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Arch Gynecol ObstetDOI 10.1007/s00404-014-3165-0

GynecOlOGIc OncOlOGy

Steroid cell tumor of the ovary in a pregnant woman whose androgenic symptoms were masked by pregnancy

Murat Öz · Emre Özgü · Mengü Türker · Salim Erkaya · Tayfun Güngör

Received: 20 December 2013 / Accepted: 16 January 2014 © Springer-Verlag Berlin Heidelberg 2014

Introduction

Ovarian steroid cell tumors are very rare sex cord-stromal tumors (ScST) comprising <0.1 % of all ovarian tumors. A subtype of this tumor type, called “not otherwise specified” (nOS) accounts for approximately one-half of all ovarian steroid cell tumors [1]. In a series of 63 cases from Mas-sachusetts General Hospital, 94 % of tumors were found unilateral and 28.6 % were malignant [2]. As the most of these tumors are diagnosed at an early stage and do not recur or metastasize, little is known about their response to therapies such as chemotherapy or radiation [2]. These tumors should be considered a cause of isosexual preco-cious puberty in children and virilization in adults, such as hirsutism, temporal balding and amenorrhea [3].

Case report

A 24-year-old primigravida was referred to our hospital at 39 weeks of gestation with a solid, homogenous tumor in the right adnexa (8 × 8 × 6 cm). She had noticed excessive hair growth in her face, legs, back and chest and acne formation in her face, chin and chest from the beginning of the pregnancy (Fig. 1). She had oligomenorrhea before pregnancy. Her voice was deepened and slight enlargement of her clitoris was noted (11 mm length). She was obese (body mass index was 41 kg/m2), and arterial blood pressure was 130/80 mmHg. laboratory analysis showed increased serum androgen levels (total testosterone = 112 nmol/l; dehydroepiandrosterone sulfate = 17.6 μmol/l; androstenedione = 412 nmol/l).

She had cesarean section at 39 weeks of gestation for the purpose of simultaneous exploratory laparotomy. A healthy, 3,860-g male fetus was delivered via cesarean section. APGAR scores for the infant were 7 and 9 for

Abstract Introduction Ovarian steroid cell tumors are very rare sex cord-stromal tumors, and most of them are unilateral and almost one-third of the cases are malignant.Case Report Here, we present a pregnant woman, who diagnosed with steroid cell tumor of the ovary and under-went surgical staging.Discussion We will discuss the clinical presentation of the case, management options and follow-up strategies.

Keywords Steroid cell tumor · Sex cord-stromal tumor · Virilization · Ovarian mass in pregnancy

M. Öz · e. Özgü · S. erkaya · T. Güngör Department of Gynaecological Oncology, Zekai Tahir Burak Women’s Health Hospital, Talatpasa Blv. Altindag, Ankara, Turkeye-mail: emreozgu@hotmail.com

S. erkaya e-mail: salimerkaya@yahoo.com.tr

T. Güngör e-mail: gungortayfun@yahoo.com

Present Address: M. Öz (*) Ugur Mumcu Mah. 1649. Sk. B6 blok no:2 yenimahalle, Ankara, Turkeye-mail: ozmurat@gmail.com

M. Türker Department of Pathology, Zekai Tahir Burak Women’s Health Hospital, Ankara, Turkeye-mail: mengubel@hotmail.com

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the fifth and tenth minutes postpartum, respectively. cys-tectomy was performed for the right ovary. There was no sign for peritoneal spread or metastasis. The mass was well circumscribed, 8 cm in diameter and had a pale pink cut surface with mild necrotic areas. The tumor was well differentiated and there were 4–5 mitotic figures per each 10 high-power field (HPF) (Fig. 2). Immunohistochemi-cal staining was performed. Tumoral tissue showed dif-fuse immunostaining for calretinin and inhibin, whereas there were no tissue staining for eMA, synaptophysin, chromogranin, S-100 and SAl-4. These findings were

consistent with ovarian steroid cell tumor, not otherwise specified.

Serum androgen levels decreased to normal levels short after the surgery. Serum total testosterone and androstene-dione levels were 1.1 and 3.9 nmol/l, respectively, 2 weeks after the surgery.

