Juvenile granulosa cell tumor of the ovary associated with tuberous sclerosis

BACKGROUND: Tuberous sclerosis is a neurocutaneous syndrome characterized by benign tumors that can affect many organs. Juvenile granulosa cell tumors of the ovary are rare neoplasms that typically occur in the first three decades of life and have excellent prognosis for early-staged disease. CASE REPORT: We report the first case of an 8-year-old white female with tuberous sclerosis and juvenile granulosa cell tumor of the ovary. She presented with a 20 x 22 cm pelvic mass and received a right salpingo-oophorectomy. Three months later, she recurred and underwent a left salpingo-oophorectomy, lymphadenectomy, and omentectomy followed by four cycles of Bleomycin, Etoposide, and Cisplatin chemotherapy. She is currently free of disease 8 years after her recurrence. CONCLUSION: Treatment options and a review of the literature pertaining to juvenile ovarian granulosa cell tumors and tuberous sclerosis are discussed.     

Androgenic juvenile granulosa cell tumor of the ovary with cystic presentation: a case report

Granulosa cell tumors account for approximately 1-2% of all ovarian tumors. There are two types: adult granulosa cell tumor and juvenile granulosa cell tumor. Juvenile granulosa cell tumors constitute 5% of this histological subtype, and the prognosis is good because the majority present as Stage I tumors. The treatment can consist of conservative surgery. Androgen production is rare and produces virilization in women. These tumors are usually solid or predominantly solid. We describe the case of a 13-year-old girl with androgenic manifestations and increased abdominal size. Her plasma testosterone level was elevated. A left adnexal cyst (14.4 x 9.1 x 9.7 cm) was revealed at pelvic ultrasonography. The patient underwent an exploratory laparotomy, revealing a left ovarian cystic tumor. Diagnosis was juvenile granulosa cell tumor.     

卵巢颗粒细胞瘤预后影响因素的分析

目的 探讨卵巢颗粒细胞瘤临床、病理因素对预后的影响。方法 回顾性分析我院１９５８年至１９９５年收治的１００例卵巢颗粒细胞瘤患者的年龄、临床分期、核分裂相及早期患者的治疗方法选择等因素与预后的,并对复发与未复发患者,近期复发（〈１０年）与远期复发（≥１０年）患者进行比较。结果 全组总的５年和１０年生存率分别为８０％和７２％。不同年龄患者（≥４０岁,〈４０岁）的５年和１０年生存率,分别比较,差异无显著性（Ｐ〉０．０５）。临床分期为Ⅰ期者５年和１０年生存率分别为９８％和９６％,Ⅱ期分别为７０％和６０％,Ⅲ～Ⅳ期均为０％;外院治疗后复发或未控者５年和１０年生存率分别为５８％和４０％,分别比较,差异均有显著性（Ｐ均〈０．０５）。４７例有核分裂相计数的患者中,核分裂相〈５／１０高倍视野（ＨＰＦ）的５年和１０年生存率均为９６     

GnRH antagonist in the adjuvant treatment of a recurrent ovarian granulosa cell tumor: a case report

BACKGROUND: Ovarian granulosa cell tumors (GCT) are usually treated by surgery and chemotherapy. Successful response to GnRH agonists as an adjuvant therapy has previously been reported. In this case of recurrent GCT, we used a GnRH antagonist. CASE: A 78-year-old woman underwent surgery for an ovarian granulosa cell tumor (pT1a N0 Mx). Six months later, laparotomy revealed an inoperable recurrence of the tumor. Experimental treatment with a GnRH antagonist was not clearly successful. This is in contrast to the previously proven benefit of GnRH agonist therapy in this type of malignancy and to the positive response elicited by GnRH antagonists in epithelial ovarian tumors. CONCLUSION: GnRH antagonist therapy had no demonstrable efficacy in the treatment of a poorly differentiated and aggressive recurrent granulosa cell tumor.     

