Recurrent Granulosa Cell Tumor Research Articles

Hormonal treatment of a recurrent granulosa cell tumor of the ovary: case report and review of the literature

Background Granulosa cell tumors of the ovary are rare, primarily treated surgically. In advanced or recurrent disease, data are inconclusive regarding the benefit of either primary or adjuvant chemotherapy. Hormonal therapy has been suggested as an alternative treatment. Case Our patient had three recurrences of estrogen receptor negative and progesterone receptor positive GCT, the first two treated by surgery with or without adjuvant chemotherapy. For the third recurrence, the patient received alternating biweekly cycles of megestrol and tamoxifen. Computed tomography showed stable disease at 6 months, partial response at 18 months, and complete response at 22 months. The patient continues on hormonal therapy and has been disease-free for 5 years. Conclusion This study and others suggest that hormonal therapy may provide another option for treating these relatively rare tumors.

Long natural history of recurrent granulosa cell tumor of the ovary 23 years after initial diagnosis: a case report and review of the literature

Background Granulosa cell tumors (GCTs) of the ovary are rare, hormonally active neoplasms characterized by endocrine manifestations, an indolent course, and late relapse. Case We report a case of a prolonged history of ovarian GCT managed primarily with repeat surgical resections. Conclusion This case illustrates the benefits of cytoreductive surgery for the management of recurrent disease, the use of serum tumor markers to help guide therapy, and the importance of extended follow-up.

Hepatic Radio frequency Ablation of Metastatic Ovarian Granulosa Cell Tumors

Intrahepatic recurrences of a granulosa cell tumor of the ovary after primary resection has traditionally been considered a relative contraindication to surgical management. Improvements in ablative technologies such as radiofrequency ablation (RFA) offer the surgeon additional alternatives in the management of selected intrahepatic tumors. We present a case report of an intrahepatic recurrence of a metastatic ovarian granulosa cell tumor 6 months after primary resection. The patient received RFA of the intrahepatic lesions and the patient remains free of detectable disease 14 months later. A review of the literature is presented. This is the first known report of the use of RFA for intrahepatic recurrence of a metastatic ovarian granulosa cell tumor. In selected cases of metastatic ovarian granulosa cell tumors to the liver RFA may increase the percentage of patients considered surgically treatable.

Clinical parameters and treatment results in recurrent granulosa cell tumor of the ovary

Objectives The objectives of this study were to evaluate the patients’ characteristics and treatment results for 11 recurrent granulosa cell tumors (GCT) of the ovary. Methods Tumor registries were screened retrospectively for all patients treated between 1979 and 1999 for ovarian tumors at the University of Istanbul. All information about these patients was obtained from operation, pathology, and follow-up reports. Then the clinical data were extracted. The patients were classified in stages according to FIGO criteria. There were 952 ovarian carcinomas, of which 45 were GCT. Eleven of 45 patients (24%) developed recurrent disease on follow-up. Results All patients but one had advanced (III–IV) disease at diagnosis. The median progression-free interval (PFI) was 16 months (range, 5–39 months) with a marked difference in PFI between patients receiving (24 months) and not receiving (8 months) initial chemotherapy. Among patients received chemotherapy (six patients), two complete and two partial responses were observed, for an overall response rate of 67%. The median survival for all patients was 26 (4–73) months with a longer survival (38 versus 8 months) for patients retreated with a platinum-containing regimen. Conclusions Despite the fact that small number of treated cases does not allow an adequate evaluation, retreatment with cis-platinum-containing regimens may be the treatment of choice for patients with recurrent disease.

Granulosa Cell Tumor of the Ovary

BACKGROUND Late recurrence can be extensive with initial, clinically undetectable, microscopic granulosa cell tumor of the ovary. CASE We describe an 83-year-old patient who presented with extensive recurrent granulosa cell tumor of the ovary 6 years after undergoing abdominal hysterectomy and bilateral salpingo-oophorectomy for atypical endometrial hyperplasia with an incidental microscopic finding of ovarian granulosa cell tumor. CONCLUSION Patients must be monitored closely after a diagnosis of ovarian granulosa cell tumor, even if the tumor is occult.

