J o u r n a l o f C a s e s i nObs te trics & G ynecology

J Cases Obstet Gynecol, 2017;4(2):45-48

Case Report

Granulosa cell tumor of the ovary: An incidental finding during caesarean section

Safinaz Abdelrahman1, Saeeda ALBalooshi1, Safa ALShaikh2, Roopa Arora2, Hafsa ALBuarki1,*

1Department of Obstetrics and Gynecology, Salmaniya Medical Complex, Kingdom of Bahrain2 Department of Pathology, Salmaniya Medical Complex, Kingdom of Bahrain

Abstract

Approximately one-fourth of the ovarian neoplasms and cysts are diagnosed incidentally during caesarean section. The possibility of malignancy should be considered although existence of ovarian malignancy in pregnancy is rare. A 24-year-old pregnant woman was admitted to our hospital at 38 weeks of gesta-tion for cesarean section in view of Breech presentation, fortuitously during intraoperative pelvic examination; a large ovarian unhealthy mass was detect-ed. Thus, the team proceeded with oophorectomy and removal of the tumor. Histopathological findings, including immuno-histochemical study, led to the diagnosis of juvenile granulosa cell tumor (JGCT). In this report, the histological features of the JGCT and the optimal management of such adnexal masses during pregnancy are discussed. A JGCT that is confined to the ovary appears to have an excellent prognosis and can be treated by unilateral oophorectomy.

Key Words:

Granulosa cell tumor, oophorectomy, pregnancy, ovarian cancer

Introduction

Article History:Received: 11/12/2016Accepted: 28/01/2017

*Correspondence: Dr. Hafsa ALBuarkiAddress: Department of Obstetrics and Gynecology, Salmaniya Medical Com-plex, Manama, Kingdom of Bahrain. P.O. Box 12Tel: 00973 17284511E- mail: hafsaivf@hotmail.com

Journal of Cases in Obstetrics & Gynecology45

Approximately 24% of the ovarian tumors are incidentally discovered at caesarean section, inspite of the routine pre-natal ultrasonography [1]. This underlines the importance of instilling ovarian examination habit at operation. Granu-losa cell tumors of the ovary are a rare ovarian malignancy presenting 3-5% of ovarian tumors. Histologically, there are two distinct types of granulosa cell tumor: the most com-mon type is the adult granulosa cell tumors with a frequen-cy of 95% of all granulosa cell tumors; it occurs usually in perimenopausal and post-menopausal women with a peak

incidence at 50-55 yrs. The second type is the juvenile gran-ulosa cell tumors, which is less frequent and rare; presenting 5% of granulosa cell tumors and common in young women [2]. Those tumors are the most frequent hormone - secreting ovarian tumors and are generally characterized by insidious growth, low malignancy potential and late recurrence [3].Occurring in patients with an active sexual life and in repro-ductive age, granulosa cell tumors can be associated with pregnancy. In the literature, 10% of granulosa cell tumors were discovered during pregnancy [3]. The management of this association is a real challenge because it must consider the pregnancy and the fertility outcome. We report a case of malignant juvenile-type granulosa cell tumor (GCT) found incidentally during caesarean section performed in our hos-pital. So far, very few such cases have been reported world-wide that not only its rarity adds to a diagnostic dilemma but also to the difficultly in the formulation of a definite plan of management and follow-up protocol remains a tricky territo-ry along with individualization of treatment for each patient.

J o u r n a l o f C a s e s i nObs te trics & G ynecology

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Case Presentation

A 24-year old primigravid women without any known medical illnesses with an uneventful antenatal period, presented at 38 weeks’ gestation to our obstetrics & gy-necology emergency department with painful abdominal contractions. The Abdomen was soft and non-tender on ex-amination. Blood pressure was 116/66 mmHg, pulse 106/min and normal temperature. CTG was reactive. Ultra-sound confirmed a single viable fetus within the uterus with breech presentation. The team decided for caesarean section in view of breach presentation in labor and a baby girl (3.0 kg) was delivered, Apgar scores were 9-10-10. Intraopera-tively, proceeding further, a large unhealthy nodular ovari-an mass was found measuring 20x11x4 cm (approximately 300gr) and there was yellowish ascetic fluid Figures (1) (2). The left ovary was normal in size and shape. Right oopho-rectomy was performed and the specimen sent for histopa-thology with peritoneal wash for cytology. The rest of the operation and post-operative period went uneventfully and the patient was discharged on the forth post-operative day. Histological examination showed juvenile granulosa cell tu-mor of the right ovary that composed of variably sized lob-ules with focal cyst formation. Neoplastic cells were mono-morphic with round to oval vesicular nuclei and prominent nucleoli. Some foci showed frequent mitoses. Figures (3) In term of immunostaining; the tumor cells were positive