Masculinizing granulosa cell tumor of the ovary in a postmenopausal woman. A case report.

BACKGROUND: A total of 32 cases of virilizing granulosa cell tumors of the ovary have been reported. The current case has some unique features not previously reported. CASE: A 78-year-old woman presented with symptoms and signs of masculinization. A large, painless abdominal mass was discovered. Exploration revealed the mass to be originating in the left ovary, and surgical resection resulted in prompt reversal of the clinical and biochemical hyperandrogenic manifestations. Morphologic studies demonstrated a homogeneous granulosa cell tumor. CONCLUSION: This is the oldest patient on record with a masculinizing granulosa cell tumor and also the only masculinizing tumor presenting with advanced, stage III disease. Such tumors, although rare, should be considered in the differential diagnosis in postmenopausal women presenting with masculinizing symptoms.     

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

Granulosa cell tumors are ovarian sex cord stromal cancers that are unique for their indolent nature and late recurrence. Standard treatment regimens utilized include surgery, chemotherapy, and radiotherapy. However, hormonal suppression with aromatase inhibitors, which have shown promising results, may be a viable alternative to these modalities. 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.     

Synchronous ovarian granulosa cell tumor and uterine serous carcinoma: a rare association of a high-risk endometrial cancer with anestrogenic ovarian tumor

BACKGROUND: Ovarian granulosa cell tumors are often associated with endometrial hyperplasia or carcinoma. The endometrial carcinoma is thought to occur under the influence of the estrogen receptor pathway and is typically a low-grade, low-stage endometrioid adenocarcinoma. CASE: We present a case of a woman with a granulosa cell tumor of the ovary and a synchronous serous carcinoma of the endometrium. Immunohistochemical stains for estrogen receptors, progesterone receptors, and p53 protein were performed on both tumors. CONCLUSIONS: Not all uterine tumors associated with ovarian granulosa cell tumors have low-risk histology. Preoperative evaluation of the uterus with attention to tumor subtyping is important for optimum staging and therapy.     

Extraovarian granulosa cell tumor.

OBJECTIVE: The aim of this study was to report a case of extraovarian granulosa cell tumor and to describe its relevance to the histologic origin of granulosa cell tumors and to clinical practice. METHODS: The clinical course and histopathology of the case were reviewed, and a literature search for other reported cases was performed. RESULTS: A 67-year-old woman presented with postmenopausal bleeding and a pelvic mass. Laparotomy revealed a 16-cm mass arising from the right pelvic sidewall, filling the pelvis, and involving the bladder and rectosigmoid colon. Both ovaries appeared normal and were separate from the mass. Pathologic examination revealed granulosa cell tumor. A literature search revealed no recently reported cases of extraovarian granulosa cell tumor. CONCLUSIONS: Granulosa cell tumors can arise in locations other than the ovary and may be derived from the mesenchyme of the genital ridge. Women who have undergone oophorectomy may have the potential to develop granulosa cell tumors.     

Trisomy 12 in juvenile granulosa cell tumor of the ovary during pregnancy. A report of two cases.

BACKGROUND: Granulosa cell tumors constitute only 5% of ovarian neoplasms, and their coexistence with pregnancy is extremely rare. Juvenile granulosa cell tumor has a good prognosis if it is confined to the ovary, but this type behaves more aggressively than the adult type at advanced stages. CASES: We report on successful completion of two singleton pregnancies and deliveries of normal infants in two young women with juvenile granulosa cell tumor diagnosed and treated during pregnancy. This tumor has rarely been described in association with pregnancy. The presence of trisomy 12 as a single chromosomal abnormality was detected in these two tumors. Both tumors were localized strictly to the ovary, so conservative surgery was applied and proved sufficient to remove all tumor tissue. Follow-up showed no signs of recurrence 18 and 53 months after the interventions. CONCLUSION: These cases support the contention that trisomy 12 is a nonrandom chromosome abnormality in juvenile granulosa cell tumors and that pregnancy may affect nuclear stability in this tumor.     