Granulosa cell tumor of the ovary: extensive late recurrence after initial occult microscopic disease

BACKGROUND: Late recurrence can be extensive with initial, clinically undetectable, microscopic granulosa cell tumor of the ovary. CASE: We describe an 83-year-old patient who presented with extensive recurrent granulosa cell tumor of the ovary 6 years after undergoing abdominal hysterectomy and bilateral salpingo-oophorectomy for atypical endometrial hyperplasia with an incidental microscopic finding of ovarian granulosa cell tumor. CONCLUSION: Patients must be monitored closely after a diagnosis of ovarian granulosa cell tumor, even if the tumor is occult.

Continuous Intraoperative Intraperitoneal Hyperthermic Chemoperfusion (CIIPHCP) in the Treatment of Advanced Stage and Recurrent Granulosa Cell Tumors. Report of Two Cases

Treatment of advanced stages and recurrent ovarian granulosa cell tumors, has not been established yet. The effectiveness of radiation therapy could not be proven. Systemic chemotherapy has shown promising results, but with severe side effects and high incidence of relapse. We report of one patient with advanced stage III C, and one patient with bulky recurrent ovarian granulosa cell tumors. Both patients were treated with a combination of surgical debulking, Continuous Intraoperative Intraperitoneal Hyperthermic Chemoperfusion (CIIPHCP) with Cisplatin and one of them with adjuvant systemic chemotherapy. CIIPHCP appears to offer a promising procedure in addition to surgical debulking and systemic chemotherapy for treatment of advanced or recurrent ovarian granulosa cell tumors. The present report is the first concerning the question of adding Intraoperative Hyperthermic Chemoperfusion in the treatment of advanced or recurrent ovarian granulosa cell tumors.

Bone Metastasis from a Granulosa Cell Tumor of the Ovary

Background. Granulosa cell tumors (GCT) of the ovary generally have a good prognosis. Recurrences tend to be late and are usually abdominopelvic. Bone metastases are extremely rare.Case. A case of recurrent GCT with vertebral metastasis is presented. Radiologic studies were helpful in documenting the presence of an invasive tumor destroying the vertebral body of T7. Bone scintigraphy excluded other metastatic sites. Diagnosis could not be established by CT-scan-directed fine-needle aspiration cytology or trocar biopsies. Since the lesion was isolated and resectable, aggressive surgery with complete tumoral excision was performed followed by local radiation therapy. Megestrol acetate was given as systemic treatment.Conclusion. Multiple treatments of GCT may alter the pattern of recurrence. Every symptom should be thoroughly evaluated. Bone metastases may be treated aggressively.

Recurrent granulosa cell tumor of the ovary: Retrospective analysis

Recurrent granulosa cell tumor of the ovary: Retrospective analysis

Liver invasion by recurrent granulosa cell tumour of the ovary: imaging findings

Granulosa cell tumour of the ovary is a rare neoplasm of low malignant potential, late recurrences, local spread and high survival rates. We report the MR imaging appearance of invasion of the liver parenchyma by recurrent granulosa cell tumour of the ovary 15 years after initial diagnosis.

#409 Myeloablative therapy with ABMT and local radiation in the successful treatment of recurrent advanced stage juvenile granulosa cell tumor of the ovary

#409 Myeloablative therapy with ABMT and local radiation in the successful treatment of recurrent advanced stage juvenile granulosa cell tumor of the ovary

Diagnostic Utility of Müllerian Inhibiting Substance Determination in Patients with Primary and Recurrent Granulosa Cell Tumors

Objectives.In this study we evaluated changes in serum Müllerian inhibiting substance (MIS) concentration in a large number of patients with granulosa cell tumors (GCT) to determine whether MIS is elevated at the time of presentation and whether MIS is an index of successful surgical resection and management of recurrences.Methods.We retrospectively reviewed MIS levels from 17 subjects prior to tumor resection and studied serial MIS samples from 56 subjects following initial tumor resection. Clinical follow-up information was available for 36 of those with postoperative MIS values. Serum MIS was measured by an ELISA. MIS values were compared to a combination of normative values previously established in our laboratory and from more recently obtained samples from older pre- and postmenopausal women, using this assay.Results.Serum MIS was elevated pre-operatively in 6 of 8 (75%) subjects with juvenile GCTs and in 7 of 9 (78%) of those with adult GCTs relative to age-matched controls (76% for both types combined). Post-operative clinical correlation was available for 36 patients. There was no clinical recurrence in 21 subjects with normal or undetectable postoperative values, and incompletely resectable tumor or recurrence was identified in 6 of 15 patients with elevated postoperative values.Conclusions.The results of this study demonstrate that postoperative serum MIS concentrations may be used to evaluate the completeness of tumor removal following initial surgery and that serial MIS determinations may allow the detection of recurrences.

