Journal of Human Reproductive Science
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Year : 2018  |  Volume : 11  |  Issue : 2  |  Page : 190-192

Adult granulosa cell tumor: A sinister differential for clomiphene-resistant infertility

1 Department of Obstetrics and Gynecology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
2 Department of Cytology and Gynecological Pathology, Postgraduate Institute of Medical Education and Research, Chandigarh, India

Date of Web Publication1-Aug-2018

Correspondence Address:
Dr. Japleen Kaur
Department of Obstetrics and Gynecology, Postgraduate Institute of Medical Education and Research, Chandigarh
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/jhrs.JHRS_142_17

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Granulosa cell tumors (GCTs) are rare sex cord–stromal tumors of the ovary. They may present with features of hyperestrogenism. We present a case of a 29-year-old nulliparous female, with infertility and oligomenorrhoea, initially managed with a provisional diagnosis of polycystic ovarian syndrome. She did not respond to multiple cycles of ovulation induction with clomiphene citrate. Later, an ovarian mass was detected, and she was initially planned for laparoscopy. Magnetic resonance imaging pelvis revealed a solid-looking mass in the ovary, with increased vascularity. Fine-needle aspiration cytology from the mass suggested GCT. She underwent staging laparotomy with fertility-preserving surgery. Thereafter, she conceived on first cycle of clomiphene citrate. She delivered twins and is presently 8 months postpartum. Thus, a high index of suspicion for underlying androgen- or estrogen-secreting tumor in cases of clomiphene-resistant infertility with ovarian cysts is advisable.

Keywords: Clomiphene, follow-up, granulosa cell tumor, infertility

How to cite this article:
Gainder S, Kaur J, Siwatch S, Gupta N. Adult granulosa cell tumor: A sinister differential for clomiphene-resistant infertility. J Hum Reprod Sci 2018;11:190-2

How to cite this URL:
Gainder S, Kaur J, Siwatch S, Gupta N. Adult granulosa cell tumor: A sinister differential for clomiphene-resistant infertility. J Hum Reprod Sci [serial online] 2018 [cited 2022 Jun 26];11:190-2. Available from:

   Introduction Top

Granulosa cell tumors are one of the rare tumors of ovary.[1] These sex cord stromal tumors of ovary are characterized by affection at younger age group and good prognosis with early detection and treatment.[2] They are estrogen secreting tumors and commonly present with menstrual disturbances and features of hyperestrogenism in the reproductive age women.[1] We present a case of a 29 year old female who presented with infertility and ovulated with clomiphene citrate, after surgical excision of the tumor.

   Case Report Top

A 29-year-old nulliparous female presented to our outpatient department with the inability to conceive for 4 years. She also complained of amenorrhea, with menstruation occurring only after progesterone withdrawal. There were no associated complaints of acne, hirsutism, weight gain, or galactorrhea. She had been evaluated at a local private hospital and was being treated as a case of polycystic ovarian syndrome. She had received multiple cycles of ovulation induction with clomiphene citrate as well as gonadotropins but did not ovulate. There was no significant family history. At our institute, she was prescribed tablet metformin and given clomiphene citrate for ovulation induction, with no success. After 3 months of treatment, pelvic sonography revealed bulky left ovary with hemorrhagic/endometriotic cyst. She was thus planned for laparoscopy. She returned after 3 months, and a magnetic resonance imaging pelvis was done, which reported a large (5.7 cm × 5.3 cm × 5.3 cm) mass in left adnexa with increased vascularity likely sclerosing stromal tumor. Ultrasound-guided fine-needle aspiration was done, which revealed granulosa cell tumor (GCT). By this time, cystic mass was palpable anterior to uterus on bimanual examination. Her serum anti-Müllerian hormone (sAMH) was >20 ng/mL, whereas inhibin B was >1122 pg/mL (normal range 14–362 pg/mL). Endometrial biopsy showed proliferative endometrium. She underwent staging laparotomy with left salpingo-oophorectomy and multiple peritoneal and omental biopsies. Intraoperatively, there was 6 cm × 6 cm left ovarian mass with surgical spill, right ovary and tube was normal, no evidence of metastasis, and no palpable lymphadenopathy. Histopathology report showed adult GCT limited to left ovary. Her final diagnosis was adult GCT Stage IC1. Postoperative period was uneventful. She had normal menstrual cycles from the next month. She was advised clomiphene citrate as she was apprehensive and eager to conceive and there was no contraindication for its use. She conceived twins in her first clomiphene cycle. She went into preterm labor at 32-week period of gestation and delivered twins weighing 1.8 and 1.9 kg. Three months postpartum, her clinical examination was unremarkable. Inhibin levels were 15 pg/mL at 6-month follow-up. She was asymptomatic at her last follow-up visit at 8-month postpartum.