Recurrence of granulosa cell tumor 25 years after initial diagnosis. Report of a case and review of the literature

Granulosa cell tumors (GCTs) are rare functional sex cord-stromal ovarian tumors constituting approximately 2-3% of all ovarian malignancies. They are characterized by low malignant potential, local spread, late recurrence and high survival rates. We report a case of recurrent ovarian GCT in a 60-year-old woman 25 years after the initial diagnosis. The patient underwent surgical resection of the pelvic masses and refused to receive any adjuvant treatment, considering the late recurrence and high survival rates of this tumor. This case illustrates an example of a very late recurrence and emphasizes the importance of the extended follow-up required for these patients.     

Recurrent Granulosa Cell Tumor of the Ovary 37 Years after Initial Diagnosis: A Case Report and Review of the Literature

Granulosa cell tumors of the ovary (GCTs) are uncommon neoplasms that are characterized by late recurrence and high survival rates. A case of recurrent GCT presenting 37 years after initial diagnosis is reported with a review of the literature. This case illustrates an example of a very late recurrence and emphasizes the importance of the extended follow-up required for these patients.     

Tumor ovárico virilizante mixto de células de Sertoli-Leydig/granulosa (ginandroblastoma) en adolescente de 15 años

Sertoli-Leydig cell tumors constitute less than 5% of ovarian tumors. We report the case of a 15-year-old girl with virilization, amenorrhea, and abdominal pain, who was diagnosed with a left annexal tumor. Laboratory investigations revealed isolated testosterone elevation. Because the tumor was unilateral, the capsule was intact, and the patient wished to preserve her fertility, left salpingooophorectomy was performed. Histopathological examination revealed a mixed Sertoli-Leydig/juvenile granulosa cell tumor with a cartilaginous heterologous component, which could be considered a gynandroblastoma. Symptoms of virilization progressively improved.     

Early-stage granulosa cell tumor with pelvic recurrence and lung metastasis 16 years later: A case report and review of the literature

ObjectiveOnly a few cases of early-stage ovarian granulosa cell tumor (GCT) with lung metastasis have been previously documented in the literature. We present a case of stage IA adult-type ovarian GCT with late pelvic recurrence and lung metastasis and review the relevant literature.Case reportA 71-year-old female who underwent total abdominal hysterectomy and bilateral salpingo-oophorectomy for an ovarian GCT in her early 50s presented with pelvic recurrence 16 years later. Lung metastasis was accidentally discovered during a preoperative computed tomography scan of the pelvic tumor. The patient received surgical resection and adjuvant chemotherapy. She remains alive and healthy without evidence of disease after 12 months of follow up.ConclusionThis case illustrates the importance of long-term follow-up for early-stage GCTs. It also highlights the requirement of extended examination for possible extra-abdominal/pelvic tumors.     

Sequential recurrences of ovarian granulosa cell tumour 10 and 11 years after initial diagnosis as haemoperitoneum and subhepatic mass: a case report and review of the literature

Adult granulosa cell tumours (GCTs) are rare ovarian neoplasms characterised by an indolent course and a propensity for late recurrence. Due to frequent endocrine manifestations most GCTs are diagnosed at an early stage. However, clinical behaviour can not be safely predicted on the basis of conventional clinicopathologic parameters. Surgery remains the cornerstone of therapeutic management. We report on a rare case of a Stage IA GCT twice recurring ten and 11 years after initial surgical treatment. The first recurrence presented as an acute abdomen due to haemoperitoneum after tumour rupture. The second recurrence presented as a subhepatic mass. This case emphasises the need for extended, lifelong follow-up even for patients with early stage, apparently completely removed GCTs. Prognostic parameters and therapeutic options especially for patients with recurrent disease are discussed.     

