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At least 19 recordsLinked to original sources
PubMed1987

Sarcomatous change in granulosa cell tumor.

Granulosa cell tumors have a tendency for indolent growth and late recurrence. The present case of granulosa cell tumor in a 67-year-old woman is the first, to the authors' knowledge, to be reported as showing sarcomatous transformation with a rapid fatal course. Both the granulosa cell and fibrothecomatous elements appear to have undergone sarcomatous change with some evidence to suggest rhabdomyosarcomatous differentiation. The sarcomatous component was present in metastatic deposits.

Aged↗
PubMed2002

Evidence of a role for the INK4 family of cyclin-dependent kinase inhibitors in ovarian granulosa cell tumors.

Granulosa cell tumors (GCTs) of the ovary are relatively rare and account for <5% of all ovarian cancers. The molecular pathogenesis of these tumors is not well understood. We tested the hypothesis that cyclin-dependent kinase inhibitors, specifically the inhibitors of the cyclin-dependent kinase 4 (INK4) family, are targets for altered gene expression in GCTs. The status of RB1, INK4A, INK4B, INK4C, INK4D, and ARF in 13 adult and 2 juvenile ovarian GCTs was determined by reverse transcription-polymerase chain reaction of total RNA and exon-specific sequencing of genomic DNA. Tumors showing loss of INK4A expression were assayed further by exon-deletion analysis and methylation-specific PCR. None of the juvenile tumors demonstrated altered expression, but 7/12 (58%) adult GCTs lacked expression of INK4A, INK4B, or both. In one of these cases, we noted a homozygous deletion of the INK4A locus, and in the remaining tumors we found hypermethylation of the promoter region, a mechanism that can lead to gene inactivation. These data support a role for the INK4 family of CDK inhibitors in the biology of GCTs.

Adolescent↗
PubMed1990

[Juvenile granulosa cell tumor].

Granulosa cell juvenile tumours, defined in 1976 by Scully as a separate unit are found mostly in girls during the first two decades of life. On inspection under an optic microscope they are characterized by the presence of non-differentiated "blastemoid" structures and the formation of solid follicular formations and cysts. In our first case we observed a bilateral juvenile tumour made up of granulosa cells in a 8-month-old girl where the tumour produced symptoms of pseudopubertas praecox isosexualis. In the second case in a 9-month-old girl also with symptoms of pseudopubertas praecox isosexualis the authors detected in the left ovary a tumour which probably is a less differentiated variety of the juvenile granulosa cell tumour. These tumours belong into the group of little differentiated gonadal-stromal tumours with ICD-O code M-8590/1.

Female↗
PubMed1976

Hormonal function of a granulosa cell tumor.

Granulosa and theca cell tumors are rather common gonadal stromal tumors. A postmenopausal patient with a granulosa cell tumor, who complained chiefly of breast tenderness and enlarging, abdomen, is presented. Preoperative and postoperative studies including serum estrone, estradiol, prolactin, FSH, and LH,as well as urinary estrogens, 17-ketosteroids, and 17-hydroxysteroids are reported. A plan of treatment and followup is suggested. It is recommended that survival data on patients with such slow-growing tumors be adjusted to reflect the true incidence of death from the specific tumor in question.

Aged↗
PubMed2002

Gonadal tumor with granulosa cell tumor features in an adult testis.

Granulosa cell tumor is almost exclusively an ovarian tumor. Rare cases of granulosa cell tumor have been reported involving the testes. We report a testicular gonadal stromal tumor with granulosa cell differentiation in a 54-year-old white man. The tumor was discovered by an ultrasound evaluation for left hydrocele. The patient was clinically asymptomatic. On frozen section, the initial impression was a malignant lymphoma. Final histology on the orchiectomy specimen showed a gonadal stromal tumor with granulosa cell features. Immunohistochemical studies excluded malignant lymphoma and germ cell tumors, consistent with a stromal tumor. This case report illustrates the challenges for the pathologist in making an accurate diagnosis in unusual testicular tumors.

Diagnostic Errors↗
PubMed1976

Androgenic function of a granulosa cell tumor.

