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Case Study: Management with fertility preservation of an ovarian juvenile granulosa cell tumour
Management with fertility preservation of an ovarian
juvenile granulosa cell tumour presenting with
retroperitoneal spread and bilateral ureteric obstruction
Du Toit GC, MBChB, MMed, FCOG/LKOG(SA)
Part-Time Consultant, Unit of Gynaecological Oncology, Tygerberg Hospital, University of Stel enbosch Correspondence to: George du Toit, e-mail: [email protected]
Keywords: juvenile granulosa cel tumour, ureteric obstruction, fertility preservation
Peer reviewed. (Submitted: 2013-03-04. Accepted: 2013-05-07.) SASGO South Afr J Gynaecol Oncol 2013;5(1):33-35 dl. Beta human chorionic gonadotropin  (hCG), lactate dehydrogenase (LDH) and α-fetoprotein levels were Metastatic and recurrent ovarian juvenile granulosa normal. A computed tomography scan revealed a large cell tumours in young women are an uncommon abdominal tumour with solid and cystic areas. The uterus condition.1,2 Primary management in young patients was displaced to the left and the origin of the tumour includes surgery with subsequent chemotherapy could not be documented. Bilateral hydronephrosis, in selected cases. Fertility-preservation surgery more pronounced on the right, was present, and may be possible, while still achieving appropriate generalised ascites with enlarged lymph nodes below cytoreduction and staging procedures. Retroperitoneal the level of the renal vessels were noticed. There was loss spread to lymph nodes is rare and lymphadenectomy of tissue planes between the right psoas muscle and the is not routinely recommended.3 Recurrent disease or tumour, as wel as loss of plane between the tumour and persistent disease may require further surgery and the right internal iliac vessels (Figure 1).
once again, it may be possible to preserve fertility without compromising oncological outcome.
Case history
An 18-year-old nulliparous patient presented with a 24-hour history of nausea and vomiting. She reported experiencing abdominal pain for a week. The pain was exacerbated with the onset of nausea and vomiting. The patient noted no change in bowel motions and reported a normal menstrual cycle since menarche at 14 years. A clinical examination showed signs of a dehydrated patient with tachycardia. An abdominal examination revealed a 28-week mass. On palpation, the mass was fixed and tender. Bowel sounds were present. A gynaecological examination disclosed a virgo intactum. An ultrasound uncovered a semi-solid abdominal mass with bilateral hydronephrosis and ascites. Management included admission, rehydration and analgesia. Blood tests showed a raised white cell count, a raised erythrocyte sedimentation rate, a Figure 1: Sagital section with hydronephrosis (black arrow)
raised C-reactive protein and haemoglobin of 10.1 g/ and mass (white arrows) South Afr J Gynaecol Oncol


Case Study: Management with fertility preservation of an ovarian juvenile granulosa cell tumour
Case Study: Management with fertility preservation of an ovarian juvenile granulosa cell tumour
Preoperative hydronephrosis, ascites and retro- peritoneal disease favoured a malignant tumour. The normal serum tumour markers made an malignant germ cell tumour unlikely. The patient was counselled and consented to cytoreductive surgery without preservation of fertility, or with preservation of fertility dependant on operative findings.
During surgery, ascites and a large omental tumour, adherent to the anterior abdominal wall and encasing the small bowel, was encountered. The omentum was freed with sharp dissection from the anterior abdominal wall, and an infracolic omentectomy was performed. Pelvic access was obtained by sharp dissection between the mass and the anterior abdominal wall. The right retroperitoneal plane was entered using Figure 2: Haematoxylin and eosin stain revealing proliferating
atypical cells with a predominant solid growth pattern, but the technique as described by Hudson, and the right- with occasional follicles (arrow). These follicles are lined by sided hydroureter freed to the level of the uterine granulosa cells which blend into the intervening diffusely artery.4 The right-sided obturator fossa was filled with the tumour, and it was removed with sharp dissection from the underlying blood vessels. The intact right (PC) and was in remission at three months follow-up. ovary could be identified separate from the mass. A She reported a normal menstrual cycle.