for calretinin Figures (4), WT1 and Vimentin (strong and diffuse) Figures (5) and negative for CK7, AFP, AE1, AE3, Synaptophysin, Chromogranin and inhibin. CK20 was in-conclusive and regarding Reticulin, the stain showed rich staining around theca cell clusters but tumor showed poor reticulin. The tumor was FIGO IA staged (i.e. Exact Stage of the disease cannot be declared because of the absence of the full staging surgery. In this situation the patient was accept-ed as stage IA disease). Peritoneal wash was examined mi-croscopically with cytospin preparation and appeared nega-tive for malignant cell. The tumor marker CA 125 level was normal 9.3 U/mL (normal less than 35 U/mL), CA 15-3 was slightly elevated 39.3 U/mL (normal less 31.3) and all other tumor markers profiles were within normal reference ranges.In view of the potential risk for recurrence; the follow-up plan for this patient will include regular Clinic follow up appointments with detailed history and abdomino-pelvic examination in each visit, Ultrasound after three months along with tumor markers mainly Ca 125, B-hCG, Al-pha-fetoprotein (AFP) profile and Inhibin level. She was also scheduled in 6 Months for abdomino-pelvic com-puted tomography (CT). The couple agreed also for long-term follow-up and showed a good understanding.

Figure 1.

Gross of the right ovarian tumor measuring 21x11x4cm (approx. 300 gm.) with smooth intact capsule.

Figure 2.

Cross-section of the ovary showing mucinous nodular mass with multiple filled with mucinous to clear fluid.

Discussion

Sex cord–stromal tumors account for approximately 7% of all malignant ovarian neoplasms, and their extreme rar-ity represents a limitation in our understanding of their natural history, management, and prognosis.4 This group of tumors includes granulosa cell tumors, thecomas, Ser-toli-Leydig cell tumors, and gynandroblastoma.3,4 Most malignant sex cord–stromal neoplasms are GCTs [4]. Routine pelvic examination and ultrasonic scan aids diag-nosis of 62.7% of ovarian tumors in early pregnancy, 3 and the rest goes undetected as it happened in our case. In most patients, the presenting manifestation is usually abdominal pain or swelling. Some present with menstrual irregulari-ties or amenorrhea. Postmenopausal women usually present with uterine bleeding. Some others present during pregnan-cy as persistent breech presentation like our patient with failure to turn head-down or as obstructed labor, which at-tributed to the large ovarian mass causing the obstruction.

Journal of Cases in Obstetrics & Gynecology47

ALBuarki et al.

The immunoprofile of our patient was unusual and unique as it was inhibin negative and calretinin pos-itive on Immunohistochemistry (IHC). Although in-hibin has been shown to be a sensitive marker for ovar-ian sex cord-stromal and fibrous neoplasms, it may be negative in some cases. A negative inhibin on IHC does not exclude a diagnosis of GCT [5]. Calretinin, a meso-thelial marker is particularly useful in the diagnosis of sex cord-stromal and fibrous neoplasms that are inhibin negative.

Surgery remains the mainstay of initial management for patients with suspected sex cord– stromal tumors [6]. Surgery is necessary to establish a definitive tissue diag-nosis, perform staging, and debulk as much gross dis-ease as possible in case of advanced disease. The surgi-cal principles are generally identical to those used in the management of epithelial ovarian cancer, including the need for a vertical midline incision for advanced disease,which allows adequate visualization of the upper abdomen, along with careful inspection of the omentum, underside of the diaphragm, paracolic gutters, and bowel serosa.Many literatures indicate that more than 90% of these neo-plasms are unilateral and confined to the ovary [5]. Thus, a fertility-sparing surgery with unilateral salpingo-oophorec-tomy and staging seems to be reasonable in patients wish-ing to preserve their fertility in the absence of extra-ovarian spread as was performed in our patient [5]. Removals of the

Figure 3.