Virilizing granulosa cell tumors are uncommon and have not been well studied hormonally. A hirsute woman with a cystic granulosa cell tumor of the ovary is presented. Plasma hormone levles obtained before and after surgery indicate testosterone production by the tumor with LH and FSH suppression. Plasma testosterone (T) and T-index returned to normal after tumor removal, and ovulation resumed.

Adult↗
PubMed2005

High GATA-4 expression associates with aggressive behavior, whereas low anti-Müllerian hormone expression associates with growth potential of ovarian granulosa cell tumors.

CONTEXT: Granulosa cell tumors (GCTs) are ovarian malignancies that produce estrogens, inhibins, and anti-Müllerian hormone (AMH). The molecular pathogenesis of GCTs is likely to involve defects in the genes regulating normal granulosa cell proliferation during folliculogenesis. OBJECTIVE: The objective of this study was to test the role of factors regulating the normal granulosa cell function, i.e. AMH, inhibin-alpha, SF-1 (steroidogenic factor-1), and GATA transcription factors in the pathobiology and clinical behavior of GCTs. DESIGN: We selected randomly a cohort of 80 GCT patients treated at our university hospital during 1971-2003, analyzed protein expression in the tumor samples embedded on a tissue microarray by immunohistochemistry, and correlated the data to clinical and histopathological parameters. RESULTS: We found no significant differences in the immunoreactivity levels of inhibin-alpha, GATA-6, FOG-2 (friend of GATA-2), or SF-1 in GCTs compared with normal granulosa cells. AMH expression was, however, low (i.e. reduced) in 69% of GCTs and correlated inversely with tumor size (P = 0.0025). In contrast, GATA-4 expression was high (i.e. resembled normal granulosa cells) in 44% of GCTs and correlated positively with clinical stage and recurrence (P = 0.0232 and P = 0.0038, respectively). Fifty of the 80 patients had a follow-up for at least 10 yr, and 13 of them had recurrence(s). In multivariate analysis of recurrence, the high GATA-4 expression remained the only independent factor (risk ratio, 9.2; 95% confidence interval, 2.0-43.3; P = 0.0048). CONCLUSIONS: The more aggressive GCTs retain a high GATA-4 expression, whereas the larger tumors lose the proliferation-suppressing AMH expression. The high GATA-4 expression in GCTs may serve as a marker of poor prognosis.

Adult↗
PubMedDate not supplied

Juvenile granulosa cell tumor.

Juvenile granulosa cell tumor (GCT) of the ovary is a rare neoplasm occurring in premenarchal girls and young women. Juvenile GCT that occurs in premenarchal girls usually produces sexual precocity as a consequence of estrogen secretion. Juvenile GCTs are more likely to grow to a relatively large size with a much smaller likelihood of peritoneal spread, unlike their counterpart, epithelial ovarian neoplasms. We report the radiology and pathology of a patient with juvenile GCT and review the literature of this rare tumor.

Child↗
PubMed1996

Sonographic and clinical findings of granulosa cell tumor.

BACKGROUND: Granulosa cell tumor (GCT) accounts for roughly 1.5% of all ovarian neoplasms and 5-10% of ovarian cancers. GCT, which may have profound end-organ effects, has attracted a significant amount of attention despite its rarity. This tumor is rare, and difficult to diagnose before operation. Until now, no specific sonographic findings have been reported. METHODS: Twelve cases of pathologically proven GCTs were diagnosed from June 1985 to March 1993. Nine of those cases had preoperative sonographic pictures taken. RESULTS: Eight out of the nine cases tested exhibited a complex multicystic sonographic pattern. For a case evaluated by a transvaginal color and pulsed Doppler assessment, the blood vessels located in the central part with diffuse dispersed vascular arrangement were found to have a resistance index of 0.38 and a pulsatility index of 0.50. The most common complaints of our patients were postmenopausal bleeding and lower abdominal pain. CONCLUSIONS: We conclude that complex multicystic sonographic features observed by high-resolution ultrasonography, in conjuction with a high preoperative estradiol level and clinical symptoms, may help to establish a preoperative diagnosis of GCT.

Adult↗
PubMed2005

Apoptosis and differentiation induced by staurosporine in granulosa tumor cells is coupled with activation of JNK and suppression of p38 MAPK.

