Overview of sex cord-stromal tumors of the ovary
- David M Gershenson, MD
David M Gershenson, MD
- J Taylor Wharton MD Distinguished Chair in Gynecologic Oncology
- Professor of Gynecologic Oncology
- The University of Texas MD Anderson Cancer Center
- Section Editors
- Barbara Goff, MD
Barbara Goff, MD
- Section Editor — Gynecologic Oncology
- Professor of Gynecologic Oncology
- University of Washington
- Rochelle L Garcia, MD
Rochelle L Garcia, MD
- Section Editor — Obstetric and Gynecologic Pathology
- Professor of Pathology
- Adjunct Professor of Obstetrics & Gynecology
- University of Washington Medical Center
- Don S Dizon, MD, FACP
Don S Dizon, MD, FACP
- Section Editor – Gynecologic Oncology
- Clinical Co-Director, Gynecologic Oncology
- Founder and Director, The Oncology Sexual Health Clinic
- Massachusetts General Hospital Cancer Center
- Associate Professor of Medicine
- Harvard Medical School
- Deputy Editors
- Sandy J Falk, MD, FACOG
Sandy J Falk, MD, FACOG
- Senior Deputy Editor — UpToDate
- Deputy Editor — Obstetrics, Gynecology and Women's Health
- Clinical Instructor of Obstetrics, Gynecology and Reproductive Biology
- Harvard Medical School
- Sadhna R Vora, MD
Sadhna R Vora, MD
- Deputy Editor — Oncology
- Instructor in Medicine
- Harvard Medical School
Ovarian sex cord-stromal neoplasms are a heterogeneous group of benign or malignant neoplasms that develop from the dividing cell population that would normally give rise to cells surrounding the oocytes, including the cells that produce ovarian hormones (the nongerm cell and nonepithelial components of the gonads) (figure 1 and table 1) . Malignant ovarian sex cord-stromal neoplasms are rare, comprising only 1.2 percent of all primary ovarian cancers (malignant neoplasms) .
In contrast with epithelial ovarian cancer, most patients with malignant sex cord-stromal neoplasms are diagnosed with early-stage disease; even malignant neoplasms are generally considered to be low grade . Lymph node metastases are rare from these neoplasms [3-5].
Some sex cord-stromal neoplasms produce sex steroid hormones, including estrogen and androgens [6,7]. These may result in symptoms of estrogen excess or other effects, and measurement of these and other tumor markers may play a role in diagnosis.
General principles of ovarian sex cord-stromal neoplasms are reviewed here. Histologic subtypes are discussed separately:
- Young RH. Sex cord-stromal tumors of the ovary and testis: their similarities and differences with consideration of selected problems. Mod Pathol 2005; 18 Suppl 2:S81.
- Quirk JT, Natarajan N. Ovarian cancer incidence in the United States, 1992-1999. Gynecol Oncol 2005; 97:519.
- Brown J, Sood AK, Deavers MT, et al. Patterns of metastasis in sex cord-stromal tumors of the ovary: can routine staging lymphadenectomy be omitted? Gynecol Oncol 2009; 113:86.
- Abu-Rustum NR, Restivo A, Ivy J, et al. Retroperitoneal nodal metastasis in primary and recurrent granulosa cell tumors of the ovary. Gynecol Oncol 2006; 103:31.
- Thrall MM, Paley P, Pizer E, et al. Patterns of spread and recurrence of sex cord-stromal tumors of the ovary. Gynecol Oncol 2011; 122:242.
- Varras M, Vasilakaki T, Skafida E, Akrivis C. Clinical, ultrasonographic, computed tomography and histopathological manifestations of ovarian steroid cell tumour, not otherwise specified: our experience of a rare case with female virilisation and review of the literature. Gynecol Endocrinol 2011; 27:412.
- Busquets M, Gonzalez-Bosquet E, Muchart J, et al. Granulosa cell tumor and endometrial cancer: a case report and review of the literature. Eur J Gynaecol Oncol 2010; 31:575.
- Boyce EA, Costaggini I, Vitonis A, et al. The epidemiology of ovarian granulosa cell tumors: a case-control study. Gynecol Oncol 2009; 115:221.
- Shah SP, Köbel M, Senz J, et al. Mutation of FOXL2 in granulosa-cell tumors of the ovary. N Engl J Med 2009; 360:2719.
- Heravi-Moussavi A, Anglesio MS, Cheng SW, et al. Recurrent somatic DICER1 mutations in nonepithelial ovarian cancers. N Engl J Med 2012; 366:234.
- Al-Agha OM, Huwait HF, Chow C, et al. FOXL2 is a sensitive and specific marker for sex cord-stromal tumors of the ovary. Am J Surg Pathol 2011; 35:484.
- Kommoss S, Gilks CB, Penzel R, et al. A current perspective on the pathological assessment of FOXL2 in adult-type granulosa cell tumours of the ovary. Histopathology 2014; 64:380.