Radiation Treatment of Advanced or Recurrent Granulosa Cell Tumor of the Ovary

Background.Because granulosa cell tumors of the ovary are rare, the optimal treatment for women with gross residual disease after primary surgery or recurrence is not known. Our objective was to review the results of radiotherapy for advanced or recurrent granulosa cell tumor of the ovary.Methods.This retrospective review identified 34 patients with ovarian granulosa cell tumors treated with radiation at the University of Texas M. D. Anderson Cancer Center between 1949 and 1988. Fourteen received treatment for clinically measurable disease; 20 received adjuvant radiotherapy after surgery for minimal residual (<1 cm) or microscopic residual disease. The 14 patients with measurable disease formed the basis for this review.Results.Ten of 14 patients were treated with moving-strip whole-abdomen radiation (27–28 Gy), 9 with60Co, and 1 with 6-MeV photons and a pelvic boost of 28 Gy with 22–25 MeV photons. The other 4 patients were treated with pelvic radiotherapy (45–61 Gy) with 22–25 MeV photons. Six of 14 patients (43%) had a clinical complete response to radiotherapy, with a median follow-up of 13 years (range, 5–21 years). Three of 6 who responded to radiation had relapse 4–5 years later; 2 of these 3 died of disease and 1 was alive with disease at last follow-up. Three responders remain alive without evidence of disease 10–21 years after treatment. The 8 nonresponders had a median survival of 12.3 months (range, 1–60 months).Conclusions.Radiotherapy can induce a clinical response with occasional long-term remission in patients with persistent or recurrent granulosa cell tumor of the ovary.

Cell Cycle Control of Ovarian Granulosa Cells in Tumors and Cysts

Ovarian granulosa cell tumors (GCTs) behave unpredictably. Stage I patients suffer recurrences many years after treatment, and histopathologic evaluation of the primary GCT offers few clues. p21IPl/wafl (Waft), the principle downstream effector of the p53-dependent pathway of growth control, inhibits cyclin-dependent kinases responsible for conversion of GI to S in the cell cycle. This study hypothesizes that immunohistochemistry for these proliferation-related markers will help discern granulosa cell growth control and may predict the GCTs' clinical behavior. Paraffin sections from a surgical series of 43 GCTs (34 primary and 9 recurrent: 19 diffuse and 18 typical adult; 6 juvenile type) and 12 benign cysts (8 follicular and 4 corpora luteal) were immunostained for Waft and p53. Ki67 (MIB-1 clone) proliferation index is the percent of nuclei immunoreactive on a count of at least 400. The 43 GCTs stained as follows: 40% Waft + (11 St = &lt; 10%, 4 S2 = 10-50%, and 2 S3 = &gt; 50% of nuclei) and 28% p53 + (2 W = weak, 8 S 1, 2 S2). All p53 + GCTs stained with Waf 1; the number of immunoreactive nuclei correlated (P &lt; .00001). Juvenile more often than adult type GCTs exhibited Waf 1 (6/6) and p53 staining (5/6) (P &lt; .001). No difference in pS3 or Waft staining was present in primary compared with recurrent GCTs. Ki67 proliferation index for GCTs ranged from 1 to 50% (mean, 13.8%; median, 10.9%) and associated with both p53 and Waft (P &lt; .000 1). The 12 benign cysts stained as follows: 100% Waft + (6 S1, 5 S2, 1 S3) and 75% p53+ (4 W, 4 S1, 1 S2). Of the 43 patients, 41 were available for follow-up study: 15 suffered recurrences after 16-133 (mean 59.3, median 55) months, and 26 were disease-free 21-369 (mean 78.2, median 57.5) months after diagnosis. Waft staining of the primary GCT does not help predict recurrence. All GCTs immunoreactive for p53 produce Waft, suggesting detection of an active wild type p53 rather than overproduction of mutant p53. Waft is produced by granulosa cells in all benign functional cysts, suggesting a physiologic role in the ovulation sequence. Waf t's association with proliferation in GCTs suggests possible physiologic feedback. Proliferation (correlated with histopathologic grading) in GCTs may signify appropriate feedback control; thus it is not a predictor of aggressive clinical behavior.

