Granulosa-Theca Cell Tumors Treatment & Management

  • Author: Chad M Michener, MD; Chief Editor: Warner K Huh, MD   more...
 
Updated: Jan 4, 2010
 

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.[42] Eight of 14 had no response to treatment and had a median survival of 12.3 months overall. In patients with pelvic recurrences, radiotherapy as adjuvant therapy should be considered because a clinical response occurs in almost half of patients treated with radiation therapy.
  • Treatment of recurrent GCTs with leuprolide acetate has been described but exhibited only marginal success in a small number of patients. Treatment with anastrazole and other hormonal therapies is currently considered experimental.
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Surgical Care

  • Standard of care for initial management of GCTs remains surgical.[8] 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).[40]
  • 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.[44]
    • Staging should 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.
    • 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.[6]
  • 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.
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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

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.

Coauthor(s)

David C Starks, MD  Fellow, Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, Cleveland Clinic Foundation

Disclosure: Nothing to disclose.

Specialty Editor Board

Bruce A Meyer, MD, MBA  Executive Vice President for Health System Affairs, Chief Clinical Officer, Interim CEO, University Hospitals; 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: American College of Obstetricians and Gynecologists, American College of Physician Executives, American Institute of Ultrasound in Medicine, Association of Professors of Gynecology and Obstetrics, Massachusetts Medical Society, Medical Group Management Association, and Society for Maternal-Fetal Medicine

Disclosure: Nothing to disclose.

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

Disclosure: Medscape Salary Employment

Frederick B Gaupp, MD  Consulting Staff, Department of Family Practice, Hancock Medical Center

Frederick B Gaupp, MD is a member of the following medical societies: American Academy of Family Physicians

Disclosure: Nothing to disclose.

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, American Society of Clinical Oncology, Massachusetts Medical Society, and Society of Gynecologist Oncologists

Disclosure: MERCK Consulting fee Consulting; GSK Consulting fee Consulting; ROCHE PHARMA/DIAGNOSTICS Consulting fee Consulting; HOLOGICS Consulting fee Consulting; HELIX BIOPHARMA Consulting fee Consulting; COVIDIEN Consulting fee Consulting; INTUITIVE SURGICAL Surgical Proctor

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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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