| Japanese Journal of Clinical Oncology | Pages |
Hemoperitoneum is an Initial Presentation of Recurrent Granulosa Cell Tumors of the Ovary
Introduction
Case report
Discussion
Acknowledgments
References
Hemoperitoneum is an Initial Presentation of Recurrent Granulosa Cell Tumors of the Ovary
INTRODUCTION
Although repeat of acute abdomen as the first presentation of recurrent ovarian carcinoma has been well documented, it often occurs within 5 years after initial treatment. Acute abdomen is often secondary to intestinal obstruction or partial intestinal obstruction; furthermore, the patients still undergo close regular follow-up. If an acute abdominal attack occurs 10 years later, it is rational to overlook the possibly of recurrent ovarian carcinoma. The following case report demonstrates such a rare occurrence.
Case report
A 44-year-old woman came to our emergency room with a chief complaint of acute abdomen for half a day. The patient's vital signs revealed a body temperature of 101°F, blood pressure 70/undetectable mmHg, pulse 142 beats/min and respiratory rate 30 breaths/min. Although looking pale, her consciousness was still clear. Laboratory data showed hemoglobin 5.6 gm/dl, platelet count 124 000/mm3 and normal renal and hepatic profiles. Physical examination showed generalized abdominal tenderness with significant rebounding pain and muscle guarding. She had a history of an exploratory laparotomy with the diagnosis of granulosa cell tumors (GST) of the left ovary stage IA (Fig. 1) when she was 34 years of age. At that time, in order to preserve fertility, unilateral salpingo-oophorectomy and complete staging surgery were performed. No adjuvant therapy was administered. She followed up regularly at our clinic and delivered a normal baby 3 years later. Other histories were unremarkable. Ten years after the initial treatment, she was well without evidence of recurrence. In this case, abdominal pain was abrupt followed by unstable vital signs. Under the impression of internal bleeding and pending shock, immediate laparotomy was performed and showing 3000 ml of hemoperitoneum and ruptured ovarian tumor of the right ovary. Macroscopic examination revealed predominantly cystic mass with numerous locules filled with clotted blood and separated by gray-white solid tissue. Frozen biopsy showed granulosa cell tumor of the right ovary (Fig. 2). A thorough staging surgery was followed including total abdominal hysterectomy, retroperitoneal lymph node sampling, infracolic omentectomy and excision of any suspicious lesions within the abdominal cavity. The final pathology confirmed GST of the right ovary; surgical-pathological staging IC was impressed owing to ruptured ovarian tumor pre-operatively. The patient then received six courses of postoperative adjuvant chemotherapy with CAP regimen (cisplatin 50 mg/m2, adriamycin 50 mg/m2 and cyclophosphamide 500 mg/m2, intravenously every 3 weeks). At present, the patient is alive without evidence of recurrent disease after 14 months.
Figure 1. Granulosa cell tumor composed of cords and gyriforms of granulosa cells. HE; ×100. Figure 2. Granulosa cell tumors. The cells have scant to moderate amounts of cytoplasm and pale, oval and angular nuclei. A few nuclei have grooves and prominent nucleoli. HE; ×200. Granulosa cell tumors of the ovary are frequently referred to as low-grade malignancies and are prognostically similar to epithelial borderline neoplasms of the ovary (1), probably because most of these tumors are diagnosed at an early stage and have a propensity for slow growth and late recurrence (2-23). Patients with late recurrence could be delayed for up to 10 years after initial diagnosis (Table 1). However, despite the rather large lesion at the time of diagnosis, 80-90% of patients will present with stage I disease (1). The majority of patients will present one or a combination of symptoms such as vaginal bleeding, abdominal distention and/or abdominal pain (1). Nevertheless, the last symptom is most attributable to the gross size of the tumor (15). Although sometimes acute abdominal pain will occur, the etiology of such acute severe pain is generally adnexal torsion, hemorrhage into the tumor or rupture of a cystic component (1). In fact, there are many case reports which have described acute abdominal pain secondary to rupture of GST (24-28). To our limited knowledge, this may be the first case of recurrent GST of the ovary that presented as an initial symptom and sign of recurrence by intra-abdominal bleeding and acute abdomen. Although