Laparoscopic Ovariectomy in 65 Mares

Veterinary Surgery — Thu, 23 Dec 2010 00:00:00 +0100

Conclusions: All attempts to remove the target ovary were successful. The approach is safe for the mare, as complications encountered were similar to those recently reported for other approaches. (Source: Veterinary Surgery)

Sex cord stromal tumors of the ovary in children: A clinicopathological report from the Italian TREP project

Pediatric Blood and Cancer — Wed, 15 Dec 2010 00:00:00 +0100

ConclusionsCompleteness of resection and histology were important prognostic factors; in our series the Sertoli–Leydig Cell tumor was the most aggressive variety. Hormonal signs (precocious puberty, telarca, menarche) were common in younger patients and led to an early diagnosis. Cisplatin based chemotherapy seemed to be effective for locally advanced tumors. Pediatr Blood Cancer © 2010 Wiley‐Liss, Inc. (Source: Pediatric Blood and Cancer)

Differential apoptotic activities of wild-type FOXL2 and the adult-type granulosa cell tumor-associated mutant FOXL2 (C134W)

Oncogene — Mon, 29 Nov 2010 00:00:00 +0100

Authors: J-H Kim, S Yoon, M Park, H-O Park, J-J Ko, K Lee & J Bae (Source: Oncogene)

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Two Atypical Cases of Granulosa Cell Tumours in Belgian Blue Heifers

Reproduction in Domestic Animals — Thu, 18 Nov 2010 00:00:00 +0100

ContentsThis paper describes two atypical cases of granulosa cell tumours (GCTs) in Belgian Blue heifers. In the first case, an 18‐month‐old heifer died after ovariectomy, and a granulosa‐theca cell tumour was diagnosed post‐mortem. The second heifer (31 months of age) was near term and was successfully treated surgically for a malignant granulosa cell tumour. Unfortunately, no further reproductive data are available, as the heifer was sold for slaughter. This is the first report describing GCTs in Belgian Blue beef cattle. (Source: Reproduction in Domestic Animals)

Uterine tumors resembling ovarian sex cord-stromal tumors: synchronous uterine tumors resembling ovarian sex cord-stromal tumors and ovarian sex cord tumor

Annals of Diagnostic Pathology — Tue, 16 Nov 2010 12:51:14 +0100

Abstract: Uterine tumors resembling ovarian sex cord-stromal tumors (UTROSCTs) are very rare. In this article, we present 3 cases that manifest classical histomorphological features alongside diverse immunohistochemical findings. As a distinctive finding, one of the patients had UTROSCT in the uterus and an ovarian sex cord tumor, called granulosa cell tumor, in the left ovary, simultaneously. Problems in diagnosing such pathologic condition generally arise because of the variable histologic picture of UTROSCT and may cause problems for general and other nongynecologic surgical pathologists. Immunohistochemically, these tumors express different markers that indicate their polyphenotypic origins. (Source: Annals of Diagnostic Pathology)

Vascular Endothelial Growth Factor and Its Receptor VEGFR-2 Are Highly Expressed in Ovarian Granulosa Cell Tumors.

European Journal of Endocrinology — Mon, 01 Nov 2010 00:00:00 +0100

Conclusions The results suggest an important role for VEGF and VEGFR-2 in GCT pathology and support the possibility of applying novel VEGF or VEGFR-2 targeted treatments to patients with GCT. PMID: 21041381 [PubMed - as supplied by publisher] (Source: European Journal of Endocrinology)

Isolated FSH deficiency revealing a granulosa cell tumor.

Annales d'Endocrinologie — Tue, 19 Oct 2010 23:00:00 +0100

We report a case of a 41-year-old woman with a recent secondary amenorrhea and infertility. The initial assessment ruled out premature ovarian failure, polycystic ovary syndrome and led to suspect a hypothalamo-pituitary cause. However, the unusual hormone pattern with a very low level of FSH, normal levels of LH and estradiol, associated with a positive progesterone test suggested the presence of a FSH inhibiting factor: the unexpectedly high levels of inhibin B and AMH were suggestive of a granulosa cell tumor as showed by the radiologic findings. This prompted a surgical exploration, which confirmed the putative diagnosis. This case report illustrates the inhibin B and AMH values and the modern-day pelvic imaging data encountered in menstrual irregularities caused by a granulosa cell tu...

Unusual Presentation of Granulosa Cell Tumor of the Ovary [DIAGNOSIS IN ONCOLOGY]

Journal of Clinical Oncology — Thu, 07 Oct 2010 22:02:34 +0100

(No abstract is available for this citation) (Source: Journal of Clinical Oncology)

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Extraordinarily Prolonged Disease Recurrence in a Granulosa Cell Tumor Patient

Karger Publishers — Wed, 08 Sep 2010 05:12:08 +0100

Case Rep Oncol 2010;3:310â314 (DOI:10.1159/000320740) (Source: Karger Publishers)

Sex cord-stromal tumors of the testis in children. A clinicopathologic report from the Italian TREP project

Journal of Pediatric Surgery — Tue, 31 Aug 2010 23:00:00 +0100

Conclusions: Our experience confirmed the rarity of testicular SCST. They have to be considered in the differential diagnosis of testicular solid masses, taking into account that hormonal signs are present in a minority of cases. All patients were cured with surgery alone. The sparing surgery represented a choice in selected cases. (Source: Journal of Pediatric Surgery)

Juvenile granulosa cell tumour with hepatocyte‐like cells and raised serum alpha‐fetoprotein

Histopathology — Tue, 31 Aug 2010 23:00:00 +0100

(Source: Histopathology)

Identification of a Novel Distal Control Region Upstream of the Human Steroidogenic Acute Regulatory Protein (StAR) Gene That Participates in SF-1-dependent Chromatin Architecture [Gene Regulation]

Journal of Biological Chemistry — Fri, 27 Aug 2010 13:40:49 +0100

StAR (steroidogenic acute regulatory protein) mediates the transport of cholesterol from the outer to the inner mitochondrial membrane, the process of which is the rate-limiting step for steroidogenesis. Transcriptional regulation of the proximal promoter of the human StAR gene has been well characterized, whereas analysis of its distal control region has not. Recently, we found that SF-1 (steroidogenic factor 1) induced the differentiation of mesenchymal stem cells (MSCs) into steroidogenic cells with the concomitant strong induction of StAR expression. Here, we show, using differentiated MSCs, that StAR expression is regulated by a novel distal control region. Using electrophoretic mobility shift (EMSA) and chromatin immunoprecipitation (ChIP) assays, we identified novel SF-1 binding sit...

Identification of a Novel Distal Control Region in Human StAR [Gene Regulation]

Journal of Biological Chemistry — Fri, 27 Aug 2010 13:40:49 +0100

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Menopause, hormone replacement and gynaecological cancers

Menopause International — Fri, 20 Aug 2010 22:03:49 +0100

Approximately 18,000 women are diagnosed with a gynaecological cancer in the UK each year. Predisposing risk factors for some of these gynaecological cancers include an early menarche/late menopause and hormone replacement therapy (HRT). Furthermore, treatment of gynaecological malignancies often induces an iatrogenic menopause, which may be more severe than a natural onset. HRT is an extremely effective treatment that may dramatically improve physical and psychological symptoms and ultimately quality of life in patients with cancer. However, the safety of using HRT in patients with gynaecological cancer is a controversial issue and not entirely clear. The main concern is the theoretical risk of the stimulation of residual cancer cells by estrogen replacement. The review of the evidence in...

Development of a second generation Inhibin B ELISA.

Journal of Immunological Methods — Thu, 19 Aug 2010 23:00:00 +0100

Authors: Kalra B, Kumar A, Patel K, Patel A, Khosravi MJ Inhibins are heterodimeric protein hormones secreted by the granulosa cells of the ovary in the female and the sertoli cells of the testis in the male. Published research studies have assessed Inhibin B levels in sertoli cell function, ovarian reserve and granulosa cell tumors. A two-step sandwich-type enzymatic microplate assay to measure Inhibin B levels within 3.5 hours is reported, sample pre-treatment is not required. The assay measures Inhibin B in 50 muL of serum or Li-Hep plasma sample against Inhibin B calibrators (10-1000pg/mL). The highly characterized antibody pair used in the assay measures 100% Inhibin B and no response was detected above the sensitivity of the assay with Inhibin A, Activin A, Activin B, Activin AB,...

Homologous illegitimate random integration of foreign DNA into the X chromosome of a transgenic mouse line

BMC Molecular Biology - Latest articles — Thu, 12 Aug 2010 23:00:00 +0100

Background: It is not clear how foreign DNA molecules insert into the host genome. Recently, we have produced transgenic mice to investigate the role of the fad2 gene in the conversion of oleic acid to linoleic acid. Here we describe an integration mechanism of fad2 transgene by homologous illegitimate random integration. Results: We confirmed that one fad2 line had a sole integration site on the X chromosome according to the inheritance patterns. Mapping of insertion sequences with thermal asymmetric interlaced and conventional PCR revealed that the foreign DNA was inserted into the XC1 region of the X chromosome by a homologous illegitimate replacement of an entire 45,556-bp endogenous genomic region, including the ovarian granulosa cell tumourigenesis-4 allele. For 5' and 3' junction se...

