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Granulosa-Theca Cell Tumors Treatment & Management

  • Author: David C Starks, MD, MPH; Chief Editor: Warner K Huh, MD  more...
 
Updated: Jan 15, 2015
 

Medical Care

Primary treatment for patients with GCTs is surgical. Chemotherapy and/or radiotherapy are reserved for patients with advanced disease by surgical staging, and for patients with recurrent tumor.

Surveillance for patients postoperatively consists of frequent pelvic examinations and assessment of tumor markers (if applicable) to detect recurrences as early as possible. Findings from physical examination or laboratory studies that are suggestive of recurrence should be further evaluated with abdominopelvic CT scan or other diagnostic imaging modalities.

Radiotherapy for patients with advanced or recurrent GCTs has been studied and appears to have limited efficacy.

In a 1999 study by Wolf et al at the MD Anderson Cancer Center, 6 of 14 patients with measurable disease had complete clinical responses to pelvic radiation and 3 patients were without evidence of disease 10-21 years after radiation. However, 3 patients experienced a recurrence 4-5 years after radiation.[12] Eight of 14 had no response to treatment and had a median survival of 12.3 months overall.

A more recent study by Hauspy et al reviewed 45 years of GCT treatment at Princess Margaret Hospital. Thirty-one of 103 women received abdominal and/or pelvic radiation as adjuvant therapy. Multivariate analysis showed that adjuvant radiation significantly improved survival and that stage III disease was independently predictive of a poor response. They concluded that patients receiving radiation had better disease-free survival (251 mo vs 114 mo for those not receiving radiation). However, 86% of those receiving radiation were stage I versus only 52% of those who did not receive radiation. Moreover, only 2 of the 103 patients received chemotherapy.[13]

Currently, radiation is considered an option for advanced-stage patients and, in patients with pelvic recurrence, radiotherapy should be considered because a clinical response occurs in almost half of patients treated with radiation therapy.

Adjuvant therapy for GCTs has typically been carried out using chemotherapy. There is also data available regarding hormonal manipulation of these tumors using GnRH analogues and aromatase inhibitors. See additional discussion under "Experimental medications" below.

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Surgical Care

Standard of care for initial management of GCTs remains surgical.[14] Surgical management allows for staging and tissue diagnosis.

Surgical management of patients who present with signs and symptoms concerning for GCTs begins with a thorough preoperative evaluation.

Preoperative imaging and laboratory studies are helpful for measuring the extent of disease permitting proper patient counseling (see Lab Studies and Imaging Studies).

Appropriate staging with intact removal of the tumor and optimal cytoreduction are the main goals of surgical therapy. Several studies have shown that FIGO stage is the most prognostic factor for granulosa cell tumors.

In a 2003 study, Uygun et al showed a definite survival benefit for patients with lower-stage tumors and for patients who had no residual disease at surgery (mean overall survival 108 mo) versus those with residual disease at the end of surgery (mean 42 mo, p = 0.001).[15]

Prepare patients for the possibility of bowel resection and/or ostomy placement if diffuse spread is suggested following the preoperative assessment. A mechanical bowel preparation, with or without antibiotics, should be used in all patients undergoing surgery for a pelvic mass.

Complete surgical staging consists of a thorough examination of the pelvic and intra-abdominal structures. If disease is identified outside the ovary, optimal debulking should be performed so that all remaining tumor nodules are smaller than 1 cm, but goal should still be complete resection of all visible tumor. Optimal tumor debulking improves overall survival and decreases recurrences.