CD56 expression in ovarian granulosa cell tumors, and its diagnostic utility and pitfalls

OBJECTIVE: The purpose of this study is to investigate CD56 staining in ovarian granulosa cell tumor and its morphological mimics in order to determine the value of CD56 staining in a diagnostic setting. MATERIALS AND METHODS: Tissue samples taken from 82 ovarian tumors, 26 extra-ovarian tumors and 11 normal ovaries were immunohistochemically stained using monoclonal anti-CD56 antibody. Ovarian tumors comprised 32 granulosa cell tumors, 3 Sertoli-stromal cell tumors, 14 fibrothecomas, 6 carcinoid tumors, 1 large cell neuroendocrine carcinoma, 17 endometrioid adenocarcinomas and 9 poorly differentiated serous adenocarcinomas. Extra-ovarian tumors comprised 22 uterine endometrial stromal sarcomas and 4 pulmonary small cell carcinomas. Normal ovaries contained 47 ovarian follicles. RESULTS: All of the 32 granulosa cell tumors, all of the 3 Sertoli-stromal cell tumors, all of the 4 small cell carcinomas, 1 of 1 large cell neuroendocrine carcinoma, 11 of 14 fibrothecomas, 5 of 6 carcinoid tumors, 17 of 22 endometrial stromal sarcomas and 7 of 9 poorly differentiated serous adenocarcinomas were positive for CD56. No immunoreactive cells were observed in 17 endometrioid adenocarcinomas or 47 ovarian follicles. All the immunoreactive cells showed membranous staining except for fibrothecomas where vague cytoplasmic staining was seen. CONCLUSION: CD56, known as a neuroendocrine marker, is a sensitive marker of granulosa cell tumors, but since granulosa cell tumors and neuroendocrine tumors may be morphologically similar, CD56 positivity represents a significant diagnostic pitfall. CD56 is useful in distinguishing between granulosa cell tumor and normal ovarian follicles or endometrioid adenocarcinoma. Lack of membranous CD56 expression in fibrothecoma may help differentiate it from granulosa cell tumor. However, CD56 is of limited use for distinguishing between granulosa cell tumor and poorly differentiated carcinoma or endometrial stromal sarcoma. Appropriate and cautious interpretation of CD56 expression should lead to a more accurate diagnosis of granulosa cell tumor.     

Theca and granulosa cell tumors and endometrial adenocarcinoma

A retrospective study of 74 cases of theca and granulosa cell tumors of the ovary is presented. In 15% of women with theca cell tumors endometrial adenocarcinoma was found; the same was true for 8% of women in the granulosa cell tumor group and two out of four women with a mixed type of tumor had endometrial adenocarcinoma. Granulosa cell tumors should be regarded as malignant and treated accordingly; treatment for theca cell tumors is surgical removal. Endometria should always be examined. Long-term follow-up is compulsory because of the possibility of late recurrences.     

Anastrozole therapy in recurrent ovarian adult granulosa cell tumors: a report of 2 cases

BACKGROUND: Ovarian sex cord stromal tumors are frequently hormonally active, and adult granulosa cell tumors often demonstrate estrogen receptor positivity. Thus, hormonal agents have been evaluated as potential treatments for advanced stage or recurrent adult granulosa cell tumors. CASE: Two cases of patients with recurrent adult granulosa cell tumors are presented. Each patient received multiple treatment modalities including chemotherapy and had previously progressed on leuprolide. Both patients were started on anastrozole with subsequent normalization of inhibin B levels and clinical exams. They have been maintained on treatment for 14 and 18 months, respectively, and have tolerated the drug without difficulty. CONCLUSION: Aromatase inhibitors may be a viable treatment option for women with advanced stage or recurrent ovarian adult granulosa cell tumors.     