Granulosa cell tumor of the ovary and antecedent of adjuvant tamoxifen use for breast cancer

World Journal of Surgical Oncology — Wed, 11 Aug 2010 23:00:00 +0100

Conclusions: Use of tamoxifen has been found to be associated with gynecological tumors like endometrial carcinoma. Its association with granulosa cell tumor of the ovary is uncommon. Only two previous cases have been reported in literature. (Source: World Journal of Surgical Oncology)

The FOXL2 C134W mutation is characteristic of adult granulosa cell tumors of the ovary

Modern Pathology AOP — Thu, 05 Aug 2010 23:00:00 +0100

Authors: Stacey Jamieson, Ralf Butzow, Noora Andersson, Maria Alexiadis, Leila Unkila-Kallio, Markku Heikinheimo, Peter J Fuller & Mikko Anttonen (Source: Modern Pathology AOP)

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The chromosome Y-linked testis-specific protein locus TSPY1 is characteristically present in gonadoblastoma

Human Pathology — Sun, 25 Jul 2010 23:00:00 +0100

Summary: Gonadoblastoma is a rare gonadal neoplasm that occurs almost exclusively in individuals who are phenotypically females. Most cases develop in women who have an abnormal karyotype in which at least a portion of the centromeric region of the short arm of chromosome Y is present, a region often referred to as the GBY locus. Of the several genes present in the GBY locus, the TSPY1 gene (which encodes testis-specific protein, a protein thought to have a role in cell cycle regulation) appears to be the most likely to have a critical role in the pathogenesis of gonadoblastoma. To evaluate the association of TSPY1 with the tumor, we developed an interphase fluorescent in situ hybridization assay that uses probes that target the region of the GBY locus that contains TSPY1 and a commerciall...

Ovarian frozen section diagnosis: use of whole-slide imaging shows excellent correlation between virtual slide and original interpretations in a large series of cases.

Archives of Pathology and Laboratory Medicine — Wed, 30 Jun 2010 23:00:00 +0100

CONCLUSIONS: The correlation between original FS and WSI interpretations was very high. The few discordant cases represent recognized differential diagnostic issues. Ability to examine gross pathology and real-time consultation with surgeons might be expected to improve performance. Ovarian FS diagnosis by WSI is accurate and reproducible, and thus, remote interpretation, teaching, and digital archiving of ovarian FS specimens by this method can be reliable. PMID: 20586631 [PubMed - in process] (Source: Archives of Pathology and Laboratory Medicine)

Genetic evidence that SMAD2 is not required for gonadal tumor development in inhibin-deficient mice

Reproductive Biology and Endocrinology — Sun, 20 Jun 2010 23:00:00 +0100

Conclusions: SMAD2 is not required for mediating tumorigenic signals of activin in ovarian tumor development caused by loss of inhibin. (Source: Reproductive Biology and Endocrinology)

Homeobox A7 increases cell proliferation by up-regulation of epidermal growth factor receptor expression in human granulosa cells

Reproductive Biology and Endocrinology — Sun, 13 Jun 2010 23:00:00 +0100

Conclusions: Our present study reveals a novel mechanistic role for HOXA7 in modulating granulosa cell proliferation via the regulation of EGFR. This finding contributes to the knowledge of the pro-proliferation effect of HOXA7 in granulosa cell growth and differentiation. (Source: Reproductive Biology and Endocrinology)

Role of Adjuvant Radiotherapy in Granulosa Cell Tumors of the Ovary

International Journal of Radiation Oncology * Biology * Physics — Mon, 17 May 2010 00:00:00 +0100

Conclusion: Ovarian GCTs can be indolent, with patients achieving long-term survival. In our series, adjuvant RT resulted in a significantly longer DFS. Ideally, randomized trials with long-term follow-up are needed to define the role of adjuvant RT for ovarian GCTs. (Source: International Journal of Radiation Oncology * Biology * Physics)

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Granulosa cell tumours of the ovary

The Australian and New Zealand Journal of Obstetrics and Gynaecology — Tue, 04 May 2010 23:00:00 +0100

Granulosa cell tumours are rare, potentially malignant sex cord stromal tumours of the ovary. They are unique in their presentation and histological features. Many of them are hormone-producing and this property helps them to present early unlike other epithelial ovarian cancers. As a result, most of them will be in an early stage at the time of initial diagnosis. The tumour can manifest in young girls as a juvenile form and conservative management with unilateral salpingo-opherectomy may be an option in them as 95% are unilateral. Surgery is the treatment of choice and initial staging laparatomy a determinant recurrence. Advance stage of the tumour, its size (>5 cm), mitotic figures (>10/hpf), nuclear atypia and absence of call-exner bodies are poor prognostic factors. Such tumours are ch...

Solid ovarian tumours in childhood: a 35-year review in a single institution

Clinical and Translational Oncology — Thu, 29 Apr 2010 21:02:55 +0100

Conclusions Although rare, ovarian tumours must be included in the differential diagnosis of abdominal pain in childhood. Our results confirm their excellent prognosis using conservative surgery and platinum-based chemotherapy. The key point is to maintain excellent outcome while reducing associated morbidity and preserving fertility. Content Type Journal ArticleCategory Research ArticlesDOI 10.1007/s12094-010-0505-9Authors María del Mar Andrés, Hospital Universitario Infantil La Fe Paediatric Oncology Unit Avenida de Campanar, 21 ES-46009 Valencia SpainElisa Costa, Hospital Infantil La Fe Department of Paediatric Surgery Valencia SpainAdela Cañete, Hospital Universitario Infantil La Fe Paediatric Oncology Unit Avenida de Campanar, 21 ES-46009 Valencia SpainLucas...

[Review] Testicular and paratesticular tumours in the prepubertal population

The Lancet Oncology — Tue, 27 Apr 2010 23:00:00 +0100

Prepubertal testicular and paratesticular tumours are a rare group of tumours, distinct from postpubertal paediatric and adult tumours of this region. Tumours within this group are testicular germ-cell tumours (such as benign teratoma, epidermoid cyst and malignant yolk-sac tumours) and stromal tumours (such as juvenile granulosa-cell, leydig-cell, and sertoli-cell tumours). Paratesticular tumours can be benign (lipoma, leiomyoma, haemangioma) or malignant (rhabdomyosarcoma, melanotic neuroectodermal tumour of infancy). Because of their rarity, centralised pathology and treatment, and national collaborative clinical trials have been important in establishing the optimum management of malignant tumours in this group. We provide an up-to-date and comprehensive review of the clinical presenta...

Unusual Virilization in Girls with Juvenile Granulosa Cell Tumors of the Ovary Is Related to Intratumoral Aromatase Deficiency

Karger Publishers — Wed, 14 Apr 2010 23:00:00 +0100

Horm Res Paediatr (DOI:10.1159/000313396) (Source: Karger Publishers)

Cellular and molecular evidence for a role of tumor necrosis factor alpha in the ovulatory mechanism of trout

BioMed Central — Sun, 11 Apr 2010 23:00:00 +0100

Conclusions: In view of these results, we propose that TNF alpha could have an important role in the biomechanics of follicle weakening, ovarian rupture and oocyte expulsion during ovulation in trout, primarily through its stimulation of follicular cell apoptosis and the expression of genes involved in follicle wall proteolysis and contraction. (Source: BioMed Central)

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Juvenile Granulosa and Theca Cell Tumor of the Ovary as a Rare Cause of Precocious Puberty: Case Report and Review of Literature

Journal of Pediatric and Adolescent Gynecology — Sun, 04 Apr 2010 23:00:00 +0100

Conclusion: Juvenile granulosa and theca cell tumor of the ovary is a rare cause of peripheral precocious puberty, even more so than juvenile granulosa cell tumor, due to the theca component. Treatment is surgical and an excellent prognosis is possible for early stage disease. (Source: Journal of Pediatric and Adolescent Gynecology)

Granulosa cell tumor with activated mTOR-HIF-1α-VEGF pathway

Journal of Obstetrics and Gynaecology Research — Thu, 25 Mar 2010 00:00:00 +0100

The DNA-binding activity of hypoxia-inducible factor-1 [alpha] (HIF-1[alpha]) has been analyzed for various gynecological tumors. Among the tumors that were studied, there was a finding of a high level of DNA-binding HIF-1[alpha] activity, although it was limited to one case of adult type granulosa cell tumor (GCT). In this case a 60-year-old female had marked immunohistochemical expression of HIF-1[alpha]. The expressions of the mammalian target of rapamycin (mTOR) and phosphorylated-mTOR (p-mTOR) were also marked, and vascular endothelial growth factor (VEGF) was moderately expressed. To compare the expression profiles, 11 consecutive cases with adult type GCT were used. All cases showed marked expressions of HIF-1[alpha] and mTOR, but p-mTOR expression was moderately to markedly observe...