tumour, adherent to the bladder, was freed with sharp dissection. The left ovary was totally displaced by the tumour. The left retroperitoneal space was entered and the left hydroureter freed to the level of the uterine Granulosa cell tumours account for 2% of ovarian artery. The tumour displaced the entire left ovary and tumours, and can be divided into adult (95%) a left-sided salpingo-oophorectomy was performed. and juvenile (5%) histological types. JGCTs occur Further examination of the abdomen revealed a small predominantly in women under the age of 30. A bowel loop encased in the tumour. A resection with nulliparous state is seen in 30%. In up to 80% of anastomosis was performed. cases, the tumours are associated with isosexual pseudopuberty. Virilising symptoms, hirsutism and On completion of the surgery, the only residual oligomenorrhoea occur in 3%. Oestrogen production tumour was in the subdiaphragmatic areas with small results in endometrial hyperplasia (30%) and (less than 1 mm) peritoneal seedlings. The surgical endometrial adenocarcinoma in 8% of cases.1 The result was optimal cytoreduction of a tumour arising majority of juvenile tumours present with unilateral within, displacing the left ovary and spreading intra- localised disease. A clinical examination reveals peritoneally, retroperitoneally and to the omentum.
palpable masses in up to 95% of cases and ascites in 10%. The differential diagnosis of solid ovarian masses Histology confirmed a juvenile granulosa cell in young women includes germ cell tumours and sex tumour (JGCT) (Figure 2). Immunohistochemistry cord stromal tumours. Malignant germ cell tumours was positive for S100, vimentum, inhibin and calretin. may be associated with raised tumour markers, e.g. Epithelial membrane antigen (EMA), CD30, beta hCG, beta hCG, LDH and α-fetoprotein.
chromagranin and α-fetoprotein immunohistochemistry were negative. Submucosal smal bowel involvement Tumour markers can be useful in the management with tumour embolus formation was documented. of primary or recurrent JGCTs.2 Raised inhibin The bladder's muscularis propria was infiltrated by the distinguishes stromal ovarian tumours from other ovarian neoplasms, but is not specific to granulosa cell tumours. Raised serum oestradiol is present in Subseqeunt to histological confirmation, blood levels approximately 70% of cases. MIF and calretin are of estradiol and Müllerian inhibiting factor (MIF) were potential serum markers. In the current case, serum normal. The patient received six courses of bleomycin, oestradiol and MIF levels were normal. Initial surgery etoposide, and cisplatin (BEP) chemotherapy. At in younger women includes fertility-preservation six months fol ow-up, an asymptomatic, 35.5 mm procedures, e.g. unilateral salpingo-ooferectomy. x 34 mm right-sided pelvic solid mass was diagnosed The preservation of the uterus and right ovary in by ultrasound. The mass was completely resected at the current case represents a unique approach to relaparotomy. Histology confirmed a JGCT. The patient preserve fertility in advanced-stage disease. Surgical underwent six courses of paclitaxel and carboplatin staging is limited to intraperitoneal procedures and South Afr J Gynaecol Oncol Case Study: Management with fertility preservation of an ovarian juvenile granulosa cell tumour
Case Study: Management with fertility preservation of an ovarian juvenile granulosa cell tumour
Case Study: Management with fertility preservation of an ovarian juvenile granulosa cell tumour
lymphadenectomy should be omitted.5 Brown et tailored surgery with chemotherapy resulted in the al reported 111 cases of completely and partially preservation of fertility.
staged patients with no lymph node involvement. The authors reported that 67% of cases were diagnosed as stage I, and 22% as stage III disease.3 The current case presented with widespread disease and this 1. Kanthan R, Senger J, Kanthan S. The multifaceted granulosa cell is unusual. Abu-Rustum and Thrall documented tumours - myths and realities: a review. ISRN Obstet Gynecol. similar findings with regard to pelvic and paraaortic 2. Geetha P, Nair MK. Granulosa cell tumours of the ovary. Aust N Z lymphadenectomy, thus, as part of initial staging, it is J Obstet Gynaecol. 2010;50(3):216-220.