早期成人型卵巢颗粒细胞瘤复发相关因素分析北大核心CSCD

目的探讨国际妇产科联盟(FIGO)(2014版)Ⅰ期成人型卵巢颗粒细胞瘤复发的相关高危因素。方法回顾性分析首都医科大学附属北京朝阳医院及中国医学科学院北京协和医院1995年1月至2010年1月收治的FIGOⅠ期成人型卵巢颗粒细胞瘤。分析患者临床及病理相关因素与肿瘤复发的关系。结果研究共纳入18例FIGOⅠ期成人型卵巢颗粒细胞瘤患者,患者中位年龄为43岁(31~69岁)。初始治疗中7例行单纯肿瘤剥除/单侧附件切除术,8例行子宫双附件切除术,3例行卵巢肿瘤全面分期术。患者术后5年和10年总生存率分别为94.4%和83.3%。共6例患者复发,中位复发时间为76个月。肿瘤直径>10cm、术中瘤体破裂是患者近期复发(<5年)的高危因素。低分化、术中瘤体破裂、高核分裂象(≥4/10HPF)是患者远期复发(≥5年)的高危因素。结论早期成人型卵巢颗粒细胞瘤整体预后好,高核分裂象、术中瘤体破裂可能是早期卵巢颗粒细胞瘤复发的潜在高危因素。     

Granulosa cell tumors of the ovary: the clinical value of serum inhibin A and B levels in a large single center cohort

OBJECTIVES: In patients with a granulosa cell tumor of the ovary, the value of serum inhibin A and B concentrations for the assessment of disease status was investigated. METHODS: In 30 consecutive patients with a stage I-III granulosa cell tumor, inhibin A and B concentrations were measured in pre- and post-treatment serum samples. Clinical data concerning diagnosis, treatment and follow-up of these patients were related to serum inhibin A and B concentrations. Serum samples from 41 premenopausal females with cervical dysplasia served as controls. RESULTS: In 30 patients, 13 (43%) recurrences were observed during a median follow-up of 10 years (range 1-31 years). Serum inhibin A and B concentrations were elevated in respectively 67% and 89% of the patients at diagnosis, and in 58% and 85% at recurrence. Inhibin A and B concentrations were normal in all controls. Sensitivity of inhibin A testing for the diagnosis of granulosa cell tumor was 67% with a specificity of 100%, compared to 89% and 100% respectively for inhibin B (ns). Elevations in serum inhibin B concentrations predated recurrences by a median of 11 months. None of the patients in remission showed increased concentrations of inhibin A and B. CONCLUSION: Inhibin B seems to be the predominant form of inhibin secreted by granulosa cell tumors and appears to reflect disease status more accurately than inhibin A. Measurement of serum inhibin B concentrations may be preferred for the follow-up of granulosa cell tumors.     

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

OBJECTIVES: Very little is known about the biology of granulosa cell tumors of the ovary. A hallmark of granulosa cell tumors of the ovary is extensive growth, distant metastases however, are rarely found. We hypothesise that granulosa cell tumors of the ovary on the one hand need to stimulate vascularisation; on the other hand glucose metabolism has to be altered to ensure the supply of nutrients and metabolites. Increased glycolysis, the main source of energy supply, is considered to be important during malignant transformation. Thus, we focussed on a selection of key factors in angiogenesis and tumor glycolysis to study metabolic characteristics of granulosa cell tumors of the ovary. STUDY DESIGN: We analysed 32 tumor specimens for immunohistochemical expression of vascular endothelial growth factor, phosphorylated Akt, M2 pyruvate kinase isoenzyme, and transketolase-like enzyme 1. As controls, we stained 10 samples of normal ovaries. RESULTS: We found expression of vascular endothelial growth factor in 94%, transketolase-like enzyme 1 in 81%, and phosphorylated Akt as well as M2 pyruvate kinase isoenzyme in 53% of the specimens. There were no significant differences between the expression levels in primary and those in recurrent tumors. Temporal analysis of marker expression in primary tumors and recurrences in the same patients revealed no increase or decrease of marker expression overtime. In contrast to granulosa cell tumors, normal ovaries showed no expression of the markers analysed in granulosa cells. 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.