Brenner tumors (BTs) of the ovary are rare epithelial tumors that account for 1% - 2% of all ovarian neoplasms. Proliferative BT of the ovary was first described in 1971 by Roth and Sternberg [1] , and was confirmed by Miles and Norris [2] .

The terms of borderline malignancy and proliferating in reference to BTs were equated in the WHO publication [3] . It is a separate category of BT, being intermediate in its histologic appearance and biological aggressiveness compared with benign and malignant types of BTs [2] [4] [5] . There is a general agreement that BTs are derived from the surface epithelium of the ovary which has the properties of coelemic epithelium, and therefore, it undergoes metaplastic change to transitional or urothelial-like morphology [6] . We present here an extremely rare case of proliferative BT with borderline mucinous cystadenocarcinoma of the ovary in a 75-year-old woman, in which immunohistochemistry of CK 7 and CK 20 was useful for the diagnosis.

A 75-year-old Japanese woman, gravida 0, visited our hospital complaining of dyspnea with abdomen distension. She had undergone an abdominal hysterectomy and rt-salpingo-oophorectomy due to leiomyoma and rt-ovarian benign cystic tumor at the age of 40-year-old. She had a mild senile dementia. Thus, she might not notice the abdominal distension. The detailed examination with CT revealed right-massive pleural effusion (Figure 1) and no other tumors except for pelvic mass were detected. She inserted a thoracic trocar tube due to dyspnea before surgery. The detailed examination with MRI showed a 10 × 8 cm, combined with solid and cystic parts (Figure 2). In a solid area, small cysts were frequently seen. Diffusion-weighted MRI suspected malignant ovarian neoplasms (Figure 3). The preoperative serum tumor markers were showed that CA125 was 521.2 (normal ≤35 IU/ml), and CA19-9 was 83.3 (normal ≤37 IU/ml). Her plasma luteinizing hormone, follicle stimulating hormone, estradiol and testosterone were 0.87, 4.18, ≤10 and 0.37, respectively. The cytology of the pleural effusion was positive.

Under the working diagnosis of malignant ovarian tumor, the patient underwent an exploratory laparotomy and the lt-ovarian mass had adhered to the small intestine firmly. A massive ascites was also collected. The tumor was extracted after exfoliation from the small intestine. There were no peritoneal implants or metastases to other abdominal organs. The resected tumor size was over 10 cm in diameter, and the cut surface showed cystic areas with gelatinous material and solid areas of white-yellow (Figure 4). Cytology of the resected tumor suggested a mucus-producing malignant tumor (Figure 5).

The patient had a normal postoperative recovery without any complications. The diagnosis of proliferative BT with borderline mucinous cyst adenocarcinoma of the ovary was established from the histopathologic examination. Microscopically, the cysts were lined broad papillae with fibrovascular cores covered by transitional cells resembling low-grade transitional cell carcinoma of the urinary tract, with squamous metaplasia and mu-

cus-producing part (Figure 6(a)). No invasion was demonstrated. The immunohistopathological examination for the tumor was positive for CK 7 (Figure 6(b)) and negative for CK 20 (Figure 6(c)), suggesting the tumor arising from transitional cells, not from mucus-producing tumor. Based on these findings, the tumor was diagnosed as a proliferative BT with borderline mucinous cystadenocarcinoma, metastasizing to the pleura in FIGO stage IV.

The thoracic trocar tube was removed on post-operative day 7, because discharge of pleural effusion disappeared. She underwent four courses of chemotherapies with paclitaxel (135 mg/m²) and carboplatin (350

mg/body, AUC 5), accompanied in malignant BT cases [7] . The patient showed no signs of recurrence 16 months after the surgery.

Ovarian BTs are rare adenofibromas that account for 1% - 2% of all ovarian neoplasms. It is now generally accepted that BTs derive directly from the epithelium of ovarian cortex or from celomic inclusion cysts, which are formed by invaginations of the ovarian celomic epithelium [6] [8] [9] . Histologically, benign BTs have solid or microcystic epithelial cell nests surrounded by dense fibrous stroma. Borderline BTs resemble low-grade transitional carcinoma without stromal invasion, whereas malignant BTs resemble malignant invasive transitional carcinoma with stromal invasion. There is less intervening fibrous stroma in borderline and malignant BTs than in benign BTs [4] .

A BT is a rare adenofibroma of the ovary; the epithelial component consists of transitional cells similar to those observed in the urothelium. The most frequent histological subtypes are serous and mucinous lesions [2] [10] . In the present case, massive pleural effusion might be due to both pseudo-Meigs’ syndrome and metastasis

from the borderline mucinous cystadenocarcinoma derived from proliferative BT through metaplasia. Immunohistochemical profiles of the borderline mucinous cystadenocarcinoma and proliferative BT were same (positive for CK 7 and negative for CK 20) [11] . In addition, cytological findings of the pleural effusion were similar to those of the imprint cytology for the tumor. In the present case, the patient might not notice any subjective symptoms for a long time, until the ovarian mucinous tumor had metastasized to the pleura due to her senile dementia.

In general, the prognosis of a borderline BT is excellent. It is considered to be a tumor of very low risk for recurrence or metastases even many years after excision. Proliferative BTs presumably have non-aggressive biologic behavior, possibly because treatment involves the complete removal of the tumor. Generally, no therapy in addition to surgery is needed [12] . However, we considered that this case needed chemotherapy, because of the pleural metastasis, in a similar manner to malignant BTs [7] .

The authors declare that they have no competing interests.

We thank the editor and reviewers for their constructive comments, which helped us to improve the manuscript.