not warranted.6,7 Metastatic disease requires optimal 3. Brown J, Sood AK, Deavers MT, et al. Patterns of metastasis cytoreductive surgery. Prognosis links directly to in sex cord-stromal tumors of the ovary: can routine staging a residual tumour on completion of the surgery. lymphadenectomy be omitted? Gynecol Oncol. 2009;113(1):86- Lymphadenectomy may be indicated in cases of bulky lymph nodes.
4. Hudson CN. Surgical treatment of ovarian cancer. Gynecol Oncol. 8 Features that are associated with poor prognosis include advanced-stage disease, tumours 5. Sehouli J, Drescher FS, Mustea A, et al. Granulosa cell tumor of of more than 5 cm in diameter and high mitotic count the ovary: 10-year follow-up data of 65 patients. Anticancer Res. (more than 10 human papillomavirus types) with nuclear atypia and the absence of Call-Exner bodies.2 6. Abu-Rustum NR, Restivo A, Ivy J, et al. Retroperitoneal nodal metastasis in primary and recurrent granulosa cell tumors of the Chemotherapy is indicated in advanced and recurrent ovary. Gynecol Oncol. 2006;103(1):31-34.
disease. Currently, the Gynaecology Oncology Group is 7. Thrall MM, Paley P, Pizer E, et al. Patterns of spread and recurrence of sex cord-stromal tumors of the ovary. Gynecol Oncol. performing a randomised control trial that compares BEP to PC in this scenario.8 In disease recurrence 8. Gershenson DM. Current advances in the management of subsequent to primary chemotherapy, Tao et al malignant germ cell and sex cord-stromal tumors of the ovary. reported antiangiogenic activity in eight cases that Gynecol Oncol. 2012;125(3):515-517.
were treated with bevacizumab.9 Hormonal suppression 9. Tao X, Sood AK, Deavers MT, et al. Antiangiogenesis therapy with treatment with aromatase  inhibitors, megestrol and bevacizumab for patients with ovarian granulosa cell tumors. Gynecol Oncol. 2009;114(3):431-436. tamoxifen, and a gonadotropin-releasing hormone (GnRH) antagonist in recurrent ovarian granulosa cell 10. Ameryckx L, Fatemi HM, De Sutter P, Amy JJ. GnRH antagonist in the adjuvant treatment of a recurrent ovarian granulosa cell tumours has been described with conflicting reports tumor: a case report. Gynecol Oncol. 2005;99(3):764-746.
of efficacy.10-13 Chemotherapy has the potential for 11. Hardy RD,  Bell JG,  Nicely CJ,  Reid GC. Hormonal treatment of premature ovarian failure. Whitehead et al reported a a recurrent granulosa cell tumor of the ovary: case report and 100% return of menstruation in patients who received review of the literature. Gynecol Oncol. 2005;96(3):865-869.
BEP chemotherapy.14 Fertility-preservation surgery and 12. Tamura R, Yokoyama Y, Yanagita T, et al. Presentation of two chemotherapy with subsequent normal pregnancy has patients with malignant granulosa cell tumours, with a review of the literature. World J Surg Oncol. 2012;10:185. been documented.15 13. 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(1):340-344.
The current case of ovarian JGCT illustrates that 14. Weinberg LE,  Lurain JR, Singh DK,  Schink JC.  Survival and retroperitoneal spread of disease, even if uncommon, reproductive outcomes in women treated for malignant ovarian germ cell tumors. Gynecol Oncol. 2011;121(2):285-298.
may occur. This spread resulted in hydronephrosis. 15. Powell JL, Connor GP, Henderson GS. Management of recurrent The case further illustrates that lymphadenectomy juvenile granulosa cell tumor of the ovary. Gynecol Oncol. was needed as a debulking procedure and that South Afr J Gynaecol Oncol

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