Recurrent granulosa cell tumor of the ovary 37 years after initial diagnosis: a case report and review of the literature: Hines J.F.; Khalifa M.A.; Moore J.L.; Fine K.P.; Lage J.M.; Barnes W.A. USA Gynecol Oncol 1996 60/3 (484–488)

International Journal of Gynecology & ObstetricsVolume 54, Issue 3 p. 316-316 Citations from the literature case report of interest Recurrent granulosa cell tumor of the ovary 37 years after initial diagnosis: a case report and review of the literature Hines J.F.; Khalifa M.A.; Moore J.L.; Fine K.P.; Lage J.M.; Barnes W.A. USA Gynecol Oncol 1996 60/3 (484–488) First published: September 1996 https://doi.org/10.1016/0020-7292(96)81559-1AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat No abstract is available for this article. Volume54, Issue3September 1996Pages 316-316 RelatedInformation

Transformation in recurrent ovarian granulosa cell tumors: Ki67 (MIB-1) and p53 immunohistochemistry demonstrates a possible molecular basis for the poor histopathologic prediction of clinical behavior

Ovarian granulosa cell tumors (GCTs) behave unpredictably. Stage I patients suffer recurrences many years after treatment, and histopathologic evaluation of the primary GCT offers only a few clues. Grading, in particular, is largely ineffective. Ki67 (MIB-1) and p53 monoclonal antibodies (active on paraffin embedded tissues) provide insight into nuclear proliferation and control, respectively. In this study, the authors hypothesized that these molecular markers will help predict the clinical behavior of GCTs. Paraffin sections from 68 GCTs (arising in 56 patients: 53 primary and 15 recurrent) including 34 typical and 27 diffuse adult, and seven juvenile types were immunostained for Ki67 (MIB-1 clone; Immunotech, Westbrook, ME) and p53 (D07 clone; Novacastra Laboratories, UK). The Ki67 proliferation index (Ki67PI = percentage immunoreactive on a count of at least 400 nuclei) ranges from 1 to 50% (mean, = 12.2%; median, 9.3%). Nineteen percent of GCTs exhibited focal p53 immunoreactivity; the number of GCTs and proportion of nuclei decorated were as follows: four, <1%; seven, 1% to 10%; and one, 20%. Ki67PI was higher in recurrent tumors ( P < .001) and correlated with mitotic rate ( r = .75; P < .0001). p53 staining was associated with juvenile type GCTs ( P < .001) and higher Ki67PI ( P < .005). Other histopathologic features exhibited no association with p53 staining or Ki67PI. Follow-up was available for 54 of 56 patients: 18 suffered recurrences after 16 to 229 months (mean, 72.1 months; median, 59 months), and 36 were disease free 16 to 369 months (mean, 78.2 months; median, 70 months) after diagnosis. Curiously, high Ki67PI and mitotic rates of the primary GCT correlated weakly with a disease-free course ( P = .03 and .07, respectively). Disease recurrence was associated with stage > I ( P < .0005), vessel invasion in the capsule ( P < .001), ruptured tumors ( P < .005), and older patients ( P < .02). p53 staining and size or subtype of GCT exhibited no prognostic value. For 12 patients, paired primary and first recurrence of GCT showed a striking increase in Ki67PI ( P < .00005) and mitotic activity ( P < .02) in the recurrence. p53 expression also appeared (de novo) in two recurrent GCTs. The interpretation of focal p53 staining (>10% nuclei decorated in only one GCT) is controversial. Some investigators suggest that this represents overexpression of wild type p53 rather than p53 gene mutation. Primary GCTs exhibit a wide spectrum of proliferative activity, and the seven juvenile GCTs (the most proliferative type) demonstrated no recurrences in this study. Recurrent GCTs displayed a transformation of molecular markers to increased proliferative activity and overexpression of p53, fundamentally, by these markers, a different GCT than the primary one. These findings suggest a molecular basis for the lack of histopathologic predictors for recurrence. Factors other than proliferation of the primary GCT (which relates most closely to grading) either extrinsic to the neoplasm (host dependent) or as yet undetectable must determine malignant behavior.