In younger patients who desire future fertility, a unilateral salpingo-oophorectomy almost always provides sufficient treatment because most of these tumors are stage I (see Staging). Zanagnolo et al, in a review of 63 cases of sex cord stromal tumors, reported that conservative surgical management was performed in 23% of early stage tumors. No recurrences were noted and 5 out of 11 patients became pregnant.[16]

Staging should generally be performed and consists of pelvic washings, selective ipsilateral pelvic and bilateral periaortic lymph node sampling, peritoneal biopsies, partial omentectomy, and biopsy of the contralateral ovary (only if it appears abnormal). Previously, biopsy of the contralateral ovary was considered a routine part of the staging procedure but now is not required because only approximately 2% of tumors are bilateral and biopsy may lead to adhesion formation and subsequent problems with pain and/or fertility.

A retrospective study from MD Anderson has called into question the need for lymphadenectomy to be routinely performed as part of the standard staging procedure for GCTs due to the low risk of lymph node metastasis even in cases of advanced stage disease. Because hormone overproduction is common with GCTs, dilatation and curettage should be considered to help rule out a neoplastic process of the endometrium in younger patients undergoing fertility-sparing surgery, especially if abnormal uterine bleeding was part of their clinical presentation.[17]

A more recent study by Thrall et al supports the concept of avoiding lymphadenectomy. In their study, there were no lymph node metastases in 47 patients who had at least some lymph nodes removed, with a median lymph node count of 14 in 36 of these patients. However, 2 of 18 patients who recurred did not undergo initial nodal dissection. Moreover, they noted that 60% of patients who were stage II or higher had only microscopic extraovarian disease.[18]

Although data on the clinical utility of lymphadenectomy in sex cord stromal tumors is mounting, there are no uniform recommendations and there remains an important role for surgical staging/biopsy based on incidence of microscopic extraovarian disease.

For patients in whom future fertility is not a concern, surgical therapy should consist of bilateral salpingo-oophorectomy and total abdominal hysterectomy, in addition to the staging procedures.

Treatment of recurrent GCTs is not as uniform as it is for the primary tumors. Surgical debulking can be of value if the tumor appears to be focal on imaging studies. Chemotherapy, radiotherapy, and hormonal treatments have been used with variable success. All appear to have some benefit for improving long-term survival and the progression-free interval. Mean survival after a recurrence has been diagnosed is approximately 5 years for adult GCTs.[19]

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Consultations

Gynecologic oncologist or surgical oncologist

Consultation is appropriate to help treat patients with GCTs. Unfortunately, the diagnosis of GCT usually is not made until the histologic review is completed. Therefore, appropriate preoperative consultation and intraoperative frozen sections help to ensure that patients are appropriately staged and have the best chance to be optimally debulked during their initial laparotomy.

For patients in whom the diagnosis is made postoperatively, consultation with a gynecologic oncologist or hematologic oncologist still should be pursued.

The question of when to obtain preoperative consultation with a gynecologic oncologist can be difficult to delineate. A good rule of thumb is that all postmenopausal and premenarchal patients with adnexal masses should have the benefit of a consultation with an oncologist because the risk of malignancy is greater.

In reproductive-aged patients, the vast majority of adnexal masses are benign. Patients with radiologic or sonographic findings suggestive of malignancy (solid or mixed solid and cystic tumors, ascites, etc) and patients with endocrinologic symptoms and an adnexal mass should have the benefit of a preoperative consultation with a gynecologic oncologist. Patients with a question of malignancy preoperatively can also be evaluated with serum tumor markers including CA125, CA19-9, LDH, AFP, beta-hCG, and inhibin levels. Appropriate referral should be made if any of these are significantly elevated.

Gastroenterologist

Patients with primarily GI complaints may benefit from a consultation with a gastroenterologist to rule out a primary GI source prior to surgical exploration. Endoscopy can be performed during this preoperative evaluation if indicated.

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Diet

No dietary restrictions or requirements are needed.

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Activity

No activity restrictions are needed, outside of the normal postoperative recovery time.

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Contributor Information and Disclosures
Author

David C Starks, MD, MPH Faculty Staff, Avera Medical Group Gynecologic Oncology, Avera Cancer Institute

Disclosure: Nothing to disclose.

