Ovarian GCT is classified as a sex cord-stromal tumor and is treated as a borderline malignant tumor. These tumors show the clinical and pathological features of malignancy at a rate of 20 to 30%, and comprise 2 to 5% of ovarian malignant tumors [
1,
2]. Prognostically, the 5-year survival rate of patients with stage I or II disease is thought to be 95%, and that of patients with stage III or IV disease is 59% [
8]. However, some patients experience relapse 20 to 30
years after the initial surgery [
4,
5], and there have been a few reports published on the clinical phenotype of those with rapid progression [
6]. Jozwicki
et al. reported a patient with a very aggressive ovarian GCT, composed of granulosa, sarcomatoid, and fibrothecomatous tissues [
6]. The tumor recurred rapidly, and the patient died 16
months later [
6].
The histopathological characteristics of GCTs include cells with a coffee bean-like longitudinal nuclear groove and a micro-follicular structure termed the ‘Call-Exner body’. In patients with malignancy, a large number of mitoses and dyskaryoses are also seen. According to one report, the number of mitoses is a pathological prognostic factor [
9]. Alpha Inhibin-alpha is a sensitive immunohistochemical marker of GCT of the ovary, and is of value in the differential diagnosis of ovarian neoplasia [
10] as shown in the two patients presented.
Because it is difficult to distinguish GCTs from epithelial ovarian tumors pre-operatively, and because the accuracy of intraoperative rapid pathological diagnosis is not good, basic techniques used for the management of ovarian cancer (bilateral adnexectomy plus+total hysterectomy+plus omentectomy) and staging laparotomy are recommended as the initial therapy [
11]. Indications and protocols for adjuvant therapy have not yet been established because GCTs are rare, and a large-scale clinical study has not been conducted. In general, chemotherapy is recommended for patients with residual foci, a high risk of recurrence (tumor rupture, stage Ic or greater, a poorly differentiated tumor, or a tumor diameter of >100 to 150
mm); or actual recurrence. PVB (cisplatin
+
vinblastin
+
bleomycin) therapy [
12] and BEP (bleomycin
+
etoposide
+
cisplatin) therapy [
13] are considered effective regimens, based on the results of clinical studies that showed a relatively high response rate. The target of both therapies is the progressive, recurrent GCT, and the response rates to PVB and BEP therapies were given as 60.5% and 37%, respectively [
12,
13]. Although retrospective, a study of the combination therapy of taxane-based drugs and platinum-based drugs in patients with recurrences showed a response rate of 54% [
14]. Drugs with an anti-estrogenic effect, such as gonadotropin-releasing hormone agonists and aromatase inhibitors, have recently been suggested to be effective [
15-
17]. Aromatase inhibitors exhibit an anti-estrogen effect by binding to aromatase, an enzy\me required for the conversion of androgen to estrogen, and inhibiting its activity. Although aromatase inhibitors are used clinically to treat post-menopausal women with estrogen receptor-positive breast cancer [
18], there are some reports of patients in whom an aromatase inhibitor was effective against GCTs with repeated recurrences [
15-
17], as for patient 2.
Patient 1 had a reduction in the size of lesions in lymph nodes after BEP therapy, confirming the efficacy of the treatment. However, because serious interstitial pneumonia also occurred in this patient, as has been reported for other cases in which bleomycin was implicated in treatment-related death, the use of this treatment needs to be reconsidered. By contrast, even though the intraperitoneal tumor recurred in patient 2 after the start of aromatase inhibitor administration, the tumors were small, suggesting that the aromatase inhibitor slowed tumor growth, and that this drug is effective against recurrent tumors.
1 Takeshi Yanagita,1 Yukiko Matsumura,1 Kazuhiro Abe,1 Ryousuke Taniguchi,1 and Hideki Mizunuma1