Ovarian pathology in rhesus macaques: a 12-year retrospective

Journal of Medical Primatology — Mon, 15 Mar 2010 00:00:00 +0100

Conclusions Ovarian lesions of the rhesus macaque are similar to those of cynomolgus macaques and humans. These lesions are frequently incidental findings but may impact metabolic and neurocognitive studies. (Source: Journal of Medical Primatology)

Metastatic adult granulosa cell tumor mimicking a benign pancreatic cyst

Annals of Diagnostic Pathology — Fri, 12 Feb 2010 00:00:00 +0100

We report an unusual case of metastatic adult granulosa cell tumor in the head of pancreas mimicking a benign pancreatic cyst in a 43-year-old female. Clinically, it was considered a benign cyst of the pancreas based on its appearance by imaging and that repeated fine-needle aspiration and cytologic examination of cystic fluid failed to identify malignant cells. The cyst in her pancreas grew slowly during the 15 months of close follow-up. Subsequent drainage and open biopsy of the cyst wall established the diagnosis of metastatic adult granulosa cell tumor that was confirmed in pancreaticoduodenectomy specimen. Immunohistochemical study and clinical history were critical to make the correct diagnosis and to differentiate this tumor from other more commonly encountered cystic neoplasms of t...

A Phase I Safety and Pharmacokinetic Study of the Death Receptor 5 Agonistic Antibody PRO95780 in Patients with Advanced Malignancies.

Clinical Cancer Research — Tue, 09 Feb 2010 00:00:00 +0100

CONCLUSIONS: PRO95780 is safe and well tolerated at doses up to 20 mg/kg. Evidence of activity was noted in several different tumor types at 4 and 10 mg/kg. Pharmacokinetic analysis supports a dosing regimen of 10 to 15 mg/kg every 2 to 3 weeks. Clin Cancer Res; 16(4); 1256-63. PMID: 20145186 [PubMed - as supplied by publisher] (Source: Clinical Cancer Research)

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Clinicopathological aspects and their relation to prognosis in adult-type granulosa cell tumor of the ovary

Jornal Brasileiro de Patologia e Medicina Laboratorial — Sat, 23 Jan 2010 14:50:58 +0100

CONCLUSION: ACGT generally occurs after menopause and intraoperative biopsies are commonly inconclusive. Only advanced staging was related to the worst prognosis.INTRODUÇÃO E OBJETIVO: O tumor de células da granulosa tipo adulto (TCGA) corresponde a menos de 5% das neoplasias ovarianas. São de baixo potencial de malignidade, podem recorrer depois de muitos anos, e o diferencial deve ser feito com outras neoplasias primárias ou metastáticas. Analisamos os aspectos clínicos e patológicos do tumor, relacionando-os à evolução. MÉTODOS: Na revisão de 10 anos dos arquivos do laboratório de Anatomia Patológica do Hospital das Clínicas da Universidade de Campinas (UNICAMP), 20 casos de TCGA foram encontrados. Os prontuários e as lâminas foram revisados e considerados: idade, sint...

Mutational analysis of FOXL2 codon 134 in granulosa cell tumour of ovary and other human cancers

The Journal of Pathology — Tue, 19 Jan 2010 00:00:00 +0100

A missense somatic mutation in the FOXL2 gene affecting codon 134 has recently been reported in granulosa cell tumour (GCT) and thecoma of the ovary. Such a recurrent nature of the mutation strongly suggests that the FOXL2 mutation may play an important role in the development of ovarian sex cord-stromal tumours. The aim of this study was to characterize the FOXL2 mutation in human tumour tissues. We analysed 1353 tumour tissues from various origins, including ovarian tumours and other common cancers, by single-strand conformation polymorphism analysis. We found the FOXL2 codon 134 missense mutation in 53 of 56 adult GCTs (94.6%) and two of the 16 thecomas (12.5%), but none in other tumours. Histologically, FOXL2 mutation-negative adult GCT showed that GCT cells were admixed with fibrothec...

Nearly 30 Years of Treatment for Recurrent Granulosa Cell Tumor of the Ovary:A Case Report and Review of the Literature

Karger Publishers — Tue, 12 Jan 2010 23:00:00 +0100

Case Rep Oncol 2010;3:1418 (DOI:10.1159/000274590) (Source: Karger Publishers)

Cytomorphology of adult granulosa cell tumor in ascitic fluid.

Indian Journal of Pathology and Microbiology — Fri, 01 Jan 2010 00:00:00 +0100

Authors: Azad K, Khunger JM Adult granulosa cell tumors (AGCT) are associated with ascites in 10% of the cases. Although these tumors form two per cent of all ovarian tumors, they may create a diagnostic challenge in cytologic preparations. The tumor cells are not readily shed in the fluid. A case of a 47-year-old woman with presence of granulosa tumor cells in ascitic fluid is presented. Because of its rarity, AGCTs can be confused with other ovarian tumors. PMID: 20090239 [PubMed - in process] (Source: Indian Journal of Pathology and Microbiology)

Pediatric ovarian malignancy presenting as ovarian torsion: incidence and relevance

Journal of Pediatric Surgery — Thu, 31 Dec 2009 15:18:28 +0100

Conclusion: By combining our series with 13 in the literature, a 1.8% malignancy rate occurred in 707 patients with ovarian torsion, markedly less than the reported malignancy rate of 10% in children with ovarian masses. Thus, neither a pathologic nor malignant lead point should be assumed in cases of torsion. In our series, which represents the largest series of torsion in the pediatric literature, all malignancies presented as stage I. These data further support the implementation of operative detorsion and close postoperative ovarian surveillance, with reoperation for persistent masses. Further study is needed to determine if delaying resection by weeks in those cases of persistent masses would result in tumor progression and thus change prognosis. (Source: Journal of Pediatric Surgery)

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A Mouse Surgical Model for Metastatic Ovarian Granulosa Cell Tumor.

Comparative Medicine — Sun, 27 Dec 2009 10:56:02 +0100

Authors: Nadeau ME, Kaartinen MJ, Laguë MN, Paquet M, Huneault LM, Boerboom D We recently described a genetically engineered mouse model that develops ovarian granulosa cell tumors (GCTs) that mimic many aspects of the advanced human disease, including distant dissemination. However, because the primary tumors killed their hosts before metastases were able to form, the use of these mice to study metastatic disease required the development of a simple, reliable, and humane surgical protocol for the excision of large GCTs from debilitated mice. Here we describe a protocol involving multimodal anesthesia, tumor removal through ventral midline celiotomy and perioperative fluid therapy, and analgesia that led to the postoperative survival of more than 90% of mice, despite the removal o...

The histology and management of ovarian cysts found in children and adolescents presenting to a children's hospital from 1991 to 2007: a call for more paediatric gynaecologists.

BJOG : An International Journal of Obstetrics and Gynaecology — Sat, 19 Dec 2009 01:38:37 +0100

Conclusions We recommend the greater use of imaging of the pelvis and tumour markers preoperatively. There should be greater use of conservative expectant management or ovarian-sparing surgery in view of the low risk of malignancy in this age group. The practice of removing ovaries for benign cysts may be overcome by appointing more gynaecologists with advanced training skills training in paediatric and adolescent gynaecology. PMID: 20002396 [PubMed - in process] (Source: BJOG : An International Journal of Obstetrics and Gynaecology)

Adult-Type Granulosa Cell Tumors and FOXL2 Mutation

Cancer Research — Tue, 15 Dec 2009 05:07:47 +0100

Little is known about the pathogenesis of ovarian granulosa cell tumors. Recently, we reported the identification of a somatic FOXL2 402C->G mutation that is present in virtually all adult-type granulosa cell tumors, but not in a wide range of other tumor types. This finding has important implications for the diagnosis and classification of ovarian sex cord-stromal tumors, provides insight into the pathogenesis of adult-type granulosa cell tumors, and opens possibilities for the development of targeted therapies. [Cancer Res 2009;69(24):9160–2] (Source: Cancer Research)

FOXL2 Mutation Associated With Adult Ovarian Granulosa Cell Tumors

Medscape Ob/Gyn & Women's Health Headlines — Wed, 11 Nov 2009 21:07:04 +0100

Dr. Maurie Markman comments on a study published in The New England Journal of Medicine highlighting the role of a mutation in FOXL2 in the development and/or progression of granulosa cell tumors. Medscape Genomic Medicine (Source: Medscape Ob/Gyn & Women's Health Headlines)

WNT signaling in ovarian follicle biology and tumorigenesis.