We report here that staurosporine can induce apoptosis or differentiation of granulosa tumor cells depending on its dosage. In presence of staurosporine concentrations > 50 nM, apoptosis was triggered in human granulosa cell tumor cells COV434. In the presence of concentrations < 50 nM, the shape of the otherwise globular granulosa cells differentiated into a flattened epithelioid-like appearance. The process was associated by the induction of prostaglandin synthase-2 (PGS-2) and C/EBPbeta expression and by an increase in progesterone production in the supernatant culture medium. The observed effects of staurosporine were synergized by forskolin. With phosphorylation-specific Western blotting and protein kinase assays, it was demonstrated that staurosporine suppresses the phosphorylation of p38 and activates JNK. These results suggest that p38MAPK and JNK signal transduction pathways were involved in the regulation of granulosa cell differentiation by staurosporine. These results may indicate the usefulness of staurosporine or its analogs for the development of a future medical treatment of granulosa tumors.

Apoptosis↗
PubMed1986

Gonadotropin, steroid, and thyroid hormone milieu of young SWR mice bearing spontaneous granulosa cell tumors.

Young SWR mice possessing spontaneous ovarian granulosa cell (GC) tumors were examined for evidence of endocrine dysfunction associated with tumorigenesis. Tissue levels of hormones in tumor host and normal control females were measured by radioimmunoassays, ovarian luteinizing hormone (LH) receptors by uptake of 125I-labeled human chorionic gonadotropin (hCG) administered iv, and ovarian 3-beta-hydroxysteroid dehydrogenase (3-beta-OH) activity by histochemical techniques. When data from tumor host mice were compared with control data, hypothalamic gonadotropin releasing hormone content was not significantly different. Pituitary LH and follicle-stimulating hormone (FSH) contents were significantly decreased. Serum FSH, but not LH, levels were significantly reduced. No specific uptake of 125I-labeled hCG by tumor tissue was detected, whereas uptake by nontumorous contralateral ovaries was identified and found to be similar to that of control ovaries. With respect to serum steroids in tumor host mice, progesterone, dihydrotestosterone, and testosterone were significantly reduced, whereas androstenedione, dehydroepiandrosterone, corticosterone, estrone, and estradiol were normal. Frozen sections of tumor tissue failed to show any 3-beta-OH activity, whereas prominent activity was observed in non-tumorous contralateral and control ovaries. Serum thyroxine levels, evaluated because of the known depressive effects of hypothyroidism on reproductive function, were found to be significantly elevated in tumor host mice. The above results suggest that in SWR mice with spontaneous GC tumors, gonadotropins are moderately suppressed; the granulosa tumor cells do not have LH-hCG receptors; steroidogenesis by tumor tissue is reduced, whereas peripheral conversion of adrenal androgen precursors to estrogens is normal; and elevated serum thyroxine levels have a secondary role in established GC tumors.

Animals↗
PubMed2005

Combined adult granulosa cell tumor and mucinous cystadenoma of the ovary: granulosa cell tumor with heterologous mucinous elements.

We describe an unusual ovarian neoplasm in a 57-year-old woman composed of an admixture of mucinous cystadenoma and adult granulosa cell tumor (AGCT). In areas the two components were separate but elsewhere there was intermingling of the two elements. The combination of mucinous cystadenoma and AGCT has only rarely been reported. Theories of histogenesis include a collision tumor and heterologous mucinous differentiation within an AGCT. We favor the latter theory in this case, because in many areas there was an intimate admixture of the two components. Because heterologous mucinous elements are well described in other ovarian sex-cord-stromal neoplasms, especially but not exclusively Sertoli Leydig cell tumors, it is not unexpected that a similar phenomenon could occur in an AGCT. We review the previously reported cases of combined mucinous cystadenoma and granulosa cell tumor of the ovary.

Appendectomy↗
PubMed1984

Establishment and characterization of an estrogen-producing human ovarian granulosa tumor cell line.

Cells designated HTOG and HTOT were established by long-term culture from a human ovarian granulosa cell and a theca cell tumor, respectively. The HTOG line grew well forming colonies and multilayered rapidly without contact inhibition; serial passages of HTOG were performed over 100 times successively within 25 months. HTOG were spindle cells, polygonal or spherical in shape, revealed neoplastic and pleomorphic features, and produced estrone (E1) and 17 beta-estradiol (E2). The chromosome number varied considerably and showed hyperploidy; the modal chromosome number was in the hypertriploid-tetraploid range. When HTOG cells were heterotransplanted into the subcutis of BALB/c nude mice, they produced a sarcomatous diffuse type of granulosa cell tumors. In contrast, HTOT cells grew slowly while forming monolayers and underwent five successive passages in about 100 days, but a theca cell tumor line could not be established. HTOT cells were fibroblastic in shape and also produced E1 and E2. The majority of the cells showed diploidy and karyologic normality.