Coauthor(s)

Daniel K Chan, MD, PhD Resident Physician, Department of Obstetrics and Gynecology, Magee-Womens Hospital of UPMC

Daniel K Chan, MD, PhD is a member of the following medical societies: American Association for Cancer Research, American College of Obstetricians and Gynecologists, American Medical Association, Association of Professors of Gynecology and Obstetrics, American Congress of Obstetricians and Gynecologists, American Physician Scientists Association

Disclosure: Nothing to disclose.

Specialty Editor Board

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

Chief Editor

Warner K Huh, MD Professor, Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, Senior Scientist, Comprehensive Cancer Center, University of Alabama School of Medicine

Warner K Huh, MD is a member of the following medical societies: American College of Obstetricians and Gynecologists, American College of Surgeons, Massachusetts Medical Society, Society of Gynecologic Oncology, American Society of Clinical Oncology

Disclosure: I have received consulting fees for: Merck; THEVAX.

Additional Contributors

Bruce A Meyer, MD, MBA Executive Vice President for Health System Affairs, Executive Director, Faculty Practice Plan, Professor, Department of Obstetrics and Gynecology, University of Texas Southwestern Medical School

Bruce A Meyer, MD, MBA is a member of the following medical societies: Medical Group Management Association, American College of Obstetricians and Gynecologists, American Association for Physician Leadership, American Institute of Ultrasound in Medicine, Association of Professors of Gynecology and Obstetrics, Massachusetts Medical Society, Society for Maternal-Fetal Medicine

Disclosure: Nothing to disclose.

Acknowledgements

Alfonso Barnes, MD, Director of Gynecologic Oncology, Department of Obstetrics and Gynecology, Bethesda Hospitals; Director of Gynecology Service, Department of Obstetrics and Gynecology, Providence Hospital

Disclosure: Nothing to disclose.

Chad M Michener, MD Assistant Professor, Obstetrics/ Gynecology and Women's Health Institute, Section of Gynecologic Oncology, The Cleveland Clinic

Chad M Michener, MD is a member of the following medical societies: American College of Obstetricians and Gynecologists and Society of Gynecologist Oncologists

Disclosure: Nothing to disclose.

Allan Y Wu, MD Director, The Midwest Women's Specialty Group; Adjunct Clinical Professor, Department of Molecular Biology, The Terre Haute Center for Medical Education, Indiana University School of Medicine

Allan Y Wu, MD is a member of the following medical societies: American College of Obstetricians and Gynecologists

Disclosure: Nothing to disclose.

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Microfollicular pattern of an adult granulosa cell tumor at 100X magnification. Inset is characteristic Call-Exner bodies and nuclear grooves (400X). Image courtesy of James B. Farnum, MD, TriHealth Department of Pathology.
Less well-differentiated diffuse pattern of adult granulosa cell tumor. Monotonous pattern can be confused with low-grade stromal sarcoma (200X). Inset is high-power magnification demonstrating nuclear grooves and nuclear atypia. Image courtesy of James B. Farnum, MD, TriHealth Department of Pathology.
Juvenile granulosa cell tumor. Multiple follicles in various shapes and sizes (200X). Inset shows nuclei that are rounded, hyperchromatic, lacking grooves and showing atypia, and are abnormal mitotic figures (400X). Image courtesy of James B. Farnum, MD, TriHealth Department of Pathology.
Gyriform pattern of adult granulosa cell tumor. Undulating single-file rows of granulosa cells (200X). Image courtesy of James B. Farnum, MD, TriHealth Department of Pathology.
Theca cell tumor. Typical thecoma with lipid-rich cytoplasm, pale nuclei, and intervening hyaline bands (200X). Image courtesy of James B. Farnum, MD, TriHealth Department of Pathology.
Luteinized thecoma. Vacuolated theca cells with an abundant fibromatous stroma (200X). Image courtesy of James B. Farnum, MD, TriHealth Department of Pathology.
 
 
 
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