Trends in Endocrinology and Metabolism: TEM — Tue, 27 Oct 2009 00:00:00 +0100

Authors: Boyer A, Goff AK, Boerboom D The WNTS are an expansive family of glycoprotein signaling molecules known mostly for the roles they play in embryonic development. WNT signaling first caught the attention of ovarian biologists when it was reported that the inactivation of Wnt4 in mice results in partial female-to-male sex reversal and oocyte depletion. More recently, studies using loss- and gain-of-function transgenic mouse models demonstrated the requirement for Wnt4, Fzd4 and Ctnnb1, components of the WNT pathway, for normal folliculogenesis, luteogenesis and steroidogenesis, and showed that dysregulated WNT signaling can cause granulosa cell tumor development. This review covers our current knowledge of WNT signaling in ovarian follicles, highlighting both the great promise an...

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Alterations of the pituitary-ovarian axis in dogs with a functional granulosa cell tumor

Theriogenology — Mon, 12 Oct 2009 00:00:00 +0100

Abstract: Information on the pituitary-ovarian axis in dogs with a granulosa cell tumor (GCT) is lacking. Therefore, we investigated the plasma concentrations of luteinizing hormone (LH) and estradiol before and after gonadotropin-releasing hormone (GnRH) administration in seven bitches with a functional GCT (GCT-total), of which three were intact (GCT-intact) and four had remnant ovarian tissue (GCT-ROT). The results of the GnRH stimulation test were compared with those in six anestrous and six ovariectomized bitches. The most noteworthy results were as follows. The basal plasma LH concentrations of the GCT-ROT bitches were higher (P (Source: Theriogenology)

Smad1-Smad5 Ovarian Conditional Knockout Mice Develop a Disease Profile Similar to the Juvenile Form of Human Granulosa Cell Tumors.

Endocrinology — Thu, 08 Oct 2009 23:00:00 +0100

Authors: Middlebrook BS, Eldin K, Li X, Shivasankaran S, Pangas SA Granulosa cell tumors (GCTs) of the ovary are rare sex cord stromal tumors. Although generally indolent, GCTs recur, and if not diagnosed and treated in early stages, survival rates are significantly shortened. Very little is known regarding GCT etiology. Because of the low incidence of cases and lack of standard diagnostics, mouse models for granulosa cell tumors are a valuable tool for studying GCTs and provide models for developing diagnostic and treatment strategies. We recently developed a novel mouse model of metastatic granulosa cell tumors by genetic deletion of the bone morphogenetic protein signaling transcription factors (SMADs) in granulosa cells of the ovary. Histological and serum hormone analyses reveal t...

Mono-(2-ethylhexyl) phthalate induces NR4A subfamily and GIOT-1 gene expression, and suppresses CYP19 expression in human granulosa-like tumor cell line KGN.

Toxicology Letters — Thu, 08 Oct 2009 23:00:00 +0100

Authors: Ohno S, Yukinawa F, Noda M, Nakajin S The mechanism for transcriptional suppression of CYP19 by mono-ethylhexyl phthalate (MEHP) in a human ovarian granulosa cell-line (KGN) was investigated. It is known that the CYP19 gene transcript in KGN cells predominantly includes exon PII among the 11 alternate exon I sequences. MEHP was found to significantly suppress Forskolin (FSK)-induced CYP19 gene transcription, CYP19 promoter II activity and CYP19 enzyme activity in a dose-dependent manner. Promoter assays using 5'-deleted promoter II reporter constructs suggested that the region important for responsiveness to MEHP exposure includes a putative CRE-like sequence and an SF-1 (NR5A1)/LRH-1 (NR5A2) binding sequence. Meanwhile, MEHP exposure rapidly and transiently induced nuclear re...

Unusual and late recurrences in ovarian adult granulosa cell tumours.

Annals of the Academy of Medicine, Singapore — Thu, 01 Oct 2009 00:00:00 +0100

Authors: Kaluarachchi A, Marasinghe JP PMID: 19890588 [PubMed - in process] (Source: Annals of the Academy of Medicine, Singapore)

Estrogen-induced myelotoxicity in dogs: A review.

The Canadian Veterinary Journal — Thu, 01 Oct 2009 00:00:00 +0100

Authors: Sontas HB, Dokuzeylu B, Turna O, Ekici H Exogenous estrogens used for therapeutic purposes or endogenous estrogen sources such as functional Sertoli cell or ovarian granulosa cell tumors may cause bone marrow toxicity in dogs. The condition is characterized by hematologic abnormalities including thrombocytopenia, anemia, and leukocytosis or leukopenia. Despite intensive therapy with blood or platelet-rich transfusions, broad-spectrum antibiotics, steroids, and bone marrow stimulants, prognosis is unfavorable. Due to the the risk of stimulating the development of uterine diseases and the potential for inducing aplastic anemia, estrogen use in dogs is best avoided where possible. This paper describes the causes of estrogen-induced myelotoxicity, the clinical presentation of the ...

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Granulosa cell tumor arising in an ovary with mature teratoma.

Indian Journal of Pathology and Microbiology — Wed, 30 Sep 2009 23:00:00 +0100

We report a case of GCT and mature teratoma occurring synchronously in the same ovary in a perimenopausal woman. PMID: 19805973 [PubMed - in process] (Source: Indian Journal of Pathology and Microbiology)

Ovarian cancer mouse models: A summary of current models and their limitations

Journal of Ovarian Research — Sun, 27 Sep 2009 23:00:00 +0100

Development of mouse models representing human spontaneous ovarian cancer has been hampered by the lack of understanding of the etiology of this very complex disease. Mouse models representing the different types of ovarian cancer are needed to understand how epithelial ovarian cancer differs from granulosa cell tumors. Many different methods have been used to generate a viable genetic model with limited success. This review focuses on the methods of various investigators and the limitations of each model in establishing a reproducible and inheritable line to study this disease. (Source: Journal of Ovarian Research)

Spontaneous pathology of the baboon endocrine system

Journal of Medical Primatology — Sun, 27 Sep 2009 23:00:00 +0100

Conclusions Endocrine disease in baboons is common and shares clinical and biochemical characteristics with endocrine disease in humans. (Source: Journal of Medical Primatology)

Cell Type-Specific Targeted Mutations of Kras and Pten Document Proliferation Arrest in Granulosa Cells versus Oncogenic Insult to Ovarian Surface Epithelial Cells

Cancer Research — Tue, 11 Aug 2009 23:00:00 +0100

The small G-protein KRAS is crucial for mediating gonadotropin-induced events associated with ovulation. However, constitutive expression of KrasG12D in granulosa cells disrupted normal follicle development leading to the persistence of abnormal follicle-like structures containing nonmitotic cells. To determine what factors mediate this potent effect of KrasG12D, gene profiling analyses were done. We also analyzed KrasG12D;Cyp19-Cre and KrasG12;Pgr-Cre mutant mouse models that express Cre prior to or after the initiation of granulosa cell differentiation, respectively. KrasG12D induced cell cycle arrest in granulosa cells of the KrasG12D;Cyp19-Cre mice but not in the KrasG12D;Pgr-Cre mice, documenting the cell context–specific effect of KrasG12D. Expression of KrasG12D silenced the K...

Loss of inhibin alpha uncouples oocyte-granulosa dynamics and disrupts postnatal folliculogenesis.

Developmental Biology — Thu, 06 Aug 2009 23:00:00 +0100

Authors: Myers M, Middlebrook BS, Matzuk MM, Pangas SA Targeted disruption of the inhibin alpha gene (Inha(-/-)) in mice results in an ovarian phenotype of granulosa cell tumors that renders the animals infertile. Little is known about the reproductive defects prior to tumor development. Here, we report novel data on early follicle dynamics in Inha(-/-)mice, which demonstrate that inhibin alpha has important consequences upon follicle development. Morphological changes in both germ and somatic cells were evident in postnatal day 12 ovaries, with Inha(-/-)mice exhibiting numerous multilayered follicles that were far more advanced than those observed in age-matched controls. These changes were accompanied by alterations in follicle dynamics such that Inha(-/-)ovaries had fewer follicles ...

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Ovarian Aging in Squirrel Monkeys (Saimiri sciureus).

Reproduction — Tue, 04 Aug 2009 23:00:00 +0100

Authors: Walker M, Anderson D, Herndon J, Walker L In female squirrel monkeys (Saimiri sciureus), the reproductive period normally extends from around 2.5 years to the mid-teens. In the present study we examined the age-associated cytological changes in the ovaries of 24 squirrel monkeys ranging in age from newborn to approximately 20 years. We found a significant, age-related decline in the number of primordial follicles, with the most pronounced loss occurring between birth and 5 years. After around 8 years of age, relatively few primordial follicles were evident in the ovarian sections examined. An unusual feature of the aging squirrel monkey ovary is the emergence of highly differentiated, encapsulated clusters of granulosa cells that increase in size and number, particularly after...

Testicular granulosa cell tumors: rare tumors need to be studied too.