proper staging surgery is warranted in any patient with ovarian GST, unilateral salpingo-oophorectomy is an appropriate therapy for women wishing to preserve fertility, especially stage IA tumor (29). It is acceptable that this patient received a conservative treatment. Furthermore, hysterectomy and salpingo-oophorectomy should be performed in menopausal women; if this was not done at the time of first surgery, the benefit of a second laparotomy to remove the internal reproductive apparatus is debatable (1). In addition, although accurate and complete staging was not performed in most of the published series, overall 10-year survival occurs consistently (70-90%) (1). Because of frequent late recurrence of ovarian GST, many studies have tried to evaluate some prognostic factors correlating such a phenomenon (12,30-32). Some hinted that Ki-67 reactivity (30) and p53 overexpression (30,32) are associated with stages of disease, recurrent onset and survival. Some believed that serum inhibin levels reflect tumor burden and may be valuable in assessing response to chemotherapy or predicting recurrent disease in women with ovarian GST (31). However, in a series from the Anderson Cancer Center, Houston, USA, they concluded that it is difficult to predict early recurrence and impossible to predict late recurrence using conventional clinical and pathological parameters (12). In our hospital, inhibin was still unavailable, so we cannot make any comment concerning the value of serum inhibin. Indefinite follow-up of patients with ovarian GST has been emphasized by others (7,20). Table 1. Our patient is a victim of recurrent ovarian GST. After completing staging surgery, what is the next step? Although responses to a number of combination regimens have been reported, the small number of patients in each series makes it difficult to draw definitive conclusions (1,33). These combination regimens include the combination of actinomycin D, 5-fluorouracil and cyclophosphamide (34), doxorubicin-cisplatin (35), doxorubicin-cisplatin-cyclophosphamide (CAP) (36-38), vincristine-actinomycin-D-cyclophosphamide (39), cisplatin-vinblastine-bleomycin (40-42) and bleomycin-etoposide-cisplatin (1,43). We selected the CAP regimen for six courses, showing satisfactory results because the patient has been followed for only 14 months. Although we could not comment on the benefit of this protocol for postoperative adjuvant chemotherapy, it is important that patients with these tumors are followed-up indefinitely. Ovarian GST has been reported to have high levels of receptors for gonadotropins (44) and gonadotropin-releasing hormone (GnRH) also has receptor sites identifiable in GST (45). A rationale for GnRH agonist use may be used based on the above-mentioned reason. Indeed, leuprolide acetate, a GnRH agonist, induced a partial response in two of four available patients (46). Two women had stable disease for 3 and 16 months. Treatment was well tolerated; therefore, GnRH-a might be used as a second line therapeutic modality for GST. In addition, in our experience, patients administered GnRH-a to treat persistent sex-cord tumor (steroid cell tumors of the ovary, non-specified) after complete operation have shown promising results (47). We have used GnRH-a as neoadjuvant therapy for managing a testosterone-secreting ovarian tumor when contraindicating urgent operation (48) or as an alternative therapy for patients with presumed ovarian androgen-secreting tumor deemed medically unable to tolerate surgery (49). In conclusion, late recurrence is a hallmark of ovarian GST. If an attack of acute abdomen is presented in these patients, a differential diagnosis of possible recurrence of GST should be made. Last of all, we emphasize the importance of lifetime follow-up.
DISCUSSION
Author
Time to presentation of recurrence (years)
Anikwue et al. [2]
24
Asschenfeldt and Thind [3]
24
Costa et al. [4]
19
Evans et al. [5]
23
Fox and Langley [6]
19
Hines et al. [7]
37
Hitchcock et al. [8]
26
Li and van der Walt [9]
22
Lusch et al. [10]
18
Malmstrom et al. [11]
18
Miller et al. [12]
>10
Pal and Chowdhury [13]
25
Pankratz et al. [14]
14
Piura et al. [15]
24
Sommers et al. [16]
26
Stage and Grafton [17]
13
Stenwig et al. [18]
22
Lee et al. (this work)
10
Acknowledgments
The authors acknowledge the contributions of Dr Jen-Yu Tseng for professional linguistic support and a grant (1998) from the Taipei Veterans General Hospital in Taiwan for editorial assistance.
References
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