Virilizing Steroid Cell Tumor of the Ovary: Successful Surgical Management of an Enigma

Background

Ovarian steroid cell tumors are an uncommon group of neoplasms classified under sex cord tumors. They account for less than 0.1% of all ovarian neoplasms [1] and have been known to present at any age. In this case report, we present the case of a 50-year-old lady with “not otherwise specified” subtype of ovarian steroid cell tumor who presented with features of hirsutism, male pattern baldness, uncontrolled diabetes, and hypertension, managed successfully with surgery and relieved of symptoms postsurgery.

Case Presentation

A 55-year-old postmenopausal, multiparous woman presented to our department with three-year history of hirsutism, male pattern baldness, change in character of voice, and six-month history of mass in the abdomen (Fig. 1). She also gave history of diabetes mellitus for the past 6 years for which she was on oral hypoglycemic agents and recent onset hypertension of 6 months duration for which she took antihypertensives. She had been diagnosed with malignant epithelial ovarian carcinoma at a peripheral hospital based on ultrasound-guided fine needle aspiration cytology. She had received three cycles of Paclitaxel plus carboplatin chemotherapy at the same hospital with apparently no response and she defaulted for six months with no further treatment taken. Her relevant blood investigations at presentation to our hospital are listed in Table 1. Contrast CT showed a heterogeneously enhancing complex solid cystic mass measuring 19.4 × 19.3 × 12.3 cm engulfing the uterus with multiple calcifications within and mild ascites (Fig. 2a).

Fig. 1.

Preoperative clinical appearance

Table 1.

Relevant blood investigations of the patient

Investigations done at diagnosis
Parameters	Lab value	Normal range
CA125	16.5 U/ml	< 35 U/ml
CEA	2.7 ng/ml	0–3.4 ng/ml
FSH	0.11 mIU/ml	19.3–100.6 mIU/ml
LH	0.22 mIU/ml	14.2–52.3 mIU/ml
Prolactin	6.35 ng/ml	5.18–26.5 ng/ml
b HCG	< 0.10 mIU/ml	0–1 mIU/ml
LDH	905 U/l	230–460 U/l
Inhibin	230.35 pg/ml	5.0–33 pg/ml
Testosterone	2143 ng/ml	0.15–0.51 ng/ml
DHEA – S	22.4 micgm/dl	29.70–182.20 micgm/dl
T3 total	0.78 ng/ml	0.6–1.8 ng/ml
T4 total	6.1 micgm/dl	5.0–12.4 micgm/dl
TSH	5.08 micIU/ml	0.35–5.5 micIU/ml
Investigations done after 6 months
Parameter	Lab value	Normal value
Inhibin	2.8 pg/ml	5–33 pg/ml
DHEA – S	24.10 micgm/dl	29.7–182.2 micgm/dl
Testosterone	20.08 ng/ml	14–76 ng/ml

Fig. 2.

Contrast CT of abdomen (a) and post operative gross appearance of tumor confined to left ovary with normal appearing uterus (b)

Patient underwent total abdominal hysterectomy with bilateral salphingoophrectomy and infracolic omentectomy. Intraoperatively, disease was found to be confined to the left ovary with no omental or peritoneal deposits. There were no enlarged or palpable lymph nodes in the bilateral iliac and paraaortic region.

Histopathology was suggestive of 18 × 12 × 6 cm well-encapsulated, bosselated mass in the left ovary with no capsular breach (Fig. 2b). It was composed of solid sheets of cells with eosinophilic and granular cytoplasm suggestive of steroid cell tumor of ovary not otherwise specified. Mitotic count was 1–2/10 hpf. Cells stained strongly positive for inhibin and calretinin and were negative for EMA. Patient had an uneventful postoperative period. Since her tumor was benign in nature, she was advised regular follow-up.

Our patient has been on follow-up for 2 years and so far, she has regression of virilizing symptoms with decrease in facial hair and male pattern baldness. Her serum testosterone levels fell to normal levels within 2 weeks of surgery and continued to remain within the normal range. Her inhibin and DHEA-S values were also within the normal range, 6 months after treatment completion. Values are listed in Table 1.

Discussion

Steroid cell tumors of the ovary are rare tumors arising from sex cord components of the ovary. They are usually benign and characterized by proliferation of steroid cells. They have been classified into three types, namely Leydig cell type, stromal luteal type, and not otherwise specified type which accounts for majority of the cases reported in medical literature [2]. The ovarian steroid cell tumors were first described by Hayes and Scully, who reported a case series of 63 cases [3]. In their paper, they identified five pathological features that are highly associated with malignancy, namely more than two mitoses per ten high-power fields, size of 7 cm or more, necrosis, hemorrhage, and Grade 2 or 3 nuclear atypia. Besides this case series, a number of case reports have been published describing steroid cell neoplasms of the ovary [4–7].

Patients with steroid cell tumors of the ovary usually present with complaints of amenorrhoea, oligomenorrhea, and features of virilization like regression in breast size, hirsutism, male pattern baldness, and clitoral hypertrophy. Our patient had features of hirsutism, male pattern baldness, and change in character of voice.

Patients who present with features of virilizing tumors should undergo testing for testosterone and dehydroxyepiandrosterone sulfate (DHEA-S) [8]. If values are elevated, they should be imaged using ultrasound of the abdomen with pelvis followed by contrast CT of the abdomen and pelvis. Our patient had elevated levels of inhibin, testosterone, and LDH along with new onset hypertension. Diagnosis of steroid cell tumors is confirmed by histopathology. Tumors are typically solid and composed of polygonal to round cells with distinct cell borders, abundant cytoplasm, and absence of Reinke’s crystals3. Inhibin and calretinin are used to differentiate sex chord tumors from other ovarian neoplasms.

Due to their low incidence, the role of radiotherapy and chemotherapy in management of steroid cell tumors is not clearly defined. Surgery is the mainstay of treatment [9]. In older postmenopausal patients, total abdominal hysterectomy with bilateral salphingoophrectomy is done, and in younger patients, if disease is unilateral, fertility reservation can be attempted. In patients with malignant or recurrent steroid cell tumors, chemotherapy can be given in the form of cisplatin, doxorubicin, cyclophosphamide [10] or Bleomycin, Etoposide, and Cisplatin [11]. Gonadotropin-releasing hormone agonists have been tried as an adjuvant therapy especially in recurrent settings [12] but currently there is no recommendation for using the same method.

High index of clinical suspicion in patients with ovarian mass and virilizing symptoms may help in early diagnosis and appropriate treatment. During follow-up, the patient should be evaluated clinically for progression or regression of virilizing symptoms and regular testing of serum testosterone should be done.

Conclusion

Steroid cell tumors of the ovary are rare neoplasms of the ovary presenting with androgenic symptoms. They are diagnosed clinically based on virilizing symptoms, high testosterone levels, and imaging. Diagnosis is confirmed by histopathology and immunohistochemistry. As most of these patients have benign disease, surgery is the definitive treatment. Malignant steroid cell tumors can be treated with chemotherapy.