Animals↗
PubMed1999

Adult granulosa cell tumor of the ovary with foci of hepatic cell differentiation: a report of four cases and comparison with two cases of granulosa cell tumor with Leydig cells.

We report four ovarian granulosa cell tumors of the adult type containing small foci of hepatic cell differentiation. The patients ranged in age from 35 to 54 years and had unilateral adnexal masses. The smallest tumor was 4.0 cm in diameter and the largest, 11.0 cm in diameter. Three tumors were solid and cystic, and one was cystic. Microscopic examination showed typical patterns of adult granulosa cell tumor, with the additional finding of scattered islands of large cells with abundant eosinophilic, slightly granular cytoplasm and central round nuclei containing single prominent nucleoli. Bile pigment was detected in canaliculi between some of the large cells in three tumors. The hepatic cells were positive immunohistochemically for cytokeratin (CAM 5.2) and epithelial membrane antigen in two cases and alpha-fetoprotein in one of two cases. Carcinoembryonic antigen was stained in a canalicular pattern in two cases. Staining for vimentin and alpha-inhibin was negative. Liver cells in granulosa cell tumors must be differentiated from Leydig cells, which are found very rarely in granulosa cell tumors, and luteinized stromal and granulosa cells, which are present more commonly in these tumors; all three of the latter cell types are positive for alpha-inhibin.

Adult↗
PubMedDate not supplied

Ovarian granulosa cell tumors in childhood.

Granulosa cell tumors (GCT) of the ovary are prepubertal in 5% of the patients. In girls less than 20 years old, 80% of GCTs differ from those among adults. These juvenile granulosa cell tumors (JGCTs) are usually benign. GCTs belong to ovarian sex cord-stromal tumors, the more common ovarian tumors being epidermal and germinal. The etiology of GCT remains unknown. Most young children with GCT present with precorious pseudopuberty. Among adolescents GCT often causes menstrual irregularities, virilization, abdominal swelling, and pain. When JGCT is limited to the ovaries the outcome is excellent with only salpingo-oophorectomy. However, more widely spread tumors are difficult to treat and cause mortality. Cisplatin-containing chemotherapy can induce remissions in adult GCTs. Estrogens and peptide hormones, i.e., inhibin, are useful in the follow-up of the patients. The authors describe 3 children with GCT and review current data on this rare tumor from molecular biology to clinical aspects.

Child↗
PubMed1998

No evidence of a role for mutations or polymorphisms of the follicle-stimulating hormone receptor in ovarian granulosa cell tumors.

The molecular pathogenesis of granulosa cell tumors of the ovary is not understood, although recent studies have shown that immunoreactive inhibin secretion by these tumors may be used as a tumor marker. Granulosa cell tumors exhibit many features of normal granulosa cells, including a response to FSH and inhibin secretion. FSH levels are suppressed in patients with inhibin-secreting granulosa cell tumors, suggesting FSH-independent growth of these tumors. Activating mutations of the FSH receptor might, therefore, be involved in tumorigenesis. We sought to identify mutations in the FSH receptor genes of these tumors using PCR to amplify the exon encoding the transmembrane and cytoplasmic domains from the tumor DNA. Analysis of the amplicons for single strand conformational polymorphisms and direct sequencing confirmed a previously reported polymorphism in the C-terminal region of the receptor, but did not identify tumor-specific missense mutations and/or polymorphisms. In addition, ribonucleic acid from 3 granulosa cell tumors was used to confirm expression of the FSH receptor; expression was unexpectedly also observed in several ovarian mucinous cystadenocarcinomas used as controls. In conclusion, our failure to identify activating mutations of the FSH receptor in 15 granulosa cell tumors argues against a role for the FSH receptor in tumorigenesis and suggests that some subsequent component of this signal transduction pathway may be activated.

Alleles↗