The patients had a second laparotomy for staging pro-cedure because the tumor had necrosis and showed 4–5 mitotic figures per 10 HPF, 2 months after the initial sur-gery. Right salpingo-oophorectomy with systematic bilat-eral pelvic and para-aortic lymph node dissection, omen-tectomy and appendectomy as well as exploration of all peritoneal surfaces with peritoneal washings was per-formed. left adnexa and uterus were left in situ for fertil-ity preserving purpose. All dissected lymph nodes (total of 24), right ovary, omentum, appendix and peritoneal wash-ings were negative for tumor metastasis.

The patient was discharged after 6 days of un-eventful postoperative follow-up.

A written informed consent was obtained from the patient for publication purposes.

Discussion

Steroid cell tumor of the ovary was first described by Scully in 1979 [4]. There are three steroid cell tumor sub-types: steroid cell tumors nOS, stromal luteomas and leydig cell tumors. Steroid cell tumors nOS, account for approximately 60 % of all steroid cell tumors of the ovary [5]. Steroid cell tumors are generally composed of granular eosinophilic or vacuolated cytoplasm which is often posi-tive for fat stains. In addition to these microscopic findings, steroid cell tumors would require immunohistochemical markers for accurate diagnosis. Inhibin and calretinin are the most useful markers for discrimination of ScST from other ovarian neoplasms [6]. And steroid cell tumors are mostly negative for eMA [7].

Virilization is the most common symptom in steroid cell tumors nOS, occurring in 56–77 % of all patients [8]. The average age at diagnosis is 43 years [5, 9, 10]. In most cases, both androstenedione and testosterone levels are elevated with serum levels of androstenedione increasing more than testosterone [11] but serum total testosterone level is a good tumor marker for follow-up of disease. The source of excessive serum levels of testosterone (usually above 20 ng/l) is almost always ovarian tissue in female [6].

We found a total of 122 reported ovarian steroid cell tumor cases in PubMed search. Most of them are case reports, three of them are reported as patient series [10, 12, 13], but there is only one case diagnosed during preg-nancy [14]. In this report, clinical presentation was pretty

Fig. 1 24-year-old patient with BMI 41 kg/m2 suffering from acne formation and excessive hair growth in her face

Fig. 2 Mitotic figures are shown. (H&e staining ×40 mag.)

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much similar with our case like deepening of voice, facial hirsutism and elevated serum androgen levels. The patient had undergone exploratory laparotomy with left salphingo-oopherectomy at 16 + 5 weeks gestation. eventually at 23 + 6 gestational weeks, the patient had preterm labor with contractions and cervical dilatation. The fetus had died during labor and the patient delivered a male fetus of 640 g with no obvious macroscopic malformations.

When maternal virilization is observed during preg-nancy, several diagnoses have to be considered includ-ing, ovarian pathology, adrenal pathology and iatrogenic causes. The luteoma of the pregnancy and hyperreactio luteinalis are the most common benign causes for maternal virilization during pregnancy [15]. ScST are less common and may have malignant potential [8]. Male fetus usually was not affected, as well as virilization for female fetus is uncommon due to excessive aromatization capacity of the placenta [16].

In adults, approximately 25–43 % of all steroid cell tumors are malignant. However, most of these tumors are diagnosed in an early stage and do not recur or metastasize [17]. Hayes and Scully [10] determined the pathological characteristics, which are most predictive of malignancy (Table 1).

Our patient met the first three criteria which are highly associated with malignancy. In our patient, the disease was confined to one ovary, means Stage 1A disease according to the FIGO Staging system for ovarian neoplasms, further adjuvant therapy is not necessary even though histologi-cal behavior of the tumor is malignant. The average age of patients with a malignant steroid cell tumor nOS is higher than of those with benign tumor; 54 and 38 years, respec-tively [10].

like other ScST of the ovary, steroid cell tumors are managed surgically. Solid mass in the ovary, or cystic mass >5 cm in diameter which does not diminish during follow-up or becomes symptomatic, are indications for surgical intervention during pregnancy [15, 18]. Malignant ster-oid cell tumors nOS should be managed with appropriate staging procedure followed by combination chemotherapy

as necessary [19]. Wang et al. [20] suggested that ovar-ian androgen secreting tumors depend on continuous gon-adotropin stimulation. Therefore, GnRH-agonists could be an adjuvant therapy in managing persistent or recurrent hormone producing steroid cell tumors of the ovary [11]. Treatment should be individually based on pathological and histological features of the tumor, surgical stage of dis-ease, and desire for future fertility.