Photomicrograph (HPF) showing monomorphic neo-plastic cells with round to oval nuclei in diffuse sheets and prominent nucleoli with lack coffee bean nuclei that seen in adult type.

Figure 4.

Positive Immunohistochemical staining for calretinin

References

1. Kottarathil VD, Antony MA, Nair IR, Pavi-thran K. Recent Advances in Granulosa CellTumor Ovary: A Review. Indian Jour-nal of Surgical Oncology. 2013;4(1):37-472. Van Holsbeke C, Domali E, Holland TK, Acht-en R, Testa AC, Valentin L. Imaging of gyneco-logical disease (3): clinical and ultrasound char-acteristics of granulosa cell tumors of the ovary. Ultrasound Obstet Gynecol. 2008 Apr;31(4):450-6.3. Chen YC, Chang LC, Soong RS. A late recurring

and easily forgotten tumor: ovarian granulosa cell tumor. World J Surg Oncol. 2012 May 16;10:85.4. Lauszus FF, Petersen AC, Greisen J, Jakobsen A. Granulosa Cell Tumor of the Ovary: A Popula-tion-Based Study of 37 Women with Stage I Dis-ease. Gynecol Oncol. 2001 Jun;81(3):456- 60.5. Geerts I, Vergote I, Neven P, Billen J. The Role of Inhibins B and Antimullerian Hormone for Diagnosis and Follow-up of Granulosa Cell Tu-mors. Int J Gynecol Cancer. 2009 Jul;19(5):847-55.

6. Korach J, Perri T, Beiner M, Davidzon T, Frid-man E, Ben-Baruch G. Promising Effect of Aro-matase Inhibitors on Recurrent Granulosa Cell Tu-mors. Int J Gynecol Cancer. 2009 Jul;19(5):830-3.7. Marret H, Lhommé C, Lecuru F, Canis M, Lévèque J, Golfier F et.al. Guidelines for the management of ovarian cancer during pregnancy. Eur J Ob-stet Gynecol Reprod Biol. 2010 Mar;149(1):18-21

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J o u r n a l o f C a s e s i nObs te trics & G ynecology

other ovary and total abdominal hysterectomy are reasonable considerations at the conclusion of childbearing and post- menopause, though this point is still controversial. Some authors reported a worse survival for patients undergoing fertility-sparing surgery, but this was related mostly to a higher stage of disease in the group analyzed [5,6]. No post-operative treatment is required for patients with early stage disease (stage I and II) as they have a very good prognosis with five-year disease-free-interval and overall- survival of 89 % and 99 % respectively [3]. However, patients with advanced stages of disease associated with poor prognostic factors like large tumor size or high mitotic index, have a higher chance of relapse, and may benefit with postoperative treatment but role of chemotherapy is still debatable [3, 5].

In case there is any evidence of recurrence during fol-low-up, keeping in mind that most recurrences are con-fined to the abdomen and pelvis, an abdominopelvic CT scan should be performed to look for recurrent tumors. Other imaging studies may be ordered as indicated by physical examination findings. Long-term follow-up is re-quired in all patients with GCTs because at least 50% of recurrences are found more than 5 years after initial treat-ment. Recurring granulosa cell tumors of the ovary are usually treated by surgical resection, chemotherapy or radiation, or a combination of the treatment modalities. However, the results of such treatment are disappointing. Recurrent ovarian granulosa cell tumors may also be treat-ed with an aromatase inhibitor, with promising results [7].Approximately one-fourth of the ovarian neoplasms and cysts are diagnosed incidentally during caesarean section. We report a case of a rare solid malignant tumor of the ovary incidentally found during caesarean section. Oophorectomy was done and histopathology revealed it to be a granulosa cell tumor. Equipped with these knowledge physicians can be made aware of the existence of this little-known ovarian neoplasm along with its rare association with pregnancy. Also one can better manage, counsel and follow-up the patients after delivery, given the knowledge of the tumors’ inevita-ble malignant potential and its high incidence of recurrence.

AcknowledgementNone

Declaration of InterestNone

Figure 5.

Diffuse, strongly positive Immunohistochemical staining for vimentin