A Prospective Study of Inhibin in Granulosa Cell Tumors of the Ovary

Elevated preoperative serum inhibin concentrations have been reported in patients with granulosa cell tumor of the ovary. The aim of this study was to determine if elevations in serum inhibin predated clinical recurrence in patients with a diagnosis of granulosa cell tumor. Twenty-seven consecutive patients with granulusa cell tumor were followed prospectively to assess the relationship between serum inhibin concentrations and disease status. The serum inhibin concentrations in normal postmenopausal women were <77-130 U/liter. In patients with granulosa cell tumor at initial surgery, mean inhibin concentrations preoperatively were 2831 U/liter in 4 postmenopausal subjects (range 2130-3323 U/liter) and 3680 U/liter in each of 2 premenopausal women. In 5 postmenopausal subjects with a histological diagnosis of granulosa cell tumor who underwent secondary surgery because of a recurrent palpable mass, mean inhibin concentrations were 4216 U/liter (range 2672-7360). In 3 patients with known or suspected residual disease despite a secondary debulking operation the serum inhibin concentrations were 475, 1000, and 2541 U/liter. In 13 subjects who were clinically disease free with a previous diagnosis of granulosa cell tumor, serum inhibin concentrations remained within the normal range for reproductive status. We conclude: (1) Preoperative serum inhibin concentrations are typically elevated sevenfold above the normal premenopausal follicular phase levels in women with granulosa cell tumor; (2) after surgery, serum inhibin levels may become elevated up to 2 years before further surgery is undertaken; and (3) serum inhibin concentrations appear to be a valuable tumor marker for the diagnosis of primary or recurrent granulosa cell tumor.

Cisplatin (P), vinblastine (V), and bleomycin (B) combination chemotherapy in recurrent or advanced granulosa cell tumor of the ovary (GCTO): An EORTC Gynecologic Cancer Coop. Group (GCCG) study

Cisplatin (P), vinblastine (V), and bleomycin (B) combination chemotherapy in recurrent or advanced granulosa cell tumor of the ovary (GCTO): An EORTC Gynecologic Cancer Coop. Group (GCCG) study

Cisplatin (P), vinblastine (V), and bleomycin (B) combination chemotherapy in recurrent or advanced granulosa cell tumor of the ovary (GCTO): An eortc gynecology cancer cooperative group study

Cisplatin (P), vinblastine (V), and bleomycin (B) combination chemotherapy in recurrent or advanced granulosa cell tumor of the ovary (GCTO): An eortc gynecology cancer cooperative group study

Steroid-receptor proteins in nonepithelial malignancies of the ovary

Tissue samples from 20 patients with nonepithelial ovarian malignancies were assayed for cytosol estrogen (ER c) and in selected samples progestin-receptor (PR c) proteins. The nine germ cell malignancies assayed were low in ER c. One recurrent granulosa cell tumor had an ER c concentration of 36 fmole/mg cytosol protein (fmole/mg c.p.) while three other stromal tumors were low in ER c. Three of seven mixed mesodermal tumors had a high ER c concentration (34–91 fmole/c.p.). Two primary and one recurrent granulosa cell tumors and one endodermal sinus tumor had borderline to elevated PR c levels (18–254 fmole/c.p.). Four of seven mixed mesodermal tumors had borderline to slightly elevated PR c concentrations (13–22 fmole/c.p.). The low ER c in germ cell malignancies of the ovary is consistent with previous clinical observations that the growth of these tumors is not influenced by removal of the contralateral ovary. The high ER c levels detected in three of seven mixed mesodermal ovarian tumors and one of three granulosa cell tumors suggest that hormone-related therapy should be investigated in the management of patients with these malignancies.