- World Health Organization Classification of Tumours of Female Reproductive Organs, 4th edition, Kurman RJ, Carcangiu ML, Herrington CS, Young RH (Eds), International Agency for Research on Cancer, Lyon 2014. Vol 6.
- Chen VW, Ruiz B, Killeen JL, et al. Pathology and classification of ovarian tumors. Cancer 2003; 97:2631.
- Outwater EK, Wagner BJ, Mannion C, et al. Sex cord-stromal and steroid cell tumors of the ovary. Radiographics 1998; 18:1523.
- Miller BE, Barron BA, Wan JY, et al. Prognostic factors in adult granulosa cell tumor of the ovary. Cancer 1997; 79:1951.
- Young RH, Scully RE. Well-differentiated ovarian Sertoli-Leydig cell tumors: a clinicopathological analysis of 23 cases. Int J Gynecol Pathol 1984; 3:277.
- Gershenson DM, Morris M, Burke TW, et al. Treatment of poor-prognosis sex cord-stromal tumors of the ovary with the combination of bleomycin, etoposide, and cisplatin. Obstet Gynecol 1996; 87:527.
- Homesley HD, Bundy BN, Hurteau JA, Roth LM. Bleomycin, etoposide, and cisplatin combination therapy of ovarian granulosa cell tumors and other stromal malignancies: A Gynecologic Oncology Group study. Gynecol Oncol 1999; 72:131.
- Brown J, Shvartsman HS, Deavers MT, et al. The activity of taxanes in the treatment of sex cord-stromal ovarian tumors. J Clin Oncol 2004; 22:3517.
- Hölscher G, Anthuber C, Bastert G, et al. Improvement of survival in sex cord stromal tumors - an observational study with more than 25 years follow-up. Acta Obstet Gynecol Scand 2009; 88:440.
- Wolf JK, Mullen J, Eifel PJ, et al. Radiation treatment of advanced or recurrent granulosa cell tumor of the ovary. Gynecol Oncol 1999; 73:35.
- National Comprehensive Cancer Network (NCCN). NCCN Clinical practice guidelines in oncology. http://www.nccn.org/professionals/physician_gls/f_guidelines.asp (Accessed on February 27, 2016).
- Salani R, Backes FJ, Fung MF, et al. Posttreatment surveillance and diagnosis of recurrence in women with gynecologic malignancies: Society of Gynecologic Oncologists recommendations. Am J Obstet Gynecol 2011; 204:466.
- Färkkilä A, Koskela S, Bryk S, et al. The clinical utility of serum anti-Müllerian hormone in the follow-up of ovarian adult-type granulosa cell tumors--A comparative study with inhibin B. Int J Cancer 2015; 137:1661.
- Sehouli J, Drescher FS, Mustea A, et al. Granulosa cell tumor of the ovary: 10 years follow-up data of 65 patients. Anticancer Res 2004; 24:1223.
- Mangili G, Sigismondi C, Frigerio L, et al. Recurrent granulosa cell tumors (GCTs) of the ovary: a MITO-9 retrospective study. Gynecol Oncol 2013; 130:38.
- Colombo N, Sessa C, Landoni F, et al. Cisplatin, vinblastine, and bleomycin combination chemotherapy in metastatic granulosa cell tumor of the ovary. Obstet Gynecol 1986; 67:265.
- Martikainen H, Penttinen J, Huhtaniemi I, Kauppila A. Gonadotropin-releasing hormone agonist analog therapy effective in ovarian granulosa cell malignancy. Gynecol Oncol 1989; 35:406.
- Fishman A, Kudelka AP, Tresukosol D, et al. Leuprolide acetate for treating refractory or persistent ovarian granulosa cell tumor. J Reprod Med 1996; 41:393.
- Korach J, Perri T, Beiner M, et al. Promising effect of aromatase inhibitors on recurrent granulosa cell tumors. Int J Gynecol Cancer 2009; 19:830.
- Alhilli MM, Long HJ, Podratz KC, Bakkum-Gamez JN. Aromatase inhibitors in the treatment of recurrent ovarian granulosa cell tumors: brief report and review of the literature. J Obstet Gynaecol Res 2012; 38:340.
- Brown J, Brady WE, Schink J, et al. Efficacy and safety of bevacizumab in recurrent sex cord-stromal ovarian tumors: results of a phase 2 trial of the Gynecologic Oncology Group. Cancer 2014; 120:344.
- EPIDEMIOLOGY AND RISK FACTORS
- Cell population
- Patterns of spread
- CLINICAL FEATURES
- Clinical presentation
- Physical examination
- Tumor markers
- Imaging studies
- Endometrial sampling
- Staging and surgical treatment
- - Preoperative preparation and evaluation
- - Staging system and procedure
- - Fertility preservation
- Postoperative treatment
- POSTTREATMENT SURVEILLANCE
- HORMONE THERAPY FOLLOWING TREATMENT
- APPROACH TO RECURRENT DISEASE
- INFORMATION FOR PATIENTS
- SUMMARY AND RECOMMENDATIONS