Conflict of interest The authors certify that no conflict of interest in relation to this article exists.

References

1. Kim yT, Kim SW, yoon BS, Kim SH, Kim JH, Kim JW et al (2007) An ovarian steroid cell tumor causing virilization and massive ascites. yonsei Med J 48(1):142–146

2. Selvaggi SM (2000) Tumors of the ovary, maldeveloped gonads, fallopian tube, and broad ligament. Arch Pathol lab Med 124(3):477

3. Jiang W, Tao X, Fang F, Zhang S, Xu c (2013) Benign and malignant ovarian steroid cell tumors, not otherwise specified: case studies, comparison, and review of the literature. J Ovarian Res 6(1):53

4. Scully R (1979) Tumors of the ovary and maldeveloped; Atlas of Tumor Pathology, vol pt 16, 2nd edn. Armed Forces Institute of Pathology, Washington, pp 215–220

5. Wang PH, chao HT, lee Rc, lai cR, lee Wl, Kwok cF et al (1998) Steroid cell tumors of the ovary: clinical, ultrasonic, and MRI diagnosis–a case report. eur J Radiol 26(3):269–273

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9. Reedy MB, Richards We, Ueland F, Uy K, lee ey, Bryant c et al (1999) Ovarian steroid cell tumors, not otherwise specified: a case report and literature review. Gynecol Oncol 75(2):293–297

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11. Brewer cA, Shevlin D (1998) encouraging response of an advanced steroid-cell tumor to GnRH agonist therapy. Obstet Gynecol 92(4 Pt 2):661–663

12. li y, Guo DH (2009) Ovarian steroid cell tumor: clinico-pathologic study of 6 cases. Zhonghua Bing li Xue Za Zhi 38(9):621–622

13. Jones MW, Harri R, Dabbs DJ, carter GJ (2010) Immunohis-tochemical profile of steroid cell tumor of the ovary: a study of 14 cases and a review of the literature. Int J Gynecol Pathol 29(4):315–320

14. Sielert l, liu c, nagarathinam R, craig lB (2013) Androgen-pro-ducing steroid cell ovarian tumor in a young woman and subsequent spontaneous pregnancy. J Assist Reprod Genet 30(9):1157–1160

15. Mcclamrock HD, Adashi ey (1992) Gestational hyperandrogen-ism. Fertil Steril 57(2):257–274

Table 1 Pathological characteristics of steroid cell tumors nOS associated with malignancy

Pathologic characteristics of malignancy Percentage associated with malignancy (%)

Two or more mitotic figures per 10 HPF

92

Tumor necrosis 86

Tumor diameter >7 cm 78

Tumor hemorrhage 77

Grade 2–3 nuclear atypia 64

From Hayes and Scully [9]

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16. lo Jc, Schwitzgebel VM, Tyrrell JB, Fitzgerald PA, Kaplan Sl, conte FA et al (1999) normal female infants born of mothers with classic congenital adrenal hyperplasia due to 21-hydroxy-lase deficiency. J clin endocrinol Metab 84(3):930–936

17. liu AX, Sun J, Shao WQ, Jin HM, Song WQ (2005) Steroid cell tumors, not otherwise specified (nOS), in an accessory ovary: a case report and literature review. Gynecol Oncol 97(1):260–262

18. young RH, Dudley AG, Scully Re (1984) Granulosa cell, Sertoli-leydig cell, and unclassified sex cord-stromal tumors associated with pregnancy: a clinicopathological analysis of thirty-six cases. Gynecol Oncol 18(2):181–205

19. nichols cR, catalano PJ, crawford eD, Vogelzang nJ, einhorn lH, loehrer PJ (1998) Randomized comparison of cisplatin and etoposide and either bleomycin or ifosfamide in treatment of advanced disseminated germ cell tumors: an eastern cooperative Oncology Group, Southwest Oncology Group, and cancer and leukemia Group B Study. J clin Oncol 16(4):1287–1293

20. Wang PH, chao HT, lee Wl (1998) Use of a long-acting gon-adotropin-releasing hormone agonist for treatment of steroid cell tumors of the ovary. Fertil Steril 69(2):353–355