   Discussion Top

GCT is a type of sex cord–stromal tumor of ovary. With an incidence of about 0.58–1.6 per 100,000 women per year, it contributes to <5% of ovarian tumors.[1]

Some characteristic features of GCTs in contrast to the more common epithelial tumors include affecting younger age group, features of hyperestrogenism, detection at early stage, and good prognosis with surgical cure.[1] It is also a differential diagnosis of isosexual precocious puberty. Initial symptoms may be nonspecific like pain abdomen or distension. About 30% of patients in reproductive age group present with menstrual disturbances, as seen in our patient.[1]

Adult variety of GCT is generally seen in the premenopausal or early postmenopausal women and the median age of diagnosis is 51 years, although it has been reported from 9 to 93 years, our patient being 29 years.[2] Physical examination may reveal a pelvic mass, as was seen in our patient.

Ultrasonography is nonspecific and may show a unilateral echogenic cystic or solid mass, with no papillary projections and thickened endometrium.[3] Serum inhibin B, sAMH, and 17B estradiol may help in indicating toward the underlying pathology. Inhibin B has a reported sensitivity of up to 89% and specificity of almost 100%.[4] AMH is also a reliable tumor marker with sensitivity between 76% and 100%.[5] Our patient also had high inhibin B and sAMH values. sAMH and inhibin B are also useful for posttreatment follow-up and detection of tumor recurrence. Preoperative workup must include endometrial biopsy as endometrial hyperplasia is found in 25%–50% of cases, whereas endometrial carcinoma has been seen in 5%–13% of cases.[6] Final diagnosis is made on histopathology.

Surgery is the primary treatment modality. When fertility preservation is not desired, staging laparotomy through midline vertical incision involves total abdominal hysterectomy and bilateral salpingo-oophorectomy, exploration of peritoneal cavity, washings for cytology, multiple peritoneal biopsies, and omentectomy. Routine lymphadenectomy is not shown to improve survival.[7] In young patients with Stage 1a tumor, unilateral salpingo-oophorectomy is a feasible option.[8] As bilaterality is encountered in <2% patients, wedge biopsy of contralateral ovary is controversial. Complete surgery, although not imperative, can be considered after childbearing.[8]

A decrease in 25-year survival from 86% in patients with Stage Ia disease to 60% in patients with Stage Ic has been reported.[6] In a recent study by Park et al., the 5-year disease-free survival and overall survival rates in early stage (Stage I and II) disease were 89% and 99%, respectively, whereas, in advanced stage (Stage III and IV) disease, it was 72% and 80%, respectively.[9]

As patients with early stage disease (Stage I and II) have a very good prognosis, postoperative treatment is usually not required. Some studies have shown that patients with Stage Ic disease with poor prognostic factors such as large tumor size, high mitotic index, tumor rupture, or incomplete staging have a higher chance of relapse and may benefit with postoperative treatment.[10] Platinum-based chemotherapy (bleomycin, etoposide, and cisplatin) for 6 cycles is most commonly used for adjuvant chemotherapy in advanced stage. The response rates have varied from 60% to 93% and duration of response 5–58 months.[9] Radiation is not routinely recommended for treatment of primary tumor.[11]