Oncology (Williston Park, N.Y.) — Fri, 31 Jul 2009 23:00:00 +0100

Authors: Bosl GJ PMID: 19777767 [PubMed - in process] (Source: Oncology (Williston Park, N.Y.))

Response to antiangiogenesis therapy in a patient with advanced adult-type testicular granulosa cell tumor.

Oncology (Williston Park, N.Y.) — Fri, 31 Jul 2009 23:00:00 +0100

We report the case of an advanced granulosa cell tumor of the testis with a confirmed partial response to an angiogenesis inhibitor after initial resistance to cytotoxic chemotherapy. PMID: 19777766 [PubMed - in process] (Source: Oncology (Williston Park, N.Y.))

Mutant FOXL2 may be involved in pathogenesis of ovarian granulosa-cell tumors

MedWire News - Ob/Gyn — Tue, 07 Jul 2009 11:17:51 +0100

Study results show that recurrent somatic mutations in the winged helix/forkhead transcription factor gene are present in 97 percent of adult-type granulosa-cell tumors. (Source: MedWire News - Ob/Gyn)

Juvenile Granulosa Cell Ovarian Tumor: A Case Report and Review of Literature

Journal of Pediatric and Adolescent Gynecology — Sun, 05 Jul 2009 23:00:00 +0100

Conclusion: Survival rates are >95% among patients diagnosed under 10 years of age. Tumor recurrence is rare but can occur as late as 48 months. Therefore, tumor surveillance is warranted for patients with even a Stage IA JGCT and involves monitoring serial inhibin B levels along with intermittent imaging. (Source: Journal of Pediatric and Adolescent Gynecology)

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Three-month-old Boy With Juvenile Granulosa Cell Tumor of Testis and Ossifying Renal Tumor of Infancy

Urology — Wed, 01 Jul 2009 23:00:00 +0100

We describe a 3-month-old male infant who presented with gross hematuria and was found to have a renal mass and a testicular mass representing these two entities. This is the first case report of these two lesions presenting concomitantly. (Source: Urology)

ORIGINAL ARTICLE: Mutation of FOXL2 in Granulosa-Cell Tumors of the Ovary

New England Journal of Medicine — Tue, 23 Jun 2009 23:00:00 +0100

Somatically acquired mutations, which contribute to tumorigenesis, are usually specific to tumor tissue. Sequencing of the whole transcriptome -- the entire set of messenger RNAs -- in ovarian granulosa-cell tumors implicated a somatic mutation in FOXL2 in a large majority of the tumors that were analyzed. (Source: New England Journal of Medicine)

Discovery of Genetic Mutation May Improve Diagnosis and Treatment of Granulosa-Cell Ovarian Tumors

Medscape Medical News Headlines — Fri, 12 Jun 2009 12:21:06 +0100

Accurate diagnosis of granulosa-cell tumors in the ovaries can be problematic, but the discovery of a new mutation might make it easier and could spur the development of new treatments. Medscape Medical News (Source: Medscape Medical News Headlines)

The Spelling Mistake In The Genetic Code That Causes A Type Of Ovarian Cancer

Health News from Medical News Today — Fri, 12 Jun 2009 10:00:00 +0100

Eureka! Vancouver scientists from the Ovarian Cancer Research (OvCaRe) Program at BC Cancer Agency and Vancouver Coastal Health Research Institute have discovered that there appears to be a single spelling mistake in the genetic code of granulosa cell tumours, a rare and often untreatable form of ovarian cancer. (Source: Health News from Medical News Today)

Found: 1 in 3 billion

EurekAlert! - Cancer — Wed, 10 Jun 2009 04:00:00 +0100

(University of British Columbia) Vancouver scientists from the Ovarian Cancer Research (OvCaRe) Program at BC Cancer Agency and Vancouver Coastal Health Research Institute have discovered that there appears to be a single spelling mistake in the genetic code of granulosa cell tumors, a rare and often untreatable form of ovarian cancer. The discovery marks the beginning of a new era of cancer genomics. (Source: EurekAlert! - Cancer)

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No Activating Mutations of FSH Receptor in Four Children with Ovarian Juvenile Granulosa Cell Tumors and the Association of These Tumors with Central Precocious Puberty

Journal of Pediatric and Adolescent Gynecology — Sun, 31 May 2009 23:00:00 +0100

Conclusions: We did not find any activating mutation in exon 10 of the FSHR in our patients, and one patient developed precocious puberty after removal of her tumor. The development of ovarian tumors in these patients may have been caused by mutations at other exons of the FSHR and G protein subunits, so the association noted between central precocious puberty and granulosa cell tumors might not be coincidental. (Source: Journal of Pediatric and Adolescent Gynecology)

Association of luteinizing hormone receptor gene expression with cell cycle progression in granulosa cells

AJP: Endocrinology and Metabolism — Mon, 25 May 2009 04:00:00 +0100

During hormonally induced ovarian follicle growth, granulosa cell proliferation increases and returns to baseline prior to the administration of an ovulatory stimulus. Several key genes appear to follow a similar pattern, including the luteinizing hormone receptor (LHCGR), suggesting an association between cell cycle progression and gene expression. The expression of LHCGR mRNA in granulosa cells isolated from immature rats and treated in culture with FSH increased in a time-dependent manner, whereas administration of the cell cycle inhibitor mimosine completely suppressed expression. Although forskolin was able to induce luteinization in cells treated with mimosine, human chorionic gonadotropin had no effect, indicating the functional loss of LHCGR. The effects of mimosine on cell cycle p...

[Epidemiology and pathological profile of childhood ovary tumours in Togo: about 32 cases.]

Bulletin du Cancer — Tue, 19 May 2009 23:00:00 +0100

ConclusionThe childhood ovary tumours although rare, exist in Togo dominated by Burkitt lymphoma. PMID: 19457758 [PubMed - as supplied by publisher] (Source: Bulletin du Cancer)

Dysregulation of WNT/CTNNB1 and PI3K/AKT signaling in testicular stromal cells causes granulosa cell tumor of the testis

Carcinogenesis — Thu, 30 Apr 2009 04:00:00 +0100

Synergistic effects of dysregulation of the WNT/CTNNB1 and phosphatidylinositol 3-kinase (PI3K)/AKT pathways are thought to be important for the development and progression of many forms of cancer, including the granulosa cell tumor of the ovary. Sustained WNT/CTNNB1 signaling in Sertoli cells causes testicular degeneration and the formation of foci of poorly differentiated stromal cells in the seminiferous tubules in mice. To test if concomitant dysregulation of the WNT/CTNNB1 and PI3K/AKT pathways could synergize to cause testicular cancer, Ptentm1Hwu/tm1Hwu;Ctnnb1tm1Mmt/+;Amhr2tm3(cre)Bhr/+ mice that express a dominant, stable CTNNB1 mutant and lack the expression of phosphatase and tensin homolog (PTEN) in their Sertoli cells were generated. These mice developed aggressive testicular c...

Secondary Amenorrhea with Low Serum Luteinizing Hormone and Follicle-stimulating Hormone Caused by an Inhibin A- and Inhibin B-producing Granulosa Cell Tumor

Taiwanese Journal of Obstetrics and Gynecology — Mon, 06 Apr 2009 15:21:06 +0100

Objective: Here, we report a case of secondary amenorrhea with low serum luteinizing hormone and follicle-stimulating hormone levels due to an inhibin A- and inhibin B-producing granulosa cell tumor of the ovary. Case Report: A woman aged 26 ...more (Source: Taiwanese Journal of Obstetrics and Gynecology)

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Extraovarian granulosa cell tumor.

Indian Journal of Pathology and Microbiology — Wed, 01 Apr 2009 04:00:00 +0100

Authors: Paul PC, Chakraborty J, Chakrabarti S, Chattopadhyay B Extraovarian granulosa cell tumor (GCT) is a very uncommon tumor, assumed to arise from the ectopic gonadal tissue along the embryonal route of the genital ridge. One such rare case of extraovarian GCT was encountered in a 58-year-old female who presented with a large intraabdominal lump. Computerized tomography revealed one large retroperitoneal mass measuring 15 cm x 16 cm and another mesenteric mass of 8 cm x 5 cm size. The patient had a history of hysterectomy with bilateral salpingooophorectomy 20 years ago for uterine leiomyoma. Ultrasonography-guided aspiration smears revealed cytological features suggestive of GCT. Histopathological examination of the excised masses showed features of adult-type GCT. Because metast...

Adult granulosa cell tumor: Findings for MR imaging assessment and correlation with pathological data

European Journal of Radiology Extra — Wed, 01 Apr 2009 04:00:00 +0100

Abstract: Adult granulosa cell tumors were initially assessed by MR imaging in two women, age 31 and 34 years; radiologic–pathological correlation was performed thereafter. These sex-cord stromal tumors consist of a solid multinodular non-necrotic mass with fibrous septas and external wall surrounding granulosa cells islets, in which few small central and peripheral cysts are present. Some cysts are hemorrhagic, and parenchymal vasculature is poor. MR imaging is effective in our experience to assess this type of tumor prior to histological confirmation. (Source: European Journal of Radiology Extra)

Compilation of classical and contemporary terminology used to describe morphological aspects of ovarian dynamics in cattle.