Lifelong follow-up with clinical examination, ultrasound, and inhibin measurement is recommended as recurrences are late. For recurrent disease, combined modality of treatment, usually involving debulking of the disease followed by radiation or chemotherapy, is the norm and may prolong the DFS.[12] Hormonal therapies such as medroxyprogesterone acetate, megestrol acetate, tamoxifen, aromatase inhibitors, and gonadotropin-releasing hormone agonists have been tried for recurrent and advanced disease but with varied success.[6]

   Conclusion Top

GCT is indolent tumors which should be considered as differential diagnosis in infertility patients resistant to ovulation induction. Survival rates are high with primary treatment in early stages. Long-term surveillance is essential to detect late recurrences.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient has given her consent for her images and other clinical information to be reported in the journal. The patient understands that name and initial will not be published and due efforts will be made to conceal identity, but anonymity cannot be guaranteed.

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Conflicts of interest

There are no conflicts of interest.

   References Top

Ranganath R, Sridevi V, Shirley SS, Shantha V. Clinical and pathologic prognostic factors in adult granulosa cell tumors of the ovary. Int J Gynecol Cancer 2008;18:929-33.  Back to cited text no. 1
Zhang M, Cheung MK, Shin JY, Kapp DS, Husain A, Teng NN, et al. Prognostic factors responsible for survival in sex cord stromal tumors of the ovary – An analysis of 376 women. Gynecol Oncol 2007;104:396-400.  Back to cited text no. 2
Ko SF, Wan YL, Ng SH, Lee TY, Lin JW, Chen WJ, et al. Adult ovarian granulosa cell tumors: Spectrum of sonographic and CT findings with pathologic correlation. AJR Am J Roentgenol 1999;172:1227-33.  Back to cited text no. 3
Mom CH, Engelen MJ, Willemse PH, Gietema JA, ten Hoor KA, de Vries EG, et al. Granulosa cell tumors of the ovary: The clinical value of serum inhibin A and B levels in a large single center cohort. Gynecol Oncol 2007;105:365-72.  Back to cited text no. 4
Chang HL, Pahlavan N, Halpern EF, MacLaughlin DT. Serum müllerian inhibiting substance/anti-müllerian hormone levels in patients with adult granulosa cell tumors directly correlate with aggregate tumor mass as determined by pathology or radiology. Gynecol Oncol 2009;114:57-60.  Back to cited text no. 5
Kottarathil VD, Antony MA, Nair IR, Pavithran K. Recent advances in granulosa cell tumor ovary: A review. Indian J Surg Oncol 2013;4:37-47.  Back to cited text no. 6
Brown J, Sood AK, Deavers MT, Milojevic L, Gershenson DM. Patterns of metastasis in sex cord-stromal tumors of the ovary: Can routine staging lymphadenectomy be omitted? Gynecol Oncol 2009;113:86-90.  Back to cited text no. 7
National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology. 2018. Version 2.2018, [Last accessed on 2018 Mar 27].  Back to cited text no. 8
Park JY, Jin KL, Kim DY, Kim JH, Kim YM, Kim KR, et al. Surgical staging and adjuvant chemotherapy in the management of patients with adult granulosa cell tumors of the ovary. Gynecol Oncol 2012;125:80-6.  Back to cited text no. 9
Lee IH, Choi CH, Hong DG, Song JY, Kim YJ, Kim KT, et al. Clinicopathologic characteristics of granulosa cell tumors of the ovary: A multicenter retrospective study. J Gynecol Oncol 2011;22:188-95.  Back to cited text no. 10
Hauspy J, Beiner ME, Harley I, Rosen B, Murphy J, Chapman W, et al. Role of adjuvant radiotherapy in granulosa cell tumors of the ovary. Int J Radiat Oncol Biol Phys 2011;79:770-4.  Back to cited text no. 11
Mangili G, Ottolina J, Gadducci A, Giorda G, Breda E, Savarese A, et al. Long-term follow-up is crucial after treatment for granulosa cell tumours of the ovary. Br J Cancer 2013;109:29-34.  Back to cited text no. 12

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