Theriogenology — Mon, 30 Mar 2009 04:00:00 +0100

Authors: Peter AT, Levine H, Drost M, Bergfelt DR Veterinarians and scientists involved in applied and basic research in cattle require a lexicon of terms that is used uniformly so that diagnoses and inference of results between and among studies can be correctly interpreted and substantiated or negated and therapy and hypotheses can be formulated without unnecessary confusion and redundancy in treatments and experiments. This review provides a compilation of many of the classical and contemporary terms used in association with ovarian dynamics primarily during the estrous cycle in cattle, which can also apply to other reproductive states. While many classical terms used to describe healthy and diseased conditions associated with follicles and corpora lutea are still applicable today, ...

Isolated breast metastasis from granulosa cell tumor of the ovary

Archives of Gynecology and Obstetrics — Sat, 21 Mar 2009 08:54:25 +0100

We present such a case of ovarian granulosa cell tumor with metastasis to the breast, which was the presenting symptom. The patient was treated with total abdominal hysterectomy and bilateral salpingo-oophorectomy which was followed by chemotherapy. The patient is relapse free 2 years after completion of treatment. Content Type Journal ArticleCategory Case ReportDOI 10.1007/s00404-009-1025-0Authors Ashok Chauhan, Post Graduate Institute of Medical Sciences Department of Radiotherapy Rohtak IndiaPushpa Dahiya, Post Graduate Institute of Medical Sciences Department of Obstetrics and Gynaecology Rohtak IndiaHarmeet Singh, Post Graduate Institute of Medical Sciences Department of Radiotherapy Rohtak IndiaMeenu Gill, Post Graduate Institute of Medical Sciences Department of Patholog...

Review Articles: Pathogenesis and Diagnostic Significance of Nuclear Grooves in Thyroid and Other Sites

International Journal of Surgical Pathology — Wed, 18 Mar 2009 04:00:00 +0100

Nuclear grooves are longitudinal invaginations of the nuclear envelope bilayer, which constitute a characteristic feature of papillary thyroid carcinoma. Their pathogenesis is not yet clear, but there is evidence for the involvement of a signaling pathway downstream of the protooncogene RET. The presence of nuclear grooves is not specific for papillary thyroid carcinoma because it has been documented in other types of thyroid neoplasms, in nonneoplastic thyroid lesions, in ovarian neoplasms (Brenner, adult granulosa cell, and transitional cell tumors), in breast carcinomas, in cervicovaginal and endometrial smears, in papillary neoplasms of several organs (such as papillary transitional cell carcinoma of the bladder, papillary renal cell carcinoma, papillary endometrioid carcinoma of the p...

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Association of Luteinizing Hormone Receptor Gene Expression with Cell Cycle Progression in Granulosa Cells.

Am J Physiol Endocri... — Tue, 17 Mar 2009 04:00:00 +0100

Authors: Cannon JD, Seekallu S, Vandevoort CA, Chaffin CL During hormonally-induced ovarian follicle growth, granulosa cell proliferation increases and returns to baseline prior to the administration of an ovulatory stimulus. Several key genes appear to follow a similar pattern, including the luteinizing hormone receptor (LHCGR), suggesting an association between cell cycle progression and gene expression. The expression of LHCGR mRNA in granulosa cells isolated from immature rats and treated in culture with FSH increased in a time-dependent manner, while administration of the cell cycle inhibitor mimosine completely suppressed expression. While forskolin was able to induce luteinization in cells treated with mimosine, hCG had no effect, indicating the functional loss of LHCGR. The eff...

TRAIL pathway components and their putative role in granulosa cell apoptosis in the human ovary.

Differentiation — Sun, 15 Mar 2009 13:52:46 +0100

Authors: Jääskeläinen M, Kyrönlahti A, Anttonen M, Nishi Y, Yanase T, Secchiero P, Zauli G, Tapanainen JS, Heikinheimo M, Vaskivuo TE Extensive apoptotic oocyte reduction occurs during fetal ovarian development. The regulatory pathways responsible for oocyte selection to programmed cell death are, however, poorly understood. The aim of this study was to investigate the potential involvement of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and its death receptors TRAIL-R1/DR4 and TRAIL-R2/DR5 and decoy receptors TRAIL-R3/DcR1 and TRAIL-R4/DcR2 in the apoptotic process characterizing human fetal and adult ovaries. For this purpose, in situ hybridization and immunohistochemistry were applied to human fetal and adult ovarian samples to study the mRNA a...

Virilization persists in a woman with an androgen-secreting granulosa cell tumor

Fertility and Sterility — Sun, 01 Mar 2009 05:00:00 +0100

Conclusion(s): Adult-type GC tumor is an extremely rare cause of virilization. Masculinization features may persist in the absence of high androgen levels. (Source: Fertility and Sterility)

Secondary amenorrhea with low serum luteinizing hormone and follicle-stimulating hormone caused by an inhibin A- and inhibin B-producing granulosa cell tumor.

Taiwanese Journal of Obstetrics and Gynecology — Sun, 01 Mar 2009 05:00:00 +0100

CONCLUSION: A granulosa cell tumor secretes inhibin A and B, which suppress follicle-stimulating hormone and luteinizing hormone release through a central mechanism. This leads to amenorrhea, which can be misdiagnosed as hypothalamic amenorrhea. Inhibin producing ovarian tumors must be considered in the assessment of patients with apparent hypothalamic amenorrhea. PMID: 19346197 [PubMed - in process] (Source: Taiwanese Journal of Obstetrics and Gynecology)

Juvenile granulosa cell tumor of the ovary presenting with pleural effusion and ascites

International Journal of Clinical Oncology — Thu, 19 Feb 2009 14:58:34 +0100

We report this rare tumor with an aim of reviewing the diagnosis and management from the reported literature. Content Type Journal ArticleCategory Case ReportDOI 10.1007/s10147-008-0805-zAuthors Harpreet Kaur, Post Graduate Institute of Medical Education and Research (PGIMER) Department of Obstetrics and Gynaecology Sector-12 Chandigarh 160012 IndiaRashmi Bagga, Post Graduate Institute of Medical Education and Research (PGIMER) Department of Obstetrics and Gynaecology Sector-12 Chandigarh 160012 IndiaSubhash Chandra Saha, Post Graduate Institute of Medical Education and Research (PGIMER) Department of Obstetrics and Gynaecology Sector-12 Chandigarh 160012 IndiaShalini Gainder, Post Graduate Institute of Medical Education and Research (PGIMER) Department of Obstetrics and Gynaecology ...

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[Juvenile granulosa-cell tumor: Clinical and molecular expression.]

Gynecologie, Obstetrique & Fertilite — Tue, 30 Dec 2008 05:00:00 +0100

Authors: Kalfa N, Philibert P, Patte C, Thibaud E, Pienkowski C, Ecochard A, Boizet-Bonhoure B, Fellous M, Sultan C Ovarian sex cord-stromal tumors are rare tumors that originate from the nongerminal cells of ovary. Two decades ago, the identification of juvenile granulosa-cell tumors (GCT), as a specific entity inside this group, allowed a better treatment of these tumors in children. However, little data have been reported on the natural course of the disease and reliable prognostic factors have not been yet defined. We here review the clinical and genetics aspects of granulosa tumors, based on a series of 40 children. This national collaborative study involved the French Society of Children Cancer and eight clinical departments of pediatric endocrinology. We found that early diagnos...

Neonatal bilateral ovarian sex cord stromal tumors

Pediatric Blood and Cancer — Thu, 04 Dec 2008 05:00:00 +0100

A child was referred for evaluation after prenatal diagnosis with macrosomia, clitoromegaly, labial hypertrophy, and a left ovarian cyst. The karyotype was 46,XX. The postnatal pelvic ultrasound was normal. High levels of anti-mullerian hormone and testosterone led to a hCG stimulation test, which was followed by isosexual precocious puberty and the appearance of a bilateral ovarian enlargement with a left tumoral mass. A left ovarian tumorectomy revealed a fibrothecoma. Six weeks later, a tumoral relapse occurred and completion of oophorectomy revealed a juvenile granulosa cell tumor (JGCT). Whereas hormonal levels decreased after surgery, a new rise associated with an enlargement of the right ovary led to the diagnosis of right JGCT. A right oophorectomy was proposed to the parents, who ...

Spontaneous transformation of human granulosa cell tumours into an aggressive phenotype: a metastasis model cell line

BMC Cancer — Tue, 04 Nov 2008 05:00:00 +0100

Conclusion: KGN cells cultured in vitro acquire an aggressive phenotype, which was confirmed by the analysis of cellular activities and the expression of biomarkers. Interestingly, KGN cells injected s.c. are metastatic with nodule formation occurring mostly in the bowel. Thus, this cell line is a good model for analysing GCT progression and the mechanism of metastasis in vivo. (Source: BMC Cancer)

Synergistic effects of Pten loss and WNT/CTNNB1 signaling pathway activation in ovarian granulosa cell tumor development and progression

Carcinogenesis — Fri, 31 Oct 2008 04:00:00 +0100

The mechanisms of granulosa cell tumor (GCT) development may involve the dysregulation of signaling pathways downstream of follicle-stimulating hormone, including the phosphoinosite-3 kinase (PI3K)/AKT pathway. To test this hypothesis, a genetically engineered mouse model was created to derepress the PI3K/AKT pathway in granulosa cells by conditional targeting of the PI3K antagonist gene Pten (Ptenflox/flox;Amhr2cre/+). The majority of Ptenflox/flox;Amhr2cre/+ mice featured no ovarian anomalies, but occasionally (~7%) developed aggressive, anaplastic GCT with pulmonary metastases. The expression of the PI3K/AKT downstream effector FOXO1 was abrogated in Ptenflox/flox;Amhr2cre/+ GCT, indicating a mechanism by which GCT cells may increase proliferation and evade apoptosis. To relate these fi...

Investigating differentiation mechanisms of the constituent cells of sex cord-stromal tumours of the ovary

Virchows Archiv — Wed, 01 Oct 2008 09:19:20 +0100

Abstract SOX-9, an essential factor for male sexual development, can be induced by prostaglandin D2 in a Sry-independent mechanism. Recent data suggest that the hedgehog pathway is involved in the differentiation of normal Sertoli and Leydig cells. The purpose of our study was to investigate the mechanisms involved in the differentiation of ovarian sex cord-stromal tumour (SCST) cells. Two Sertoli–Leydig cell tumours and two granulosa cell tumours with a minor Sertoli element were studied using immunohistochemistry on paraffin-embedded tissue sections. Sertoli cells expressed anti-Mullerian hormone (AMH), SOX-9, prostaglandin D synthase (Pgds) and bcl-2 (in four of four cases); sonic hedgehog (Shh) and p53 (in three of four cases) and androgen receptors (AR; in one of fo...

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Granulosa Cell Tumor of the Ovary: Tumor Review

Integrative Cancer Therapies — Tue, 23 Sep 2008 04:00:00 +0100

Granulosa cell tumors of the ovary are rare neoplasms that originate from sex-cord stromal cells. The long natural history of granulosa cell tumors and their tendency to recur years after the initial diagnosis are the most prominent of their characteristics. The secretion of estradiol is the reason for signs at presentation such as vaginal bleeding and precocious puberty. Abdominal pain and hemoperitoneum, which occasionally can occur, are attributable to tumor rupture. The most common finding in pelvic examination is a tumor mass, which is subsequently confirmed with imaging techniques. Surgery is the mainstay of initial management for histological diagnosis, appropriate staging, and debulking. A more conservative unilateral salpingo-oophorectomy is indicated in patients with stage I dise...

Analysis of selected oncogenes (AKT1, FOS, BCL2L2, TGFbeta) on chromosome 14 in granulosa cell tumors (GCTs): A comprehensive study on 30 GCTs combining comparative genomic hybridization (CGH) and fluorescence-in situ-hybridization (FISH).

Pathology, Research and Practice — Fri, 05 Sep 2008 04:00:00 +0100

Authors: Mayr D, Hirschmann A, Marlow S, Horvath C, Diebold J In previous studies, we have demonstrated a number of cytogenetic alterations in granulosa cell tumors (GCTs), especially on chromosomes X, 12, 14, and 22. However, little is known about specific loci on 14q, which could play an important role in tumor pathology. Therefore, we assessed four important genes in 30 GCTs using fluorescence-in situ-hybridization (FISH). Comparative genomic hybridization (CGH) was performed on paraffin-embedded material. Then, we applied FISH with gene-specific DNA probes for AKT1 (14q32.32), FOS (14q24.3), BCL2L2 (14q11.2-q12), and TGFbeta3 (14q24), and tried to find a correlation between CGH, FISH, tumor stage, and survival. In CGH, 7 of 30 cases (23.3%) showed complete gains on chromosome 14. F...

The use of bevacizumab in refractory ovarian granulosa-cell carcinoma with symptomatic relief of ascites: A case report.

Gynecologic Oncology — Sat, 16 Aug 2008 04:00:00 +0100

CONCLUSION: Bevacizumab may have a role in the management of malignant ascites in the patient with refractory granulosa-cell carcinoma of the ovary which should be confirmed in a larger series of well selected patients. PMID: 18710781 [PubMed - as supplied by publisher] (Source: Gynecologic Oncology)

Regulation of bovine tumor necrosis factor alpha induced protein 6 in ovarian follicles during the ovulatory process and promoter activation in granulosa cells.

Endocrinology — Thu, 07 Aug 2008 04:00:00 +0100

Authors: Sayasith K, Bouchard N, Doré M, Sirois J To study the regulation of bovine tumor necrosis factor alpha induced protein 6 (TNFAIP6) prior to ovulation, preovulatory follicles obtained after the treatment with human chorionic gonadotropin (hCG) were used. RT-PCR analyses showed that levels of TNFAIP6 mRNA were low before hCG, but significant increased after hCG treatment in follicles. Further analyses and immunohistochemistry indicated that this increase in transcript and protein levels occurred in theca and granulosa cells. To investigate molecular mechanisms involved in TNFAIP6 transactivation, the activity of bovine TNFAIP6 promoter was studied in granulosa cell cultures. Mutant studies identified the minimal region conferring full-length promoter activity, in which AP1 ...

Management of granulosa cell tumour of the ovary.

Current Opinion in Oncology — Wed, 06 Aug 2008 09:48:59 +0100

Page: 560DOI: 10.1097/CCO.0b013e328306316fAuthors: Jamieson, Stacey; Fuller, Peter J (Source: Current Opinion in Oncology)

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[Editorials] Prognostic factors in ovarian adult granulosa cell tumour

Journal of Clinical Pathology — Mon, 28 Jul 2008 04:00:00 +0100

(Source: Journal of Clinical Pathology)

[Original articles] Prognostic value of mitotic counts and Ki-67 immunoreactivity in adult-type granulosa cell tumour of the ovary

Journal of Clinical Pathology — Mon, 28 Jul 2008 04:00:00 +0100

Conclusions: These results suggest that proliferation assessment is of limited value in the pathological assessment of GCT. Future studies should carefully specify the methods of assessing cell proliferation to ensure a reliable comparison of results. (Source: Journal of Clinical Pathology)

Expression of CD56 isoforms in primary and relapsed adult granulosa cell tumors of the ovary

BioMed Central — Wed, 09 Jul 2008 04:00:00 +0100

Conclusions: Expression of CD56 is an additional sensitive and helpful immunohistochemical tool for histopathologists diagnosing a GCT. It does not seem possible to provide a validly individual risk assessement. However, the different expression of CD56 isoforms might indicate important changes in the course to a more malignant behaviour. (Source: BioMed Central)

Expression of anti-Müllerian hormone (AMH) in equine granulosa-cell tumors and in normal equine ovaries.

Theriogenology — Wed, 02 Jul 2008 04:00:00 +0100

In conclusion, AMH was strongly expressed by granulosa cells in equine GCT and in normal antral follicles. Therefore, anti-Müllerian hormone may be a useful biomarker for detection of GCT in the horse. PMID: 18599114 [PubMed - as supplied by publisher] (Source: Theriogenology)

Role of cell death ligand and receptor system on regulation of follicular atresia in pig ovaries.

Reproduction in Domestic Animals — Tue, 01 Jul 2008 04:00:00 +0100

Authors: Manabe N, Matsuda-Minehata F, Goto Y, Maeda A, Cheng Y, Nakagawa S, Inoue N, Wongpanit K, Jin H, Gonda H, Li J Several hundred thousand primordial follicles are present in the mammalian ovary, however, only a limited number develop to the pre-ovulatory stage, and then finally ovulate. The others, more than 99%, will be eliminated through a degenerative process called 'atresia'. The endocrinological regulatory mechanisms involved in follicular development and atresia have been characterized to a large extent, but the precise temporal and molecular mechanisms involved in the regulation of these events have remained unknown. From many recent studies, it is suggested that the apoptosis in ovarian granulosa cells plays a crucial role in follicular atresia. Notably, death ligand-rec...

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Testicular granulosa cell tumor, adult type.

Indian Journal of Pathology and Microbiology — Tue, 01 Jul 2008 04:00:00 +0100

We report a case of granulose cell tumor of the testis, adult type. PMID: 18723972 [PubMed - in process] (Source: Indian Journal of Pathology and Microbiology)

Laparoscopic fertility-sparing staging in unexpected early stage ovarian malignancies

Fertility and Sterility — Thu, 12 Jun 2008 23:00:00 +0100

Conclusion(s): Laparoscopic fertility-sparing staging in early ovarian malignancies is feasible and safe in selected and counseled patients and should be performed in experienced gynecological oncology centers trained in endoscopic procedures. (Source: Fertility and Sterility)

Laparoscopic fertility-sparing staging in unexpected early stage ovarian malignancies.

Fertility and Sterility — Thu, 12 Jun 2008 04:00:00 +0100

CONCLUSION(S): Laparoscopic fertility-sparing staging in early ovarian malignancies is feasible and safe in selected and counseled patients and should be performed in experienced gynecological oncology centers trained in endoscopic procedures. PMID: 18555237 [PubMed - as supplied by publisher] (Source: Fertility and Sterility)

Hepatic Metastases of Granulosa Cell Tumour of the Ovary

HPB Surgery — Tue, 03 Jun 2008 22:13:49 +0100

A case of metastatic granulosa cell tumour of the ovary is reported. Investigations revealed a secondary tumour in segment VI and VII of the liver. Right hepatic resection was performed. Microscopic findings revealed a tumour with histological features identical to that removed eleven years before. (Source: HPB Surgery)

Laparoscopic restaging of ovarian granulosa cells tumor: three cases report

Gynecological Surgery — Tue, 27 May 2008 06:04:59 +0100

We report three cases of laparoscopic restaging of GCT. The patients were treated in our Institution from August 2005 to January 2007. They were diagnosed an ovarian cyst and underwent laparoscopic adnexectomy. Histology showed a GCT (one case of juvenile type in a 38-year-old woman). All the patients were submitted to laparoscopic restaging with pelvic and para-aortic lymphadenectomy. Mean operation time was 195 min. A mean number of 32 lymph nodes were removed. No major intraoperative or postoperative complication occurred. Patients were discharged on the second or third postoperative day. All the patients are well and without disease. Laparoscopic restaging of GCT is feasible and allows para-aortic and pelvic lymphadenectomy. Patients restaged by laparoscopy benefit of a les...

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Cyclooxygenases expression and distribution in the normal ovary and their role in ovarian cancer in the domestic hen ( Gallus domesticus )

Endocrine — Fri, 23 May 2008 05:54:33 +0100

Abstract Cyclooxygenase (COX) (PTGS) is the rate-limiting enzyme in the biosynthesis of prostaglandins. Two COX isoforms have been identified, COX-1 and COX-2, which show distinct cell-specific expression and regulation. Ovarian cancer is the most lethal gynecological malignancy and the disease is poorly understood due to the lack of suitable animal models. The laying hen spontaneously develops epithelial ovarian cancer with few or no symptoms until the cancer has progresses to a late stage, similar to the human disease. The purpose of this study was to examine the relative expression and distribution of COX-1 and COX-2 in the ovaries of normal hens and in hens with ovarian cancer. The results demonstrate that COX-1 was localized to the granulosa cell layer and cortical in...

Outcome of an Adult Granulosa Cell Tumour in an Adolescent Initially Managed by Laparoscopy

European Journal of Pediatric Surgery — Thu, 22 May 2008 16:35:54 +0100

We describe a case of adult granulosa cell tumour in a 14-year-old girl who initially underwent laparoscopy for an “unsuspicious” cyst. Management was then modified according to oncological guidelines because of the histological nature of this cyst.[...]© Georg Thieme Verlag KG Stuttgart · New YorkGet connected:Table of contents | Abstract | Full text (Source: European Journal of Pediatric Surgery)

Adult granulosa cell tumor of the ovary: Fine-needle-aspiration cytology of 10 cases and review of literature

Diagnostic Cytopathology — Wed, 16 Apr 2008 04:00:00 +0100

This study reviews the cytologic features of adult GCT of the ovary diagnosed by fine-needle aspiration (FNA). We reviewed slides from ten cases diagnosed by CT guided FNA from 1995 to 2007 at our institutions. Smears were stained with Diff-Quik and Papanicolaou stains. Patient's history and histologic diagnosis were also available and reviewed for all cases. The patients ranged in age from 39 to 83 yr. All 10 cases were hypercellular with both large and small overlapping cell clusters and individual cells. The cytologic features identified included: naked nuclei (10/10 cases), Call-Exner bodies (7/10 cases), blood vessels with prominent perivascular tumor cell growth (4/10 cases), spindle-shaped hyperchromatic stromal cells within cellular clusters (6/10 cases), mixed inflammation (3/10 c...

Glucose metabolism and angiogenesis in granulosa cell tumors of the ovary: Activation of Akt, expression of M2PK, TKTL1 and VEGF.

European Journal of Obstetrics, Gynecology, and Reproductive Biology — Wed, 02 Apr 2008 04:00:00 +0100

CONCLUSION: Our results show that granulosa cell tumors of the ovary express vascular endothelial growth factor as an important stimulator of tumor angiogenesis as well as several molecular markers for glycolysis. The dependence of granulosa cell tumors of the ovary on the glycolytic pathway may provide a biochemical basis for therapeutic strategies involving glycolytic inhibitors. PMID: 18394773 [PubMed - as supplied by publisher] (Source: European Journal of Obstetrics, Gynecology, and Reproductive Biology)

Granulosa Cell Tumors of the Ovary With a Pseudopapillary Pattern: A Study of 14 Cases of an Unusual Morphologic Variant Emphasizing Their Distinction From Transitional Cell Neoplasms and Other Papillary Ovarian Tumors.

The American Journal of Surgical Pathology — Wed, 26 Mar 2008 23:38:27 +0100

Page: 581DOI: 10.1097/PAS.0b013e31815c186fAuthors: Irving, Julie A. MD * +; Young, Robert H. MD ++ [S] (Source: The American Journal of Surgical Pathology)

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Juvenile Granulosa Cell Tumor of Testis: Case Report and Review of Literature

American Journal of Perinatology — Sat, 15 Mar 2008 01:00:46 +0100

We reported this case in a newborn who presented with unilateral scrotal swelling. Histopathology and immunohistochemistry confirmed JGCT. Follow-up at 6 months after surgery did not show any recurrence. Even though JGCT is very rare in childhood, it is one of the important differentials of newborn scrotal mass.[...]© Thieme Medical PublishersGet connected:Table of contents | Abstract | Full text (Source: American Journal of Perinatology)

Imaging of gynecological disease (3): clinical and ultrasound characteristics of granulosa cell tumors of the ovary

Ultrasound in Obstetrics and Gynecology — Thu, 13 Mar 2008 04:00:00 +0100

To describe the clinical and ultrasound characteristics of granulosa cell tumors (GCTs) of the ovary, and to define the ultrasound appearance of GCTs based on pattern recognition.Databases of four gynecological ultrasound centers were searched to identify patients with histologically proven GCTs who had undergone a standard preoperative ultrasound examination.A total of 23 women with confirmed GCT were identified. Twelve (52%) women were postmenopausal, nine (39%) were of fertile age and two (9%) were prepubertal. Clinical symptoms were abdominal distension (7/23, 30%), pain (5/23, 22%) and irregular vaginal bleeding (6/23, 26%). Seven patients (30%) were asymptomatic. Endometrial pathology was found in 54% (7/13) of the patients from whom endometrial biopsies were taken. On ultrasound sca...

Cytologic detection of Call-Exner bodies in Sertoli cell tumors from 2 dogs.

Veterinary Clinical Pathology — Sat, 01 Mar 2008 05:00:00 +0100

Authors: Masserdotti C, De Lorenzi D, Gasparotto L A 14-year-old Italian Griffon and an 11-year-old mixed breed dog were presented to our clinic with monolateral testicular enlargement. In both dogs, a firm, nodular, and nonpainful mass was palpated, and ultrasonographic examination of testicular parenchyma showed a large and irregular nodular area with hyperechogenic features. Fine-needle aspirates of the masses were highly cellular and consisted of populations of large elongated vacuolated cells in sheets and palisades, with finely granular chromatin and prominent nucleoli, consistent with neoplastic Sertoli cells. A variable number of structures also were observed that consisted of a central round area of amorphous, deeply eosinophilic, hyaline material surrounded by a peripheral, r...

Juvenile Granulosa Cell Tumor of Adult Testis: A Case Report.

Urology — Thu, 28 Feb 2008 05:00:00 +0100

This report describes a case of a 27-year-old man who presented with a JGCT in his right testis. Orchiectomy was performed. No recurrence was noted during an 8-year follow-up. This is the first reported case of JGCT occurring in adult testis. The benign behavior of testicular JGCT mandates that it should be distinguished from other, much more aggressive neoplasms it resembles. PMID: 18313118 [PubMed - as supplied by publisher] (Source: Urology)